WO2021142224A1 - Hemostatic gauze comprising carbon - Google Patents

Abstract

Methods for promoting wound healing and promoting hemostasis comprising application of a wound dressing composition, wherein in certain embodiments the wound dressing composition comprises a cellulosic fiber, a carbonaceous material and, if needed, a binder, and wherein the carbonaceous material comprises synthetic carbon particles containing micropores, mesopores, macropores, or combinations thereof.

Description

HEMOSTATIC GAUZE COMPRISING CARBON

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Application Serial No. 62/958,402 filed January 8, 2020, and entitled “Hemostatic Gauze Comprising Carbon,” which is incorporated by reference herein in its entirety.

TECHNICAL FIELD

[0002] Generally disclosed herein are compositions and methods for treating wounds. More particularly disclosed herein are carbon containing dressing compositions and methods of their preparation and use for treating wounds.

BACKGROUND

[0003] Wounds are defined as an injury to living tissue typically one in which the skin is cut or broken. Wounds can be classified as acute or chronic. Acute wounds, typically those received as a result of surgery or trauma, usually heal uneventfully within an expected time frame. Acute wounds may be characterized by an active bleeding site comprising detectable, un-clotted blood. The rapid control of topical bleeding at active bleeding wound sites is of critical importance in wound management, especially for the management of trauma. On the other hand, a chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time. Wounds that do not heal within three months are often considered chronic. Chronic wounds seem to be detained in one or more of the phases of wound healing.

[0004] An ongoing need exists for novel dressing compositions capable of treating the need to prevent blood loss in the case of acute wounds or for promoting wound healing in the case of chronic wounds.

BRIEF DESCRIPTION OF THE DRAWINGS [0005] Figure 1 illustrates a SEM image of the texture of particulate carbons revealing interpenetrating network of macropores.

[0006] Figure 2 illustrates a proposed quasi-macrocyclic structure of high-ortho Novolac hexamer.

[0007] Figure 3 illustrates the effect of increasing ethylene glycol content in the resin composition on the pore size of cured resins and derived carbonized beads. [0008] Figure 4 illustrates the relationship of the pore size and the bulk density of carbonized beads, derived from resin compositions with pure ethylene glycol.

[0009] Figures 5A-5B illustrate the effect of partial substitution of ethylene glycol with water in the resin compositions on the relationship of the pore size and the bulk density of derived carbonized beads. Solid lines represent series of samples derived from compositions with increasing content of pure ethylene glycol, whereas branches of dotted lines represent samples with increasing degree of substitution of ethylene glycol with water. Each dotted branch corresponds to series of samples with constant Pore former to (Novolac + Hexamine) ratio.

[0010] Figures 6A-6B illustrate the effect of gradual increase of sodium hydroxide concentration in the resin compositions on the relationship of the pore size and the bulk density of derived carbonized beads. Solid lines represent series of samples with increasing content of pure ethylene glycol (no NaOH added), whereas branches of dotted lines represent samples with increasing concentrations of sodium hydroxide.

[0011] Figure 7 illustrates AFM images of the textures of 3 carbonized beads derived from resin compositions with constant Pore Former/(Novolac+EG ) = 2.25 ratio, but containing some sodium hydroxide (sample 1), pure ethylene glycol (sample 2) and ethylene glycol with water (sample 3). The sizes of primary spheroid carbon nano domains could be estimated by roughness values.

[0012] Figure 8 illustrates a 2D model of the effect of the nano domain diameter on the size of intraparticulate voids. Surface area of voids corresponds to the meso/macropore volume in 3D variant.

[0013] Figure 9 illustrates the effect of additional selective catalytic activation of the activated Kynol carbon cloth on the pore size distributions, derived from nitrogen adsorption isotherms at - 195.8 C, interpreted with BJH model. Characteristic feature - significant increase of the pore volumes, though corresponding to mesopores of different sizes, smaller for Ca- catalyzed and larger - for Fe- catalyzed materials, with very little changes in the surface areas, located mainly in micropores.

[0014] Figure 10 illustrates the effect of the mesopore size on the kinetics and capacity of adsorption of the medium size molecules (Vitamin B12).

[0015] Figure 11 is a depiction of a wound dressing of the type disclosed herein. DETAILED DESCRIPTION

[0016] In a non-limiting aspect, a method for promoting wound healing in a subject is described herein. The term “subject,” as used herein, comprises any and all organisms and includes the term “patient.” The patient may be a human, horse, bird, dog, cat, sheep, cow, monkey, or other mammal. In an aspect the method for promoting hemostasis comprises application of a composition of the type disclosed herein to the wound site.

[0017] Further disclosed herein are wound dressing compositions (WDC). Also disclosed are methods of preparing and using WDCs. In an aspect, the WDC is used to promote healing of a chronic wound. In another aspect, a WDC may be used to promote hemostasis at the active bleeding site or active wound site of a subject such as to control a hemorrhage.

[0018] In some aspects, the WDCs are able to positively impact healing and/or hemostasis with little or no concomitant contribution toward embolus formation. WDCs of the present disclosure for use in the treatment of a chronic wound are designated C-WDCs while WDCs formulated for the treatment of an acute wound are designated A-WDC.

Carbon-Impregnated WDCs

[0019] In a non-limiting aspect, WDCs of the disclosure comprise a cellulosic fiber, a carbonaceous material and, if needed, a binder. In some aspects, the carbonaceous material may be immobilized on the cellulosic fabric, for example, the cellulosic fiber may be impregnated with the carbonaceous material. Immobilization of the carbonaceous material may comprise: (i) a network of fibers that comprise the cellulosic fabric; (ii) the use of a binder that covalently bonds to both the fabric and the carbonaceous particle; (iii) a network of ionic bonds within the cellulosic fabric; or (iv) combinations of thereof. In some aspects, the cellulosic fabric and the carbonaceous material may be ionically linked, covalently linked, of combinations of thereof.

[0020] In an aspect, the cellulosic fabric may comprise cellulosic gauze, modified cellulosic gauze, and combinations thereof. Modified cellulosic gauze may be prepared by contacting cellulosic gauze with chemical reagents wherein the chemical reagents enhance the medicinal properties of the cellulosic gauze. In a non-limiting aspect, medicinal properties that may be enhanced by chemical modification include liquid adsorbent capacity, hemostatic capacity and combinations thereof. A non-exhau stive list of chemical modifications which can enhance the medicinal properties of the gauze include oxidation, bleaching, acidification, and combinations thereof. The term “gauze” will be taken to represent cellulosic gauze, modified cellulosic gauze, and combinations thereof through the remainder of the present disclosure.

[0021] In an aspect, the WDCs of the present disclosure comprise a carbonaceous material, such as synthetic carbon particles containing micro-, meso-, and macropores, or combinations thereof. A synthetic carbon particle of the type disclosed herein may be prepared using any suitable methodology. Alternatively, the synthetic carbon particle is prepared using a phenolic resin. As used herein, the term “micropore” refers to pores with diameter <2 nm, as measured by nitrogen adsorption and mercury porosimetry methods and as defined by IUPAC. As used herein, the term “mesopore” refers to pores with diameter from ca. 2 nm to ca. 50 nm, as measured by nitrogen adsorption and mercury porosimetry methods and as defined by IUPAC. As used herein, the term “macropore” refers to pores with diameters larger than 50 nm, as measured by nitrogen adsorption and mercury porosimetry methods and as defined by IUPAC. In macroporous beads the pores are located within beads and formed by pore-formers. The pores may have a size from 50-500 nm, typically 70-200 nm. These macropores are very effective in adsorption of cytokine and other larger molecules and complexes.

[0022] A synthetic carbon particle suitable for use in the present disclosure may have any shape compatible with the compositions and methodologies disclosed herein. For example, the shape of the synthetic carbon particle may be that of an irregular granule, a low angularity shape, spherical (e.g., bead), pellet, minilith, monolith, etc. For simplicity, the present disclosure may refer to the use of beads of the synthetic carbon particle, however it is to be understood the synthetic carbon particle may be of any suitable shape. The synthetic carbon particles may be formed using any suitable methodology to result in a material having the properties disclosed herein. In some methods for the formation of a synthetic carbon particle a precursor resin formulation is used which comprises a large proportion of pore former (e.g., 250 parts ethylene glycol or other pore former to 100 parts of resin-forming components).

[0023] In some aspects herein, a mesoporous resin may be formed by condensing a nucleophilic component which comprises a phenolic compound or a phenol condensation prepolymer with at least one electrophilic cross-linking agent selected from formaldehyde, paraformaldehyde, furfural, and hexamethylene tetramine in the presence of a pore-former selected from the group consisting of a diol (e.g., ethylene glycol), a diol ether, a cyclic ester, a substituted cyclic ester, a substituted linear amide, a substituted cyclic amide, an amino alcohol, and a mixture of any of the above with water to form a resin. The pore-former is present in an amount effective to impart meso- or macroporosity to the resin (for example, at least 120 pbw of the pore former being used to dissolve 100 pbw of the total resin forming components (i.e., the nucleophilic component plus electrophilic component)), and it is removed from the porous resin after condensation by cascade washing with water or by vacuum drying and further recycled. The resulting resin may be carbonized by heating in an inert atmosphere to a temperature of at least 600°C to give a material having a bimodal distribution of pores, the pore structure as estimated by nitrogen adsorption porosimetry comprising micropores and mesopores or macropores. The value for the differential of pore volume with respect to the logarithm of pore radius (dV/dlogR) for the mesopores is greater than 0.2 for at least some values of pore size in the range of 2-500 nm. The mesoporous carbon may have a BET surface area of 250-800 m²/g without activation. It may be activated by heating it at high temperature in the presence of carbon dioxide, steam or a mixture thereof, e.g. by heating it in carbon dioxide at above 800 °C, or it may be activated by heating it in air at above 400 °C. It may then have surface areas of up to 2000 m²/g and even higher e.g. 1000-2000 m²/g. As used herein the term “BET surface area” is determined by the Brunauer, Emmett, and Teller (BET) method according to ASTM D 1993-91, see also ASTM D6556-04. [0024] In an aspect, the nucleophilic component may comprise a phenolic Novolac resin (i.e., “Novolac”) or other similar oligomeric starting material, which is partially polymerized and confers less exothermicity and hence more controllability during the polymerization reaction to the desired resin. In another aspect, Novolac may be characterized by AMW in the range of from 300 to 3000 prior to cross-linking (corresponding to a DP with respect to phenol of about 3-30). Where Novolacs are used, they may be solids with melting points in the region of 100 °C. Novolacs of AMW less than 2000, alternatively less than 1500, tend to require lower amounts of pore former to produce resins comprising carbons with desired post-carbonization pore size distributions. Novolacs are thermally stable in that they can be heated so that they become molten and cooled so that they solidify repeatedly without structural change. They are cured on addition of cross-linking agents and heating. Fully cured resins are infusible and insoluble. Whilst commercial Novolacs are largely produced using phenol and formaldehyde, a variety of modifying reagents can be used at the pre -polymer formation stage to introduce a range of different oxygen and nitrogen functionalities and cross-linking sites.

[0025] In a non-limiting aspect, modifying reagents may comprise dihydric phenols (e.g., resorcinol or hydroquinone), or nitrogen containing compounds. Both resorcinol and hydroquinone are more reactive than phenol and can lead to some cross-linking at the pre-polymer production stage. Both resorcinol and hydroquinone may be introduced at the cross-linking stage to provide different cross-linking paths. Both resorcinol and hydroquinone also increase the oxygen functionality of the resins. Nitrogen containing compounds that are active in polycondensation reactions include urea, aromatic amines (e.g., aniline or m-amino phenol) and heteroaromatic amines (e.g., melamine). Nitrogen containing compounds facilitate introduction of specific types of nitrogen functionality into the initial polymer and the final carbon and, likewise, influence the development of the mesoporous structure of both the resins and the final carbons. Hydroquinone, resorcinol, and the nitrogen containing nucleophilic modifying reagents possess two or more active sites and are more reactive in condensation reactions than phenol or Novolacs. Consequently, these compounds will react with primary cross-linking agents faster than either phenol or Novolacs resulting in in situ formation of secondary cross-linking agents that can react with phenol or Novolacs.

[0026] The nucleophilic component may be provided alone or in association with a polymerization catalyst which may be a weak organic acid miscible with the Novolac and/or soluble in the pore former (e.g., salicylic acid, oxalic acid or phthalic acid). The concentration of Novolac in the pore former may be such that when combined with the solution of cross-linking agent in the same pore former the overall ratio of pore former to (Novolac + cross-linking agent) is at least 125:100 by weight. The actual ratios of Novolac:pore former and cross-linking agenkpore former are set according to convenience in operation by the operational requirements of a bead production plant and are controlled by the viscosity of the Novolac:pore former solution such that it remains pumpable and by the ratio of cross-linking agenkpore former such that the cross-linking agent remains in solution throughout the plant.

[0027] In an aspect, the cross-linking agent is normally used in an amount of from about 5 pbw to about 40 pbw per 100 pbw of the nucleophilic components (e.g., Novolac), depending on its molecular weight. In another aspect, the cross-linking agent may comprise an aldehyde (e.g., formaldehyde or furfural), hexamethylenetetramine (i.e., hexamine), or hydroxymethylated melamine. Alternatively, the cross-linking agent is hexamine and in aspects requiring a completely cured resin the cross-linking agent is present at about 10 pbw to about 25 pbw hexamine or, alternatively about 15 pbw to about 20 pbw hexamine to 100 pbw of Novolac. In some aspects, application of the hexamine-to-Novolac ratio stated above ensures formation of the solid resin with maximal cross-linking degree and ensures the stability of the meso/macropore structure during subsequent removal of the pore former.

[0028] The pore former also acts as solvent. Thus, the pore former is used in quantities sufficient to dissolve the components of the resin system, wherein the weight ratio of pore former to the total components of the resin system resin is at least 1.25:1. The pore former may be, for example, a diol, a diol-ether, a cyclic ester, a substituted cyclic or linear amide or an amino alcohol e.g. ethylene glycol, 1,4-butylene glycol, diethylene glycol, triethylene glycol, g-butyrolactone, propylene carbonate, dimethylformamide, N-methyl-2-pyrrolidinone and monoethanolamine, ethylene glycol being preferred, and where the selection is also limited by the thermal properties of the solvent as it should not boil or have an excessive vapor pressure at the temperatures used in the curing process.

[0029] Not intending to be bound by theory, it is thought that the mechanism of meso- and macropore generation is due to a phase separation process that occurs during the cross-linking reaction. In the absence of a pore former, as the linear chains of pre-polymer undergo cross-linking, their molecular weight initially increases. Residual low molecular weight components become insoluble in the higher molecular weight regions causing a phase separation into cross-linked high molecular weight domains within the lower molecular weight continuous phase. Further condensation of light components to the outside of the growing domains occurs until the cross- linked phase becomes essentially continuous with residual lighter pre-polymer trapped between the domains. In the presence of a low level of pore former (e.g., <120 parts/100 parts Novolac for the Novolac-Hexamine-Ethylene Glycol reaction system), the pore former is compatible with the cross-linked resin domains. Most of the pore former remains within the cross-linked resin domains and the remainder of the pore former forms a solution with the partially cross-linked polymer between the domains. In the presence of higher levels of pore former, which exceed the capacity of the cross-linked resin, the pore former adds to the light polymer fraction increasing the volume of material in the voids between the domains that gives rise to the mesoporosity and/or macroporosity. In general, the higher the pore former content, the wider the mesopores, up to macropores, and the higher the pore volume.

[0030] This phase separation mechanism provides a variety of ways of controlling the pore development in the cross-linked resin structures. These include chemical composition and concentration of the pore former; chemical composition and quantity of the cross-linking electrophilic agents, presence, chemical nature and concentration of modifying nucleophilic agents, chemical composition of phenolic nucleophilic components (e.g., phenol or Novolac), the presence of water within the solvent and concentration of any curing catalyst if present.

[0031] In an aspect, the bead form may be prepared by pouring a solution of a partially cross- linked pre-polymer and cross-linking agent into a stirred hot liquid such as mineral oil containing a dispersing agent. The pre-polymer solution forms liquid drops which become solid beads as curing proceeds. The average bead particle size is controlled by several process parameters including the stirrer type and speed, the oil temperature and viscosity, the pre-polymer solution viscosity and volume ratio of the solution to the oil and the mean size can be adjusted between 5 and 2000 pm although in practice the larger bead sizes are difficult to achieve owing to problems with the beads in the stirred dispersion vessel. The beads can then be separated from the oil by filtration and/or centrifugation. Spent oil could be recycled. In a preparative example, industrial Novolac resin is mixed with (e.g., dissolved in) ethylene glycol at an elevated temperature, mixed with hexamine solution in ethylene glycol and heated to give a viscous solution which is poured into stirred mineral oil containing a drying oil as the dispersing agent, after which the mixture is further heated to effect curing. On completion of curing, the reaction mixture is cooled, after which the resulting porous resin is separated, and washed with hot water to remove pore former and a small amount of low molecular weight polymer. The cured beads are carbonized to porous carbon beads which have a pore structure as indicated above and may be activated as indicated above. It is stated that the beads can be produced with a narrow particle size distribution, for example, exhibiting a D90/D10 particle size distribution of better than 10, or better than 5. However, the bead size distribution that can be achieved in practice in stirred tank reactors is relatively wide, and the more the process is scaled up the worse the homogeneity of the mixing regime and hence the particle size distribution becomes wider. [0032] Discrete solid beads of polymeric material, for example, phenolic resin having a porous structure may be formed, which process may produce resin beads on an industrial scale without aggregates of resin building up speedily and interrupting production. The process comprises the steps of: (a) combining a stream of a polymerizable liquid precursor, for example, a Novolac and hexamine as cross-linking agent dissolved in a first polar organic liquid, such as ethylene glycol with a stream of a liquid suspension medium which is a second non-polar organic liquid with which the liquid precursor is substantially or completely immiscible e.g. transformer oil containing a drying oil; (b) mixing the combined stream to disperse the polymerizable liquid precursor as droplets in the suspension medium, for example, using an in-line static mixer; (c) allowing the droplets to polymerize in a laminar flow of the suspension medium so as to form discrete solid beads that cannot agglomerate; and (d) recovering the beads from the suspension medium.

[0033] For bead production, the pore former comprises a polar organic liquid e.g. ethylene glycol chosen in combination with dispersion medium which is a non-polar organic liquid so as to form a mainly or wholly immiscible combination, the greater the incompatibility between the pore former which forms the dispersed phase and the dispersion medium, the less pore former becomes extracted into the dispersion medium. The pore former desirably has a greater density than the dispersion medium with which it is intended to be used so that droplets of the pore former containing dissolved resin-forming components will pass down a column more rapidly than a descending flow of dispersion medium therein. Both protic and aprotic solvents of different classes of organic compounds match these requirements and can be used as pore formers, both individually and in mixtures. In addition to dissolving the reactive components and any catalyst, the pore former should also, in the case of phenolic resins, be compatible with water and/or other minor condensation products (for example, ammonia) which are formed by elimination as polymerization proceeds, and the pore former is preferably highly miscible with water so that it can be readily removed from the polymerized resin beads by washing.

[0034] The dispersion medium is a liquid which can be heated to the temperature at which curing is carried out (e.g., to 150 °C) without boiling at ambient pressure and without decomposition and which is immiscible with ethylene glycol and with the dissolved components therein. It may be hydrocarbon-based transformer oil which is a refined mineral oil and is a by product of the distillation of petroleum. It may be composed principally of C₁₅-C₄₀ alkanes and cycloalkanes, have a density of 0.8-0.9 depending upon grade and have a boiling point at ambient pressure of 260-330 °C, also depending upon grade. Transformer oil has a viscosity of about 0.5 poise at 150 °C which is a typical cure temperature. Transformer oil or other dispersion medium may be used in volumes of 3-10 times the volume of the combined streams of nucleophilic precursor and crosslinking agent, for example, at a volume of about 5 times the volume of the combined streams of nucleophilic precursor and crosslinking agent.

[0035] Preferred dispersing agents which are dissolved in the dispersion medium before that medium is contacted with the reaction mixture to be dispersed therein to retard droplet coalescence are either sold as drying oils such as Danish oil or are produced by partially oxidizing naturally occurring precursors such as tung oil, linseed oil etc. The dispersing agents are consumed as the process proceeds, so that if the dispersion medium is recycled, dispersing agent in the recycled oil stream should be replenished. The dispersing agent is conveniently supplied as a stream in solution in the dispersion medium e.g. transformer oil and e.g. in an amount of 5-10% v/v where Danish oil is used which contains a low concentration of the active component to give final concentration of the dispersant in the dispersion medium 0.2-1% v/v. Higher dispersant concentrations would be used in the case of oxidized vegetable oils.

[0036] The resin beads formed as described above may be carbonized and optionally activated. For example, carbonization and activation may comprise supplying the material to an externally fired rotary kiln maintained at carbonizing and activating temperatures, the kiln having a downward slope to progress the material as it rotates, the kiln having an atmosphere substantially free of oxygen provided by a counter-current of steam or carbon dioxide, and annular weirs being provided at intervals along the kiln to control progress of the material. In an aspect, a synthetic carbon particle suitable for use in the present disclosure is characterized by a microporou s/macroporou s structure .

[0037] In an aspect, the synthetic carbon particle has a diameter of from about 75 pm to about 1000 pm, alternatively the synthetic carbon particle has a diameter of from about 100 pm to about 750 pm, or alternatively from about 100 pm to about 500 pm, or alternative from about 5 pm to 75 pm. Herein a synthetic carbon particle suitable for use in the present disclosure may comprise a synthetic carbon particle having at least two pore size distribution such that the particulate synthetic carbon is a mixture of carbon beads having at least two distributions of macroporous pore sizes. In an aspect, the synthetic carbon particle may comprise a first population having a macroporous pore size denoted x and a second population having a macroporous pore size y where the synthetic carbon particle provides a mixture having a ratio of x/y of about 1:1; alternatively about 5:1, alternatively about 10:1, alternatively about 20:1; alternatively about 50:1, or alternatively about 100:1. In some aspects, the synthetic carbon particle comprises a mixture of two populations wherein the pore size of the first population is approximately twice the pore size of the second population. In some aspects, the synthetic carbon particle comprises a mixture of three populations where the pore size of a first population is approximately twice the pore size of the second population and the pore size of the third population is approximately two and a half times the pore size of the second population.

Carbonaceous Material from Tailored Porosity Resins

[0038] Figure 1 illustrates a SEM image of the texture of particulate carbons revealing interpenetrating network of macropores.

[0039] Figure 2 illustrates a proposed quasi-macrocyclic structure of high-ortho Novolac hexamer.

[0040] Figure 3 illustrates the effect of increasing ethylene glycol content in the resin composition on the pore size of cured resins and derived carbonized beads.

[0041] Figure 4 illustrates the relationship of the pore size and the bulk density of carbonized beads, derived from resin compositions with pure ethylene glycol.

[0042] Figures 5A-5B illustrate the effect of partial substitution of ethylene glycol with water in the resin compositions on the relationship of the pore size and the bulk density of derived carbonized beads. Solid lines represent series of samples derived from compositions with increasing content of pure ethyleneglycol, whereas branches of dotted lines represent samples with increasing degree of substitution of ethylene glycol with water. Each dotted branch corresponds to series of samples with constant Pore former to (Novolac + Hexamine) ratio.

[0043] Figures 6A-6B illustrate the effect of gradual increase of sodium hydroxide concentration in the resin compositions on the relationship of the pore size and the bulk density of derived carbonized beads. Solid lines represent series of samples with increasing content of pure ethylene glycol (no NaOH added), whereas branches of dotted lines represent samples with increasing concentrations of sodium hydroxide. [0044] Figure 7 illustrates AFM images of the textures of 3 carbonized beads derived from resincompositions with constant Pore Former/(Novolac+EG ) = 2.25 ratio, but containing some sodium hydroxide (sample 1), pure ethylene glycol (sample 2) and ethylene glycol with water (sample 3). The sizes of primary spheroid carbon nano domains could be estimated by roughness values.

[0045] Figure 8 illustrates a 2D model of the effect of the nano domain diameter on the size of intraparticulate voids. Surface area of voids corresponds to the meso/macropore volume in 3D model.

[0046] Figure 9 illustrates the effect of additional selective catalytic activation of the activated Kynol carbon cloth on the pore size distributions, derived from nitrogen adsorption isotherms at - 195.8 C, interpreted with BJH model. Characteristic feature - significant increase of the pore volumes, though corresponding to mesopores of different sizes, smaller for Ca- catalyzed and larger - for Fe- catalyzed materials, with very little changes in the surface areas, located mainly in micropores.

[0047] Figure 10 illustrates the effect of the mesopore size on the kinetics and capacity of adsorption of the medium size molecules (Vitamin B12).

[0048] Figure 11 is a depiction of a wound dressing of the type disclosed herein.

[0049] In some embodiments, the carbonaceous material may be derived from polycondensation resins and having a tailored porosity, encoded by the porosity of the precursor resin.

[0050] In some aspects a cured polycondensation resin is derived from a high-ortho phenolic resin, and has a pore size ranging from about 10 nm to about 500 nm and an intraparticular porosity ranging from about 2% to about 25%. For example, the polycondensation resin may have a pore size of from about 25 nm to about 300 nm and an intraparticular porosity ranging from about 5% to about 20%, or a pore size of from about 50 nm to about 150 nm and an intraparticular porosity ranging from about 8% to about 15%. In some aspects, the polycondensation resin may comprise a chelating agent.

[0051] In some aspects, a carbonaceous material has a pore size (p) ranging from a lower limit (a) to an upper limit (z) and a bulk density (a) ranging from a lower limit (b) to an upper limit (y) where the comparative variability (g) defined as (y-b )/(z-a) is less than 1 X 10-3. For example, the carbonaceous material may have a pore size ranging from about 10 nm to about 5000 nm and a bulk density ranging from 0.15 g/ml to 0.60 g/ml, or a pore size ranging from about 20 nm to about 300 nm and a bulk density ranging from about 0.3 g/ml to about 0.5 g/ml, or a pore size ranging from about 50 nm to about 150 nm and a bulk density ranging from about 0.3 g/ml to about 0.5 g/ml. The carbonaceous material may comprise an adsorbent or a film.

[0052] In some aspects, a carbonaceous material has a pore size (p) ranging from a lower limit (a) to an upper limit (z) and a bulk density (a) ranging from a lower limit (b) to an upper limit (y) where the comparative variability (g) defined as (y-b)/(z-a) is less than 1 X 10-5. For example, the carbonaceous material may have a pore size ranging from about 10 nm to about 5000 nm and a bulk density ranging from 0.06 g/ml to 0.15 g/ml, or a pore size ranging from about 20 nm to about 300 nm and a bulk density ranging from about 0.3 g/ml to about 0.5 g/ml, or a pore size ranging from about 50 nm to about 150 nm and a bulk density ranging from about 0.3 g/ml to about 0.5 g/ml. The carbonaceous material may comprise an adsorbent.

[0053] Disclosed herein are polycondensation resins and carbonaceous materials derived therefrom having a tailored porosity. Herein porosity is referencing primarily the pore size and the pore volume. In an aspect, materials of the type disclosed herein may be tailored to have pore size in the range of from about 10 nm to about 5000 nm, alternatively from about 100 nm to about 2500 nm, or alternatively from about 200 nm to about 1000 nm. In some aspects, the tailored porosity resins (TPRs) disclosed herein are derived from a randomly-oriented precursor material and designated R-TPR (random). In another aspect, the tailored porosity resins (TPRs) disclosed herein are derived from a high-ortho precursor material and designated HO-TPR.

[0054] In some aspects, materials of the type disclosed herein may be tailored to have pore sizes in the range of from about 10 nm to about 5000 nm, alternatively from about 100 nm to about 2500 nm, or alternatively from about 200 nm to about 1000 nm. In some aspects, the tailored porosity resins (TPRs) disclosed herein are derived from a randomly ortho/para (o/p) substituted phenolic pre-polymer (Novolac) material and designated R-TPR (random). In another aspect, the tailored porosity resins (TPRs) disclosed herein are derived from a high-ortho substituted Novolac material and designated HO-TPR.

[0055] In an aspect, resins of the type disclosed herein (i.e., TPRs) and their derived carbon materials exhibit a pore size and pore volume that may be independently varied. In an aspect, the pore size is determined utilizing mercury-intrusion porosimetry to determine pore sizes ranging from about 2 nm to greater than about 5000 nm. In such aspects, the values of corresponding pore volumes have been estimated as specific volumes of intruded mercury and could be designated as combined volumes of meso- and macropores. They do not account for the volumes of micropores. In an alternative or complementary aspect, pore sizes may be determined using nitrogen adsorption/desorption porosimetry at the appropriate temperature (e.g., nitrogen boiling temperature, -195.8 X ) giving values of surface areas consistent within the BET model but applicable only for the pore size range of from about 1.5 nm to about 80 nm.

[0056] This method allows to measure nitrogen adsorption/desorption isotherms. Interpretation of these isotherms by different theoretical models gives pore size distribution profiles in the range below 80 nm and values of surface areas. In the present studies, BJH model was used for pore size distribution (PSD) evaluation (1.5 to 80 nm) and BET model - for the surface area calculations. In the case of particulate carbon adsorbents, and especially of beads, these porosity parameters could be complemented by bulk density (alias apparent or volumetric, or tapped density) of thoroughly packed carbon bed, g (g/ml). Without going into theoretical analyses of the mathematical problem known as “close packing of spheres”, one may assume that on the condition of thorough tapped packing of freshly degassed porous carbon beads of narrow particle size distribution, that excludes filling the voids between larger particles with smaller particles, this easily measurable parameter is inversely related to the total porosity of the adsorbent: g = const/ Vtotal , where Vtotal = Vmicro + Vmeso + Vmacro+ Vclosed (1)

[0057] The last term represents inaccessible pores, which are very small in numbers in carbon adsorbents of the invention and is typically ignored. The combination of four structural parameters: pore size distribution, BET surface area, bulk density, and particle size range adequately correlates with adsorption properties of carbons towards marker molecules, representing solutes with molecular weights ranging from 300 to 65000 Da, in model solutions. These adsorption properties in vitro are typically symbatic with adsorption properties in vivo. As the matter of fact, they are symbatic with the wound healing effects as well. This leads to the conclusion that adsorption is an important mechanism (one of several) of the wound healing.

[0058] In an aspect, TPRs and carbons derived therefrom may be tailored to have a porosity ranging from about 10 nm to about 5000 nm, alternatively from about 100 nm to about 1000 nm or alternatively from about 200 nm to about 800 nm and may be further characterized by a concomitant change in bulk density of less than about 50%, alternatively less than about 45%, alternatively less than about 40%, alternatively less than about 35%, alternatively less than about 30%, alternatively less than about 25%, alternatively less than about 20%, alternatively less than about 15%, or alternatively less than about 10%.

[0059] Without wishing to be limited by theory, TPRs and carbons derived therefrom of the type disclosed herein are characterized by unusual and precisely custom-regulated structures. Further, the TPRs of this disclosure represent structured materials that retain their interconnected pore texture following carbonization thus providing carbonaceous materials having unhindered access to active sites on the material (e.g., adsorption, catalytic, ion-exchange or chelating sites). [0060] It is contemplated herein that although polycondensation resins have protonogenic (phenolic hydroxyl-groups or carboxylic groups from modifying agents like salicylic acid and the like) or proton- accepting (amino-groups from modifying agents like aromatic or hetero aromatic amines) groups in their matrix, additional ion-exchange and/or chelating sites could be introduced by any suitable methodology. These include but are not restricted to sulfonation, chloromethylation followed by amination; etc.

[0061] Porous polycondensation resins of the present disclosure could be easily converted by any suitable methodology (e.g., carbonization) into porous carbons which inherit their meso/macroporosity from the resin-precursor. In an aspect, the carbonaceous materials derived from TPRs of the type disclosed herein are characterized by surface areas ranging from about 200 m²/g to about 2000 m²/g, alternatively from about 500 m²/g to about 1500 m²/g or alternatively from about 500 m²/g to about 1000 m²/g. Without wishing to be limited by theory, carbonized materials of the present disclosure may exhibit larger surface areas due at least in part to nanopores (pores with diameter below 2 nm) appearing in the course of carbonization. In an aspect, carbonaceous materials derived from TPRs of the type disclosed herein may have the surface area modified by additional processing for example the surface area may be increased through activation.

[0062] In an aspect, a method of preparing a TPR of the type disclosed herein comprises a polycondensation process. In an alternative aspect, a method of preparing a TPR of the type disclosed herein consists or consists essentially of a polycondensation process. A polycondensation process of the present disclosure involves the following major components (i) a nucleophilic component (non-limiting examples of which include - NOVOLAC phenol- formaldehyde linear pre-polymers with or without the addition of modifying nucleophilic amines (e.g. - aniline, phenylenediamines, aminophenols, melamine), dihydric phenols, phenolcarboxylic acids (such as and without limitation salicylic acid and 5-resorcilol carboxylic acid) and other compounds with multiple nucleophilic sites; (ii) a cross-linking electrophilic component, non limiting examples of which include hexamethylenetetramine (hexamine), or formaldehyde; (iii) a solvent/pore former, non-limiting examples of which include ethylene glycol, which may or may not contain modifying additives (such as and without limitation water and polyols); and (iv) a solubility modifying agent, non-limiting examples of which include without limitation sodium hydroxide or another alkaline agent soluble in the solvent/pore former.

[0063] In an aspect, the linear phenol-formaldehyde pre-polymers NOVOLAC comprise the major nucleophilic component of the polycondensation reaction composition. In an alternative aspect, the major nucleophilic component of the polycondensation reaction composition consists essentially of the linear phenol-formaldehyde pre-polymers NOVOLACs. In an alternative aspect, the major nucleophilic component of the polycondensation reaction composition consists of the linear phenol-formaldehyde pre-polymers NOVOLACs.

[0064] As understood by the ordinarily skilled artisan, there are two structural types of industrially manufactured phenol-formaldehyde NOVOLACs. The most common of these materials are randomly substituted NOVOLACs with differing average molecular masses, including o,o-, o,p- and p,p- variants of substitution in aromatic ring of phenol using standard organic nomenclature where o refers to the ortho position and p refers to the para position. Structures involving substitution into meta-position (m-) are practically absent. However randomly substituted NOVOLAC of the present disclosure is characterized by an average molecular weight of approximately 330 g/mol with -24% of p,p’-, -49% of o,p- and - 28% of o,o’- substitutions as determined by NMR ¹³C - studies. In contrast, high o,o’-substituted NOVOLAC of the present disclosure is characterized by an average molecular weight of approximately 470 g/mol with - 1% of p,p’-, - 37% of o,p- and -59% of o,o’- substitutions. Without wishing to be limited by theory, a high proportion of o, o’ -substitutions enables the self assembling of tetramers and higher oligomers into quasi-cyclic structures stabilized by hydrogen bonds between uniformly oriented phenolic hydroxy-groups. These ordered structures are believed to survive and be stabilized by the curing sol-gel process and provide chelating sites in meso/macroporous polycondensation resins. These sites are reminiscent of crown-ethers that form highly stable complexes with alkali and alkali earth metal ions. Some of them are also highly ion- size selective. Again, without wishing to be limited by theory, the formation of such ordered structures may stabilize the cured resin matrix, so that it’s glass transition temperature T_g remains higher than the decomposition temperature range of cured phenolic resin (e.g., 350°C -400°C) even in the presence of large quantities of pore former ethylene glycol. In stark contrast, for cured randomly substituted NOVOLACs the removal of major quantities of ethylene glycol is carried out prior to carbonization in order to preserve the porous texture from collapsing because of the glass transition on heating, i.e., resin’s glass transition temperature falls below decomposition temperature if ethylene glycol is not essentially removed either by washing with water or drying in vacuum. In an aspect of the present disclosure, the TPR is a chelator able to selectively bind monovalent or divalent cations. For example, the TPR may selectively bind alkali metals or alkali earth metals. In such examples the TPR may function as a chelating agent having formation constants, K_f, ranging from about lxlO³ to about lxlO¹⁵ depending on the cation being chelated, alternatively from about lxlO⁵ to about lxlO¹² or alternatively from about lxlO⁵ to about lxlO¹⁰. [0065] In some aspects of the present disclosure, other nucleophilic modifying agents capable of polycondensation with formaldehyde or its analogues are employed alongside NOVOLACs in the production of materials of the present disclosure in order to (i) introduce additional ion- exchange groups into the porous matrix (e.g., aromatic and heteroaromatic amines, hydroxy- substituted aromatic carboxylic, sulfonic, phosphonic, boronic acids), to modify the porosity (e.g., urea, melamine) or (ii) to introduce heteroatoms (e.g., nitrogen, phosphorus, boron) into the matrix of the TPRs or carbons derived therefrom.

[0066] In some aspects, nitrogen-containing functionalities are introduced into the materials of the present disclosure via cross-linking agents such as hexamethylenetetramine (hexamine) or soluble poly-methylol derivatives of urea and melamine. As will be understood by the ordinarily skilled artisan, the stoichiometric quantity of formaldehyde and/or other curing agent required for substitution of all three reactive positions in phenolic molecule to form a cross-linked phenol- formaldehyde network is 1.5 moles per 1 mole of phenol. Without wishing to be limited by theory, mechanistically approximately 0.7 moles of formaldehyde per mole of phenol may be employed in the preparation of linear NOVOLAC pre-polymer while an additional 0.5-0.8 moles of formaldehyde or it’s synthone or synthetic equivalent could be used for stochiometric cross-linking of the material. In common practice excessive quantities of cross-linking agents are used. The present disclosure contemplates the use of an excess of crosslinking agent. Hexamine, for example, may be added in quantities ranging from about 10 to about 30 weight parts to about 100 weight parts of NOVOLAC to produce solid cross-linked porous resin, although the theoretical quantity ranges from about 14 to about 16 weight parts depending on NOVOLAC type. Such variation in composition could result in alterations of the porous structure of the resulting resins and other parameters such as the ability of the resin to swell. The use of an excess of crosslinking agent may also affect the reactivity of carbon matrix of porous carbons derived from the corresponding resins (i.e., TPRs).

[0067] Porosity in polycondensation resins of the present disclosure controls the meso/macroporosity of particulate carbons (beads and granules) and develops in the course of steady growing of cross-linked resin domains occurring at elevated temperature, for example from about 40°C to about 200°C, alternatively from about 50°C to about 175°C or alternatively from about 70°C to about 150°C. Without being limited by theory, it is contemplated that during the elevated temperature, at some stage, a nano-scale phase separation of resin rich phase (still containing some solvent) and solvent rich phase that still contains some linear or partially cross- linked polymer and curing agent occurs resulting in the formation of an interpenetrated network of pores. Typically, at this point the liquid polycondensation resin solution turns solid (sol-gel transformation) and the solvent acts as the pore former. It is further contemplated that different transformations of initially formed benzoxazine and benzylamine bridging structures (when hexamine is a curing agent) take place alongside further growth of resin domains at the expense of partially cured polymer from the solvent-rich phase. On further heating evolution of gaseous ammonia and amines occurs and the resin turns from translucent to opaque.

[0068] Increasing the content of the solvent/pore former in the resin composition results in increasing the size of meso/macro pores in the cured resin texture and their volume. This allows an accurate regulation of the meso/macro porous structure of carbonized particulate materials (granules and beads), as it replicates that of the resin precursors (see Figure 3). Increasing pore volume inversely effects the bulk density of the carbonized materials (Figure 4), in line with eq.

(1).

[0069] Surprisingly, it has recently been discovered and it is disclosed herein that substitution of a relatively small fraction of solvent/pore former (for example ethylene glycol) by water in the polycondensation resin compositions leads to significant increasing of the pore size with only slight changes in pore volumes and bulk densities of the derived particulate carbons (Figures 5A- 5B)..

[0070] Another novel method to tailor porosity of polycondensation resins relies on the alteration of the solubility of polycondensation resins by addition of minute quantities of alkaline agents (e.g., sodium hydroxide) to the reaction composition. In a surprisingly beneficial aspect, catalytic activity was not observed when utilizing alkali materials although such materials were previously utilized as catalysts in the polycondensation reactions of phenols (Figures 6A-6B). [0071] Atomic Force Microscopy (AFM) images of the internal textures of carbonized beads derived from resins of the same solvent content, but differing in the solvent composition (ethylene glycol and sodium hydroxide, pure ethylene glycol, ethylene glycol and water) clearly indicate that the size of primary carbon nano-domains increases in line with the pore size (Figure 7). This effect is graphically explained on the Figure 8.

[0072] In an aspect of the present disclosure, the TPRs and derived carbonaceous materials may be formed into any user-desired or process-desired shape. In a nonlimiting example, the TPRs and derived carbonaceous materials are formed into blocks or monoliths. Resin blocks or carbonized blocks could be ground/milled to produce granules of irregular shape. In another nonlimiting example, the TPRs and derived carbonaceous materials are formed into beads. In such an example, the average bead diameter may range from about 5 pm to about 2000 pm, alternatively from about 50 pm to about 1000 pm or alternatively from about 250 pm to about 750 pm.

[0073] In an aspect, the carbonaceous materials derived from TPRs of the type disclosed herein are produced with a narrow particle size distribution e.g. with a D90/D10 of greater than about 10, alternatively greater than about 8, or alternatively greater than about 5.

[0074] In an aspect, TPRs of the type disclosed herein are used to form a carbonaceous material having a pore size (p) ranging from a lower limit (a) to an upper limit (z) and a bulk density (s) ranging from a lower limit (b) to an upper limit (y) where the comparative variability (g) defined as (y-b)/(z-a) is less than 1, alternatively less than 1 x 10², alternatively less than 1 x 10³ or alternatively less than 1 X 10⁵. In such aspects a may have a value of from about 10 nm to about 1000 nm, alternatively from about 10 nm to about 750 nm or alternatively from about 50 nm to about 500 nm; z may have a value of from about 500 nm to about 5000 nm, alternatively from about 1000 nm to about 4000 nm or alternatively from about 1500 nm to about 3000 nm; b may have a value ranging from about 0.05 to about 0.2, alternatively from about 0.08 to about 0.2 or alternatively from about 0.1 to about 0.2 and y may have a value ranging from about 0.1 to about 0.4, alternatively from about 0.15 to about 0.4 or alternatively from about 0.2 to about 0.4.

[0075] In an aspect, the TPR has a pore size ranging from about 10 nm to about 500 nm and an intraparticular porosity ranging from about 2% to about 25%. Herein the intraparticular porosity refers to the ratio of void volume to material density and can be derived from the mercury porosimetry data. In an alternative aspect, the TPR has a pore size ranging from about 25 nm to about 300 nm with an intraparticular porosity ranging from about 5% to about 20% or alternatively a pore size ranging from about 50nm to about 150 nm with an intraparticular porosity ranging from about 8% to about 15%. In an aspect, a carbonized material derived from a TPR of the type disclosed herein has a pore size ranging from about 10 nm to about 5000 nm with a bulk density ranging from about 0.15 g/ml to about 0.6 g/ml, alternatively a pore size ranging from about 20 nm to about 300 nm with a bulk density ranging from about 0.3 g/ml to about 0.5 g/ml or alternatively a pore size ranging from about 50 nm to about 150 nm with a bulk density ranging from about 0.3 g/ml to about 0.5 g/ml.

[0076] TPRs of the type disclosed herein and the carbonaceous materials derived therefrom may be utilized in a wide variety of applications. In one aspect, the TPRs and carbonaceous materials derived therefrom are further processed to provide medical-grade adsorbents which effect the removal of one or more target molecules from a bodily fluid such as for example and without limitation whole blood, plasma, urine and cerebrospinal fluid. In such aspects, the target molecule may be an inflammatory mediator (e.g., cytokine), a cellular signaling molecule or protein. In an alternative aspect, TPRs and carbonaceous materials derived therefrom are utilized as support materials such as catalyst supports. In yet another aspect, TPRs and carbonaceous materials derived therefrom may be further processed (e.g., oxidized) and serve as catalysts for the production of oxidants (e.g., hydrogen peroxide) or may catalyze the oxidation of one or more molecules. In another aspect, TPRs and carbonaceous materials derived therefrom may find utility as components of one or more articles fashioned to enhance the structural, thermal, or mechanical characteristics of an apparatus.

[0077] Additionally, or alternatively, in some aspects, the carbonaceous material is provided in the form of a textile, cloth, or felt. The carbonaceous material may comprise or be formed as fibers, which may be woven or knitted or otherwise assembled in any of a number of ways to provide a cloth. For example, in some aspects the carbonaceous material comprises a novoloid fiber, novoloid textile or felt, suitable examples of which are commercially available as Kynol® fibers, textiles or felts for example, which may be derived from phenol-formaldehyde resin matrix) (Kynol is Registered trademark of GUN El CHEMICAL INDUSTRY, CO., LTD.). These materials are carbonized and further activated to provide carbon fibers or cloths of different thickness. They are available commercially and have high activation degrees, as manifested by high BET surface areas of around 1500 m²/g and around 2000 m²/g. These fibers and textiles also exhibit high mechanical strength.

[0078] In terms of porosity these carbon textiles are typical microporous materials, that demonstrate high adsorptive capacity towards smaller size molecules (typical marker - Methylene Blue dye, C16H18C1N3S, MW 319.85 Da), but almost no capacity towards even medium size molecules (typical marker - Vitamin B12, C63H88CoN14014P, MW 1355.4 Da). Since adsorption of large molecules like bacterial toxins, proteins, including cytokines, autoimmune complexes, etc. is deemed to be an important mechanism of wound healing it is desirable to complement well-developed microporosity of Kynol carbon textiles with mesopores.

[0079] In an aspect this could be achieved by further straightforward physical activation of carbon textiles that enforces coalescence of some micropores into larger pores. But such treatment also results in mechanical degradation of the resulting adsorbent cloth to unacceptable levels. Alternatively, complementary mesoporosity could be introduced into microporous carbon materials by the method of selective catalytic activation disclosed herein.

[0080] It is a common knowledge that alkaline, alkali earth and some transition metals in the forms of hydroxides, nitrates, carbonates and salts of carboxylic acids catalyze activation of carbon materials with steam and/or carbon dioxide. The mechanisms of the catalysis are still discussable at the moment, but its experimental manifestations are clear and comprise significant reduction of effective activation temperature and/or significant acceleration of the activation reaction at the given temperature and other constant conditions. Some appearance of meso/macroporosity was also reported in parallel with usual preferential development of micropores.

[0081] The method described herein comprises oxidation of the activated phenolic carbon cloth, it’s impregnation with aqueous solutions of calcium acetate or iron (III) nitrate, it’s drying on air, additional activation in carbon dioxide flow and at 800 °C with subsequent cooling down in the same gas flow. Resulting carbon cloth contains mineral components - calcium carbonate or nano iron oxide. These mineral compounds may be easily removed from the carbon cloth by washing with diluted acids. Effects of such additional activations on the carbon cloths porosity are demonstrated on the Figure 9. Complementary mesopores of the size 3.5 nm, introduced by activation, catalyzed with Ca-salt were not big enough to improve adsorption of Vitamin B12, but introduction of mesopores with the peak diameter 21.3 nm dramatically increased the adsorption capacity.

[0082] Obvious selectivity of the proposed method for catalytic activation could be explained by localization of metal species or their clusters due to formation of stable complexes with protonogenic oxygen containing functional groups on the surface of oxidized carbon, so that these species (clusters) catalyze corrosion of the carbon matrix with oxidizing gases (steam, carbon dioxide) only in their close vicinity. Size difference of complementary mesopores for the cases of calcium and iron could be possibly explained by the difference of the metal cluster’s sizes.

[0083] The carbon materials described herein possess well-developed meso- or macro-pores on the background of very high surface area (e.g., greater than approximately 1500 m²/g, or 2000 m²/g) and still preserve the mechanical integrity sufficient for particular practical application in wound dressing.

[0084] The presence of large pores allows for faster adsorption kinetics of smaller molecules (including those causing a foul odor) and high adsorption capacity for large molecules like cytokines, proteins, autoimmune complexes, protein bound toxins, toxic products of tissue necrosis, components of the pus. The high degree of activation (e.g., physical activation in carbon dioxide flow at temperatures above 800°C, above 900°C, and/or above 1000°C) provides higher net positive charge of the adsorbent’s surface and promotes better accumulation of negatively charged fibrinogen molecules at the exit of the bleeding wound and therefore faster formation of the blood clot.

[0085] As described herein, a well-activated carbon adsorbent with meso and/or macropores comprises the characteristic interconnected pore structures of said carbons, which enables effective mass exchange between the adsorbent and surrounding biological media and the ability of accurate tailoring quantitative parameters of the porous structure, e.g., pore size, pore volume, and surface area.

[0086] Typical activated carbon cloth conventionally used for wound dressing may comprise only micropores and therefore its adsorption capacity towards larger molecules with molecular weights greater than 1 kDa is negligible.

[0087] Embodiments of the disclosure include a method for increasing this capacity. This objective is achieved by selective introduction of mesopores into the microporous carbon matrix by low temperature physical activation in carbon dioxide flow, catalyzed by biologically compatible alkali earth or 3d-transition metals. In this way the composite of micro/mesoporous activated carbon cloth with biocompatible mineral component is prepared, where the mineral component is, but not restricted to, calcium carbonate or nano iron oxide. When the inorganic admixture is not desired, it could be easily removed by acid washing. The method could be applied to the carbon cloth of any type: knitted, woven and non-woven (felt). The preferred activated carbon cloth used for further modification is that derived from the phenolic resin cloths Kynol (Japan), because of their exceptional mechanical integrity even at high activation burn-offs. [0088] The hemostatic or wound healing carbon adsorbent should be brought into the contact with the wound in the way that excludes or at least minimizes shedding off of carbon fine particles from the application device into the wound bed. This objective could be achieved by variety of methods known in the art. These depend on the physical shape of the adsorbent: beads, granules, cloth, and in the case of the particulate form - on the particle size. By no means this could be restricted to following examples. Thus, cloth and larger beads or granules could be mechanically fixed between layers of cellulosic gauze to form patches, stabilized by stitching. Also, cloths could be additionally stabilized mechanically by laminating of one side and coating with permeable gels of the other. Smaller beads and granules could be embedded into cellulosic and other polymeric scaffolds (for example, carbon-rich paper) and matrices, gels, oils, creams, etc. These systems could be additionally stabilized by ion-exchange interactions between positively charged carbon particles with negatively charged functionalities of polymeric chains, as, for example, in carbon- rich gels of carboxy methyl cellulose salts.

Particular WDC Embodiments

[0089] In a non-limiting aspect, a method of preparing a A-WDC comprises (i) impregnating a cellulosic fabric with a coagulating agent and a carbonaceous material and (ii) recovering the products. In an alternative aspect the A-WDC comprises a carbon cloth and a coagulating agent. Herein a coagulating agent refers to a material that promotes blood clotting such as microfiber collagen, stryptics, venoms and the like. In an aspect the coagulating agent is a venom such as Russell viper venom.

[0090] One aspect of the present disclosure is a method of promoting hemostasis at the active bleeding site or active wound site of a subject. A further aspect of the present disclosure is a method of controlling hemorrhage at the active bleeding site or active wound site of a subject. Both methods comprise applying an A-WDC of the type described herein to the active bleeding site or active wound site, alternatively applying an A-WDC of the type described herein to surface of the active bleeding site or active wound site. In yet a further aspect of the methods described herein, the A-WDC is maintained in contact with the bleeding site or wound site for a period of time sufficient to control the bleeding (e.g., to clot the blood, slow the rate of bleeding, or stop the bleeding). In another aspect, the A-WDC of the present disclosure are used with concomitant application of pressure at the bleeding site or wound site (e.g., an elastic bandage may be used to maintain contact between the A-WDC and the bleeding site). In a further aspect, a method of promoting hemostasis comprises packing an internal wound with the A-WDC of the present disclosure until hemostasis is achieved.

[0091] Typically, a hemostatic dressing composition of the present disclosure will be used to inhibit or completely stop bleeding of a parenchymal organ, such as the liver, kidney, spleen, pancreas, or lungs; or to control bleeding during surgery (e.g., abdominal, vascular, gynecological, dental, tissue transplantation surgery, etc.).

[0092] It will be appreciated by those of ordinary skill in the art that existing hemostatic dressing compositions have been associated with a risk of medical complications. Use of existing hemostatic dressing compositions has been associated with macroscopic and microscopic severe changes and shock symptoms in the lungs, liver, kidneys and heart of subjects, particularly when the dressings remained in the wound site for more than 24 hours. Fibrino-gaseous embolic material found in the pulmonary arteries of the subjects indicated that residues of existing hemostatic dressings can ingress into the systemic circulation, thereby increasing the risk of embolus formation.

[0093] In an aspect, the A-WDCs of the present disclosure can be used to promote hemostasis and confer reduced risk of embolus formation with respect to existing hemostatic dressing compositions. In a further aspect, the A-WDCs of the present disclosure can be used to and/or provide hemorrhage control and confer reduced risk of embolus formation with respect to existing hemostatic dressing compositions. In a further aspect, the A-WDCs of the present disclosure can be used to promote hemostasis and/or provide hemorrhage control and confer no risk of embolus formation. In an aspect, the A-WDCs of the present disclosure can be used to promote hemostasis and/or provide hemorrhage control with little or no concomitant contribution toward embolus formation.

[0094] In one aspect, a subject suffers from a chronic wound such as a venous stasis ulcer, arterial ulcer, diabetic ulcer, pressure ulcer, traumatic ulcer and post-surgical wounds. In such aspects, a method of promoting wound healing comprise applying a C-WDC of the type described herein to the active bleeding site or active wound site, alternatively applying a C-WDC of the type described herein to surface of the wound site. In yet a further aspect of the methods described herein, the C-WDC is maintained in contact with the wound site for a specified time period before being removed and a new C-WDC applied. This method may be repeated for as many times considered sufficient by a healthcare professional.

[0095] In a non-limiting aspect, a C-WDC comprises a modified carbonaceous material. The modified carbonaceous material may be an activated carbon material that has been oxidized such that contact of the oxidized activated carbon material with an aqueous material (e.g., blood) and oxygen from the air or from the blood results in the production of oxidants such as hydrogen peroxide. In some aspects, the C-WDC comprises a carbon cloth that has been oxidized; in other aspects the C-WDC comprises a carbon cloth that has been phosphorylated; alternatively the A- WDC comprises a carbon cloth that has been sulfonated. [0096] It is contemplated that WDCs of the type disclosed herein may comprise other materials beneficial to wound management such as lubricants, antibiotics, pain relivers, transition metals (e.g., silver or copper), coatings and the like. In an aspect, the WDCs disclosed herein may be fashioned into barriers, structures, or devices useful in surgery, diagnostic procedures, or wound treatment. For example, the WDC may be formulated as a component of a bandage, suture, dressing, gauze, gel, foam, web, film, tape, or patch

[0097] An aspect of the present compositions is depicted in Figure 11 where a portion of skin 20 comprises a wound 10 which is contacted with a WDC of the type disclosed herein comprising a first layer in direct contact with the skin that is a mixture of an absorbing material 40 (e.g., absorptive fleece) and a non-absorbing material 30. Blood and extrudate are expected to be largely absorbed by this layer. In contact with this layer is another layer of material comprising an activated carbon cloth of the type disclosed herein 60 which is associated with a coagulating agent 70 (e.g., Russell Viper Venom) which may additionally comprise an adhesive 80 that functions to fasten the activated carbon cloth 60 to the absorbing material 40.

[0098] The following illustrates additional and/or alternative aspects (e.g., aspects identified as a first aspect, a second aspect, a third aspect . . . an eighteenth aspect, etc.) of the subject matter disclosed herein.

[0099] For example, a first aspect is a wound dressing composition comprising an activated carbon material and a coagulating agent.

[0100] A second aspect is a wound dressing composition of the first aspect also comprising a cellulosic material.

[0101] A third aspect is the wound dressing composition of one of the first and second aspects wherein the activated carbon material has been oxidized.

[0102] A fourth aspect is a method of treating a wound comprising applying the wound dressing composition of one of the first, second, and third aspects to a surface of the wound.

[0103] A fifth aspect is a wound dressing composition comprising a carbon adsorbent and a coagulating agent. [0104] A sixth aspect is the wound dressing composition of the fifth aspect, wherein the carbon adsorbent is characterized by BET surface area in excess of 2000 m²/g and meso/macropore volume in excess of 1 cc/g.

[0105] A seventh aspect is the wound dressing composition of the fifth or sixth aspects, wherein the carbon adsorbent is in a particulate form.

[0106] An eighth aspect is the wound dressing composition of one of the fifth through the seventh aspects, wherein the carbon adsorbent is in the form of carbon cloth.

[0107] A ninth aspect is the wound dressing composition of one of the fifth through the eighth aspects, wherein the carbon adsorbent has been oxidized.

[0108] A tenth aspect is the wound dressing composition of one of the fifth through the ninth aspects, wherein the carbon cloth adsorbent is in the composition with mineral components.

[0109] An eleventh aspect is the wound dressing composition of one of the fifth through the tenth aspects, wherein the mineral components are calcium carbonate or nano iron oxide.

[0110] A twelfth aspect is a wound dressing composition comprising a carbon adsorbent and a cellulosic material.

[0111] A thirteenth aspect is the wound dressing composition of the twelfth aspect further comprising a gel, a cream, an oil, or combinations thereof.

[0112] A fourteenth aspect is the wound dressing composition of the twelfth aspect further comprising a coagulating agent.

[0113] A fifteenth aspect is the wound dressing composition of the thirteenth aspect further comprising a coagulating agent.

[0114] A sixteenth aspect is the wound dressing composition of the twelfth aspect further comprising one of the sixth through the eleventh aspects.

[0115] A seventeenth aspect is the wound dressing composition of the thirteenth aspect further comprising one of the sixth through the eleventh aspects. [0116] An eighteenth aspect is the wound dressing composition of the fourteenth aspect further comprising one of the sixth through the eleventh aspects.

[0117] A nineteenth aspect is the wound dressing composition of the fifteenth aspect further comprising one of the sixth through the eleventh aspects.

[0118] A twentieth aspect is a method of treating a wound comprising applying the wound dressing composition of one of the fifth through the nineteenth aspects to a surface of a wound.

Claims

CLAIMS What is claimed is:

1. A wound dressing composition comprising an activated carbon material and a coagulating agent.

2. The wound dressing composition of claim 1 further comprising a cellulosic material.

3. The wound dressing composition of claim 1, wherein the activated carbon material has been oxidized.

4. The wound dressing composition of claim 2, wherein the activated carbon material has been oxidized.

5. A wound dressing composition comprising a carbon adsorbent and a coagulating agent.

6. The wound dressing composition of claim 5, wherein the carbon adsorbent is characterized by BET surface area in excess of 2000 m²/g and meso/macropore volume in excess of 1 cc/g.

7. The wound dressing composition of claim 5 or 6, wherein the carbon adsorbent is in a particulate form.

8. The wound dressing composition of one of claims 5 through 7, wherein the carbon adsorbent is in the form of carbon cloth.

9. The wound dressing composition of one of claims 5 through 8, wherein the carbon adsorbent has been oxidized.

10. The wound dressing composition of one of claims 5 through 9, wherein the carbon cloth adsorbent is in the composition with mineral components.

11. The wound dressing composition of one of claims 5 through 10, wherein the mineral components are calcium carbonate or nano iron oxide.

12. A wound dressing composition comprising carbon adsorbents and a cellulosic material.

13. The wound dressing composition of claim 12, further comprising a gel, a cream, an oil, or combinations thereof.

14. A method of treating a wound comprising applying the wound dressing composition of one of claims 1 through 13 to a surface of the wound.