Devices and materials for wound care and methods of preparation thereof

Abstract

The invention discloses a haemostatic agent for promoting blood clotting comprising zeolite doped alginate fibers comprising alginate and zeolite, characterized in that the zeolite is embedded and dispersed homogeneously within the alginate fibers.

Description

[0001] Devices and materials for wound care for humans or animals and to methods of preparation thereof

[0002] The invention disclosed in various embodiments herein relates generally to devices and materials for wound care for humans or animals and to methods of preparation thereof. More specifically, the invention relates to haemostatic fibrous materials and wound dressings and to fibrous materials and wound dressings for wound healing.

[0003] Description of the related prior art:

[0004] An injury can be defined as a physiological damage of the living tissue of humans or animals. Injuries can be caused for example mechanically by penetration of the tissue with an object and can be e.g.:

[0005] • An incision - a cut into tissue by a blade of a knife / scalpel

[0006] • A puncture wound -

[0007] • Crushing -

[0008] • Ballistic trauma - e.g. caused by a projectile discharged from a firearm

[0009] These so-called traumatic injuries lead typically to bleeding wounds and associated blood loss. Blood loss is also called bleeding, (haemorrhage) and describes the situation when blood is escaping from the circulatory system via damaged blood vessels. A healthy person can handle a blood loss of 10 to 15% of total blood volume without serious medical issues. Small bleedings are handled by the body itself without any problems but in case of large wounds or sectioning of a large artery, blood loss can be significant and can lead to life threatening conditions or even death.

[0010] Severe bleeding requires immediate first aid and medical attention, time is of the essence. Typical causes for traumatic injuries and bleeding are accidents, physical assaults, combat injuries but also medical procedures (also called surgical wounds).

[0011] Depending on size of the wound bleeding can be classified following (according to World Health Organisation):

[0012] Grade 0: No bleeding

[0013] Grade 1 : Petechial bleeding Grade 2: Mild blood loss (clinically significant)

[0014] Grade 3 : Gross blood loss requires transfusion (severe)

[0015] Grade 4: Debilitating blood loss (associated with fatality)

[0016] The healthy body first responds to bleeding by starting a complex physiological cascade of events ultimately leading to bleeding stop, also called haemostasis. Haemostasis is accomplished by different mechanisms, which all complementarily act to stop blood loss. One such mechanism is vasoconstriction, a term designing the contraction of a blood vessel to close or decrease its internal diameter, thus limiting the blood flow. This is a reflex, unconscious nervous reaction. The second mechanism involves adhesion of platelets onto collagen fibers (also called fibres), which are present in the extracellular matrix outside the blood vessels and is exposed to blood upon disruption of a blood vessel. The adhesion of platelets leads to their activation and subsequent aggregation, forming a so-called platelet plug which offers a physical barrier to the blood flow. Upon disruption of the vessel walls, cells from this wall, called endothelial cells, release factors in the blood which activate a cascade of enzymatic reactions ultimately leading to the polymerization of fibrin and the formation of a clot. This process, called coagulation, results in the formation of a stable fibrin net in which blood cells are trapped and act like a massive plug which prevents blood from leaving the damaged blood vessels.

[0017] Although a healthy body is capable of stopping moderate bleeding without support, in case of massive bleeding, an external intervention is necessary. The primary measure is the compression of the blood vessels proximally to the lesion to completely stop blood flow. However, the absence of perfusion in distal tissue can only be temporary. For evident reasons, the stabilization of the wound until surgery requires the use of haemostatic agents.

[0018] Wound healing of humans and animals is a dynamic process involving many factors and cell types. Normal wound healing is divided into several phases that overlap, specifically homeostasis, inflammation, granulation tissue formation and tissue remodelling. Chronic wounds develop because of defective regulation of one or more of the complex molecular and biological events involved in proper healing and are often stuck in the inflammatory stage. It is at this stage that harmful bacteria might develop. As a wound heals, the level of exudate it produces will decrease. However, if a wound gets stuck in the inflammatory stage of healing, it will continue to produce moderate to high levels of exudate.

[0019] Chronic wounds in diabetics are one of the most common complications. Diabetic foot ulcers and other similar chronic wounds impact approximately 3.8 million people and cost approximately £8.3bn / year in the UK alone. The critical need for management of diabetic chronic wounds is underlined by the continuous increase in type II diabetes around the globe.

[0020] In a study reported in 2020 an estimated 59% of chronic wounds healed if there was no evidence of infection compared with 45% if there was a definite or suspected infection whereas in contrast, the healing rate of acute wounds was unaffected by the presence of infection.

[0021] A problem in the healing of wounds associated with high bacterial loads may be tissue damage by release of toxins and enzymes and possible spread of infections to the blood stream. Studies have also shown that high tissue counts of microorganisms as well as dry wounds delay wound healing.

[0022] Current methods of the management of chronic wounds may consist of debridement to remove bacteria and debris. Debridement removes barriers to healing such as debris, slough, bacteria and biofilm all of which have an impact on exudate production and progression to healing. Wounds are commonly covered with a dressing which may contain an antibacterial agent.

[0023] The use of antibacterial agents such as silver has been known for a long period of time. There are several disadvantages to the use of such materials, for example, bacteria which have died can remain in the wound. Endotoxins are a component of the outer membrane of gram-negative bacteria and are released upon disruption of the intact bacteria such as by death or cell lysis and are a significant pyrogen. Their presence in the blood stream may cause septic reactions with a variety of symptoms such as fever, hypotension, nausea, shivering and shock. High concentrations can lead to serious complications including inflammation and can impair wound healing. Because wounds cannot be cleaned to remove such compounds after the application of the dressing the endotoxin can be a serious problem.

[0024] There is a need for wound dressings that can manage exudate and infection.

[0025] All haemostatic agents are based on one the mechanisms previously mentioned: Some are applied systemically to support coagulation, others are applied topically to (1) absorb water and therefore concentrate coagulation factors locally (2) Bind platelets or other blood components to create a physical barrier (3) actively stimulate the coagulation cascade. A special category of haemostatic agents act by stimulating vasoconstriction and are called styptics. They are usually ineffective when large arteries are sectioned, though.

[0026] In the following agents and wound dressings used in stopping acute haemorrhage and treatment of chronic wounds is explained in more detail.

[0027] Systemic

[0028] Topical haemostatic agents used in emergency bleeding control, e.g. in military medicine or from first responders in general. These are typically available as granular powder to be poured on wounds, embedded in wound dressings or as “styptic pencil”

[0029] Organic materials o Collagen e.g. as microfibrillar collagen. o Chitosan and its salts o Alginate

[0030] - Inorganic o Kaolin o Styptics e.g. anhydrous aluminum sulfate. o Ferric sulfate o Calcium sulfate

[0031] Wound dressings can be defined as a sterile pad applied to a wound to promote healing of the wound and protecting it from environmental influences. The dressing is in direct contact to the wound. Wound dressings can be held in place by e.g. a bandage or are designed as self-adhesive. In general and depending on the purpose wound dressings are designed to adsorb exudate and can include substances beneficial for wound healing e.g. antibiotics, antiseptic chemicals, or haemostatic agents.

[0032] Modern wound dressings may include:

[0033] - Dry or impregnated gauze

[0034] - Plastic films

[0035] Gels

[0036] - Foams

[0037] - Hydrocolloids,

[0038] - Alginates

[0039] - Hydrogels,

[0040] - Polysaccharide pastes

[0041] Granules and beads

[0042] There is e.g. alginate based wound dressings.

[0043] Calcium alginate wound dressings are a type of wound dressing made from alginate, a natural polysaccharide derived from seaweed. These dressings are highly absorbent and are commonly used for moderate to heavily exuding wounds. Alginate wound dressings are typically fibrous materials. Alginate contains alginic acid and may contain calcium, sodium, or zinc and manganese. When in contact with wound fluid calcium alginate releases calcium which is ion exchanged with sodium from the wound liquid. The alginate starts to swell and forms a gel that can absorb high quantities of liquid. The gel formed by calcium alginate helps maintain a moist environment around the wound, which is conducive to the healing process. The gel formed by the alginate can facilitate autolytic debridement, where the body's own enzymes break down dead or necrotic tissue in the wound bed. Wound dressings need to be adhered to the wound / body by for example an adhesive layer or using a bandage.

[0044] There are also other wound dressings known such as

[0045] - Hydrogel based

[0046] - Hydro colloids that are made of hydroxyalkylcellulose

[0047] - Foams such as those made from poly (urethane)

[0048] Superabsorbents containing for example poly (acrylate)s or poly (acrylate) derivatives - Fibrous dressings based on absorbent gel forming fibers such as those made from chitosan or chitosan derivatives, cross linked poly (vinyl alcohol) or from modified celluloses such as cellulose alkyl sulfonates, carboxymethyl cellulose or blends thereof.

[0049] Silver containing

[0050] - Etc.

[0051] A wide variety of medical devices destined to stop bleeding (haemostatic wound dressings) or improve wound healing (wound healing dressings) have been designed using vastly different technologies. For example, wound dressings made of cellulose, alginate, chitin, silicone-based foam or other synthetic polymers already exist. These materials have different properties e.g. chemically modified cellulose fibers swell in water, non-modified cellulose does not swell. Alginate will only swell in fluids that contain monovalent (or Mg2+) metal ions.

[0052] Based on the past battlefield duration of use since 2008 and reported good success, the CoTCCC (Committee on Tactical Combat Casualty Care in the USA) recommends QuikClot Combat Gauze as the haemostatic dressing of choice and Celox Gauze as alternative dressing when QuikClot Combat Gauze is not available.

[0053] Two haemostatic medical devices are currently known to be preferred by the US army: Quikclot® and Celox®. The former is a rayon / polyester impregnated with kaolinite. Originally, the product was impregnated with a synthetic zeolite but it was eventually replaced by kaolin because synthetic zeolite provokes an exothermic reaction upon hydration, leading to burns in patients.

[0054] This wound dressing is claimed to activate the clotting cascade through activation of Factor XII by kaolinite. Celox, on the other hand, is made of a purified chitosan, a polysaccharide extracted from the exoskeleton of crustaceans. It is claimed to accelerate blood clotting through an undefined mechanism. Generally, chitosan is believed to bind blood cells and create a plug through gelling.

[0055] There are multiple other products available on the market for wound dressings. US 4822349 A discloses the use of dehydrated zeolite as haemostatic agent. The later applied US 8252344 B2 by the same inventors describes issues with exothermic reaction of zeolites when upon contact with blood. This heat development is extremely uncomfortable for the person being treated. US 8252344 B2 therefore discloses the use of partially hydrated zeolites to ease the heat development. Nevertheless the manufacturing process associated with partially hydrated zeolites is generally more complicated and exothermic reaction might still exist.

[0056] Another approach to minimize the heat development is described in US 8252344 B2 by using coarse zeolite powder in a binder. The coarse particles in the range of 0.4 to 0.8mm are disadvantageous as due to the comparably low surface area of the coarse particles significant higher quantities of zeolite have to be used.

[0057] All of the above mentioned zeolites might be synthetic zeolites such as A-type zeolites.

[0058] It is also known from prior art that natural zeolites might be used.

[0059] CN 111001033 B e.g. discloses a haemostatic agent comprising zeolites, specifically Clinoptilolite powder, as main component. The agent additionally comprises graphene, silver and menthol powder, the components are mixed together. Use of the powder form is disadvantageous if administered to a wound as this may cause unwanted effects such as thrombosis or embolization to free particles being released in the blood vessels.

[0060] CN 115920116 A discloses a haemostatic agent that is a solid mixture of zeolite and pharmaceutical auxiliary materials e.g. alginate. The zeolite used may be natural or synthetic zeolite. The particle size used is in range of 0.3-3 mm. The zeolite is described as being sterilized but especially natural zeolite may contain impurities. The solid mixture is disadvantageous in administering to a wound.

[0061] From JP H04146218 A alginate fibers comprising silver zeolite compounds are known to be useable in wound dressings. However, the use of silver zeolite compounds is disadvantageous because silver ions can migrate into the body. Moreover, silver zeolite is expensive to manufacture.

[0062] RU 2639379 Cl discloses haemostatic coatings comprising natural zeolites.

[0063] CN 112546281 A describes an artificial zeolite, namely a ZSM-5 type zeolite, mixed with polysaccharides in a freeze-drying process to obtain a medical dressing with haemostatic properties. Artificial zeolites tend to react exothermically during hydrolysis as already described above.

[0064] Chronic wounds are wounds which do not progress through a normal and timely sequence of repair. They have emerged as an increasingly important clinical problem over the past several decades and present a significant cost to society and health care organisations.

[0065] The role of the wound dressing is to protect the wound and to maintain the moist wound healing conditions for optimal healing which was identified by George Winter in 1962. This moist environment is often at the same time a favourable environment for microbial colonization, primarily involving aerobic and anaerobic bacteria.

[0066] There is a need for dressings that can manage bacterial load by containing an antimicrobial agent such as silver EP1425050 or PHMB WO2022128996A1. Such technology relies on killing bacteria with antimicrobial agents. However, recent concerns were raised about possible resistance against silver, the release of bacterial endotoxin and cytotoxicity, all of which could hinder or delay wound healing.

[0067] EP0162026B1 discloses the use of hydrophobic groups on hydrophilic liquid absorbing fabrics. The hydrophobic groups are capable of binding bacteria by means of hydrophobic interactions. The hydrophobic groups may be a dialkylcarbamoyl chloride such as dihexadecyl-carbamoyl chloride or dioctadecyl- carbamoyl chloride.

[0068] Dressings that manage bacterial bioburden in wounds with a physical mode of action (e.g. dialkylcarbomoyl chloride (DACC)) play an important role in wound care. Such dressings use simple physical principles to effectively bind bacteria and are not known to cause antimicrobial resistance or release bacterial endotoxin or to be cytotoxic.

[0069] Dialkylcarbomoyl chloride (DACC)-coated dressings such as Cutimed Sorbact (Essity AB, Stockholm, Sweden) claim to have bacteria and fungi binding capability. DACC dressings irreversibly bind and remove bacteria without the release of active agents to the wound and the development of bacterial or fungal resistance is avoided.

[0070] DACC technology works on the principle of two hydrophobic materials being attracted to each other. Bacteria under certain conditions can have cell surface hydrophobicity (CSH) and this CSH is dependent in part on the type of bacteria and the conditions in which they are cultured. For example, Staphylococcus aureus cultured in haematin agar in air has a significantly lower CSH than Streptococcus haemolytic cultured in blood and serum in a carbon dioxide atmosphere.

[0071] According to the literature (Using the principle of hydrophobic interaction to bind and remove wound bacteria, Ljungh et al, Journal of Wound Care Vol 15, No 4, April 2006) microbial cells expressing profound to moderate CSH bind to the dressing whereas microbes expressing a hydrophilic cell surface are left behind. The evidence in this paper is that if a wound gel or irrigation solution is used then this can reduce the CSH and binding to the dressing. The ability of the bacteria to bind to the dressing is inconsistent and is dependent on the bacteria, as well as on their metabolic state, on the wound environment (e.g. CO2 and nutrient content) and on any wound treatment regime used.

[0072] Superabsorbent particle (SAP) containing dressings such as Vliwasorb (Lohmann and Rauscher, Vienna, Austria) or Sorbion (Essity, Stockholm, Sweden) are also known to be able to physically trap bacteria as the particles absorb fluid and swell. Such dressings are suitable for highly exuding wounds but are unsuitable for less exuding wounds.

[0073] In a study to evaluate the bacteria binding capability of some common non-antimicrobial dressings that are suitable for moderately exuding wounds, Bowler et al (Infection control properties of some wound dressings, Journal of Wound Care November, Vol 8, No 10, 1999) showed that alginate dressings without an antibacterial agent are not capable of absorbing and retaining significant amounts of bacteria (<15% of added gram positive bacteria and <41% of added gram negative bacteria). Carboxymethyl cellulose dressings retain <70% of both gram negative and gram positive bacteria and the DACC technology material retained <60% of added gram positive bacteria and <80% of added gram negative bacteria. In conclusion, actual data shows that, currently, no antimicrobial wound dressing demonstrates satisfying performances.

[0074] Zeolites:

[0075] Zeolites are a large family of microporous minerals within the class of aluminosilicates. There are natural zeolites such as analcime, chabazite, heulandite, natrolite and clinoptilolite, and synthetic zeolites such as zeolite A-type (LTA), zeolite X and ZSM-5. All zeolites share a stable 3 -dimensional crystal-structure, built up by interlinked SiC and AI2O3 tetrahedra, with intervening open channels and cages. Partial substitution of Si4+by Al3+within the framework results in a general negatively charged crystal lattice, often balanced by loosely bound extra-framework cations (e.g. Ca2+, Na+, K+, Mg2+).

[0076] Because of the stability of the framework, ab-, ad- and desorption of cations and / or (water-) molecules does not alter the crystal lattice, the pore- and channel-structure remains intact. The (micro)-porous nature, the ion-change behaviour and the overall negative framework charge allows zeolites to be used in a large variety of applications e.g. ion exchangers, detergents, catalysts, waste treatment, gas separation, organic synthesis, water softeners, etc. Zeolites are also known for their haemostatic effects.

[0077] Clinoptilolite, clinoptilolite-minerals and clinoptilolite-tuff:

[0078] Clinoptilolite is often used in literature for either clinoptilolite-mineral or clinoptilolite-tuff without distinguishing between these two as it is described and used further below.

[0079] Clinoptilolite-minerals, is the collective name for a group of natural, non-toxic, microporous heulandite-type zeolites. The mineral group forms monoclinic crystals and can be described as follows:

[0080] Clinoptilolite-Ca: Ca3(Si3oAl6)072'20H20

[0081] - Clinoptilolite-K: K6(Si3oAl6)072-20H20

[0082] Clinoptilolite-Na: Na6(Si3oAl6)072'20H20 Because of its monoclinic habit, clinoptilolite-minerals usually develop tabular, coffinshaped crystals.

[0083] The predominant precursor materials of larger and economically relevant clinoptilolitedeposits are acid volcanic glasses from ash-fall tuffs, from vitroclastic tuffs or from hydrothermally altered vitrophyres and vitroclastic tuffs. The zeolite formation is linked to the reaction of volcano-sedimentary vitric tuff particles with alkaline fluids (marine environment, ground water) at slightly elevated pressure and temperature conditions.

[0084] Clinoptilolite-tuff or short clinoptilolite

[0085] In natural deposits Clinoptilolite-mineral is usually not found alone as a single mineral but is accompanied by other minerals and / or rock - following this is called clinoptilolite-tuff or short just as clinoptilolite. The numbers related to clinoptilolite provided further below and in the examples (e.g. quantities, percentages, etc.) therefore always refer to Clinoptilolite-tuff

[0086] Strongly dependent on the formation history of the tuff and the composition of the precursor materials, clinoptilolite may be accompanied by other minerals such as other natural zeolites, quartz, cristobalite, opal, feldspars and clay minerals. Large deposits can be found in China, Slovakia, Korea, New Zealand, the United States, Turkey, Cuba and Jordan.

[0087] Clinoptilolite-tuff is used for animal feed, agri- and horticultural uses, soil treatment and fertilizing, water and wastewater treatment, cement production, as paper and rubber filler, to treat organic and nuclear waste as well as exhaust gases and numerous more technical, environmental and agricultural applications. Clinoptilolite recently became important for animal husbandry and human healthcare.

[0088] Clinoptilolite-minerals have chemical compositions as shown in the following table:

[0089] Mineral analyses were performed via electron-probe microanalysis on polished, carbon- coated thin-sections. A 10pm defocused beam technique was used to obtain the composition of clinoptilolite-minerals. Measurements were done against natural standards with acceleration voltage of 15kV and a beam current of 20nA. For more details see Tschegg et al. 2019, Economic Geology, Vol 114, Nr. 6.

[0090] Clinoptilolite-tuffs have chemical compositions as shown in the following table:

[0091] Clinoptilolite tuff major elements were analysed with inductively coupled plasma - mass spectrometry (ICP-MS analysis, EPA Method 6020 A; SW-846). Representative sample amounts were crushed and micronized and afterwards solved in Teflon containers using nitric acid and hydrofluoric acid at high temperature and pressure (microwave digestion). The analyses of digested samples were performed on a quadrupole mass spectrometer, calibrated on the elements of interest and their expected amounts. Measurement quality, accuracy and precision were assured analysing international reference materials parallel to the sample measurements.

[0092] Due to their porous and ion exchanging properties, natural zeolites such as clinoptilolite can contain certain heavy metal elements such as Pb, Sr, Ba, Cd, Cs and Rb, up to ppm levels. These heavy metal elements might have a negative effect on the human body due to their toxicity and bioavailability. Especially for human applications, purification of zeolites such as clinoptilolites are necessary to avoid toxic metal uptake into the organism. From prior art, methods using chelating agents such as acetyl acetone are known for purification or pretreatment. Another method for pre-treating known from EP 2040837 Bl or the corresponding US 8173101 B2 comprises the steps of:

[0093] - Exposing the zeolite with hydrochloric acid enriched with ammonium salts

[0094] - Neutralizing the zeolite

[0095] - Exposing the zeolite with ammonium salt solution

[0096] - Exposing zeolite to a saturated calcium hydroxide / chloride solution

[0097] - Decrease pH to neutral

[0098] - Rinsing zeolite with de-ionized water.

[0099] The purified or pretreated clinoptilolite typically shows the following impurity levels:

[0100] As is < lOpg / g, preferably < 2pg / g,

[0101] Ph is < lOpg / g, preferably < 3pg / g,

[0102] Cd is < lOpg / g, preferably < 2pg / g,

[0103] Ba is < 150pg / g, preferably < 75pg / g,

[0104] Mn is < 100 pg / g, preferably < 25pg / g.

[0105] Natural zeolites occur as tuffaceous rock formations and are typically processed by crushing and / or milling to a coarse-grained, fine or powder-like material.

[0106] Alginate:

[0107] Alginate is a natural polysaccharide compound found in the cell walls of brown algae. Alginate is a copolymer composed of two monomers, mannuronic acid and guluronic acid, arranged in blocks or randomly distributed along the polymer chain. The ratio of mannuronic acid to guluronic acid in alginate can vary depending on the species of algae from which it is extracted and the conditions of extraction. This variation in composition gives rise to differences in the properties of alginate, such as its gel-forming ability, viscosity, and stability.

[0108] Alginate is widely used in various industries due to its unique properties, including its ability to form a gel in the presence of divalent cations such as calcium. This property makes it useful in food, pharmaceuticals, and industries like textiles and cosmetics. In the food industry, alginate is often used as a thickening agent, gelling agent, and emulsifier in products like ice cream, salad dressings, and processed foods. Additionally, it is used in medical applications, such as wound dressings and dental impressions, because of its biocompatibility and ability to form gels while in contact with bodily fluids.

[0109] Alginates and calcium alginate in particular are known to be used to control bleeding, particularly in settings such as surgery, wound care, dentistry and emergency situations.

[0110] Alginate haemostatic agents work by absorbing blood and forming a gel-like matrix when they come into contact with wound surfaces. This gel matrix helps to promote clot formation and seal the wound, thereby stopping or reducing bleeding. Additionally, calcium alginate has properties that can help accelerate the body’s natural clotting process; calcium ions can promote blood clotting and control bleeding. These agents work by accelerating the coagulation cascade, the series of biochemical reactions that lead to the formation of a blood clot. When calcium ions come into contact with blood, they interact with various clotting factors in the blood plasma, such as prothrombin and fibrinogen, to facilitate the conversion of fibrinogen into fibrin. Fibrin forms a mesh-like structure that reinforces the platelet plug, stabilizes the clot, and stops bleeding.

[0111] Alginate is known for its haemostatic behaviour and is used, for example, in haemostatic wound dressings.

[0112] Definitions:

[0113] Wound care - definitions

[0114] Wound care relates to medical treatment of a wound of a human or an animal.

[0115] Haemostatic wound treatment or “haemostatic” relates to the field of stopping the acute bleeding of a human or an animal. In other words, a haemostatic substance or agent stops bleeding or haemorrhage. In the context of the present disclosure haemostatic does not relate to treatment of chronic wounds, slow or impaired healing wounds, foul-smelling wounds, or bleeding that might occur during the treatment of such wounds.

[0116] Wound healing relates to the field of treatment of wounds that heal by secondary intention such as chronic wounds including diabetic leg and foot ulcers, pressure ulcers and venous ulcers, slow or impaired healing wounds and foul-smelling wounds. Such wounds tend not to bleed unless debrided and so haemostatic performance is not a priority. In context of the present disclosure, wound healing does not relate to treatment of acute bleeding and the stopping thereof, and therefore does not comprise haemostatic wound care according to the above definition.

[0117] Haemostatic agent

[0118] The haemostatic agent may be the zeolite doped alginate fiber or a material comprising the zeolite doped alginate fiber such as the wound dressing or the woven or non-woven material.

[0119] Wound healing agent

[0120] The wound healing agent may be the zeolite doped alginate fiber or a material comprising the zeolite doped alginate fiber such as the wound dressing or the woven or non-woven material.

[0121] Fiber

[0122] A Fiber or fibre is a tow or continuous filament that is obtained by a continuous or semi continuous spinning process and many meters long. Usually it is used in its plural form fibers (or fibres)

[0123] Staple fiber

[0124] The Fiber can be cut to a short and easy to handle length of e.g. 38mm or 50mm. Staple fiber of 38mm or 50mm are commonly used in wound dressings and in the below examples. Of course staple fibers can have every other desirable length and the current invention is not limited to staple fibers of 38mm or 50mm length.

[0125] Reinforcing fiber or reinforcing yam

[0126] Reinforcing fiber or reinforcing yarn reinforces the woven or non-woven material to add strength. Reinforcing fiber or yam may comprise e.g. Lyocell, synthetic textile fiber or a thermoplastic bi-component fiber. Water absorbent fiber or yarn

[0127] The water absorbent fiber or yarn may be a fiber or yarn made of modified cellulose, a carboxymethyl cellulose, a cellulose alkyl sulfonate, a poly (vinyl alcohol), a poly (acrylate), or a carboxymethyl chitosan or mixtures thereof. The water absorbent fiber or yam may, due to its water absorbing properties, aid in haemostasis or the healing of a wound.

[0128] Non-woven Material

[0129] Non-woven material or fabric is formed by bonding fibers together, e.g. by some kind of chemical adhesion, mechanical or heat treatment or similar process, or a combination of those. There is no weaving, knitting or manual construction involved.

[0130] Woven Material

[0131] Woven material is formed by weaving or knitting or a similar process.

[0132] Wound dressing

[0133] The wound dressing comprises the haemostatic agent or advanced wound care agent. It comprises a form of a woven or non-woven material, staple fiber or other components, etc. Typical types of wound dressings are e.g. band aid / plaster, cloth, etc.

[0134] PSD: Particle size distribution of insoluble particles is measured according to ASTM E2651 “Standard Guide for Powder Particle Size Analysis” using a laser diffraction method and defines the relative amount (by volume) of particles present according to size (defined as equivalent spherical diameters).

[0135] PSD dso value indicate the median equivalent spherical diameter, that is, the particle diameter at which 50% (by volume) of the particles are smaller and 50% are larger. For example, PSD d50= 3 pm means that 50% of the particles are smaller and 50% are larger than 3 pm.

[0136] PSD dio value indicates the particle diameter at which 10% of the particles are smaller and 90% are larger. BET specific surface area analysis is named after the Brunauer-Emmett-Teller theory and is based on gas adsorption analysis and is calculated according to ISO 9277 standard.

[0137] Dtex (decitex) is a unit of measurement that quantifies the linear density or fineness of fibers and yams. It represents the weight in grams of a fiber or yarn per 10,000 meters.

[0138] Problem to be solved

[0139] There is therefore a need for a dressing which can absorb and bind bacteria to the dressing which is not reliant on hydrophobic interactions, and which can be used on low or moderately exuding wounds.

[0140] There is a need for an improved haemostatic agent and an easy-to-use and reliable wound dressing with improved, fast and effective haemostatic properties, intended to reduce blood loss caused by light to severe bleeding. There is furthermore a need for an improved wound dressing that is easy to apply and comforts the patient.

[0141] Summary of the invention

[0142] The present invention relates to and is suitable for treatment of wounds of a human or an animal, more specifically for treatment of acute bleeding such as an incision, a puncture wound, crushing, ballistic trauma, etc. and

[0143] - wounds that heal by secondary intention such as chronic wounds, including diabetic leg and foot ulcers, pressure ulcers and venous ulcers, slow or impaired healing wounds and foul-smelling wounds.

[0144] The invention is therefore suitable for different medical treatments as reflected in the claims, especially and principally a haemostatic agent for promoting blood clotting comprising zeolite doped alginate fibers comprising alginate and zeolite, whereby the zeolite is embedded and dispersed homogeneously within the alginate fibers. The below individual advantages and effects can occur individually or in combination and are dependent on the specific embodiment of the invention described below. Effectiveness can be seen from the description, in particular examples 1 to 28 and the Figures. They may furthermore depend on the patient e.g. age of the patient or existing preconditions.

[0145] The object of the present invention is to overcome the disadvantages of the prior art and it has been surprisingly found that adding zeolite to wound dressings may improve the bacterial and viral binding performance of calcium alginate dressings.

[0146] The object of the present invention is to overcome the disadvantages of the prior art and it has been surprisingly found that Zeolites and in particular natural zeolites such as Clinoptilolite may enhance the haemostatic performance (blood clotting properties) of calcium alginate dressings. It has also been found that natural zeolites may reduce or does not show significant heat development when applied to a patient and, therefore, it may prevent undesired burns during wound treatment.

[0147] The object is achieved by a haemostatic agent for promoting blood clotting comprising zeolite doped alginate fibers comprising alginate and zeolite, wherein the zeolite is embedded and dispersed homogeneously within the alginate fibers.

[0148] This has the advantage of the haemostatic agent promoting blood clotting and is easier to manufacture than the prior art.

[0149] In a preferred embodiment the haemostatic agent comprises a zeolite that is a clinoptilolite. Clinoptilolite may enhance the haemostatic performance of the haemostatic agent and may surprisingly reduce or does not show significant heat development during application on the patient. The bleeding may be stopped and undesired bums may be prevented during wound treatment.

[0150] In another preferred embodiment the haemostatic agent comprises a clinoptilolite content of the doped alginate fibers is 5 - 20wt%, preferred 8 - 15wt% and especially preferred 9 - 1 lwt%. Wounds treated with the haemostatic agent may show especially fast blood clotting and may reduce or do do not show significant heat development.

[0151] In a further preferred embodiment the haemostatic agent comprises a clinoptilolite that is micronized and has a PSD d50 of 1 - 5pm, preferably 1.5 - 4pm and more preferably 2 - 3.5pm.

[0152] This has the advantage that the clinoptilolite can be distributed very homogenously within the alginate fibers and may prevent zones of high zeolite content within the alginate fibers. Such zones of high zeolite content might lead to undesired breaking of fibers.

[0153] In another preferred embodiment the haemostatic agent comprises a clinoptilolite that is micronized and has a specific surface area measured as BET of 10 to 60m2 / g. This has the advantage that the haemostatic agent shows fast blood clotting and has high levels of water absorbency.

[0154] In a further embodiment the haemostatic agent comprises a pretreated clinoptilolite with depleted levels of heavy metals and / or ammonia (NH4). The depleted heavy metals comprise one or more of the group of As, Pb, Cd, Ba, Mn. The depleted level of As is < lOpg / g, preferably < 2pg / g, the level of Pb is < lOpg / g, preferably < 3pg / g, the level of Cd is < lOpg / g, preferably < 2pg / g, the level of Ba is < 150pg / g, preferably < 75pg / g, the level of Mn is < lOOpg / g, preferably < 25pg / g. This is advantageous as it reduces the risk of potential harmful effects of the said elements during wound treatment.

[0155] In another preferred embodiment the haemostatic agent comprises an alginate that has a Mannuronate content of 50-90wt% or a Guluronate content of 50-90wt%. Alginates that are rich in mannuronic acid content (High M) tend to form a soft and resilient gel and whilst alginates with a high guluronic acid content (High G) absorb fluid quickly, the gel can be less flexible and cohesive than the high M alginate. Moreover, the absorbent capacity of High M alginates is greater than that of High G alginates which is advantageous for absorbing blood or wound fluid. In another preferred embodiment, the alginate of the haemostatic agent comprises calcium alginate. This is advantageous as calcium alginate has a well characterized biological safety profile and is highly absorbent, but also because it promotes blood clotting by release of calcium ions which are responsible for activation of coagulation factors including coagulation Factor XIII.

[0156] In another embodiment the haemostatic agent according to one of the preceding claims wherein the zeolite doped alginate fibers comprise at least one further water-soluble material.

[0157] The at least one further water-soluble material is one or more of the group of

[0158] - a water-soluble cellulose derivative

[0159] - a carboxymethyl cellulose

[0160] - a poly(vinyl alcohol)

[0161] Adding a water soluble polymer to the alginate so that a co-spun fiber is formed may increase the speed of absorption of fluid such as blood in to the fiber, thereby increasing the rate of haemostasis.

[0162] In a further preferred embodiment, the haemostatic agent comprises zeolite doped alginate fibers having a thickness in the range of 5 to 50pm, preferably 10 to 30pm, more preferably 15 to 25pm. There is a balance to be struck between fibers with a higher dtex (thickness) which are strong and allow a higher level of zeolite to be added and lower dtex fibers which offer a comparatively larger surface area which may aid haemostatic performance but which are also weaker and may have lower zeolite content.

[0163] Furthermore, the haemostatic agent can comprise zeolite doped alginate fibers which are in staple form, preferably with 38mm or 50mm length. This is advantageous for manufacture of non-woven material, where too short a staple length fiber may lead to a non-woven material that lacks strength or integrity. Conversely, a very long staple length may not process in a textile card where it may, for example, wrap around the rollers and thereby clog the machine. Furthermore, the above object is achieved by a woven or non-woven material comprising the haemostatic agent. A woven or non-woven material is advantageous over e.g. a powder because it offers good integrity, is flexible and conformable and, unlike a powder, it can be removed from the wound in one piece. It also offers a stable platform for delivery of an active agent that has a long shelf life and is easy to use.

[0164] The woven or non-woven material can further comprise a reinforcing fiber or reinforcing yam. This improves strength of the woven or non-woven material which may help to prevent breakage of the product while in use. Pieces of a wound dressing that have broken off from the main body of the non-woven can be left behind in the wound and potentially cause infection or other problems. Moreover, where compression of the dressing is necessary, for example when haemostasis is required, then a stronger product is important to aid in maintaining the integrity of the dressing.

[0165] In a further embodiment the reinforcing fiber or reinforcing yam of the woven or nonwoven material comprises one or more of the group of Lyocell, synthetic textile fiber or a thermoplastic bi-component fiber. It is important for a wound dressing or a haemostatic bandage to have a high wet strength to main integrity while in use. Materials such as Lyocell fibers or synthetic fibers offer higher strength when went and may be added to the material to improve performance.

[0166] In another embodiment the woven or non-woven material comprises at least one waterabsorbent fiber or one water-absorbent yarn.

[0167] The at least one water-absorbent fiber or one water-absorbent yam can comprise one or more of the group of a modified cellulose, a carboxymethyl cellulose, a cellulose alkyl sulfonate, a poly(vinyl alcohol), a poly(acrylate), or a carboxymethyl chitosan. Water absorbent and water insoluble fibers or yarns such as these can absorb large quantities of fluid. This may be advantageous in, for example, wound care where chronic wounds may exudate large volumes of fluid necessitating frequent dressing changes. An increased absorbent capacity will reduce the frequency of dressing changes, which may be painful to the patient. In haemostatic applications, the ability to absorb more blood may increase the haemostatic performance by removing water from blood and thus facilitate the concentration of clotting factors.

[0168] In another preferred embodiment the woven or non-woven material comprises a radiopaque yarn and / or radiopaque material. This allows visibility in e.g. X-ray imaging.

[0169] In a further embodiment the radiopaque yam and / or radiopaque material comprises barium sulphate. This allows visibility in e.g. X-ray imaging

[0170] In another embodiment the non-woven material is in the form of a non-woven needled felt. Non-woven needled felts provide high performance at lower costs than traditional textile materials. The interstitial spaces can be tailored to maximize absorbency while maintaining physical strength. The blending of fibres with different performance characteristics is also possible when using such methods.

[0171] In a further embodiment the non-woven material is in combination with a substrate into which the fibers of the material are needled. A subsequent layer or layers can be added to one or both surfaces of the non-woven material to add other performance benefits.

[0172] In a further embodiment the non-woven material wherein the substrate into which the fibers of the material are needled is a fluid absorbent layer. The subsequent layer or layers which may be added to one or both surfaces of the non-woven material may comprise superabsorbent fibers or particles to further increase the fluid absorbency of the material.

[0173] In a further embodiment the non-woven material wherein the substrate into which the fibers of the material are needled is an odour absorbent layer, also called odor absorbent layer. The subsequent layer or layers which may be added to one or both surfaces of the non-woven material may comprise materials which can absorb odours.

[0174] In a further embodiment the woven material comprises zeolite doped alginate fibers. The doped alginate fibers offer inter alia improved haemostatic performance or binding of microorganisms. Furthermore, in a preferred embodiment the woven material is in combination with a substrate into which the fibers or yarns of the material are bonded. A subsequent layer or layers can be added to one or both surfaces of the non-woven material to add other performance benefits.

[0175] In another embodiment the woven material wherein the substrate into which the fibers or yams of the material are bonded to a fluid absorbent layer. The subsequent layer or layers which may be added to one or both surfaces of the non-woven material may comprise superabsorbent fibers or particles to further increase the fluid absorbency of the material.

[0176] In yet another embodiment the woven material wherein the substrate into which the fibers or yarns of the material are bonded to an odour absorbent layer. The subsequent layer or layers which may be added to one or both surfaces of the non-woven material may comprise materials which can absorb odours.

[0177] Another preferred embodiment is a haemostatic wound dressing for treating a wound comprising the haemostatic agent. This is advantageous for stopping bleeding.

[0178] The haemostatic wound dressing for treating a bleeding wound comprises at least one of the groups of:

[0179] - the haemostatic agent.

[0180] - the non-woven material.

[0181] - the woven material.

[0182] In a preferred embodiment the haemostatic wound dressing has content of haemostatic agent that is in the range of 30 to 70wt%, preferred 35 to 65wt%, especially preferred 47 to 61wt% (59 to 61wt% or 47 to 49wt%). The advantage of a dressing that does not consist in its entirety of the haemostatic agent is that other materials may be added. For example, adding a highly fluid absorbing material may offer a second haemostatic mode of action thereby improving performance in patients with coagulopathy or hypothermia. Additionally, adding a material that, for example, includes an antimicrobial agent may reduce the risk of infection. It has been surprisingly found that 47 to 61wt% is the optimum level to be added In yet another embodiment the haemostatic wound dressing comprises a cellulose derivate fiber and a reinforcing fiber. Cellulose derivatives such a carboxymethyl cellulose can absorb large quantities of fluid. This may be advantageous in haemostatic applications because the ability to absorb more blood may increase the haemostatic performance by removing water from blood, which can concentrate clotting factors. It is important for a haemostatic bandage to maintain its strength when wet to main integrity while in use. Materials such as Lyocell fibers or synthetic fibers offer high wet strength and may be added to the material to improve performance.

[0183] The object is furthermore achieved by a method of producing fibers, the method comprising the steps: spinning a dope which is an aqueous solution containing dissolved alginate and suspended zeolite into a coagulation bath containing dissolved calcium ions that cause cross-linking of the alginate and precipitation of fibers comprised of the alginate and suspended zeolite wherein the amount of suspended zeolite in the dope is 5-20% by weight of the total weight of the sodium alginate and zeolite the concentration of calcium ions in the coagulation bath is at least 0.1% and sufficient to cause cross linking of alginate fibers

[0184] Detailed description and exemplary embodiments with the following Figs:

[0185] Fig. 1 shows a Particle Size Distribution of the Clinoptilolite.

[0186] Fig 2 shows a light microscope image of the zeolite doped alginate fiber, reinforcing fiber and Carboxymethyl cellulose fiber.

[0187] Fig. 3 shows an SEM image of the zeolite doped alginate fiber and Carboxymethyl cellulose fiber.

[0188] Fig. 4 shows the Relative Haemoglobin Absorbance (RHA) in vitro

[0189] Fig. 5 illustrates the Clotting Time in vitro

[0190] Fig 6 illustrates the water absorbency

[0191] According to a first embodiment of the invention there is provided a composition comprising of calcium alginate fibers containing zeolite particles. The zeolite containing alginate fibers may be produced by spinning through a spinnerette with a solution containing dissolved sodium alginate and suspended zeolite particles into a coagulation bath containing a solution of multivalent cations to produce fibers by virtue of the multivalent cations displacing sodium ions from the alginate to effect cross-linking thereof and produce a solid fiber incorporating the zeolite. A spinnerette, or also called spinneret, is a device used in spinning processes that can be described as typically a metal nozzle having fine holes through which a spinning solution is forced to form a filament. The multivalent ion may be any water-soluble multivalent cation except magnesium, and is preferably calcium, zinc or copper or a mixture thereof. Alternatively, the multivalent ion can be a polymeric cation such as, but not limited to, PHMB, polyethyleneimine or chitosan. The multivalent ion is most preferably calcium.

[0192] The polymer solution to be spun (also known as a dope) comprises dissolved sodium alginate and suspended zeolite in the proportions required in the final fiber. Other water- soluble materials such as but not limited to glycerol, polyethylene glycol), poly(vinyl alcohol) or carboxymethyl cellulose or a water-soluble cellulose derivative (e.g. hydroxy ethyl cellulose, hydroxy propyl cellulose) or mixtures thereof may be added to the dope to alter the performance of the fibers. Antimicrobial metal salts such as salts of silver or copper may also be added to the dope. The antimicrobial metal salts may be insoluble or soluble in the polymer solution.

[0193] Alginate fibers incorporating at least one other water-soluble polysaccharide for increasing the absorbency of the resultant fibers may be prepared according to the disclosure of WO 96 / 10106 Al (Innovative Technologies Limited) or WO 2017 / 085436A1 (Advanced Medical Solutions).

[0194] The sodium alginate may have a Mannuronate content of 50-90wt% or it may have a Guluronate-content of 50-90wt%. An according mixture of Mannuronate or Guluronate containing alginate powders may be used.

[0195] Insoluble particles such as the zeolite, in particular clinoptilolite may be included in the polymer solution. The insoluble particles are in the form of a powder. The measurement of particle size distribution (PSD) of the insoluble particles is done according to ASTM E2651 “Standard Guide for Powder Particle Size Analysis” using a laser diffraction method. The insoluble particles such as the zeolite that are included in the polymer solution have typically a PSD d90less than 6pm, d50of 1 to 5pm and dio larger than 1pm, as can be seen in Fig. 1

[0196] Analysis of particle-size distribution is performed according to ASTM E2651 via laser diffraction analysis.

[0197] Approx. 0.1g of sample is dispersed in 150ml of ultrapure water, stirred for 1 minute and treated with ultrasound for 10 seconds prior to the measurement. For data interpretation, the average of 3 runs is then determined.

[0198] The corresponding specific surface area is measured via gas adsorption analysis (e.g. BET method) and may be in the range of 10 - 60m2 / g.

[0199] The alginate fibers have a diameter in the range of 5 to 50pm, preferably in the range of 10 to 30pm and more preferably from 15 to 25 pm. Accordingly, the particles of zeolite and / or other additives have preferably a particle size PSD dso in the range 1 to 5pm, more preferably from 1.5 to 4pm and more preferably from 2 to 3.5pm to prevent breakage of the fibers due to incorporation therein of "large" particles. The diameter of alginate fibers is determined by SEM imaging and / or microscope imaging; see Fig. 2 and Fig. 3. Within these figures the letters A, B, C mean:

[0200] A = reinforcing fibers

[0201] B = Carboxymethyl-cellulose fibers

[0202] C = doped alginate fibers

[0203] The polymer solution (or dope) for spinning solution comprises at least 3% and generally no more than 10% by weight of the total amount of dissolved polymer. Typically, the polymer solution contains 5-6% by weight of the polymer. The zeolite is present in the polymer solution by max. 20% of the weight of the dissolved polymer; more preferably by less than 15% of the weight of the polymer and especially preferably by less than 11% of the weight of the polymer and by min. 5% of the weight of the dissolved polymer more preferably 8wt% and more preferably 9wt% of the weight of the dissolved polymer.

[0204] The fibers in the coagulation bath may be collected into a tow and then subjected to downstream processing steps to produce fibers in a suitable form for conversion into a wound dressing.

[0205] These downstream processing steps generally include stretching, washing to remove surface salts, water removal by methods known to one skilled in the art such as, but not limited to, stretching in hot water or in steam, by passing through a series of baths containing increasing concentrations of a volatile organic solvent, by using a fish tail device as described in US 4,562,110, by mechanical removal compression followed by drying in an oven or, for example, an infra-red dryer but leaving some moisture in the fibers (typically 5-15%). The formed fibers are stable and can be subjected to further fibers processing as necessary.

[0206] The zeolite containing alginate fibers of the present invention may be processed according to methods known to one skilled in the art into a wide variety of forms, depending on their intended use. The manner in which the zeolite containing alginate fibers are processed has an effect on the properties of the final product, particularly the strength, gelling time, and absorbency. Preferred zeolite containing alginate fiber products for use in wound care articles are carded, needle-bonded nonwovens.

[0207] The zeolite containing alginate fibers may be combined with one or more reinforcing fibers as generally set forth in Hansen, US 5,981,410 titled "Cellulose-Binding Fibres"; Stengaard et al., US 6,811,716 titled "Polyolefin Fibres and Method for the Production Thereof'; Jensen et al. and US 5,958,806 titled "Cardable Hydrophobic Polyolefin Fibres Comprising Cationic Spin Finishes;".

[0208] Preferred reinforcing fibers are thermoplastic bi-component fibers, most preferably having a polyolefin component. Thus, the fibers preferably comprise a polyolefin-containing polymeric material of which the largest part (by weight) consists of homo- or copolymers of monool efins such as ethylene, propylene, 1 -butene, 4-methyl-l -pentene, etc. Examples of such polymers are isotactic or syndiotactic polypropylene, polyethylenes of different densities, such as high density polyethylene, low density polyethylene, and linear low density polyethylene and blends of the same. The polymeric material may be mixed with other non-poly olefin polymers such as polyamide or polyester, provided that polyolefins still constitute the largest part of the composition. The melts used to produce the polyolefin-containing fibers may also contain various conventional fiber additives, such as calcium stearate, antioxidants, process stabilizers, additives such as compatibilisers, and pigments. Methods for applying the thermoplastic bi-component fibers are described in EP 740 554; EP 171 806; Ejima et al., US 5,456,982; Davies, US 4,189,338; Davies, US 3,511,747; and Reitboeck et al., US 3,597,731.

[0209] The thermoplastic bi-component fibers may be of the sheath-core type with the core being located either eccentrically (off-center) or concentrically (substantially in the center), or of the side-by-side type, in which each of the two components typically has a semi-circle cross section. Bi-component fibers having irregular fiber profiles are also contemplated, e.g., fibers having an oval, ellipse, delta, star, multilobal, or other irregular cross section, as well as splittable fibers. The bi-component fibers will typically have a high melting and low melting polyolefin component which comprise, respectively, polypropylene / poly- ethylene (the polyethylene comprising HDPE, LDPE, and / or LLDPE), high density polyethylene / linear low density polyethylene, polypropylene random copolymer / poly- ethylene, or polypropylene / polypropylene random copolymer. Preferred thermoplastic bi- component fibers are commercially available from Fiber Visions Products, Inc. (Athens, GA, USA). Suitable thermoplastic bi-component fibers comprise 30, 25, 20, 18, 16, 14, 12, 10, 8, 6, or 4wt% or any range there between of the composite absorbent article. The thermoplastic bi-component fibers preferably have a linear density of about 1.7, 1.9, 2.1, 2.3, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.8, 4.0, 4.2, 4.4, 4.6, 4.8, 5.0decitex up to 16.7decitex or any range there between. However, it has been surprisingly discovered that when high- density fibers (e.g., 4.0decitex) are incorporated into the absorbent article comprising zeolite containing alginate fibers at high levels (e.g., about 20%), the absorbency of the article is not compromised. Moreover, using a reinforcing fiber having a lower linear density allows for a reduction in the weight amount of the fibers, resulting in increased transparency. Thus, in one aspect, the thermoplastic bi-component fibers preferably comprise about 10 to 30wt% (more preferably about 10 to 20%, and still more preferably about 10 to 13%) of the absorbent article and have a linear density of about 1.7 to 4.0decitex (more preferably about 1.7 to 1.9decitex). The temperature used to fuse the fibers together is typically in the range of 90 to 162°C, preferably about 120 to 125°C.

[0210] In another aspect, the reinforcing fibers comprise lyocell fibres. These fibers generally comprise regenerated cellulose obtained by an organic solvent spinning process. Preferably, the lyocell fiber is generated from cellulose fibers using various amine oxides as solvents. In particular, N-methylmorpholine-N-oxide ("NMNO") with water (about 12%) proves to be a particularly useful solvent. Examples of processes for preparing lyocell fibers are described in McCorsley et al., US 4,142,913; US 4,144,080; US 4,211,574; US 4,246,221, US 4,416,698, and others. Jurkovic et al., US 5,252,284 and Michels et al., US 5,417,909 deal especially with the geometry of extrusion nozzles for spinning cellulose dissolved in NMMO. Brandner et al., US 4,426,228, is exemplary of a considerable number of patents that disclose the use of various compounds to act as stabilizers in order to prevent cellulose and / or solvent degradation in the heated NMMO solution. Franks et al., US 4,145,532 and US 4,196,282, deal with the difficulties of dissolving cellulose in amine oxide solvents and of achieving higher concentrations of cellulose. One lyocell product produced by Lenzing Fibers Grimsby Limited, Grimsby, UK is presently commercially available as TENCEL® fibre e.g. the 1.4 dtex crimped bright norrwovens fiber grade. The methods for including these cellulose fibers into nonwoven structures to aid in integrity of the product is well known for example, GB 1 207 352. In one aspect, the lyocell fibers comprise 26, 24, 22, 20, 18, 16, 14, 12, 10, 8, 6, or 4wt% or any range there between of the composite absorbent article. The lyocell fibers preferably have a linear density of about 0.7, 0.9, 1.1, 1.3, 1.5, 1.7, 1.9, 2.1, 2.3, 2.4, 2.6, 2.8, 3.0, 3.2, 3.4, 3.8, 4.0, 4.2, 4.4, 4.6, 4.8, 5.0, 10, 15, 20, 25, up to 30decitex or any range there between. As shown in the examples below, it has been discovered that when low density fibers (e.g., about 1.2 to 1.6decitex) are incorporated into the composite absorbent article at high levels (e.g., about 10 to 30wt%, preferably about 10 to 20wt%), the wet strength is improved while absorbency is not compromised. In a particularly preferred embodiment TENCEL® fibers are incorporated at about 15 to 2 wt%, e.g. 20wt%, into zeolite containing alginate fiber nonwoven materials. In yet another aspect the zeolite containing alginate fibers of the current invention may be combined with one or more absorbent fibers to improve the ability of the product to absorb and retain fluids such as blood or wound exudate. Examples of such fibers include but are not limited to the carboxymethyl cellulose fibers of WO93 / 12275 Al, the cellulose alkyl sulfonate fibers of W02010 / 061225 A2, the hydrogel-forming multicomponent fibers of US 2020 / 141031 Al, the poly(vinyl alcohol) fibers of WO 2012 / 048768 Al, the co-spun alginate and carboxymethyl cellulose fibers of W096 / 10106 Al and WO2017 / 085436A1, the poly (acrylate) fibers of EP 269 393 A2, modified chitosan fibers such as those disclosed in CN 103 143 050 A, a blend of chitosan and a weak acid as disclosed in WO 2015 / 140563 Al or a combination thereof. Other absorbent fibers will be known to one skilled in the art.

[0211] The absorbent fibers are preferably chemically modified cellulose, more preferably a cellulose alkyl sulfonate or carboxymethyl cellulose and most preferably carboxymethyl cellulose.

[0212] In another embodiment of the invention the powdered zeolite may be added to a nonwoven or a woven fabric in the form of a powder. The fabric may be formed by any method known to one skilled in the art. The powder may be added to the fabric by, for example, electrostatic powder coating and impregnation as taught by WO 2015 / 044605 Al, WO 2005 / 038123 Al or WO 2008 / 049980 Al. A thermoplastic binder such as Griltex D 1682E may be mixed with the zeolite and the composition heated to aid binding of the zeolite to the fabric.

[0213] In another embodiment the zeolite is impregnated into a yam which can be used for future processing into a fabric or other garment.

[0214] In still yet another aspect, one or more antimicrobial agents are applied to the zeolite containing alginate fibers of the present invention. Preferred agents include silver and / or polyhexamethylene biguanide ("PHMB").

[0215] The absorbent materials of the present invention exhibit instant gelling in contact with aqueous media, good absorbency and, crucially, good retention of bacteria. This renders them ideal for use as an absorbent wound dressing, or as part of an absorbent dressing. They are particularly useful for wounds with moderate to high levels of exudates, and for flat or cavity wounds of this type. Typical examples include pressure sores and leg ulcers. They are especially useful for wounds that are infected or show signs of infection.

[0216] The use of the absorbent materials of the present invention is not limited to wound care products, and they are expected to be useful for many other applications. Their absorbent properties, biodegradability, and the fact that alginate and cellulose are renewable materials, mean that the absorbent fabric article comprising the zeolite containing alginate fibers of the invention are also particularly desirable for use in the personal care sector, particularly for disposable sanitary articles such as nappies (diapers), disposable nappies and training pants, feminine care products, e.g., tampons, sanitary towels, or napkins and pant liners, and incontinence products. The simplicity of the chemistry and the availability of the reactants enable the cost of manufacture of such articles to be kept advantageously low.

[0217] Other medical products are envisaged, for example, surgical and dental sponges. The materials could also be useful in packaging, for example as absorbent pads in food containers.

[0218] It is possible that in use as a haemostatic product or as a wound dressing certain residues may inadvertently be left in the body, in a body cavity or a deep wound after use. To aid visualization of this and to reduce the need for surgery, an X-Ray detectable component may be added so that the product residues can be seen using X-Ray imaging. A radiopaque component such as a radiopaque material or radiopaque yarn may be incorporated into the product by means known to one skilled in the art.

[0219] Known radiopaque materials used in medical applications are e.g. barium sulphate, iodinated molecules, rare earth fluorides, etc. One example of a radiopaque yam is the product Micropake® by Speciality Fibres and Materials Ltd (Coventry, UK), comprising polypropylene and a high load of barium sulphate (60 wt%). Radi opacity can be measured according to the standard method ASTM F640-23. The present technology is further illustrated by the following examples, which should not be construed as limiting in any way. They show important characteristics of the invention compared with the most popular haemostatic wound dressings currently used by professionals in the field.

[0220] Example 1: Pretreatment of Zeolite

[0221] Clinoptilolite-tuff is pretreated according to a process described in EP 2 040 837 Bl . The pretreatment results in the removal of heavy metals which, in other words, is the pretreated clinoptilolite-tuff purified.

[0222] The clinoptilolite-tuff is extracted as raw-material from the quarry and primary crushed, broken with a jaw crusher to ca. 4mm and sieved afterwards to a fraction at 0.5-4 mm.

[0223] The removal of heavy metal ions from the lattice of the zeolite mineral is achieved by exchanging existing ions with calcium ions.

[0224] This pretreatment is performed in the following steps:

[0225] 1.) The crushed zeolite rock is put in contact with 0.1M (molar) hydrochloric acid, which is enriched with ammonium salt (NH4C1). Exchangeable ions with the crystal lattice get released from the zeolite mineral.

[0226] 2.) Using concentrated ammonium salt solutions (for example, 5M NH4C1) the material is processed until equilibrium, at which a nearly complete exchange of free lattice ions with ammonium ions has been achieved.

[0227] 3.) Using concentrated CaCh solutions (for example 3M CaCh), the ammonium ions that are bound in the lattice are removed and replaced by Ca2+ions. In a parallel circle, an elevated pH value (> 8) triggers the release of ammonia.

[0228] 4.) The calcium-chloride solution is washed out of the zeolite material with aqua purificata to remove CT ions and Ca2+ions, which are not bound.

[0229] 5.) At a temperature of 105°C the zeolite rock is dried in the gas flow and transferred to the mill.

[0230] 6.) Using a jet-mill, the material is micronized to the particle size of ca. 3 pm (d50) and terminally heat treated at 160°C for 120 minutes (corresponding a dry sterilization). The particle size distribution (PSD) of the pretreated zeolite is shown in Fig. 1.

[0231] Example 2: Preparation of zeolite doped alginate fiber:

[0232] An approximately 6.0wt% (6.0% w / w) solution of sodium alginate is prepared by dissolving 8.25kg of sodium alginate grade Protanal LF10 / 60LS and 8.25kg of sodium alginate grade Manucol DH (both International Flavours and Fragrances, Inc, New York, NY, USA) in 265kg of purified water. A suspension of 1.90kg of the zeolite of Example 1 in 5.0kg of water is added to the sodium alginate solution and stirred.

[0233] The zeolite containing sodium alginate solution is transferred to a holding tank through an approximately 25 pm filter followed by the application of a vacuum to remove dissolved air from the solution.

[0234] The deaerated zeolite containing sodium alginate solution is extruded through a spinnerette containing approximately 30,000 holes into a spin bath solution containing calcium chloride at approximately 3% w / w. Ion exchange occurs between the sodium ions in the alginate and the calcium ions in the spin bath forming water insoluble zeolite containing calcium alginate fibers.

[0235] The zeolite containing calcium alginate fibers from two spinnerettes are collected via a series of godet rolls and passed through a hot water bath containing a small amount of calcium chloride and heated to at least 9O'°C. The speed of the output godet is faster than the input godet to stretch the zeolite containing calcium alginate fibers. This has the effect of not only squeezing excess water from the zeolite containing calcium alginate fibers but also imparting strength on the filaments. The zeolite containing calcium alginate fiber bundle is preferably spread by feeding through a fish tail device whose cross section gradually widens in a first direction and narrows in a second direction at right angles to the first. Overfeeding the fibers relative to the speed of the water-pervious support on which they are collected gives a substantially uniform layer of filaments with sufficient crossing over of filaments to lead to a unitary non-woven fabric when the filaments are bonded. The web of calcium alginate filaments formed on the support is preferably dried by removing surplus water under reduced pressure from beneath the water-pervious support and finally by heating, for example, by passing over cylinders heated to 120-150°C, to remove residual water.

[0236] The zeolite containing calcium alginate continuous filament fibers are collected, crimped and can further be cut to staple fiber.

[0237] Example 3 Preparation of zeolite doped alginate fiber:

[0238] Zeolite doped alginate fiber was prepared according to Example 2 using a mixture of 15.7kg of sodium alginate grade Algogel 1301 (Algaia, France) and 0.84kg of alginate grade Manucol DH in 265kg of purified water. A suspension of the 1.90kg of the zeolite of Example 1 in 5.0kg of water is added to the sodium alginate solution and stirred.

[0239] Example 4: Preparation of zeolite doped alginate fiber:

[0240] Zeolite doped alginate fiber was prepared according to Example 2 by dissolving 8.25kg of sodium alginate grade Protanal LF10 / 60FT and 8.25kg of sodium alginate grade Manucol DH (both International Flavours and Fragrances, Inc., New York, NY, USA in 265kg of purified water. A suspension of the 1.90kg of the zeolite of Example 1 in 5.0kg of water is added to the sodium alginate solution and stirred.

[0241] Example 5: Preparation of zeolite doped alginate fiber:

[0242] Zeolite doped alginate fiber was prepared according to Example 2 prepared by dissolving 7.0kg of sodium alginate grade Protanal LF10 / 60FT, 7.0kg of sodium alginate grade Manucol DH (both International Flavours and Fragrances, Inc., New York, NY, USA and 2.5kg of sodium carboxymethyl cellulose powder in 265kg of purified water. A suspension of the 1.90kg of the zeolite of Example 1 in 5.0kg of water is added to the sodium alginate solution and stirred.

[0243] In similar embodiments up to 20% of other water-soluble polymers e.g. poly (acrylic acid), poly (vinyl alcohol) or poly(ethylene glycol) or mixtures thereof are added to the alginate to increase absorbency.

[0244] Example 6: Preparation of a wound dressing

[0245] The following fibers are cut to 50mm length: Zeolite doped alginate fiber of Example 2 to Example 5 individually or in mixture.

[0246] Lyocell fibers, Tencel® 1.4 dtex crimped bright norrwovens fiber, Lenzing Fibers Grimsby Limited, Grimsby, UK. Carboxymethyl cellulose fibers, Speciality Fibres and Materials Ltd, Coventry, UK

[0247] The fibers with 50mm length are mixed in the following ratio:

[0248] Zeolite doped alginate fiber of Example 2 to Example 5 individually or in mixture: 48% Lyocell fibers: 20%; Carboxymethyl cellulose fibers: 32%

[0249] The fiber mixture is passed through a fiber opener and a fiber blender supplied by Bonino Carding Machines S.R.L. (Sandigliano, Italy) which produces a homogenous blend of fibers. The opened fibers are weighed into a textile card using a hopper and a micro-weigh system, sometimes also called microweigh system which is a system for weighing and dispensing fibers on the feedbelt to the card. The carded web is cross folded and needled punched to give a non-woven with a basis weight of 150 g / m2

[0250] Example 7 Wound Dressing 1

[0251] The following fibers are cut to 50mm length and are mixed in the following ratio:

[0252] Zeolite doped alginate fiber of Example 2 to Example 5 individually or in mixture: 60% Carboxymethyl cellulose fibers of Example 6, Speciality Fibres and Materials Ltd, Coventry, UK 40%

[0253] The fiber mixture is made into a wound dressing according to the method of Example 6.

[0254] Example 8 Wound Dressing 2

[0255] The following fibers are cut to 38mm length and are mixed in the following ratio:

[0256] Zeolite doped alginate fiber of Example 2 to Example 5, individually or in mixture: 48%

[0257] Lyocell fibers of Example 6: 20%

[0258] Carboxymethyl cellulose fibers of Example 6: 32%

[0259] The fiber mixture is made into a wound dressing according to the method of Example 6 Example 9 Wound Dressing 3

[0260] The following fibers are cut to 50mm length and are mixed in the following ratio:

[0261] Zeolite doped alginate fiber of Example 2 to Example 5, individually or in mixture: 48%

[0262] Lyocell fibers of Example 6: 20%

[0263] Poly (acrylic acid) superabsorbent fibers. Technical Absorbents Limited, Grimsby UK: 32%

[0264] The fiber mixture is made into a wound dressing according to the method of Example 6.

[0265] Example 10 Wound Dressing 4

[0266] The following fibers are cut to 50mm length and are mixed in the following ratio:

[0267] Zeolite doped alginate fiber of Example 2 to Example 5, individually or in mixture: 48%

[0268] Lyocell fibers Example 6: 20%

[0269] Carboxymethyl cellulose fibers of Example 6: 32%

[0270] The fiber mixture is airlaid and needle bonded to produce a wound dressing.

[0271] Example 11 Wound Dressing 5

[0272] The following fibers are cut to 38mm length and are mixed in the following ratio:

[0273] Zeolite doped alginate fiber of Example 2 to Example 5, individually or in mixture: 48%

[0274] PP / PE bi-component fibers

[0275] Carboxymethyl cellulose fibers of Example 6: 32%

[0276] The fiber mixture is airlaid and passed through a heated calendar to produce a wound dressing.

[0277] Example 12 Preparation of a wound dressing

[0278] The following fibers are cut to 50mm length and are mixed in the following ration:

[0279] Zeolite doped alginate fiber of Example 2 to Example 5, individually or in mixture: 60% Carboxymethyl cellulose fibers of Example 6: 40% The fiber mixture is passed through a fibre opener and a fibre blender supplied by Bonino Carding Machines S.R.L. (Sandigliano, Italy) which produces a homogenous blend of fibers. The opened fibers are weighed into a textile card using a hopper and a microweigh system. The carded web is cross folded and needled punched to give a non-woven with a basis weight of 120g / m2.

[0280] Example 13 Preparation of non-woven material

[0281] Fibers of Example 2 to Example 5, individually or in mixture are cut to approximately 50mm length passed through a fiber opener and a fiber blender supplied by Bonino Carding Machines S.R.L. (Sandigliano, Italy) which produces a homogenous blend of fibers. The opened fibers are weighed into a textile card using a hopper and a microweigh system. The carded web is cross folded and needled punched to give a non-woven material with a basis weight of 120g / m2.

[0282] Example 14 A non-woven material was produced.

[0283] Calcium alginate fibers of Example 2 to Example 5, individually or in mixture cut to approximately 50mm length are mixed with PP / PE bi-component fibers of 38mm length. The opened fibers are weighed into a textile card using a hopper and a microweigh system. The carded web is cross folded and needled punched to give a non-woven material with a basis weight of 120g / m2.

[0284] Example 15 Woven and knitted materials

[0285] There are multiple methods available for making woven material. These are e.g.

[0286] 1. Blending zeolite doped alginate fibers with or without Carboxymethyl cellulose fibers or Lyocell fibers and make a yarn

[0287] 2. Co-mingling, which is taking e.g. a thin zeolite doped alginate fibers yarn and a thin Carboxymethyl cellulose fibers and / or Lyocell fibers yam (or any combination thereof) and mixing to make a thicker composite yarn

[0288] 3. Making a yarn using e.g. ring spinning or rotor spinning

[0289] 4. Making individual yarns and e.g. weave one in the warp and one in the weft direction.

[0290] 5. Weaving with more than one yarn 6. Knitting a flat structure

[0291] 7. 3D knitting a garment such as a glove, a balaclava or a sock for use in bums or epidermolysis bullosa.

[0292] 8. There are different types of knitting

[0293] The fibers of Example 2 to Example 5 individually or in mixture were processed by collecting a carded sliver and rotor spinning to form a yarn. The yarn was knitted to form a three dimensional structure. Knitted materials have a high tensile strength while retaining some stretch and movement. These characteristics are advantageous in a wound dressing where the movement of the patient to whom the dressing has been applied may cause the dressing to distort. The flexible nature of the knitted structure allows for distortion without disruption or tearing of the dressing.

[0294] Example 16 Woven Material 2

[0295] The fibers of Example 2 to Example 5 individually or in mixture were blended with carboxymethyl cellulose fibers in a ratio 80 / 20w / w using a fiber opener and a fiber blender supplied by Bonino Carding Machines S.R.L. (Sandigliano, Italy) which produces a homogenous blend of fibers. These fibers were processed by collecting a carded sliver and rotor spinning to form a yarn. The yarn was knitted to form a dressing with improved absorbency capabilities compared to Example 15.

[0296] Example 17 Woven Material 3

[0297] The fibers of Example 2 to Example 5 individually or in mixture were blended with carboxymethyl cellulose fibers in a ratio 80 / 20w / w using a fiber opener and a fiber blender supplied by Bonino Carding Machines S.R.L. (Sandigliano, Italy) which produces a homogenous blend of fibers. These fibers were processed by collecting a carded sliver and rotor spinning to form a yarn. The yam was woven to form a dressing with improved physical handling characteristics compared to Example 15.

[0298] Example 18 Woven Material 4

[0299] The fibers of Example 2 to Example 5 individually or in mixture were blended with carboxymethyl cellulose fibers in a ratio 80 / 20w / w using a fiber opener and a fiber blender supplied by Bonino Carding Machines S.R.L. (Sandigliano, Italy) which produces a homogenous blend of fibers. These fibers were processed by collecting a carded sliver and rotor spinning to form a yarn. The yam was knitted in a three dimensional body shape to form a dressing that can be worn, such as a sock, a glove or a face mask for the treatment of bums.

[0300] Example 19 Wound Dressing 6

[0301] The following fibers are cut to 50mm length and are mixed in the following ratio:

[0302] Zeolite doped alginate fiber of Example 2 to Example 5 individually or in mixture: 50wt% Carboxymethyl cellulose fibers of Example 6, Speciality Fibres and Materials Ltd, Coventry, UK: 50wt%

[0303] The fiber mixture is made into a wound dressing according to the method of Example 6.

[0304] Example 20 Wound Dressing 7

[0305] The following fibers are cut to 50mm length and mixed:

[0306] Zeolite doped alginate fiber of Example 2 to Example 5 individually or in mixture: 100%

[0307] The fiber mixture is made into a wound dressing according to the method of Example 6.

[0308] Example 21: Haemostasis test - pig liver

[0309] In this study a pig liver was exposed via a mini -laparotomy and bleeding injuries were created using punch biopsies. A pre-weighed gauze was laid in the cavity to collect blood for evaluation of blood loss prior to application of the haemostatic product of Example 6. Using three pigs in total, one for each test material, the haemostatic dressing of Example 66 was compared to a material available on the market referenced as Material A, and to standard cotton gauze.

[0310] An 8mm biopsy punch was used to create four injuries on the liver to induce an uncontrolled haemorrhage (injuries were created one at a time). The haemorrhage was allowed to free bleed for 45 seconds; the gauze was then collected and weighed to quantify blood loss. Following the 45 seconds, the appropriate treatment dressing for each pig was applied to each punch site on the liver along with consistent pressure (compression) to control bleeding for two and a half minutes and the time to haemostasis was evaluated and recorded. Success criterion for haemostasis was defined as cessation of bleeding for five minutes following test / control article application and compression.

[0311] Table 1. Average mass of blood lost per liver injury (g)

[0312] Table 2. Haemostasis pass / fail summary (liver injury)

[0313] Haemostasis was achieved in injuries treated with the fabric of Example 6 but in only three of the four injuries treated with the gauze or Material A. Liver site 4 for both control groups (Standard Gauze and Material A) failed after the two and a half minutes of compression.

[0314] Occurrence of exothermic was monitored in the liver injury and a femoral artery injury. An exothermic was observed with the Material A dressing but not with the fabric of Example 6 or standard gauze. The attending veterinarian reported feeling warmth from the Material A dressing in all instances. Table 3. Exothermicity occurrence observed per liver injury.

[0315] Example 22 RHA - relative haemoglobin absorbance test 1

[0316] 1. lOmg of dressing were weighed in a 30ml Universal container and warmed at 37°C for 10 minutes.

[0317] 2. To each lOmg sample 200pl of Horse Blood in Alsever’s* was slowly added to the dressing followed by 20pl of CaCh (0.2 M) solution to initiate the clotting cascade.

[0318] 3. The samples were then incubated at 37°C for 3 or 5 minutes.

[0319] 4. At the designated time point, 25 ml of water were carefully added to the containers. 5. A U.V-Vis spectrophotometer was used to measure absorbance at 540nm.

[0320] 6. The relative haemoglobin absorbance (RHA) at clotting time was expressed as a percentage of the reference (whole blood plus CaCh with no dressing) at t=0. Accordingly, a value of 0 represents complete coagulation and 100 represents the absence of coagulation * Alsever’s solution is a saline liquid used to prevent coagulation of blood. It is composed of 2.05% dextrose, 0.8% sodium citrate, 0.055% citric acid, and 0.42% sodium chloride

[0321] The results are presented in the table below

[0322] 1 . Speciality Fibres and Materials Ltd, Coventry, UK

[0323] 2. Medtrade Products Limited, Crewe, UK 3. Convatec Group PLC, Reading, UK

[0324] 4. Lenzing Fibers Grimsby Ltd., Grimsby, UK

[0325] 5. Z-Medica, Wallingford, CT, USA (now Teleflex, Inc. Morrisville, NC, USA)

[0326] 6. Core Scientific Creations Ltd (d / b / a Wound-Clot), Bay Harbor Islands, FL, USA Example 23 RHA 2 - relative haemoglobin absorbance test 2

[0327] 1.37M NaCl

[0328] 27mm KC1

[0329] 100mm Na2HPO4

[0330] 18mm KH2PO4 pH 7.2

[0331] Citrate equine whole blood: Citrate content with 3.8mg / ml. 2 M CaCh: Product Nr #22317 by VWR chemicals (99% pur). lOmg wound dressing of Example 2 was soaked with 250pl citrate equine whole blood. Clotting was started by the addition of 20pl of a 2 M CaCh solution. To one set of samples 3 or 5 minutes, 5ml PBS were added after 3 minutes. To another set of samples 5ml PBS (Phosphate buffered saline) were added after 5 minutes.

[0332] After addition of the PBS free erythrocytes dispersed in the solution and dyed it red whereas clotted blood did not release any free erythrocyte and the solution remained transparent. The colour intensity was measured by photometry at a wavelength of 540nm. Results are expressed as a percentage of the value given by whole blood without dressing (RHA=relative haemoglobin absorbance).

[0333] A = Example 7

[0334] B = Material A

[0335] C = Material B

[0336] D = Material C

[0337] E = Material D

[0338] The results are displayed in Fig. 4

[0339] Example 24 in vitro clotting time test

[0340] To measure the clotting time in vitro, 1ml fresh human whole blood was added to 1cm2of wound dressing in a 15ml conical centrifuge tube. Time to clotting was visually assessed by shaking the tube manually and observing that the blood has clotted and formed a solid mass. Clotting was performed at room temperature.

[0341] A = Ctrl blood

[0342] B = Material D

[0343] C = Material B

[0344] D = Material A

[0345] E = Example 6

[0346] The results are displayed in Fig. 5

[0347] Example 25 exothermic behaviour:

[0348] Demonstration of the absence of an exothermic reaction with natural clinoptilolite compared to synthetic zeolite 4A Three zeolite samples were tested: untreated natural zeolite in the form of Clinoptilolitetuff according to (and used as) the raw material of Example 1, pretreated zeolite of Example 1 and synthetic zeolite 4A. All samples had a comparable size distribution with PSD dso of 1pm to 5 pm before testing. All material (microtubes, water, and zeolite samples) were left for 1 hour at room temperature before the experiment to allow their temperature to stabilize.

[0349] 1 gram of each sample was weighted in a 5ml microtube and a temperature sensor was placed in the center of the powder volume in the tube. The base temperature was recorded. 1ml ultrapure water was added to each sample and the temperature was recorded again after 30 seconds. The temperature difference between time 0 and time 30 seconds was calculated. Temperature was measured with a precision of 0.1 degree centigrade and the test was performed in quadruplicate.

[0350] The temperature difference for the pretreated zeolite in the form of natural clinoptilolite was -0.25°C + / - 0.5, demonstrating the absence of a relevant exothermic reaction resulting from the contact of natural clinoptilolite with water.

[0351] Example 26 Absorption capacity 1

[0352] Water absorption capacity was measured by soaking 1cm2of wound dressing of Example 6 with 5ml deionized water in a petri dish. After 10 minutes at room temperature, the dressing was carefully transferred with a forceps in a pre-weighted glass petri dish and weight gain due to water absorption was measured on a precision scale.

[0353] A = Example 7

[0354] B = Material A

[0355] C = Material B

[0356] D = Material C E = Material D

[0357] The results are displayed in Fig. 6.

[0358] Example 27 Absorption capacity 2

[0359] Measurement of fabric absorbency capacity

[0360] Soaking solution: saline (142mM NaCl + 2.5mM CaCh), prewarmed at 37°C

[0361] Free swell

[0362] Cut 5x2 cm pieces of wound dressing of Example 6 (10 cm2) in pentaplicate.

[0363] - Weigh each piece (A) in a pre-weighted petri dish.

[0364] - Add 5 ml of saline to the dressing (the volume was distributed around and in contact with the piece of wound dressing and not directly onto it) and the petri dishes were placed in an incubator set at 37°C with 95% humidity.

[0365] - After 30 minutes of incubation, remove the piece of dressing with tweezers and let the excess water drip off over the petri dish for 30 seconds. Transfer the piece of dressing to a new pre-weighed petri dish.

[0366] - Determine the amount of solution absorbed by weighing.

[0367] Under compression

[0368] The soaked pieces of wound dressing obtained in the previous protocol were used to test the absorption capacity under compression.

[0369] Following the ISO13726:2023 norm, a pression of 40mm Hg must be applied for 30 seconds. This corresponds to 54.4g per cm2, which corresponds to 544g for 10cm2.

[0370] The apparatus used to apply the required pressure on the dressing has been built by sticking a 96W multiwell plate onto a small solid plastic container with a surface of 7x3.5 cm (24.5 cm2). A pair of ring weights for water bathes was placed onto them to reach the required pressure.

[0371] The wound dressings were placed over a 96W multiwell plate and compressed with the prepared weighting apparatus for 30 seconds. Afterwards, the wound dressing was transferred to a pre-weighed petri dish and weighed to obtain the amount of solution absorbed after compression. Results

[0372] The wound dressing of example 6 :

[0373] Absorption capacity without compression: 24,82 + / - 0.68gram / 100 cm2

[0374] Absorption capacity under compression: 14.68 + / - 1.19gram / 100 cm2

[0375] Loss due to compression - 12.02 g (-45%)

[0376] The pressure applied was 1,335g per 24.5cm2, which approximately corresponds to the pressure of 40mm Hg per cm2required by the ISO norm.

[0377] Example 28: Cs and Sr sorption:

[0378] This experiment was set up to show the capacity of the wound dressing (example 6) to bind radioactive Csl34, Csl37 and Sr85 / 89 compared to standard-of-care cotton dressing. Three times 200mg of the cotton gauze and the new dressing respectively were prepared for each experiment. Treatment solutions were prepared by mixing 10ml distilled water with 0.1ml radionuclide solution (CsCl or SrC12). Subsequently, gauze and dressing were soaked with the solution, sealed in vessels and stabilized at 40°C overnight; 0.1ml aliquots were taken and analysed via gamma spectroscopy to quantify the radionuclide adsorption.

[0379] The gauze treated with Csl34 (4kBq) was capable to sorb ca. 23% of the available radionuclide, the wound dressings sorbed ca. 65%. The gauze treated with Csl37 (6kBq) was capable to sorb ca. 23% of the available radionuclide, the wound dressings sorbed ca. 65%.

[0380] The gauze treated with Sr85 / 89 (lOOBq) was capable to sorb ca. 4% of the available radionuclide, the wound dressings sorbed ca. 40%.

[0381] In the above Examples Material A to F stand for:

[0382] Material A: QuikClot Combat (Z-Medica, Wallingford, CT, USA )

[0383] Material B: QuickClot Control (Z-Medica, Wallingford, CT, USA)

[0384] Material C: Quickclot EMS (Z-Medica, Wallingford, CT, USA) Material D: Cel ox Rapid (Medtrade Products Ltd., Crewe, UK) Material E: Celox Gauze (Medtrade Products Ltd., Crewe, UK) Material F: Kaltostat (Core Scientific Creations Ltd (d / b / a Wound-Clot), Bay Harbor Islands, FL, USA)

[0385] Conclusion of the Examples: Examples 21 to 28 illustrate the fundamental properties of the present invention:

[0386] - Haemostasis is achieved faster, both in vitro and in vivo (examples 21, 22, 23 and

[0387] 24)

[0388] There is no temperature increase during fluid absorption (example 25)

[0389] - It has superior absorbance compared with leading wound dressings on the market (example 26 and 27)

[0390] - It is very efficient at sorbing radionuclides (example 28)

[0391] Some observations:

[0392] “n% of the weight”, “nwt%”, “n% per weight”, “n% w / w” and similar phrases are used synonymously.

[0393] Excerpt of the mentioned prior art:

[0394] CN 111001033 B US 4,142,913 US 2020 / 141031 Al

[0395] CN 112546281 A US 4,144,080 US 4,211,574

[0396] CN 115920116 A US 4,145,532 US 4,562,110

[0397] CN 103 143 050 A US 4,189,338 US 5,981,410

[0398] EP 2 040 837 Bl US 4,196,282 WO 2005 / 038123 Al

[0399] EP 2040837 Bl US 4,246,221 WO 2008 / 049980 Al

[0400] EP 171 806 US 4,416,698, WO 2012 / 048768 Al

[0401] EP 269 393 A2 US 4,426,228 WO 2015 / 044605 Al

[0402] EP 740 554 US 4822349 A WO 2015 / 140563 Al

[0403] EP0162026B1 US 5,252,284 WO 2017 / 085436A1

[0404] EP1425050A1 US 5,417,909 WO 96 / 10106 Al

[0405] GB 1 207 352 US 5,456,982 WO20 10 / 061225 A2

[0406] JP H04146218 A US 5,958,806 WO2017 / 085436A1

[0407] RU 2639379 Cl US 6,811,716 WO2022128996A1

[0408] US 3,511,747 US 8173101 B2 WO93 / 12275 Al

[0409] US 3,597,731 US 8252344 B2 W096 / 10106 Al

[0410] Using the principle of hydrophobic interaction to bind and remove wound bacteria, Ljungh et al, Journal of Wound Care Vol 15 , No 4 , April 2006

[0411] Infection control properties of some wound dressings, Journal of Wound Care November,

[0412] Vol 8, No 10, 1999

[0413] Tschegg et al. 2019, Economic Geology, Vol 114, Nr. 6

[0414] The content of all documents mentioned in the description is incorporated by reference into the disclosure of this application for all jurisdictions where this is possible.

Claims

- 49 -Claims:

1. Haemostatic agent for promoting blood clotting comprising zeolite doped alginate fibers comprising alginate and zeolite, characterized in that the zeolite is embedded and dispersed homogeneously within the alginate fibers.

2. Haemostatic agent according to claim 1, characterized in that the zeolite is a clinoptilolite.

3. Haemostatic agent according to claim 2, characterized in that the clinoptilolite content of the doped alginate fibers is 5 - 20 wt%, preferred 8 - 15wt% and especially preferred 9 - 1 lwt%4. Haemostatic agent according to any of claims 1 to 3, characterized in that clinoptilolite is micronized and has a PSD dso of 1 - 5pm preferably 1.5 - 4pm and more preferably 2 - 3.5pm.

5. Haemostatic agent according to any of the preceding claims, characterized in that clinoptilolite is micronized and has a specific surface area measured as BET of 10 to 60 m2 / g6. Haemostatic agent according to any of the preceding claims, characterized in that clinoptilolite is pretreated and has depleted levels of heavy metals and / or ammonia (NH4).

7. Haemostatic agent according to claim 6, characterized in that heavy metals comprise one or more of the group of As, Pb, Cd, Ba, Mn.

8. Haemostatic agent according to claim 7 characterized in that the level of As is <10pg / g, preferably <2pg / g, the level of Pb is <10pg / g, preferably <3pg / g, the level of Cd is <10pg / g, preferably <2pg / g, the level of Ba is <150pg / g, preferably <75pg / g, the level of Mn is <100pg / g, preferably <25pg / g.

9. Haemostatic agent according to any of the preceding claims, characterized in that the alginate has a Mannuronate content of 50-90wt% or a Guluronate content of 50-90wt%.

10. Haemostatic agent according to any of the preceding claims, characterized in that the alginate comprises calcium alginate.- 50 -11. Haemostatic agent according to any of the preceding claims, characterised in that the zeolite doped alginate fibers comprise at least one further water-soluble material.

12. Haemostatic agent according to claim 11, characterized in that the at least one further water-soluble material is one or more of the group of: a water-soluble cellulose derivative a carboxymethyl cellulose a poly(vinyl alcohol).

13. Haemostatic agent according to any of the preceding claims, characterized in that the zeolite doped alginate fibers have a thickness in the range of 5 to 50pm, preferably 10 to 30pm, more preferably 15 to 25pm.

14. Haemostatic agent according to any of the preceding claims, characterized in that the zeolite doped alginate fibers are in staple form, preferably with 38mm to 50mm length.

15. A woven or non-woven material comprising the haemostatic agent according to any of the claims 1 to 14.

16. The woven or non-woven material of claim 15, characterized in that it comprises a reinforcing fiber or reinforcing yarn.

17. The woven or non-woven material of claim 16, characterized in that the reinforcing fiber or reinforcing yarn comprises one or more of the group of Lyocell, synthetic textile fiber or a thermoplastic bi-component fiber.

18. The woven or non-woven material according to any of the claims 15 to 17, characterized in that it comprises at least one water-absorbent fiber or one waterabsorbent yam.

19. The woven or non-woven material according claim 18, characterized in that the at least one water-absorbent fiber or one water-absorbent yarn comprises one or more of the group of a modified cellulose, a carboxymethyl cellulose, a cellulose alkyl sulfonate, a poly(vinyl alcohol), a poly(acrylate) or a carboxymethyl chitosan.

20. The woven or non-woven material according to any of the claims 15 to 19, characterized in that it is comprising a radiopaque yarn and / or radiopaque material21. The woven or non-woven material according to claim 20, characterized in that the radiopaque yarn and / or radiopaque material comprises Barium sulphate,- 51 -22. Non-woven material according to any of the claims 15 to 21, characterized in that it is in the form of a non-woven needled felt.

23. Non-woven material according to any of the claims 15 to 21, characterized in that it is in combination with a substrate into which the fibers of the material are needled.

24. Non-woven material according claim 23, characterized in that the substrate into which the fibers of the material are needled is a fluid absorbent layer.

25. Non-woven material according claim 23, characterized in that the substrate into which the fibers of the material are needled is an odour absorbent layer.

26. Woven material according to any of the claims 1 to 14.

27. Woven material according to claim 14, characterized in that it is in combination with a substrate into which the fiber or yams of the material are bonded.

28. Woven material according claim 27, characterized in that the substrate into which the fiber or yarns of the material are bonded to a fluid absorbent layer.

29. Woven material according claim 27, characterized in that the substrate into which the fiber or yarns of the material are bonded to an odour absorbent layer.

30. Haemostatic wound dressing for treating a bleeding wound comprising at least one of the group of:- the homeostatic agent according to any of the claims 1 to 14,- the non-woven material according to any of the claims 15 to 25 or- the woven material according to any of the claims 15 to 19 and 26 to 29.

31. Haemostatic wound dressing according to claim 30, characterized in that the content of haemostatic agent is in the range of 30 to 70wt%, preferred 35 to 65wt%, especially preferred 47 to 61wt%32. A method of producing zeolite doped alginate fibers to be used in any of the claims 1 to 31, comprising the steps: spinning a dope which is an aqueous solution containing dissolved alginate and suspended zeolite into a coagulation bath containing dissolved calcium ions that cause cross- linking of the alginate and- precipitation of fibers comprised of the alginate and suspended zeolite characterized in that:- the amount of suspended zeolite in the dope is 5-20% by weight of the total weight of the dissolved alginate and suspended zeolite, and the concentration of calcium ions in the coagulation bath is at least 0.1%.

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