Cellulose dressing and method to deliver hypochlorite to wounds
A pre-incubated cellulose wound dressing addresses the challenge of delivering hypochlorite safely by absorbing and releasing it at low, effective concentrations, enhancing wound care efficacy and handling.
Patent Information
- Application Number
- PCT/EP2024/054972
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2024-02-27
- Publication Date
- 2025-09-04
AI Technical Summary
Existing wound dressings do not effectively deliver hypochlorite at safe, therapeutically effective concentrations without causing harm, due to its high reactivity and toxicity, limiting its use in wound care applications.
A cellulose-based wound dressing is pre-incubated with an aqueous OCl- solution, followed by a washing step to minimize reactive groups, allowing it to absorb and release hypochlorite at low, non-toxic concentrations for effective disinfection.
The pre-incubated cellulose dressing efficiently delivers hypochlorite at safe concentrations, providing effective disinfection while minimizing skin damage, and can be combined with commercially available antiseptics for improved handling and application.
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Figure EP2024054972_04092025_PF_FP_ABST
Abstract
Description
[0001] CM 16-P36743PC00 Cellulose dressing and method to deliver hypochlorite to woundsField of the inventionThe present invention refers to a wound dressing comprising cellulose comprising 90 wt.% or more of an aqueous liquid, and 10 wt.% or less and more than 0 wt.% of dry mass cellulose, as well as to a method for preparing such wound dressing. The presentinvention further refers to a sterile package comprising the wound-dressing of the presentinvention, to an aqueous OCl- -containing solution for use in a wound treatment, and for use in the prevention and / or treatment of inflammation. Finally, the present invention refers to a kit of parts comprising the wound dressing of the present invention and an aqueous OCl- -ion-containing solution, and to the wound dressing for use in a method oftreating wounds as well as for use in the prevention and / or treatment of inflammation.Description of the background art The classic role of wound dressings is to provide the best possible conditions for woundhealing, while at the same time the wound is protected from further trauma (damage) andinvasion by pathogens. A wound dressing should meet at least one of the following requirements: for example it should be biocompatible, it should provide a certain mechanical safety, provide for a suitable gas exchange, exudate absorption and moisture management, and it should also be easy to handle and be compatible with furthersolutions such as medical solutions (e.g., antiseptic solutions) that may be necessary forwound healing or that at least contribute advantageously to wound healing. Wounds can be classified according to many parameters, such as etiology, healing time, depth of injury, complexity, contamination status, mode of lesion, appearance, and also the colour of the injured tissue. Dependent on the classification of wound, an appropriate wound dressing has to be chosen. Examples of wound dressings are dressings fromcotton wool, lint, or gauze; and dressings including hydrogels, hydrocolloids, or semi-permeable films. As listed above, a possible material of wound dressings is cotton wool, that is, cellulose. Cellulose can be of plant origin, or of bacterial origin. Cellulose of bacterial origin is for example bacterial nanocellulose (BNC).Although there is already a large number of wound dressings available, there is still aneed for improved wound dressings that provide advantages e.g. in terms of applicability, effectiveness, and / or handling. Summary of the invention Various aspects, advantageous features and preferred embodiments of the present invention as summarized in the following items, respectively alone or in combination, contribute to solving the object of the invention.1. Wound dressing comprising a cellulose component, wherein the cellulosecomponent comprises 90 wt.% or more of an aqueous liquid, and 10 wt.% or less and more than 0 wt.-% of dry mass cellulose, wherein (A) the cellulose component exhibits substantially no carbonyl peak at 1735 cm-1+ / - 2 cm-1as determined by Fourier transform infrared (FTIR) in an infrared absorbanceATR spectrum; and / or(B) wherein the wound dressing has been pre-incubated with an aqueous OCl- -ion- containing solution. 2. Wound dressing according to item 1, wherein the cellulose component of thewound dressing does not exhibit a carbonyl peak at 1735 cm-1 + / - 2 cm-1 as determinedby FTIR in an infrared absorbance ATR spectrum, due to the wound-dressing having been pre-incubated with an aqueous OCl- -ion-containing solution, excluding a wound dressing that was not pre-incubated with an aqueous OCl- -ion-containing solution. 3. Wound dressing according to item 1 or 2, wherein the cellulose component isbacterial cellulose, preferably bacterial nanocellulose.4. Wound dressing according to any of the preceding items, wherein the aqueous OCl- -ion-containing solution, which was used for the wound dressing having been pre- incubated, is a reagent-grade solution having an OCl- concentration from 0.025% to 4%,preferably from 0.05% to 1.5%, more preferably from 0.05% to 1.0%, or from 0.1% to1.0%, and even more preferred from 0.05% to 0.5%, in particular the aqueous OCl- -ion- containing solution has an OCl- concentration of about 0.2% (0.2% + / - 0,05%). 5. Wound dressing according to any of the preceding items, wherein the aqueousOCl- -ion-containing solution, which was used for the wound dressing having been pre-incubated, is a sodium hypochlorite or hypochlorous acid solution. 6. Wound dressing according to any of the preceding items, wherein the wound- dressing has been pre-incubated with 3 to 8, preferably 4 to 7 volumes, more preferably5 volumes, of the aqueous OCl- -ion-containing solution, preferably in a concentrationfrom 1 to 10%, more preferably in a concentration from 2 to 8%, even more preferably in a concentration from 3 to 7%, and most preferably in a concentration from 4 to 5%. 7. Wound dressing according to any of the preceding items, wherein the pre-incubation has been carried out for 15 min. to 3 h, preferably for 15 min. to 2.5 h, morepreferably for 30 min to 2 h. 8. Wound dressing according to any of the preceding items, wherein after the wound dressing has been incubated, a washing step has been carried out. 9. Wound dressing according to any of the preceding items, wherein the cellulose of the wound dressing comprises 95 wt.% or more of an aqueous liquid, and 5 wt.% or less of dry mass cellulose.10. Wound dressing according to any of the preceding items, wherein the aqueousliquid and the cellulose dry mass add up to 100 wt.%. 11. Wound dressing according to any of the preceding items, wherein the wound dressing comprises, in addition to the cellulose comprising aqueous liquid and thecellulose dry mass, further components not affected by, or reacting with OCl-.12. Wound dressing according to any of the preceding items, wherein the wound dressing comprises, in addition to the cellulose comprising aqueous liquid and the cellulose dry mass, one or more further active compounds other than OCl- that does / donot interact with OCl- , preferably said further one or more active compound is / areantiseptics other than OCl-, in particular said further one or more active compound is / are antiseptics selected from the group consisting of polyhexanide (PHMB), octenidine or octenidine hydrochloride, chlorhexidine, chlorhexidine-digluconade, polyvidone (PVP)- iodine, and mafenide. 13. Wound dressing according to any of the preceding items, wherein the aqueous liquid is inert, which means that it does not react with other substances. 14. Wound dressing according to any of the preceding items, wherein the aqueousliquid is an isotonic solution, preferably the aqueous liquid is Ringer’s solution, AcetatedRinger`s solution, or a 0.9% NaCl solution. 15. Wound dressing according to any of the preceding items, wherein (C) the cellulose of the wound dressing exhibits a substantially lower molecular massdistribution of the cellulose polymer chain, when compared to the originally same cellulose material of a wound dressing that was not pre-incubated with an aqueous OCl- -ion-containing solution. 16. Wound dressing according to any of the preceding items, wherein the averagechain length of the cellulose of the wound dressing exhibits a cellulose chain length, asdetermined by a Gel Permeation Chromatography (GPC) with Multi-Angle Light Scattering Detection (MALS) method, is (i) 62.0-90.0 Mn[kg / mol], preferably 66.0-80.0 Mn[kg / mol], more preferably 68.0- 79.0 Mn[kg / mol], even more preferably 67.0-79.0 Mn[kg / mol], and most preferably 75.0-79.0 Mn [kg / mol]; and / or(ii) 100.0-180.0 Mw[kg / mol], preferably 150.0-167.0 Mw[kg / mol], more preferably 160.0-167.0 Mw[kg / mol]; and / or (iii) 220.0-290.0 Mz[kg / mol], preferably 250.0-275.0 Mz[kg / mol], more preferably 265.0-275.0 Mz[kg / mol]; and / or(iv) reduced by at least 1.0 [kg / mol] with respect to Mn [kg / mol], and / or Mw [kg / mol],and / or Mz[kg / mol], when compared to a non pre-incubated wound dressing. 17. Wound dressing according to item 16, wherein all conditions (i) to (iv) apply.18. Wound dressing according to any of the preceding items, having a thickness of0.02-10 mm and / or a length of 2-45 cm and / or a width of 2-45 cm, preferably the wound dressing has a dimension of 5 cm x 5 cm, 10 cm x 10 cm, 15 cm x 20 cm, or 20 cm x 20 cm; or wherein the wound dressing is a face mask, preferably with a length of 10-50 cm and / ora width of 10-50 cm, more preferably with a length of 20-45 cm and / or a width of 20-45cm. 19. Wound dressing according to any of the preceding items, having a dry mass corresponding to 1.5% to 3.5%, preferably 1.8% to 3.3%, more preferably 2.0% to 3.0%of the wet mass. 20. Sterile package containing a wound dressing according to any of the preceding items. 21. Method for preparing a wound dressing, preferably a wound dressing accordingto any one of items 1 to 19, comprising the steps of:(i) providing a wound dressing comprising a cellulose component, wherein the cellulose component comprises 90% or more aqueous liquid and 10% or less cellulose (dry mass); (ii) incubating the wound dressing, preferably the cellulose of the wound dressing of(i), with an aqueous OCl- -ion-containing solution, optionally using an aqueous OCl- -ion-containing solution as defined in item 3 or 4, preferably with a 0.1-0.5% NaOCl solution, more preferably for 1-5 h; (iii) washing the incubated wound dressing obtained in (ii), thereby obtaining the wound dressing. 22. Method according to the preceding item, wherein the cellulose of the wound dressing of (i) comprises 95 wt.% or more of an aqueous liquid, and 5 wt.% or less of dry mass cellulose.23. Method according to any of the preceding items, wherein the aqueous liquid andthe cellulose dry mass add up to 100 wt.%. 24. Method according to any of the preceding items, wherein the wound dressing comprises, in addition to the cellulose component comprising aqueous liquid and thecellulose dry mass, further components.25. Method according to any of the preceding items, wherein the aqueous liquid is inert, preferably the aqueous solution is Ringer solution or a 0.9% NaCl solution. 26. Method for preparing a ready-to-use wound dressing, comprising the steps of (i) to (iii) of item 21 to prepare a pre-incubated wound dressing, and subsequently comprising a step of: (iv) loading the pre-incubated wound dressing obtained in (iii) with an aqueous OCl- -ion-containing solution having an OCl- concentration in a range from 0.005% to 2.000%,preferably 0.005% to 1.500%, more preferably from 0.010% to 1.500%, even more preferably from 0.010% to 1.000%, and most preferably from 0.015% to 0.500%; or having an OCl- concentration in a range from 0.025% to 2.000%, preferably 0.100% to1.500%, further preferred 0.100% to 0.500%.In a preferred embodiment, the pre-incubated wound dressing obtained in (iii) is loaded with an aqueous OCl- -ion-containing solution having an OCl- concentration in a range from 0.005% to 1.5%, preferably from about 0.015% to 0.5%. The indicated range of from about 0.015% to 0.5% is particularly suitable if the thus- obtained ready-to use wound dressing is for use in a method of controlling infections. 27. Method according to item 26, wherein the aqueous OCl- -ion-containing solutionis a commercially available antiseptic, preferably an antiseptic that is suitable for beingused in wound treatment, e.g., Granudacyn®, Lavanox®, or Actimaris®Forte. 28. Method according to item 26 or 27, further comprising the step of (v) loading the pre-incubated wound dressing, either prior to, simultaneously with, orsubsequent to step (iv) with anyone of further active compounds other than OCl-,preferably wherein the further active compounds comprise antiseptics other than OCl-, in particular an antiseptic selected from the group consisting of polyhexanide (PHMB), octenidine or octenidine hydrochloride, chlorhexidine, chlorhexidine-digluconate, polyvidone (PVP)-iodine, and mafenide. 29. A wound dressing as defined in any of items 1 to 19, which is further loaded with an aqueous OCl- -ion-containing solution having an OCl- concentration in a range as defined in item 26.In a preferred embodiment, the aqueous OCl- -ion-containing solution has an OCl-concentration in a range from 0.005% to 1.500%, preferably from about 0.015% to 0.500%. 30. Aqueous OCl- -ion-containing solution having an OCl- concentration in a range asdefined in item 26, for use in a wound treatment, e.g., burns, wherein a wound dressingas defined in any of items 1 to 19 is loaded with said aqueous OCl- -ion-containing solution, optionally directly before the treatment and then applying the loaded wound dressing onto the treatment site.In a preferred embodiment, the aqueous OCl- -ion-containing solution has an OCl-concentration in a range from 0.005% to 1.500%, preferably from about 0.015% to 0.500%. 31. Aqueous OCl- -ion-containing solution having an OCl- concentration in a range asdefined in item 26, for use in the prevention and / or treatment of inflammation in a mammal,especially a human, preferably in the prevention and / or treatment of an inflammatory response in uncontaminated or non-infected surgical sites, wounds, trauma sites, internal inflammatory lesions or surface inflammatory lesions where there is no infection, such as in leg ulcers or other venous ulcers, or in the prevention and / or treatment of an inflammatoryskin condition such as mouth ulcers, eczema or psoriasis,wherein a wound dressing as defined in any of items 1 to 19 is loaded with said aqueous OCl- -ion-containing solution, optionally directly before the treatment and then applying the loaded wound dressing onto the treatment site. In a preferred embodiment, the aqueous OCl- -ion-containing solution has an OCl- concentration in a range from 0.005% to 1.500%, preferably from about 0.015% to 0.500%.32. Wound dressing according to item 29, or aqueous OCl- -ion-containing solutionfor use according to item 30 or 31, wherein the OCl- concentration is 0.1% to 1.5%, preferably 0.1% to 0.5%, or wherein the the OCl- concentration is 0.005% to 1.000%, preferably 0.010% to 0.090%. In a preferred embodiment, the OCl- concentration is in a range from 0.005% to 1.500%, preferably from about 0.015% to 0.500%. 33. Aqueous OCl- -ion-containing solution for use according to anyone of items 30 to32, wherein the wound treatment is antibacterial wound treatment.34. Kit of parts comprising (i) a wound dressing according to any of items 1 to 19, and (ii) an aqueous OCl- -ion-containing solution having an OCl- concentration in a rangeas defined in item 26, optionally further comprising(iii) further active compounds other than OCl-, preferably wherein the further active compounds comprise antiseptics other than OCl-, in particular an antiseptic selected from the group consisting of polyhexanide (PHMB), octenidine or octenidine hydrochloride, chlorhexidine, chlorhexidine-digluconate, polyvidone (PVP)-iodine, andmafenide.In a preferred embodiment, the OCl- concentration in (ii) is in a range from 0.005% to 1.500%, preferably from about 0.015% to 0.500%. 35. Use of a wound dressing according to any of items 1 to 19 for being loaded with an aqueous OCl- -ion-containing solution having an OCl- concentration in a range as defined in item 26.36. Use according to item 35, wherein the aqueous OCl- -ion-containing solution hasan OCl- concentration between 0.1% to 1.5%, preferably between 0.1% to 0.5% or wherein the the OCl- concentration is 0.005% to 1.000%, preferably 0.010% to 0.090%.In a preferred embodiment, the OCl- concentration is in a range from 0.005% to 1.500%,preferably from about 0.015% to 0.500%. 37. Use according to item 35 or 36, wherein the aqueous OCl- -ion-containing solution is a commercially available antiseptic, e.g., Granudacyn®, Lavanox®, orActimaris®Forte.38. Wound dressing as defined in any of items 1 to 19 for use in a method of treating wounds, such as burns.39. Wound dressing as defined in any of items 1 to 19, for use in the prevention and / ortreatment of inflammation in a mammal, especially a human, preferably in the prevention and / or treatment of an inflammatory response in uncontaminated or non-infected surgical sites, wounds, trauma sites, internal inflammatory lesions or surface inflammatory lesions where there is no infection, such as in leg ulcers or other venous ulcers, or in the preventionand / or treatment of an inflammatory skin condition such as mouth ulcers, eczema orpsoriasis.Brief description of the drawings Fig. 1 depicts antiseptic compounds used to treat infected wounds. Shown are the molecular structure and weight of compounds used in combination with BNCs. Fig.2 depicts the uptake and release capacity for bacterial nanocellulose (BNC) loadedwith 10 kDa, 70 kDa and 2,000 kDa fluorescein isothioeyanate labelled dextran (FITC-dextran) molecules. Percentage of uptake relative to the maximum absolute loading capacity of BNC (100%). * marks the significant difference (p<0.05) of the uptake of 2000 kDa FITC-dextran in comparison to the 10 kDa and 70 kDa FITC-dextrans (A). Relative concentration of FITC-dextran molecules remaining in BNC punches to the startingconcentration of each molecule. * marks the significant difference (p<0.05) in the releaseof the FITC-dextran molecules in comparison to all the other molecules (B). Diffusion profile of the FITC-dextran molecules on agarose gel. Longitudinal section of the agarose gel after contact with 8 mm BNC loaded punches for 2 h and 24 h (C). Values are shown as mean ^ SD. Fig.3 shows a hypochlorite ion detection assay using aminophenyl fluorescin (APF). Fig. 3A shows the OCl- concentration present in three commercially available hypochlorite-based antiseptic solutions (Actimaris®Forte, Lavanox® and Granudacyn®) and in two standard solutions, containing 1% and 3% NaOCl, obtained throughfluorescence intensity after short incubation with aminophenyl fluorescein (APF). Resultsexpressed in mean and standard deviation (SD). Fig.3B shows the APF Hydroxyl quantification. Fig.4 depicts the uptake of antiseptic solutions into BNC dressings.Fig. 4A to 4C shows the uptake results obtained after 10, 30 and 60 minutes of anincubation process using Granudacyn® (4A), Lavanox® (4B) and Actimaris®Forte (4C). Volumes of antiseptics 5, 10 and 20 times the volume enclosed in the BNC were used for the incubation process. Hypochlorite concentration in the post-incubation solution for each antiseptic was also measured. Results expressed in mean and standard deviation (SD). Fig.5 shows the hypochlorite concentration influence on the uptake results. Particularly, Fig. 5 shows the Incubation of BNC dressing using 5 times of standard hypochlorite solutions with 0.2%, 0.1%, 0.05% and 0.025% of OCl-. Prior to the ion detection assay, all the analyzed solutions were diluted to match the same final concentration. Resultsexpressed in mean and standard deviation (SD).Fig. 6 shows the influence of the solution comprised in the BNC dressing on the ion detection assay. Particularly, Fig.6 shows the hypochlorite concentration measured for Lavanox® and Actimaris®Forte solution mixed 1:1 with water, as negative control, andmixed 1:1 with the BNC solution extracted from the dressing. Actimaris® Forte solutionwas also mixed 1:1 with a 0.9% NaCl solution and a commercially available Ringer solution. Results are expressed in mean and standard deviation (SD). Fig. 7 shows the pre-treatment influencing the uptake results for low concentratedhypochlorite antiseptic. Specifically, Fig. 7 shows the difference on uptake capacity forGranudacyn® incubated with BNC dressing and with BNC dressing after the modification procedure. Results expressed in mean and standard deviation (SD). Fig.8 shows the molecular mass distribution of the cellulose polymer chain in the BNCdressing. The diagram shows the influence of the treatment with NaOCl on the molecularmass of the polymer chain. Fig.9 shows Infrared absorbance ATR spectra for the different BNC dressing preparation. Fourier transform infrared (FTIR) by attenuated total reflectance (ATR) spectra of the BNCdressing (-Ctrl), BNC dressing after a 30 min (30’), 120 min (120’) and 3 days (+Ctrl)incubation time with a 0.2% hypochlorite standard solution. Highlighted the spectra recorded over the range 1500-1850 cm-1. White arrows pointing two peaks, at ~1735 cm-1and at ~1615 cm-1(A). Another view of the spectra between 1850-1500 cm-1. Dotted lines indicating peaks corresponding to ~1615 cm-1, ~1635 cm-1and ~1735 cm-1. Fig.10 shows the stability of the hypochlorite molecules loaded into the BNC dressings. Uptake concentration of Actimaris® Forte solution over 2 weeks for two BNCs (epicitehydroand Suprasorb® X) without treatment and after the modification process are shown in Fig. A. Curve fit analysis of the stability over time are shown in Fig. B. Results expressed inmean and standard deviation (SD).Fig.11 shows ZOI assay results for antiseptics loaded into the BNC dressing. Adapted zone of inhibition (ZOI) assay results, expressed in percentage of the ZOI obtained for the solution control, for Staphylococcus aureus. BNC dressing after 10, 30 and 120 minincubation with Actimaris® Forte solution using 5, 10 and 20 times the volume enclosedin the BNC (Fig.11A), BNC dressing after 120 min incubation with Lavanox® 5, 10 and 20 times the volume present in the BNC dressing (Fig.11B) and BNC and modified BNC dressing after 120 min incubation with Granudacyn® with 5 times its volume (Fig.11C). Images of the ZOI for the BNC dressing (-Ctrl), non pre-incubated BNC loaded withGranudacyn® (Unmod.), pre-incubated BNC loaded with Granudacyn® (Mod.) andGranudacyn® solution (+Ctrl) (D) Results expressed in mean and standard deviation (SD). Detailed description of the invention Wound dressings are used to treat surgical or non-surgical lesions, such as burns or abrasions. Wound dressings can comprise various types of materials, for example cellulose. It has been shown that cellulose dressings that comprise cellulose component / material exhibiting a comparably low dry mass cellulose content (such asmore than 0 wt.% but 10 wt.% or less) and a comparably high water content (such as 90wt.% or more), for example bacterial nanocellulose (BNCs) dressings like e.g., epicitehydrosold by QRSKIN GmbH, are useful for delivering antiseptic compounds like the ones shown in Figure 1 [1]. As exemplified by the wound dressing epicitehydrosold by QRSKIN GmbH, due to its low cellulose content (<3%) and high-water content (>97%) the materialcan be soaked with commercially available antiseptic solutions leading to a fast diffusionof the active molecules into the dressing (see Table 1.): stock Antiseptics 30 min 60 min 120 min MBC24for MRSA solution LAVANID®2 (PHMB) 400 110 190 230 Betaisodona® (PVP) 100,000 10,000 20,000 50,000 1,024[2] Table 1: of the antiseptic solutions bacterial nanocellulose in comparison to the concentration (MBC) against methicillin-resistant Staphylococcus aureus (MRSA). Concentration in mg / L of LAVANID®2, Prontosan®, Octenisept® and Betaisodona® inBNC sheets after incubation periods of 30, 60 and 120 min. Last column shows the MBC24for (MRSA). PHMB – Polyhexanide and PVP - Polyvinylpyrrolidone. The dressing can then release the active compounds delivering the antiseptic activity [4]. This protocol has already been used in several burn centers to treat patients after soakingof the dressing in different antiseptic solutions in the surgery room prior to the application to the burn wounds [5-7]. In Fig. 1, the molecular structure and weight of antiseptic compounds used in combination with BNCs and used to treat infected wounds are shown. For example, in the antiseptic solution LAVANID® the antiseptic compound polyhexanide (PHMB) is present, a compound of 186 Dalton (Da). None of these antiseptic compoundscomprises a hypochlorite / hypochlorous acid. Bacterial nanocellulose serves as an example of the cellulose component / material of the present invention that exhibits the properties of comprising 90 wt.% or more of an aqueous liquid, and 10 wt.% or less of dry mass cellulose. While bacterial nanocellulose provides excellent use performance, any cellulose comprising 90 wt.% or more of an aqueousliquid, and 10 wt.% or less and more than 0 wt.% of dry mass cellulose can be used instead. Using prototype substances of different molecular size, it was shown that diffusion into and from the BNC is dependent on the size of the molecule (see Figure 2.) [4]: By loading BNC with 10 kDa, 70 kDa, and 2,000 kDa fluorescein isothiocyanate labelled dextran (FITC-dextran) molecules it was shown, e.g., that the bigger the size of the molecule, the greater the percentage of molecules that were retained on the BNC punches. Hypochlorous acid (HOCl), which is a major inorganic bactericidal compound of innateimmunity, is effective against a broad range of microorganisms. However, owing to itschemical nature and the high toxicity resulting therefrom, it has never been used as a pharmaceutical drug for treating infections formulated into a matrix used in wound dressings. It has high reactivity to a lot of bio- / synthetic materials used as wound dressings (such as cellulose) and its limited stability. The cytotoxicity of aqueous chlorine can causeamongst others cellular damage and pain.Nonetheless, due to its high effectiveness, there is a need for an improved wound dressing that is able to absorb (take up) OCl- and to release it on the affected site, e.g. a wound, in an amount (concentration) that is sufficient for a comparable safe disinfection of theaffected site.The present invention is based on experiments performed while studying the uptake of OCl- from different commercially available hypochlorite wound care solutions as summarized in Table 2:
[0002] Table 2. List of commercially available hypochlorite wound care products [8] Based on what has been known previously, namely that diffusion into and from the BNC (which is exemplary for all cellulose materials and especially for all nanocelluloses with the properties disclosed herein, that is, exhibiting a comparably low dry mass cellulosecontent of above 0 wt.% and 10 wt.% or less, and a comparably high water content of 90wt.% or more), is dependent on the size of the molecule, with the greater the size, the slower the diffusion into and from the BNC, it was assumed that a small molecule like OCl- ions should be taken up and released efficiently by a BNC with a high-water content. However, it was found that only solutions with a comparably high OCl- content – andtherefore being potential damaging to the skin – show a considerable uptake (and release)of the ions. In the present invention it has now surprisingly been found that this problematic effect could be counteracted by pre-incubation of the cellulose component such as thenanocellulose, which preferably is BNC, with a defined hypochlorite solution, optionallyfollowed by a washing step removing the residual hypochlorite. Such a conditioned (pre- incubated) nanocellulose is well suited to take up and release OCl- even at low concentrations as formulated in products like Veriforte®, Microdayn60® and Granudacyn®. Thus, the pre-incubated (conditioned) cellulose is very well suitable forbeing soaked / loaded with antiseptic solutions comprising hypochlorite in comparably lowconcentrations (such as commercially available antiseptics), which soaked, pre-incubated cellulose, if applied to an affected site such as a wound region, then releases OCl- at concentrations that are sufficient for disinfecting the affected site and at the same time do not or at least not significantly cause harm to the affected site. It has further been foundthat the OCl- concentration of the conditioned nanocellulose can reliably and reproduciblybe set to a defined value, even a comparably low value, while at the same time the soaked, conditioned nanocellulose, upon applying it to an affected site (or lesion), still exhibits sufficient therapeutic activity (effect). Due to the comparably low OCl- concentration, the occurrence of side effects that can be caused by OCl- is largely or even completelyprevented. The ability of the pre-incubated cellulose of taking up and release the antiseptic OCl- at comparably low concentrations is further advantageous in multiple aspects: For example, the strong oxidative property of OCl- on the one hand makes it a powerful broad-spectrum disinfectant. On the other hand, however, this strong oxidative power can also pose aserious threat to health, and thus, it is preferred to administer this disinfectant inconcentrations as low as possible for the envisaged purpose. Accordingly, commercially available disinfectants usually contain OCl- in comparably low concentration ranges, e.g. less than 0.2%, or less than 0.08%. There may however be situations which require that the OCl- is provided to a comparable big affected area, e.g. in case of burn wounds, and / orsituations where it is desired that the OCl- is released over a prolonged time period. Inthese cases, it is desired to have the OCl- on (in) a wound dressing that can be applied comparatively easy to the affected area, which wound dressing at the same time absorbs and releases sufficient OCl- for being effective. Moreover, as the wound dressing of the present invention can be combined withcommercially available disinfectants and antiseptics (which usually comprise the OCl- ina comparably low concentration), the present invention can further provide a wound dressing that is improved e.g., with regard to handling. The present invention does meet relevant needs and does provide a wound dressingwhich exhibits improved properties.These as well as further objects, which will become apparent from the following description of the present invention, are attained by the subject matter of the independent claims. Some of the preferred embodiments of the present invention are defined by thesubject matter of the dependent claims.Thus, the present invention refers to a wound dressing comprising a cellulose component / material, wherein the cellulose comprises 90 wt.% or more of an aqueous liquid, and 10 wt.% or less and more than 0 wt.% of dry mass cellulose. Additionally,according to the present invention, this cellulose exhibits substantially no carbonyl peakat 1735 cm-1+ / - 2 cm-1as determined by Fourier transform infrared (FTIR) in an infrared absorbance ATR spectrum (condition (A)), and / or the wound-dressing comprising said cellulose has been pre-incubated with an aqueous OCl- -ion-containing solution (condition (B)). It has been surprisingly been found that a wound-dressing comprising said cellulose having been pre-incubated with an appropriate aqueous OCl- -ion-containing solutioncellulose exhibits substantially no carbonyl peak at 1735 cm-1 + / - 2 cm-1 (as determinedby Fourier transform infrared (FTIR) in an infrared absorbance ATR spectrum), and thereby can be distinguished from unsuitable cellulose which – without being accordingly pre-incubated – normally does exhibit a noticeable carbonyl peak at 1735 cm-1+ / - 2 cm-1in such a FTIR of an infrared absorbance ATR spectrum.It is preferred that the aqueous liquid is inert, which means that it does not react with othersubstances. In general, wound dressings are covers of a wound such as a skin lesion. They protect the wound from external invasion, prevent infection on the wound site and contribute tothe regeneration and restoration of the injured tissue such as epidermis and dermis layers.There exist multiple types of different wound dressings, with the main material underlying these wound dressings being natural (such as collagen, gelatin, cellulose, or dextran), semi-synthetic (cellulose derivatives), or synthetic (such as polyanhydrides, poly(esteramide)s, polycarbonates). The wound dressing of the present inventioncomprises cellulose as described herein.The cellulose is present in the wound dressing of the present invention in an amount of at least 80 wt.%, preferably at least 90 wt.%, and more preferably at least 95 wt.%. In an even more preferred embodiment, the wound dressing of the present invention consists of the cellulose. In this case, the aqueous liquid and the cellulose dry mass add up to 100wt.%.Cellulose is made up of four main components, namely, a glucose unit, the C4-OH group, which is also known as a non-reducing end, the C1-OH group, which is also known as the terminating end, and lastly, a reducing end, which is made up of aldehydes. Cellulose isa non-soluble compound, due to the presence of intermolecular and intramolecular forcesthat exist between the hydrogen bonds. In general, a cellulose can be of plant or bacterial origin. Plant-derived cellulose (plant cellulose, PC) is a natural organic compound that is present in plants and makes up a major component of the cell wall in a plant. The main sources of cellulose are cotton and woods.Bacterial-derived cellulose (bacterial cellulose, BC; in the literature also referred to asbacterial nanocellulose, BNC) can for example be derived through a fermentation process, specifically if the bacteria are aerobic bacteria. BC is usually synthesized from bacteria that belong to the genera Gluconacetobacter, Agrobacterium, and Sarcina, through an oxidative fermentation process or by microbial fermentation. During the synthetic process,the glucose chains produced inside the bacterial body extrude out through tiny porespresent on their cell envelope. The glucose chains then form microfibrils that further aggregate to form cellulose ribbons. These ribbons generate a web-shaped network structure with plenty of empty spaces between the fibres. The well-separated nanofibrils of BC create an expanded surface area and highly porous matrix. The basic fibril structureconsists of a β-1→4 glucan chain with the following molecular formula: (C6H10O5)n. Thechains are held together by hydrogen bonds. BC microfibrils (fibres) are approximately 100-fold smaller (thinner) than the fibrils (fibres) of vegetal cellulose. The BNC is composed of ultrafine fibres sized in the nanometre range, for instance being in the range of, e.g., 20 to 100 nm in diameter. Suitable average pore sizes may be, for example, inthe range of 1 to 100 nm. The fibrous network of BC consists of well-arranged, three-dimensional nanofibres resulting in the formation of hydrogel film with a large surface area and considerable porosity. Additionally, compared to PC, BC is not associated with lignin or hemicelluloses as in vegetal cellulose, and thus, BC cellulose is purer; moreover, the three-dimensional nanofibril network has a high-water absorption capacity and tensilestrength when compared to PC. Bacterial cellulose (BC) forms as a white leathery pellicleat the air–liquid interface. Although its molecular structure is identical to that of vegetal cellulose, due to the absence of lignin and hemicellulose, BC has higher degrees of purity, polymerization, crystallinity, tensile strength, water absorption, water retaining capacity, and biological adaptability, thereby providing biocompatibility, biodegradability, andrenewability. In the present invention, in a preferred embodiment, the cellulose used is bacterial nanocellulose, which preferably does not contain lignin and / or hemicellulose. In a preferred embodiment, the bacterial nanocellulose does not contain lignin and hemicellulose. It is further preferred that the cellulose used in the present invention doesnot comprise herbaceous plant material, wherein preferably the term "herbaceous" refersto plants which are annual, biennial or perennial vascular plants. Herbaceous plants are characterized by parenchymal tissue having an abundance of primary cell walls within the tissue.The cellulose that is present in the wound dressing of the present invention exhibitssubstantially no carbonyl peak at 1735 cm-1+ / - 2 cm-1as determined by Fourier transform infrared (FTIR) in an infrared absorbance ATR spectrum, preferably when compared to a wound dressing that was not pre-incubated with an aqueous OCl- -ion-containing solution (also referred to herein as "comparison wound dressing"). In an even more preferredembodiment, the comparison wound dressing, that is, the dressing that has not been pre-incubated with the aqueous OCl- -ion-containing solution, is the same as (corresponds to) the wound dressing that has been pre-incubated with the aqueous OCL- -ion-containing solution, except from the fact that it has not been pre-incubated with the aqueous OCl- - ion-containing solution. For example, the respective wound dressings correspond withregard to the amount (ratio) of cellulose being present in the wound dressing, and withregard to the dry mass content and aqueous liquid content of the cellulose. In the present invention, it has also been found that, due to the pre-incubation of the cellulose with an appropriate aqueous OCl- -ion-containing solution, the carbonyl peak that is usually present at 1735 cm-1+ / - 2 cm-1as determined by Fourier transform infrared(FTIR) in an infrared absorbance ATR spectrum, is substantially not present anymore; ina not-pre-incubated state, this carbonyl peak is present and noticeable at 1735 cm-1+ / - 2 cm-1. It is hypothesized that this peak more and more disappears, due to the increasing oxidation of the reactive groups of the cellulose with increasing incubation time. Upon pre- incubating the cellulose of the wound dressing with an aqueous OCl- -ion-containingsolution, the reactive groups (carbonyl-groups) being present in the cellulose are oxidizedand thus they are no longer available for further oxidizing reactions, e.g. with OCl- ions of a hypochlorite solution. This is particularly beneficial in a later step, when the wound dressing comprising the then-pre-incubated cellulose is, for the purpose of producing the wound dressing to be therapeutically used, incubated with antiseptic solutions that exhibit oxidative activity. By way of non-limiting theory, it may be assumed that, as the reactivegroups of the cellulose of the wound dressing are no longer available for further oxidativereactions, it is possible that the antiseptic solution that is subsequently used for soaking / loading the wound dressing in a later step can thereby exhibit and make use of comparably low concentrations of the oxidizing agent, preferably in concentrations that are not overly toxic for living subjects such as humans. In this way, the finally surprisinglyobserved effective soaking and release properties of the ready-to-use wound dressingwith OCl--ion concentrations being therapeutically effective without being harmful can be explained. Such antiseptic solutions contain for example hypochlorite, and in a preferred embodiment are antiseptic solutions that are commercially available. Such solutions are for exampleavailable under the brand name Lavanox®, Granudacyn®, or Actimaris®Forte. Thesethree antiseptics contain different NaOCl concentrations: Lavanox® comprises < 0.08%, Granudacyn® comprises < 0.02%, and Actimaris® Forte comprises < 0.2%. The aqueous OCl- -ion-containing solution that is used for pre-incubating the cellulose ofthe wound dressing is preferably a reagent-grade solution having an OCl- concentrationfrom 0.025% to 4%, preferably from 0.05% to 1.5%, more preferably from 0.05% to 1.0%, or from 0.1% to 1.0%, and even more preferred from 0.05% to 0.5%. In particular the aqueous OCl- -ion-containing solution has an OCl- concentration of about 0.2% + / - 0.05%. In general, any aqueous OCl- -ion-containing solution can be used for pre-incubating thewound dressing. In a preferred embodiment, the aqueous OCl- -ion-containing solution isa sodium hypochlorite or hypochlorous acid solution. The pre-incubating of the wound dressing can be carried out over a time period that is suitable for oxidizing sufficient reactive groups of the cellulose being present in the wound dressing. A skilled person is in a position of determining whether sufficient reactive groupshave been oxidized, e.g., by determining the carbonyl peak that is usually present at 1735cm-1+ / - 2 cm-1as determined by Fourier transform infrared (FTIR) in an infrared absorbance ATR spectrum. If there is substantially no carbonyl peak present at 1735 cm-1+ / - 2 cm-1, then the conditions of the pre-incubation (such as time, temperature, concentration of the pre-incubation solution) have been suitable, and pre-incubation may be terminated.In a preferred embodiment, the wound-dressing has been pre-incubated with 3 to 8,preferably 4 to 7, more preferably 4 to 6, and even more preferably 5 volumes of the aqueous OCl- -ion-containing solution, preferably in a concentration from 1 to 10%, more preferably in a concentration from 2 to 8% or 3 to 7%; and even more preferably in a concentration of 4 to 5%. In certain embodiments, a concentration of 5% is preferred.It is further preferred that the pre-incubation has been carried out for 15 min. to 3 h,preferably for 15 min. to 2.5 h, more preferably for 30 min to 2 h. After the wound dressing has been incubated, it is preferred that a washing step is carried out. The washing step can be carried out according to a suitable method that is known to a person skilled in the art. For example, the washing process requires about 30 minutes(min) to 5 hours (h), preferably 1 h to 3 h, incubating time and can be performed at roomtemperature, and repeated multiple consecutive times e.g. three consecutive times, by using a volume of water ranging between 2 and 5 litre per wound dressing (e.g., 20 ml content, which represents a total of 100 cm2of dressing area).It is possible that the wound dressing comprises 95 wt.% or more of an aqueous liquid,and 5 wt.% or less and more than 0 wt.% of dry mass cellulose. It is also possible that in the wound dressing of the present invention, the aqueous liquid and the cellulose dry mass add up to 100 wt.%. This means, that in this case, there are no further components present in the wound dressing. It is however also possible that the wound dressing comprises, in addition to the cellulose comprising aqueous liquid and the cellulose dry mass, one or more further components not affected by or not reactive with the OCl- concentration used. Further components can for example be additional carriers. It is also possible that the wound dressing comprises, in addition to the cellulose comprising aqueous liquid and the cellulose dry mass, one or more further active compounds other than OCl- that does / do not interact with OCl- , preferably said further one or more active compound is / are antiseptics other than OCl-, in particular said further oneor more active compound is / are antiseptics selected from the group consisting ofpolyhexanide (PHMB), octenidine or octenidine hydrochloride, chlorhexidine, chlorhexidine-digluconade, polyvidone (PVP)-iodine, and mafenide. It is preferred that the aqueous liquid that is present in the wound dressing of the presentinvention is inert. The aqueous liquid can be any suitable aqueous liquid, preferably theaqueous liquid is an isotonic solution. Preferably the aqueous liquid is Ringer solution, Acetated Ringer`s solution, or a 0.9% NaCl solution. In a preferred embodiment of the present invention, the cellulose of the wound dressing,in addition to (A) and (B), additionally exhibits a substantially lower molecular massdistribution of the cellulose polymer chain, when compared to a wound dressing that was not pre-incubated with an aqueous OCl- -ion-containing solution. By incubating the cellulose with an aqueous OCl- -ion-containing solution, the average chain length of the cellulose chain is reduced when compared to a cellulose that has not been pre-incubated.In a preferred embodiment, the average chain length of the cellulose of the wounddressing exhibits a cellulose chain length, as determined by a Gel Permeation Chromatography (GPC) with Multi-Angle Light Scattering Detection (MALS) method, is (i) 62.0-90.0 Mn[kg / mol], preferably 66.0-80.0 Mn[kg / mol], more preferably 67.0- 79.0 Mn[kg / mol]; and / or(ii) 100.0-180.0 Mw [kg / mol], preferably 120.0-167.0 Mw [kg / mol], more preferably160.0-167.0 Mw[kg / mol]; and / or (iii) 220.0-290.0 Mz[kg / mol], preferably 250.0-275.0 Mz[kg / mol], more preferably 265.0-275.0 Mz[kg / mol]; and / or (iv) reduced by at least 1.0 [kg / mol] with respect to Mn[kg / mol], and / or Mw[kg / mol],and / or Mz [kg / mol], when compared to a non pre-incubated wound dressing. In apreferred embodiment, all conditions (i) to (iv) apply. In a further embodiment, the cellulose of the wound dressing or the wound dressing, respectively, has a dry mass corresponding to 1.5% to 3.5%, preferably 1.8% to 3.3%, more preferably 2.0% to 3.0% of the wet mass. In a preferred embodiment, bothconditions, the density as well as the dry mass, as indicated above are fulfilled. Thedensity can be determined according to any suitable method that is known to a skilled person, for example according to the method described elsewhere herein. The wound dressing of the present invention is particularly suitable for being used in thetreatment of skin lesions, such as burns or abrasions, or surgical sites. It is also possiblethat the wound dressing is used in the prevention of inflammation. Depending on the respective use, the wound dressing has a certain size and / or thickness that is particularly suitable for the intended use. For example, in one embodiment, the wound dressing has a thickness of 0.02-10 mm and / or a length of 2-45 cm and / or a width of 2-45 cm.Preferably, the wound dressing has a dimension of 5 cm x 5 cm, 10 cm x 10 cm, 15 cm x20 cm, or 20 cm x 20 cm. The wound dressing can be in any form, for example the wound dressing can be a face mask. In this case, in a preferred embodiment, the wound dressing being a face mask, preferably has a length of 10-50 cm and / or a width of 10-50 cm, more preferably a length of 20-45 cm and / or a width of 20-45 cm.The wound dressing can also be a dressing being designed with respect to dimensionsthat are suitable for covering specific parts of the body, e.g., the face, hands, arms, knees, back, legs, and so on. In a preferred embodiment, the wound dressing is in form of a face mask.It is one advantage of the wound dressing of the present invention that it can be stored ina suitable storage container, such as a sterile package, for a certain period of time. Only immediately prior to its intended use, the wound dressing can be taken out of the container (sterile package), and then soaked (incubated) in a further liquid, such as an aqueous OCl- -ion-containing solution. This aqueous OCl- -ion-containing solution can for examplebe any suitable commercially available antiseptic, such as Granudacyn®, Lavanox®, orActimaris®Forte. Hence, the present invention further refers to a sterile package containing a wound dressing of the present invention and as described herein.The present invention also refers to a method for preparing a pre-incubated wounddressing, comprising the steps of: (i) providing a wound dressing comprising cellulose, wherein the cellulose comprises 90% or more of an aqueous liquid and 10% or less cellulose (dry mass), preferably wherein the cellulose is as defined elsewhere herein;(ii) incubating the wound dressing, preferably the cellulose of the wound dressing of(i), with an aqueous OCl- -ion-containing solution, optionally using an aqueous OCl- -ion- containing solution as disclosed elsewhere herein, preferably with a 0.1-0.5% NaOCl solution, more preferably for 1-5 h; and (iii) washing the incubated wound dressing obtained in (ii), thereby obtaining a pre-incubated wound dressing.This pre-incubated wound dressing can then be stored in a suitable container such as a sterile package. Prior to its use, the pre-incubated wound dressing can be taken out of said container and incubated with an aqueous OCl- -ion-containing solution. After this loading of the pre-incubated wound dressing, the dressing can be used in a method oftreating wounds, such as burns. It can also be used in the prevention and / or treatment ofinflammation in a mammal, especially a human, preferably in the prevention and / or treatment of an inflammatory response in uncontaminated or non-infected surgical sites, wounds, trauma sites, internal inflammatory lesions or surface inflammatory lesions where there is no infection, such as in leg ulcers or other venous ulcers, or in the prevention and / or treatmentof an inflammatory skin condition such as mouth ulcers, eczema or psoriasis.In a further embodiment of the present invention, the cellulose of the wound dressing of (i) comprises 95 wt.% or more of an aqueous liquid, and 5 wt.% or less of dry mass cellulose. In a preferred embodiment, the aqueous liquid and the cellulose dry mass of the methodfor preparing a pre-incubated wound dressing add up to 100 wt.%. It is also possible that the wound dressing comprises, in addition to the cellulose comprising aqueous liquid and the cellulose dry mass, further components. The presence of these further components depends for example on the intended use of the (final) wound dressing, that is, of the pre-incubated and loaded wound dressing. Accordingly, themethod for preparing a pre-incubated wound dressing can include an additional step ofadding further component(s). The aqueous liquid in step (i) is as disclosed elsewhere herein. Preferably, the aqueous liquid is inert, more preferably the aqueous solution is Ringer solution or a 0.9% NaClsolution.The pre-incubated wound dressing as disclosed herein, and / or as prepared by a method as described herein can, in a next step, be loaded (soaked / incubated) with an aqueous OCl- -ion-containing solution. This pre-incubated, loaded wound dressing can then beused in a method of treating affected skin, such as burned skin or otherwise injured skin,or in a method of preventing or treating inflammation. Thus, the present invention further refers to a method for preparing a pre-incubated wound dressing that is loaded with an aqueous OCl- -ion-containing solution having an OCl-concentration between 0.025% and 2%, preferably 0.1% to 1.5%, further preferred 0.1%to 0.5%, comprising, in addition to the steps (i) to (iii) as disclosed herein, a further step (iv) of loading the pre-incubated wound dressing obtained in (iii) with an aqueous OCl- - ion-containing solution. This aqueous OCl- -ion-containing solution can be any suitable solution having an OCl- concentration between 0.025% and 2%, preferably 0.1% to 1.5%,further preferred 0.1% to 0.5%, or, alternatively, having an OCl- concentration in a rangefrom 0.005% to 2.000%, preferably 0.005% to 1.500%, more preferably from 0.010% to 1.500%, even more preferably from 0.010% to 1.000%, and most preferably from 0.015% to 0.500% In a preferred embodiment, the aqueous OCl- -ion-containing solution is a commercially available antiseptic, preferably an antiseptic that is suitable for being usedin wound treatment, e.g., Granudacyn®, Lavanox®, or Actimaris®Forte. The obtainedwound-dressing is ready-to use. It is further possible that the method comprises an additional step (v) of further loading the pre-incubated wound dressing, either prior to, simultaneously with, or subsequent to step (iv), with anyone of further active compounds other than OCl-. Preferably, the further activecompounds comprise antiseptics other than OCl-, in particular an antiseptic selected fromthe group consisting of polyhexanide (PHMB), octenidine or octenidine hydrochloride, chlorhexidine, chlorhexidine-digluconate, polyvidone (PVP)-iodine, and mafenide. By this additional loading of the pre-incubated, loaded wound dressing, an even more effective wound dressing can be obtained. The present invention further refers to an aqueous OCl- -ion-containing solution having an OCl- concentration in a range from 0.005% to 2%, preferably 0.005% to 1.500%, more preferably from 0.010% to 1.500%, even more preferably from 0.010% to 1.000%, and most preferably from 0.015% to 0.500%; or having an OCl- concentration in a range from0.025% to 2.000%, preferably 0.100% to 1.500%, further preferred 0.100% to 0.500%, foruse in a wound treatment e.g., burns, wherein a wound dressing as disclosed elsewhere herein is loaded with said aqueous OCl- -ion-containing solution directly before the treatment, and the loaded wound dressing is then applied onto the treatment site.During the body’s innate response to infections, neutrophiles act applying a myriad ofstrategies to control the microbial invasion [13, 14]. One of these strategies is the production of hypohalous acids, including hypochlorous acid (HOCL). The reaction to produce HOCl occurs inside the phagosomal compartments, present in the cytoplasm of these leukocytes, and using hydrogen peroxide (H2O2) and ions chloride
[0015] . HOCl is oneof the most reactive species produced by our body and has a high oxidizing capacity, evenhigher for biomolecules than H2O2
[0016] . Human serum albumin (HSA), a highly abundant protein present in the blood and interstitial fluids, is one example of a biomolecule that is targeted by the reactive capacity of HOCl [16, 17]. The product of this reaction is a modified version of this protein, a molecule with the capacity to influence neutrophileresponse and increase their lifespan, among other important roles in the innate immuneresponse
[0016] , providing it a pro-inflammatory stimuli component
[0014] . In vitro tests showed improved cell migration for the treatment with low doses of HOCl
[0018] . Reports using animal models also showed positive wound healing effects and anti-inflammatory response for treatments using 0.015% stabilized HOCl
[0019] . Congruently, clinical studies also showed the efficiency of low dose HOCl for the wound closure
[0020] . Furthermore,another work described positive influence on epithelialization after topical application ofHOCl on skin grafts donor sites
[0021] . The similarity of the stabilized HCOl solution to the same molecule produced by neutrophiles, and the low dosage, which is also observed at the wound level
[0014] , appears to be the main reason for this enhanced wound healing process observed. Hence, the present invention further refers to an aqueous OCl- -ion-containing solution having an OCl- concentration in a range from 0.005% to 2%, preferably 0.005% to 1.500%, more preferably from 0.010% to 1.500%, even more preferably from 0.010% to 1.000%, and most preferably from 0.015% to 0.500%; or having an OCl- concentration in a rangefrom 0.025% to 2.000%, preferably 0.100% to 1.500%, further preferred 0.100% to0.500%, for use in the prevention and / or treatment of inflammation in a mammal, especially a human, preferably in the prevention and / or treatment of an inflammatory response in uncontaminated or non-infected surgical sites, wounds, trauma sites, internal inflammatory lesions or surface inflammatory lesions where there is no infection, such as in leg ulcers orother venous ulcers, or for use in the prevention and / or treatment of an inflammatory skincondition such as mouth ulcers, eczema or psoriasis, wherein a wound dressing as disclosed herein is loaded with said aqueous OCl- -ion-containing solution directly before the treatment, and the loaded wound dressing is then applied onto the treatment site. In a further preferred embodiment, the aqueous OCl- -ion-containing solution for use in awound treatment, e.g. burns, and for use in the prevention and / or treatment ofinflammation in a mammal, exhibits an OCl- concentration of about 0.005% to 1.500%, preferably of about 0.015% to 0.500%. In a preferred embodiment, the wound treatment is antibacterial wound treatment. The present invention further refers to a kit of parts comprising (i) a wound dressing as disclosed herein, which means, a conditioned (pre-incubated) wound dressing, and (ii) an aqueous OCl- -ion-containing solution having an OCl- concentration in a range from 0.005% to 2%, preferably 0.005% to 1.500%, more preferably from 0.010% to1.500%, even more preferably from 0.010% to 1.000%, and most preferably from 0.015%to 0.500%; or having an OCl- concentration in a range from 0.025% to 2.000%, preferably 0.100% to 1.500%, further preferred 0.100% to 0.500%, optionally further comprising (iii) further active compounds other than OCl-, preferably wherein the further active compounds comprise antiseptics other than OCl-, in particular an antiseptic selected fromthe group consisting of polyhexanide (PHMB), octenidine or octenidine hydrochloride,chlorhexidine, chlorhexidine-digluconate, polyvidone (PVP)-iodine, and mafenide. The wound dressing of (i) is a wound dressing as disclosed elsewhere herein, that is, a wound dressing comprising cellulose, wherein the cellulose comprises 90 wt.% or more of an aqueous liquid, and 10 wt.% or less of dry mass cellulose, wherein(A) the cellulose exhibits substantially no carbonyl peak at 1735 cm-1 + / - 2 cm-1 asdetermined by Fourier transform infrared (FTIR) in an infrared absorbance ATR spectrum; and / or (B) wherein the wound-dressing has been pre-incubated with an aqueous OCl- -ion- containing solution. The present invention further refers to the use of a conditioned (pre-incubated) wound dressing of the present invention for being loaded with an aqueous OCl- -ion-containing solution having an OCl- concentration in a range from 0.005% to 2%, preferably 0.005% to 1.500%, more preferably from 0.010% to 1.500%, even more preferably from 0.010%to 1.000%, and most preferably from 0.015% to 0.500%; or having an OCl- concentrationin a range from 0.025% to 2.000%, preferably 0.100% to 1.500%, further preferred 0.100% to 0.500%. In a preferred embodiment, the aqueous OCl- -ion-containing solution has an OCl- concentration in a range from 0.005% to 1.500%, preferably from about 0.015% to 0.500%. It is additionally preferred that the aqueous OCl- -ion-containing solution is acommercially available antiseptic, e.g., Granudacyn®, Lavanox®, or Actimaris®Forte. The wound dressing of the present invention can be used in a method of treating wounds, such as burns. It can also be used in the prevention and / or treatment of inflammation in a mammal, especially a human, preferably in the prevention and / or treatment of an inflammatory response in uncontaminated or non-infected surgical sites, wounds, traumasites, internal inflammatory lesions or surface inflammatory lesions where there is noinfection, such as in leg ulcers or other venous ulcers, or in the prevention and / or treatment of an inflammatory skin condition such as mouth ulcers, eczema or psoriasis. Consequently, the present invention also refers to a wound dressing as disclosed herein, for use in a method of treating wounds, such as burns.Finally, the present invention refers to a wound dressing as disclosed herein, for use inthe prevention and / or treatment of inflammation in a mammal, especially a human, preferably in the prevention and / or treatment of an inflammatory response in uncontaminated or non- infected surgical sites, wounds, trauma sites, internal inflammatory lesions or surface inflammatory lesions where there is no infection, such as in leg ulcers or other venous ulcers,or in the prevention and / or treatment of an inflammatory skin condition such as mouth ulcers,eczema or psoriasis. DefinitionsWithin the meaning of the present invention, the term "reagent grade" in connection witha chemical or a reagent denotes the degree of chemical purity of said chemical or reagent. Within the meaning of the present invention, the term "reagent grade" defines that the respective solution exhibits a purity of equal to or more than 95%. Thus, the respective solution is acceptable for food, drug, or medicinal use. Within the meaning of the present invention, the expression "substantially the same", if a number is indicated, defines a deviation from the indicated number of 10% or less, preferably 5% or less, more preferably 3% or less, and even more preferably 2% or less. Most preferred, there is no detectable deviation.If the expression "substantially the same" refers to a condition, then this expressionpreferably defines that there is no detectable difference between these conditions. The expression "substantially no carbonyl peak at 1735 cm-1+ / - 2 cm-1as determined by Fourier transform infrared (FTIR) in an infrared absorbance ATR spectrum" refers to a cellulose having a carbonyl peak at 1735 cm-1+ / - 2 cm-1that is detectably smaller thanthat of a comparison cellulose. The comparison cellulose is a cellulose that correspondsto the cellulose of the wound dressing with regard to the amount of aqueous liquid in wt.%, with regard to the amount of dry mass cellulose in wt.%, and with regard to its origin (plant origin or bacterial origin). Thus, in a preferred embodiment, the comparison cellulose is a cellulose comprising 90 wt.% or more of an aqueous liquid, and 10 wt.% or less of drymass cellulose.If the cellulose being comprised in a wound dressing is of bacterial origin, the comparison cellulose correspondingly also of bacterial origin.In a preferred embodiment, the cellulose being comprised in the wound dressing isadditionally directly obtained from bacteria. Thus, in a preferred embodiment, the carbonyl peak at 1735 cm-1+ / - 2 cm-1of the cellulose of the wound dressing is detectably smaller than the carbonyl peak at 1735 cm-1 + / - 2 cm-1 of a cellulose that is directly obtained from bacteria.In a further preferred embodiment, there is no detectable carbonyl peak at 1735 cm-1+ / - 2 cm-1in the cellulose of the wound dressing when compared to the comparison cellulose. Additionally, or in a further embodiment, the expression "substantially no carbonyl peakat 1735 cm-1 + / - 2 cm-1 as determined by Fourier transform infrared (FTIR) in an infraredabsorbance ATR spectrum" refers, for example, to a ratio of the absorbance of the carbonyl peak / carboxyl peak (with the carboxyl peak being at 1615 cm-1+ / - 2 cm-1) being less than 0.5, preferably less than 0.4, more preferably less than 0.2, even more preferably less than 0.1. Within the meaning of the present invention, the expression "substantially lower" defines that the specified figure is at least 2% lower than the indicated reference figure, preferably at least 3% lower, more preferably at least 5% lower, and even more preferably at least 10% lower.For example, within the meaning of the present invention, the expression "the cellulose ofthe wound dressing exhibits a substantially lower molecular mass distribution of the cellulose polymer chain" denotes a molecular mass distribution that is e.g., at least 2% lower than the indicated reference molecular mass.If the expression "substantially the same" refers to a condition, then this expressionpreferably defines that there is no detectable difference between these conditions. The term "inert" defines that a specific compound or substance is not chemically reactive. In other words, it does not react with other compounds or substances. The term “room temperature” defines a temperature range being between 20 to 25°C. Methods Determining dry mass of cellulose In general, the dry mass of cellulose can be determined by any suitable method that is known to a skilled person. In the meaning of the present invention, the dry mass content was determined by carrying out a full dehydration of the sample, followed by determiningthe dried mass in wt.%. The full dehydration was carried out as follows: circular pieces of3 cm diameter with a known weight of the bacterial cellulose were placed into incubators with an internal temperature at 32°C. The pieces were left uncovered in order to allow a complete evaporation of the water content. The weight of the material was checked regularly, with the utilization of a precision scale, at different time points until threeconsecutives measurements where no weight variation was observed. Detecting the carbonyl peak In general, the presence or absence of a carbonyl peak in a specific sample can be determined by any suitable method that is known to a person skilled in the art. In the meaning of the present invention, the presence or absence of a carbonyl peak isdetermined by Fourier transform infrared (FTIR), by attenuated total reflectance (ATR), asdescribed in Schwanninger, et al.2004
[0022] , preferably as follows: air-dried samples were cut and placed on a Bruker Vector 22 IR spectrometer. The samples were analyzed using the so-called ATR method (Attenuated Total Reflection), where the samples were put, under pressure, into contact with a crystal, through which the infrared radiation (in themid-infrared range, 400-4000 cm-1) is guided in reflection. The radiation interacts mainlywith the sample surface in contact with the crystal (penetration depth approximately 0.5 μm), the spectral information about the chemical composition is then acquired and represented in the form of characteristic absorption in the spectrum. Data were then collected and plotted into a graph. Determining OCl- concentration Hypochlorite ions concentration was detected using aminophenyl fluorescein (APF). This molecule is e.g. applied in biological assays to detect hypochlorite ions generated in stimulated neutrophils, and it could be shown in the present invention that this assay canalso be applied to detect hypochlorite ions in solutions. As shown herein, e.g. in Example1, this assay is also suitable for the detection of this ion in solution. Washing step After the incubation of the wound dressing, a washing step is preferably carried out. In thepresent invention, the washing step is performed using an incubation step of 30 min to 5h,preferably 1h to 3h, at room temperature, using deionized water / MilliQ water. The washing step is performed three consecutive times using a volume of water ranging from 2 L to 5 L per dressing (20 mL content, which represent a total of 100 cm² of dressing area).Gel Permeation Chromatography (GPC) with Multi-Angle Light Scattering Detection(MALLS) method In order to determine molecular distribution of a polymeric system, such as a cellulose molecule, a gel permeation chromatography coupled to a multi-angle laser light scattering (GPC / MALLS) technique was applied. The GPC system consisted of a HPLC pump (Kontron 420; Kontron Instruments, Milano, Italy), an autosampler (G1367B; Agilent Technologies, Waldbronn, Germany), MALLS detector (Wyatt Dawn DSP200 with argonion laser, λ0= 488 nm; Wyatt Technology, Santa Barbara, US), and a refractive index detector (Shodex RI-71; Showa Denko America Inc., New York, US). Four serial GPC columns, PLgel-mixed ALS, 20 µm, 7.5 × 300 mm (Agilent Technologies, Waldbronn, Germany) were used as the stationary phase. The GPC operating conditions were as follows: 1.00 mL / min flow rate, 100 µL injectionvolume, and 45 min run time. DMAc / LiCl (0.9%, w / v) filtered through a 0.02 µm filter was used as an eluent. All samples were filtered through a 0.45 µm syringe filter prior to analysis. Samples were measured in duplicates to assure higher accuracy of the data. The following examples illustrate preferred embodiments of the present invention. Examples Example 1. Standard curves for OCl- ions concentration in solutions using APFHypochlorite ions concentration was detected using aminophenyl fluorescein (APF). This molecule is applied in biological assays to detect hypochlorite ions generated in stimulated neutrophils
[0010] . To check whether this assay is suitable for the detection of this ion, all the analyzed solutions were diluted prior to the APF incubation to match the same concentration range (~2.5 ppm). A serial dilution was prepared to produce standardcurves and test if the assay is dose dependent. Three antiseptics comprising different NaOCl concentrations were used: Actimaris®Forte (< 0.2%), Lavanox® (< 0.08%) and Granudacyn® (< 0.02%); and two standard solutions adjusted to match 1% and 3% of NaOCl concentration were tested. The results were then plotted in a graph (Fig.3). All the tested solutions achieved comparable fluorescence results, apart from Granudacyn®.Granudacyn® solution achieved results 4 to 5 times lower than the expected. Nevertheless, all the standard curves achieved linear regressions with a r² higher than 0.92. The assay was used to determine the conc. Of OCl- ions in samples from solutions after isolation from the cellulose dressings. All the analyzed solutions were diluted to fit a NaOCl concentration range of ~2.5 ppm. Samples were pipetted into a a Corning® 96Well Black Polystyrene Microplate (CLS3603 SIGMA) and shortly incubated with an APFsolution of 5 mM in a 1:250 ratio. Using a spectrophotometer (Infinite® 200 PRO, TECAN Trading AG, Switzerland), the fluorescence intensity for the samples were analyzed. The excitation / emission spectrum for the measurements was set as 460 nm and 515 nm, respectively.Fig. 3 shows a hypochlorite ion detection assay using aminophenyl fluorescein (APF).Example 2. Uptake capacity of the BNC dressing for three commercially available antiseptics BNC dressings were incubated for different time points with commercially availablesolutions containing hypochlorite ions as their active compound. At first, the exact sameprocedure was performed as previously: an incubation process at room temperature was done using a volume of antiseptic 5 times higher than the volume of the solution comprised in the BNC dressing. The incubation was established in an environment protected from light for 10-, 30- and 60-min. After this process, the loaded solution extracted from thedressing was diluted with a 1:50 factor for Granudacyn®, 1:200 for to Lavanox® and 1:400for Actimaris®Forte and the hypochlorite ion concentration was measured using the APF molecule (Fig. 4). As a matter of comparison, the solutions post incubation were also analyzed. The analysis offered results lower than the expected for all the tested antiseptics. The uptake results for Granudacyn® (Fig.4A) and Lavanox® (Fig.4B) wereclose to zero for all the analyzed time points. Lower results were also observed forActimaris®Forte after 10 and 30 min of incubation (Fig.4C). To better understand what could have happened, the same experiment was performed with increased incubation volume. Therefore, volumes 10 and 20 times higher were used in the incubation process. This method indeed offered higher results, when compared tothe incubation performed using 5 times the volume of the liquid comprised into the BNC. However, the results were still lower than the obtained for the previous tests using different antiseptic solutions and molecules of larger size. Fig.4 depicts the uptake of antiseptic solutions into BNC dressings.BNC dressings were incubated for 120 min with NaOCl standard solutions adjusted tohave a concentration of 0.2%, 0.1%, 0.05% and 0.025%. After the incubation process, the loaded solution was extracted and the final concentration of all the samples was diluted adjusted to the same starting concentration (Fig. 5). Obtained results were analyzed relative to the starting solution. A concentration influence was observed since nomeasurement was obtained on the lowest concentrated solution and a very low result wasobserved for the 0.05% solution relative to its starting solution. Whereas 0.1% solution achieved results lower than 50% of the starting solution and 0.2% solution reached more than 75% of the initial solution. Further experiments were conducted to test if a certain proportion of the OCl- ions couldhave reacted with liquid in the BNC or with the scaffold.Fig.5 shows the hypochlorite concentration influence on the uptake results. Example 3. Influence of the solution comprised in the BNC on hypochlorite ion concentrationBNC dressing is almost completely constituted by a Ringer solution, around 98% of thetotal weight. The solution once extracted from the BNC through centrifugation presented a pH varying from 4.8 to 5.8. To test if the solution alone could impact the hypochlorite ion concentration measured with the APF assay, a short test was conducted. Lavanox® and Actimaris®Forte were mixed in a ratio 1:1 with either eluted BNC solution or with water,working here as a negative control. Additionally, Actimaris®Forte solution was mixed inthe same ratio with a 0.9% NaCl solution and with a commercially available Ringer solution. These two solutions presented a pH in a range of 7.0 and 7.4. The mixed solutions were then incubated for 120 min in a dark place and at room temperature. The concentration of the final solutions was adjusted with a dilution of 1:200 for Lavanox® and1:400 for Actimaris®Forte and measured using the APF assay (Fig. 6). A statisticallydifference was observed for Lavanox® mixed with the eluted BNC solution in comparison to the negative control (p < 0.02) and for Actimaris®Forte solution mixed with eluted BNC solution in comparison to the mix with the Ringer solution (p < 0.03). However, these observed interferences were not even comparable to the results post incubation with the dressing itself.Fig. 6 shows the influence of the solution comprised in the BNC dressing on the iondetection assay. Example 4. Pre-treatment of BNC with hypochlorite solution The hypothesis was drawn that the interaction of the OCl- with the cellulose networkpresent in the BNC dressing being the main reason for the lower detection of OCl-molecules by reaction of the molecule with the cellulose. The oxidation of nanocellulose using -OCl-molecules has been described in the literature [11, 12]. The pre-treatment applied in the Example 4 consisted of an incubation using a reagent-grade 0.2% NaOCl solution for a 2h, followed by three consecutive washing steps using Mili-Q® water. Afterthe BNC is pre-incubated, a new uptake process was performed, and the obtained resultswere unambiguously favorable (Fig.7). The incubation was done using the same method previously described, using 5 volumes of Granudacyn®. An uptake using an unmodified BNC was done to be used as control. After uptake, the eluted solution extracted from both BNC materials were diluted with a 1:100 factor and analyzed using the APF assay. Evenafter merely 10 min, the uptake concentration was more than eight thousand times higherthan the observed for the untreated BNC. Fig. 7 shows the pre-treatment influencing the uptake results for low concentrated hypochlorite antiseptic.To analyze the influence of the modification process on the cellulose network present inthe dressing, the polymeric structure of the cellulose chains was studied using a Gel Permeation Chromatography (GPC) with Multi-Angle Light Scattering Detection (MALS) method. For that purpose, a BNC-dressing untreated was used as negative control. BNC samples were incubated for 30- and 120-min using 5 volumes of a 0.2% NaOCl solution.As positive control, BNC samples were incubated using a 3% NaOCl solution for a totalof 3 days. All samples were washed 3 times using 2 L of deionized water for each washing step. Descriptive results can be observed in Table 3. It is possible to observe that molar mass values (Mn, Mw and Mz) decreased with the time of incubation, when compared to the reference material. Concentration of reducing end groups (REGs), on the other hand, increased with the incubation time. The combination of these results indicates that themodification process influences the cellulose chain size. Polydispersity index (Ð) of thetested samples and the negative control also indicate a variation on the size of the polymer chain. Additionally, difference on the molar mass distribution (Fig. 8) reaffirms the influence of the treatment time and concentration on the molecular size of the polymer chains. BNC MnMwMzC=O REGs Ð sample [kg / mol] [kg / mol] [kg / mol] [µmol / g] [µmol / g] Ctrl A 79.49 168.0 275.8 14.73 12.58 2.11 Ctrl B 90.82 178.8 282.4 14.52 11.01 1.97 Table 3 Table 3: GPC / MALLS analysis of the poly molecular weight distribution of the BNC dressings. Gel Permeation Chromatography (GPC) followed by multi angle laser lightscattering (MALLS) of BNC dressing (Ctrl A and B), BNC dressing after a 30 min (30’Aand B), 120 min (120’A and B) and 3 days (+Ctrl A and B) incubation time with a 0.2% hypochlorite standard solution. Results represent values in duplicate for number average molecular weight (Mn), weight average molecular weight (Mw) and higher average molecular weight (Mw), carbonyl group concentration (C=O) and polydispersity index (Ð). Fig.8 shows the molecular mass distribution of the cellulose polymer chain in the BNC dressing. The diagram shows the influence of the treatment with NaOCl on the molecular mass of the polymer chain. Using the Fourier transform infrared (FTIR) by attenuated total reflectance (ATR) spectra method (Fig.9), it was possible to observe strong similarities between the spectra of the BNC samples after 30- and 120-min incubation with 5 volumes of a 0.2% NaOCl solution (Fig.9A). When the spectra range of 1500 to 1850 cm-1is analyzed (Fig.9B), a peak at~1735 cm-1 for the negative control sample can be observed, corresponding to C=O(carbonyl group) stretching of -COOH (carboxyl group) groups. This absorption band is important for the determination of the degree of oxidation for the analyzed molecule. The absorption in the other samples indicate a less oxidized material. Another absorption peak on the negative control can be observed at ~1635 cm-1, corresponding to O-H bending ofresidual water. For all the treated samples, a reduction on the peak at ~1735 cm-1 wasobserved. Likewise, the peak corresponding to the adsorbed water decreased. For the positive control sample, however, a peak at ~1615 cm-1can be observed, which possibly correspond to C=O stretching of -COO-Na+.Fig. 9 shows Infrared absorbance ATR spectra for the different BNC dressingpreparation. Example 5. Stability of the hypochlorite solution loaded into the BNC dressing Due to the reactivity of the NaOCl solution with the cellulose fibres present in the BNCdressing, the stability of the antiseptic solution over time was analyzed. The BNC dressingwas incubated with Actimaris®Forte for 120 min with or without any pre-incubation with a hypochlorite solution. Hypochlorite ions were detected at extremely low concentrations after 7 days and no detection was observed after 14 days using non pre-incubated BNC (see Fig.10A). Around 66% of the antiseptic solution loaded into the pre-incubated BNCremained active after 7 days. After 14 days, around 22% of the hypochlorite ions detectedat t=0 were still active. For the same period of time, Actimaris®Forte solution remained stable, showing similar detection results for t=0 and after 14 days (data not showed). Calculating the non-linear fit for the stability over time, BNC without pre-incubation showed good fit for the one phase decay model (r² of 0.95, 0.99 and 0.95, respectively; see Fig. 10B), whereas the pre-incubated BNC showed a better fit for a simpler model (straightline model, with a r² of 0.911).Fig.10 shows the stability of the hypochlorite molecules loaded into the BNC dressings. Example 6. Efficacy of the pre incubate BNC dressing against S. aureusTo test the efficacy of the loaded antiseptic solutions against Staphylococcus aureus, anadapted zone of inhibition assay was performed [4]. All the results are presented relative to the ZOI achieved by the solutions applied directly on the culture medium (Fig.11). As previously observed for the detection of hypochlorite ions, incubation time and the volume ratio where the unmodified BNC dressings were incubated can influence the efficacyagainst S. aureus. Increase of the incubation volume for a 10 min uptake using Actimaris®Forte does not translate into a higher efficacy (Fig.11A). An incubation with a volume of Actimaris® Forte 20x higher than the volume of solution present in the unmodified BNC dressing reached an efficiency of around 45% the ZOI achieved by the solution control. A comparable result was obtained by an incubation of 60 min using 5x the volume of solutionpresented in the dressing. After 60 min of incubation, both dressings incubated with 10xand with 20x their volumes reached similar results (above 70%). For Lavanox® antiseptic, no considerable ZOI were obtained for incubation periods lower than 120 min using unmodified BNCs (Fig.11B). At this incubation time, the obtained ZOIs were still lower than the solution used as control, with only the BNC incubated with 20x itsvolume reaching an average ZOI of more than 50% the area achieved by the control. Nostatistically difference was obtained for the ZOI of the incubation with 5x the volume in comparison to with 10x the volume. Similarly, no significant difference was obtained for the incubation with 10x and 20x the volume. The only difference observed was obtained when the ZOI of the BNC incubated using 5x the volume of Lavanox® was compared tothe incubation with 20x (p = 0.04). To test the efficacy of the non pre-incubated BNC is compared to the pre-incubated after an incubation with Granudacyn® for 120 min, using 5x the volume of solution enclosed in the dressing, was performed (Fig. 11C). The non pre-incubated BNC loaded with Granudacyn® reached a ZOI around 20% of the obtained by the antiseptic applied directlyin the culture medium. The pre-incubated BNC however achieved a far superior ZOI,achieving in average an efficacy 60% higher than the control. Figure 11D illustrate the results obtained for the efficacy of the modified BNC compared to unmodified dressing. Fig.11 shows ZOI assay results for antiseptics loaded into the BNC dressing. Example 7. Anti-biofilm activity of BNC loaded hypochlorite antispetics Pathogenic biofilms are considered a major contributing factor for disturbed wound healing, subsequently leading to chronic wounds. Attempts to eradicate pathogenic biofilms and treat chronic wound infections are to date limited to the use of conventionalsystemic antibiotics and antiseptics. The antimicrobial activity of antiseptic-loaded BNCagainst in-vitro biofilms of Gram-positive and -negative bacteria as well as fungi was tested. BNC was loaded with the commercially available antiseptics Lavanox® and Actimaris®. The silver-based dressing Aquacel®Ag+ was used as a positive control. Biofilm efficacy of loaded BNC was tested against an in-vitro 24-hour biofilm ofStaphylococcus aureus according to the standard ASTM E2647-13 as well as Candidaalbicans and Pseudomonas aeruginosa 48-hour biofilm according to the standard ASTM E2562-17. BNC loaded with hypochlorite antiseptics showed a significant reduction of all three biofilms with similar efficacy as the control sample, Aquacel®Ag Extra (see Table 4). Complete eradication of the S.aureus and C. albicans biofilm was shown. P.aureginosabiofilm was eliminated to lesser extent using Lavanox.Thus the BNC wound dressings present a highly effective carrier for antiseptics in the treatment of biofilms. Prevention and treatment of chronic wound infections is therefore considered feasible with this novel approach and even superior to existing modalities. Table 4: Reduction of biofilms by BNC loaded with different antiseptics. Reference list 1. de Mattos, I.B., et al., Uptake of PHMB in a bacterial nanocellulose-based wound dressing: A feasible clinical procedure. Burns, 2019.45(4): p.898-904. 2. Bernardelli de Mattos, I., et al., Delivery of antiseptic solutions by a bacterialcellulose wound dressing: Uptake, release and antibacterial efficacy of octenidine and povidone-iodine. Burns, 2020.46(4): p.918-927. 3. Luca-Pozner, V., et al., The use of a novel burn dressing out of bacterial nanocellulose compared to the French standard of care in paediatric 2nd degree burns - A retrospective analysis. Burns, 2021.4. Schiefer, J.L., et al., Comparison of wound healing and patient comfort in partial- thickness burn wounds treated with SUPRATHEL and epicte(hydro) wound dressings. Int Wound J, 2021. 5. Cattelaens, J., et al., The Impact of a Nanocellulose-Based Wound Dressing in the Management of Thermal Injuries in Children: Results of a RetrospectiveEvaluation. Life, 2020.10(9). 6. Koburger, T., et al., Standardized comparison of antiseptic efficacy of triclosan, PVP-iodine, octenidine dihydrochloride, polyhexanide and chlorhexidine digluconate. Journal of Antimicrobial Chemotherapy, 2010.65(8): p.1712-1719. 7. Hardy, K., et al., Increased Usage of Antiseptics Is Associated with ReducedSusceptibility in Clinical Isolates of Staphylococcus aureus. mBio, 2018.9(3). 8. Severing, A.L., et al., Safety and efficacy profiles of different commercial sodium hypochlorite / hypochlorous acid solutions (NaClO / HClO): antimicrobial efficacy, cytotoxic impact and physicochemical parameters in vitro. J Antimicrob Chemother, 2019.74(2): p.365-372.9. Setsukinai, K., et al., Development of novel fluorescence probes that can reliablydetect reactive oxygen species and distinguish specific species. J Biol Chem, 2003. 278(5): p.3170-5. 10. Wu, C.N., et al., TEMPO-Oxidized Bacterial Cellulose Pellicle with Silver Nanoparticles for Wound Dressing. Biomacromolecules, 2018.19(2): p.544-554.11. Tang, Z., et al., TEMPO-Oxidized Cellulose with High Degree of Oxidation.Polymers (Basel), 2017.9(9). 12. Kiamco, M.M., et al., Hypochlorous-Acid-Generating Electrochemical Scaffold for Treatment of Wound Biofilms. Sci Rep, 2019.9(1): p.2683. 13. Papayannopoulos V., Neutrophil extracellular traps in immunity and disease. Nature Reviews Immunology. 2017;18(2):134-47.14. Ulfig A, Leichert LI., The effects of neutrophil-generated hypochlorous acid and other hypohalous acids on host and pathogens. Cellular and molecular life sciences : CMLS.2021;78(2):385-414. 15. Biedron R, Konopinski MK, Marcinkiewicz J, Jozefowski S., Oxidation by neutrophils-derived HOCl increases immunogenicity of proteins by converting theminto ligands of several endocytic receptors involved in antigen uptake by dendritic cells and macrophages. PloS one.2015;10(4):e0123293. 16. Ulfig A, Schulz AV, Muller A, Lupilov N, Leichert LI., N-chlorination mediates protective and immunomodulatory effects of oxidized human plasma proteins. Elife. 2019;8.17. Himmelfarb J, McMonagle E., Albumin is the major plasma protein target of oxidant stress in uremia. Kidney Int.2001;60(1):358-63. 18. Sakarya S, Gunay N, Karakulak M, Ozturk B, Ertugrul B., Hypochlorous Acid: an ideal wound care agent with powerful microbicidal, antibiofilm, and wound healing potency. Wounds. 2014;26(12):342-50. da Costa MC, Ferreira BA, de Moura FBR, de Lima LG, Araujo FA, Mota FCD., Evaluation of 4% stabilized Sodium Hypochlorite activity in the repair of cutaneous excisional wounds in mice. Injury.2021;52(8):2075-83. Burian EA, Sabah L, Kirketerp-Moller K, Gundersen G, Agren MS., Effect ofStabilized Hypochlorous Acid on Re-epithelialization and Bacterial Bioburden inAcute Wounds: A Randomized Controlled Trial in Healthy Volunteers. Acta Derm Venereol.2022;102:adv00727. Burian EA, Sabah L, Kirketerp-Møller K, Ibstedt E, Fazli MM, Gundersen G,. The Safety and Antimicrobial Properties of Stabilized Hypochlorous Acid in Acetic AcidBuffer for the Treatment of Acute Wounds—a Human Pilot Study and In Vitro Data.The international journal of lower extremity wounds.2021;22(2):369-77. Schwanninger M, Rodrigues JC, Pereira H, et al.; Effects of short-time vibratory ball milling on the shape of FT-IR spectra of wood and cellulose. Vibrational Spectroscopy 2004;36(1):23-40.
Claims
Claims1. Wound dressing comprising a cellulose component, wherein the cellulosecomponent comprises 90 wt.% or more of an aqueous liquid, and 10 wt.% or less and more than 0 wt.-% of dry mass cellulose, wherein (A) the cellulose component exhibits substantially no carbonyl peak at 1735 cm-1+ / - 2 cm-1as determined by Fourier transform infrared (FTIR) in an infrared absorbanceATR spectrum; and / or(B) wherein the wound dressing has been pre-incubated with an aqueous OCl- -ion- containing solution.
2. Wound dressing according to claim 1, wherein the cellulose component isbacterial cellulose, preferably bacterial nanocellulose.
3. Wound dressing according to claim 1 or 2, wherein (C) the cellulose of the wound dressing exhibits a substantially lower molecular mass distribution of the cellulose polymer chain, when compared to the originally samecellulose material of a wound dressing that was not pre-incubated with an aqueous OCl--ion-containing solution.
4. Wound dressing according to any one of claims 1 to 3, wherein the average chain length of the cellulose of the wound dressing exhibits a cellulose chain length, asdetermined by a Gel Permeation Chromatography (GPC) with Multi-Angle LightScattering Detection (MALS) method, is (i) 62.0-90.0 Mn[kg / mol], preferably 66.0-80.0 Mn[kg / mol], more preferably 68.0- 79.0 Mn[kg / mol], even more preferably 67.0-79.0 Mn[kg / mol], and most preferably 75.0- 79.0 Mn[kg / mol]; and / or(ii) 100.0-180.0 Mw [kg / mol], preferably 150.0-167.0 Mw [kg / mol], more preferably160.0-167.0 Mw[kg / mol]; and / or(iii) 220.0-290.0 Mz[kg / mol], preferably 250.0-275.0 Mz[kg / mol], more preferably 265.0-275.0 Mz[kg / mol]; and / or (iv) reduced by at least 1.0 [kg / mol] with respect to Mn[kg / mol], and / or Mw[kg / mol], and / or Mz[kg / mol], when compared to a non pre-incubated wound dressing.
5. Sterile package containing a wound dressing as defined in any one of claims 1 to 4.
6. Method for preparing a wound dressing, comprising the steps of:(i) providing a wound dressing comprising a cellulose component, wherein thecellulose component comprises 90% or more aqueous liquid and 10% or less cellulose (dry mass); (ii) incubating the wound dressing with an aqueous OCl- -ion-containing solution; (iii) washing the incubated wound dressing obtained in (ii), thereby obtaining thewound dressing.
7. Method according to any of the preceding claims, wherein the aqueous liquid and the cellulose dry mass add up to 100 wt.%.
8. Method for preparing a ready-to-use wound dressing, comprising the steps of (i)to (iii) of claim 6 to prepare a pre-incubated wound dressing, and subsequently comprising a step of: (iv) loading the pre-incubated wound dressing obtained in (iii) with an aqueous OCl- - ion-containing solution having an OCl- concentration in a range from 0.005% to 2.000%.
9. Method according to claim 8, further comprising the step of (v) loading the pre-incubated wound dressing, either prior to, simultaneously with, or subsequent to step (iv), with anyone of further active compounds other than OCl-, preferably wherein the further active compounds comprise antiseptics other than OCl-, inparticular an antiseptic selected from the group consisting of polyhexanide (PHMB),octenidine or octenidine hydrochloride, chlorhexidine, chlorhexidine-digluconate, polyvidone (PVP)-iodine, and mafenide.
10. A wound dressing as defined in any of claims 1 to 4, which is loaded with anaqueous OCl- -ion-containing solution having an OCl- concentration in a range from0.005% to 2.000%.
11. Aqueous OCl- -ion-containing solution having an OCl- concentration in a range from 0.005% to 2.000%, for use in a wound treatment, wherein a wound dressing asdefined in any of claims 1 to 4 is loaded with said aqueous OCl- -ion-containing solution,optionally directly before the treatment and then applying the loaded wound dressing onto the treatment site.
12. Aqueous OCl- -ion-containing solution having an OCl- concentration in a rangefrom 0.005% to 2.000%, for use in the prevention and / or treatment of inflammation in amammal, where there is no infection, or in the prevention and / or treatment of an inflammatory skin condition, wherein a wound dressing as defined in any of claims 1 to 4 is loaded with said aqueous OCl- -ion-containing solution, optionally directly before the treatment and then applyingthe loaded wound dressing onto the treatment site.
13. Kit of parts comprising (i) a wound dressing according to any of claims 1 to 4, and (ii) an aqueous OCl- -ion-containing solution having an OCl- concentration in a rangefrom 0.005% to 2.000%, optionally further comprising(iii) further active compounds other than OCl-,.
14. Use of a wound dressing according to any of claims 1 to 4 for being loaded with an aqueous OCl- -ion-containing solution having an OCl- concentration in a range from0.005% to 2.000%.
15. Wound dressing as defined in any of claims 1 to 4 for use in a method of treating wounds, or for use in the prevention and / or treatment of inflammation in a mammal.
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