Statement of Government Support

This invention was made with government support under contract No. N00014-16-C3025 awarded by the Department of the Navy. The government has certain rights in the invention.

Background of the Invention

The delivery of oxygen has many practical applications, but continues to suffer from challenges that inhibit some potential uses of current oxygen delivery solutions. For instance, it is often difficult to find oxygen delivery methods that are capable of providing sufficient amounts of oxygen without compromising the stability of the composition or carrier, or the usability of the composition with the desired target.

Fields such as fermentation applications and microbial based remediation both require oxygen delivery, and particularly, there is a need in the field of wound care technology to deliver oxygen to severely injured limbs, such as injuries that may require the application of a tourniquet for extended periods of time. Typically, in terms of wound care, the need may arise in military or disaster relief settings in which there can be a significant time lapse between the injury event and

transportation of the injured patient to a definitive treatment facility. Flowever, many wounds and wound types could benefit from the rapid, accessible delivery of oxygen delivery from a shelf-stable source.

Many methods have been developed for oxygen delivery in biological settings, such as by using fluorocarbons, the use of modified hemoglobin, or hydrogen oxygen fuel cells. Flowever, none of these methods of oxygen delivery has been successful in forming an oxygen delivery system that is capable of generating a large amount of oxygen as compared to the system’s mass, or that was usable with, or in contact with, injured tissue.

Therefore, another solution has been to use solid peroxides, such as sodium percarbonate and calcium peroxide, which have the ability to degrade into hydrogen peroxide when exposed to moisture. The hydrogen peroxide further degrades into oxygen in aqueous environments, providing the source of oxygen. These compounds have a large oxygen generating capacity for their mass.

Flowever, high concentrations of the compounds may not directly contact a wound or tissue, limiting their use to applications in which the oxygen is generated in a separate area (such as a pump, and in bandages in which a barrier is used between the solid peroxide and the wound) or applications which utilize relatively small amounts of the solid oxygen generating compound. Therefore, in the wound care field, solid peroxides have seen limited use for direct contact use in wound dressings.

However, for transport and storage in medical emergency situations, it would be beneficial to have an oxygen delivery composition that does not require the use of a pump. It would be a further advantage to have an oxygen delivery composition that can directly contact the injured skin or tissue to deliver a high concentration of oxygen to the wound. It would be a further advantage if an oxygen delivery composition could be incorporated into a wound dressing for delivery of oxygen and protection of injured tissue. It would also be advantageous to have an oxygen delivery composition that could remain in contact with the tissue even after the oxygen delivery composition has been activated or used. There is also a need for an easy-to-use product to apply oxygen to wounds to accelerate or begin healing. Such a method and/or product should have relatively few components and be intuitive to use, without the need for special dressings or other

requirements, so as to be easily accessible in the field.

SUMMARY

The present disclosure, in one embodiment, may generally be directed to a composition for delivering oxygen to a tissue of a mammal. The oxygen delivery composition may comprise a polymer matrix comprising at least one polymeric hydroperoxide and a catalyst, where the catalyst is contained in the polymer matrix.

Furthermore, the polymer matrix may comprise fibers. In a further

embodiment, the polymer matrix may comprise a nonwoven material. In yet a further embodiment, the polymer matrix may comprise one or more particles.

In an embodiment of the present disclosure, the at least one polymeric hydroperoxide may have an active oxygen content of from about 5 wt.% to about 40 wt.% by weight based on the total weight of the polymeric hydroperoxide.

Additionally, or alternatively, the polymeric hydroperoxide may have at least one hydroperoxide functional group and a polymer backbone, where the at least one hydroperoxide functional group is bonded to the polymer backbone such that the at least one hydroperoxide functional group remains bonded to the polymer backbone and contained in the polymer matrix until contacted by a fluid.

In one embodiment, the catalyst contained in the polymer matrix may comprise a metal. In a further embodiment, the catalyst may be manganese, silver, copper, platinum or combinations thereof.

In an oxygen delivery composition of the presently pending claims, the polymeric hydroperoxide and the catalyst may be incorporated into the polymer matrix such that a polymeric alcohol and oxygen are formed when the polymer matrix is contacted with a fluid.

Additionally or alternatively, the polymer matrix of the oxygen delivery composition of the present disclosure may include a polymer. In an embodiment, the polymer matrix may include a polymer that comprises a polyacrylic acid polymer, polymethacrylic acid, polyvinyl alcohol, a PEG functionlized polymer, an elastomer, or combinations thereof.

The present disclosure also includes a method of forming a composition for delivering oxygen to a tissue of a mammal. The method comprises attaching at least one hydroperoxide group to a polymer backbone to form a polymeric hydroperoxide, and processing the polymeric hydroperoxide and a catalyst to form a polymer matrix.

In one embodiment, the polymeric hydroperoxide and the catalyst may be processed by melt spinning, a spun-bond process, melt casting, spin casting from a solvent, solvent casting, thermoforming, electrospinning or combinations thereof, to form a nonwoven polymer matrix. In an additional or alternative embodiment, the polymeric hydroperoxide and the catalyst are processed by spray drying or emulsion evaporation to form particles. In a further embodiment, the polymer matrix may be formed into a wound dressing. In an additional or alternative embodiment, a polymer may be incorporated into the polymer matrix.

In a further embodiment, the polymeric hydroperoxide and the catalyst may be processed to form a nonwoven polymer matrix, and the nonwoven polymer matrix may be formed into a wound dressing. Additionally or alternatively, the nonwoven polymer matrix may be incorporated into a wound dressing. In yet a further embodiment, the particle or particles may be applied to a wound dressing.

The present disclosure also contemplates the formation of a wound dressing. A wound dressing according to the present disclosure may include a substrate and an oxygen delivery composition. The oxygen delivery composition may comprise a polymer matrix formed from at least one polymeric hydroperoxide and a catalyst, where the catalyst is contained in the polymer matrix.

Other features and aspects of the present disclosure are discussed in greater detail below.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features and aspects of the present disclosure and the manner of attaining them will become more apparent, and the disclosure itself will be better understood by reference to the following description, appended claims and accompanying drawings, where:

Fig. 1 provides a view of a polymeric matrix of the present disclosure;

Fig. 2 illustrates a wound dressing of the present disclosure;

Fig. 3 schematically illustrates the protective and oxygen delivery

characteristics of a wound dressing of the present disclosure.

DETAILED DESCRIPTION

Reference will now be made in detail to one or more embodiments of the invention, examples of which are illustrated in the drawings. Each example and embodiment is provided by way of explanation of the invention, and is not meant as a limitation of the invention. For example, features illustrated or described as part of one embodiment may be used with another embodiment to yield still a further embodiment. It is intended that the invention include these and other modifications and variations as coming within the scope and spirit of the invention.

Generally speaking, the present disclosure is directed to a composition for the delivery of oxygen that produces oxygen upon contact with a fluid without generating byproducts that will need to be removed prior to contact with the oxygen delivery target. Particularly, an oxygen delivery composition of the present disclosure may be beneficial for use with injured tissue or limbs, as the

hydroperoxide component of the oxygen delivery composition does not come into direct contact with the tissue or limb, and does not decompose into substances that need to be separated from the oxygen prior to contact with the tissue or limb, for example, compounds or ions such as sodium and calcium that may have a toxicity effect at high concentrations, necessitating removal or minimization. Further, the oxygen delivery composition of the present disclosure may not require a separate component for storage and delivery of the oxygen delivery composition, and, instead, the oxygen delivery composition may be completely self-contained. Particularly, polymeric hydroperoxides, or a polymer backbone that has been functionalized with a hydroperoxide group or groups, may decompose into a polymeric alcohol and oxygen when exposed to moisture. Further, such polymeric hydroperoxides may be processed into a matrix or a particle, such that a catalyst for the delivery of oxygen is contained within the matrix or particle. Such a matrix or particle may then allow the oxygen generated from the decomposition of the hydroperoxide functional groups to be released from the matrix or particle without allowing the hydroperoxide functional groups to directly contact the surface to which the oxygen delivery composition is applied. Thus, while the present disclosure may teach efficient compositions for the generation and delivery of oxygen, the compositions also may be used in direct contact with injured tissue, making the oxygen delivery compositions effective for the delivery of oxygen to injured tissue or a wound.

Therefore, a feature of the oxygen delivery composition of the present disclosure is that it may be incorporated into a wound dressing, or may serve as a wound dressing such as a gauze, and has the ability to generate oxygen. The composition may then subsequently deliver this oxygen to the wound and the surrounding tissue. According to the present disclosure, a wound, tissue, or injured tissue may generally refer to the tissue of a mammal (e.g. a human), and the terms may be used interchangeably to refer to injuries to a mammal that would benefit from the delivery of oxygen. Moreover, the term wound dressing is used herein to generally refer to a dressing that may be applied to a wound as defined above. For instance, without intending to be limited to the following and for example only, the term wound dressing may be used in reference to a bandage, a gauze, a wound covering, a wrap, a woven or nonwoven material, film, elastic, self-adhesive material, combinations thereof, as well as other wound dressing substrates known in the art.

The oxygenation needs of the human skin are typically met by the

combination of direct oxygen uptake from the ambient air and by tissue

oxygenation from the vasculature. Dissolved oxygen is essential at all stages of the wound healing process. Poor tissue oxygenation can result in impaired healing. Chronic wounds are notably hypoxic, with an oxygen tension of 5 to 20 mmHg, compared to an oxygen tension of 30 to 50 mmHg in healthy tissue. In healing tissue, oxygen is required as a substrate for the production of biological energy, resistance to infection, collagen synthesis, blood vessel formation, cell migration, and cell proliferation. In addition, oxygen also serves as a signaling molecule to initiate cell motility and enhance the expression of several pro- inflammatory and angiogenic growth factors. In the human skin, adequate oxygen supply is a balance between proper oxygen transport by the blood and direct uptake from the atmosphere. Therefore, oxygen delivery to the wound is dependent on multiple factors including blood perfusion of the tissue, capillary density, arterial partial oxygen pressure (poxygen), the blood hemoglobin level, and local oxygen consumption. Oxygen is not stored in the tissue and several systemic conditions, including advancing age and diabetes, can endanger its availability. Consequently, it is imperative that upon injury, the healing tissue quickly adapts to continuously meet the oxygen requirements for proper healing and repair. Although wounded tissue demands high oxygen levels, the overall oxygen needs of a wound vary at the different stages of the wound healing process.

Healthy tissue needs to be able to adjust oxygen delivery when there is an increase in oxygen demand. In the human skin, oxygen delivery occurs by diffusion via direct uptake from the atmosphere and from the vasculature, where the oxygen moves from areas of high concentration to areas of low concentration. Satisfactory oxygen supply to subcutaneous tissue highly depends on appropriate oxygen transport through the blood at a sufficient bulk flow rate. After tissue injury, blood supply decreases due to disruption of the blood vessels. As a consequence, there is a marked decrease in oxygen delivery after an injury. Although wounded tissue is equipped with all the necessary tools to repair the damage and restore blood supply, there are intrinsic and extrinsic factors that can impair this process, resulting in prolonged oxygen deficiency or chronic tissue hypoxia. Because adequate oxygen supply is essential for successful tissue repair, inability of the wounded tissue to meet oxygen demand can be pathological, resulting in cell death and tissue necrosis.

Therefore, the goal of an oxygen-based therapy for wound care is to fulfill the oxygen demand of the healing tissue and maintain an oxygenation level near an oxygen tension of about 40 mmHg, which is the average oxygen tension found in healthy, well-perfused tissue. Delivery of oxygen as part of oxygen-based therapy has been used clinically as an effective therapy for wound healing since the 1960s with the administration of systemic hyperbaric oxygen (HBO).

Throughout the years, scientific advancements have been made to improve oxygen-based therapies for wound healing. In recent years, new oxygen delivery technologies have emerged that aim to locally provide oxygen to the wounded tissue using faster and more efficient methods than HBO therapy via topical administration. Clinical results have shown that topical delivery of oxygen to the wounded tissue can enhance the rate of epithelialization, induce extracellular matrix protein synthesis, and the expression of angiogenic factors. It should be understood that topically-delivered oxygen only targets the wounded tissue and, as a result, it does not involve high pressure and does not risk the potential for systemic oxygen toxicity.

In furtherance of the development of oxygen-based therapies and oxygen delivery compositions, the present disclosure is directed to an oxygen delivery composition that includes a polymeric hydroperoxide that has an unexpected efficiency in producing free oxygen and also may directly contact a wound or injured tissue. Therefore, polymeric hydroperoxides may have the same or comparable efficiency per mass as a solid peroxide, but do not have the same drawbacks in regards to the limitations in contacting a wound or tissue.

For instance, the polymeric hydroperoxides according to the present disclosure have an oxygen generating capacity per mass comparable to solid peroxides. Specifically, depending on the degree of functionalization of the polymer with hydroperoxide groups, the polymeric hydroperoxide may have an active oxygen content as a percentage by weight of the polymeric unit, where the polymeric unit may generally refer to the polymer backbone that has been functionalized, including the hydroperoxide functional groups, according to the present disclosure, or the portion of the polymer measured in calculating the amount of oxygen, of from about 5 wt.% to about 40 wt.%, such as from about 7.5 wt.% to about 35 wt.%, such as from 10 wt.% to about 30 wt.%, or from about 15 wt.% to about 27.5 wt.%. Thus, according to the above weight percentages, assuming the polymeric hydroperoxide composition weighs 100 grams, the composition may have an oxygen generating capacity of from about 5 grams to about 40 grams, as well as any amount between 5 grams and 40 grams as disclosed by any of the ranges above in terms of the weight percentages, where the weight percentage of the active oxygen content correlates to the oxygen generating capacity.

The oxygen generating capacity may depend on the starting material and degree of functionalization of the polymer backbone with hydroperoxide functional groups. For instance, a hydroperoxide may generally have a formula such as:

where R ¹ may be a straight or branched chain, saturated or unsaturated, alkyl radical having from 1 to about 100 carbons, R ³ may be may be a straight or branched chain, saturated or unsaturated, alkyl radical having from 0 to about 100 carbons or a hydrogen, R ² may be a terminal group terminating the polymer and may be a straight or branched chain, saturated or unsaturated alkyl radical having from about 0 to about 100 carbons or a hydrogen, and n may be an integer ranging from 1 to about 10,000. For instance, as an example and not intending to be an exhaustive list, a hydroperoxide having such a formula may have one of the following structures:

fa)

Further, the active oxygen content calculated as a weight percentage of the polymeric unit as disclosed above may be calculated as one half of the molar mass of oxygen present in each repeating unit, divided by the molar mass (mm) of the entire repeating unit, or active oxygen = ½ x (mm Oxygen / mm polymeric unit), where, as disclosed above, the polymeric unit may generally refer to the polymer backbone that has been functionalized, including the hydroperoxide functional groups, according to the present disclosure, or the portion of the polymer measured in calculating the amount of oxygen. As an example, in structure (a) above, assuming n=1 , the active oxygen or free oxygen = ½ x (molar mass of Oxygen x 8 / ((molar mass of Oxygen x 8) + (molar mass of Hydrogen x 4) +

(molar mass of Carbon x 9)), or 27.1 %. Particularly, per polymeric unit, half of the oxygen present in the unit can be converted into active oxygen content and the remaining half would form the alcohol groups as will be discussed further below.

Thus, in one embodiment, R ¹ as discussed above may be selected to be an alkyl radical having from about 1 to about 10 carbons, such as from about 1 to about 7 carbons, such as from about 1 to about 5 carbons, such as from about 1 to about 3 carbons. Particularly, R ¹ may have more than 10 carbons in some embodiments, or may have less, as the length of the carbon chain in the repeating unit may be selected to increase or decrease the active oxygen content per unit. For instance, a shorter R ¹ chain, such as from about 1 to about 5 carbons, may be selected for a polymeric unit where a higher active oxygen content is desired, whereas a longer chain may be used in embodiments where a lower active oxygen content is needed.

In a further embodiment, a hydroperoxide may generally have a formula:

where R ¹ , R ² , R ³ , and n, are defined as above, m may be an integer ranging from 1 to about 10,000, and R ⁴ may be a straight or branched chain, saturated or unsaturated, alkyl radical or a hydrogen. For instance, as an example and not intending to be limiting, a hydroperoxide having such a formula may have the following structure:

Regardless of the structure of the polymeric backbone unit and/or degree of functionalization of the polymeric unit, in one embodiment, each of the

hydroperoxide groups may be a pendant functional group. In such an embodiment, R ² may be an alkyl radical of from 1 to about 100 carbons, such that the

hydroperoxide functional group is never present as an end group.

Generally speaking, a peroxide compound has a structure RO-OR’ and a hydroperoxide compound may generally have a structure RO-OH. While specific hydroperoxides are not identified by chemical name in the present disclosure, a number of polymers or polymer precursor starting materials are disclosed as well as potential methods of forming hydroperoxides according to the present disclosure, which will be discussed below. Thus, the present disclosure

contemplates that one having skill in the art would understand the names and common identifiers of the taught hydroperoxy- compounds, as well as those that would be understood according to the present disclosure due to the exemplary compounds taught and discussed.

While one having skill in the art may appreciate that polymeric

hydroperoxides according to the present disclosure may be formed using various methods, in one embodiment, polymeric hydroperoxides for use as an oxygen supplying composition for tissue may be formed from irradiating a polyolefin film, such as a polybutadiene film for example, with a UV light. Particularly, a polyolefin may undergo photooxidation, forming hydroperoxides. In an alternative method, a polymer may undergo a redox reaction with hydrogen peroxide in the presence of an acid. In this instance, an alcohol or an alkene may be used, as well as at least one initiator, or an initiator having at least one location to begin initiation, however, multiple initiation locations may be preferred. Moreover, a polymeric hydroperoxide may be formed by the oxidation of polypropylene or polybutadiene by reaction with singlet oxygen. In one such formation method, singlet oxygen reacts with a polymer having an allylic hydrogen, forming a pendant hydroperoxide functional group. Thus, while one having skill in the art may understand that differing methods may be used to form polymeric hydroperoxides according to the presently pending claims, the above have been provided as exemplary methods for forming such polymeric hydroperoxides.

While varying polymeric hydroperoxides may ultimately be selected based upon the present disclosure, by way of example, a t-butyl analog, such as composition (b) described above, will be referenced. Particularly, referring to Table 1 below, and as discussed above, a polymeric hydroperoxide of the present disclosure may have an oxygen generating capacity of from about 5 wt.% to about 40 wt.%, or may generate of from about 5 grams (g) to about 40 g of free oxygen per 100 g of polymer matrix. However, in this example, the t-butyl analog may deliver a total of about 18 wt.% or about 18 g of oxygen per 100 g of polymer matrix, as a t-butyl analog according to composition (b) contains about 36 wt.% oxygen in terms of the total mass of the polymer unit. As shown in Table 1 below, such a composition, utilizing calculated theoretical delivery maximums, would provide superior amounts of free oxygen as compared to haemoglobin, epiflow fuel cells, transCu0 ₂ fuel cells, natrox fuel cells, and hydrogen peroxide. Moreover, as previously discussed, the polymeric hydroperoxide would deliver comparable amounts of oxygen as a solid peroxide (e.g., calcium peroxide), but does not suffer from the same limitations in use with tissue as a solid peroxide, namely the need to remove salts resulting from the calcium peroxide decomposition.

Notwithstanding the polymeric hydroperoxide or organic hydroperoxide base unit selected, the polymeric hydroperoxide may be processed into a fiber(s) or particle(s). For instance a polymeric hydroperoxide may undergo melt spinning, a spun-bond process, melt casting, spin casting from a solvent, solvent casting, thermoforming, electrospinning or combinations thereof, or other process as known in the art, to form a nonwoven matrix. Alternatively, a polymeric

hydroperoxide of the present disclosure may be processed into a particle (e.g., a microparticle or a nanoparticle), such as by spray drying or emulsion evaporation methods as may be known in the art. Regardless of the processing method used, the processed polymeric hydroperoxide may form a polymeric matrix such as generally shown in Fig. 1. Particularly, the oxygen delivery composition 111 may be formed from a matrix 104 that may“contain” the hydroperoxide functional groups 106 within the matrix 104, by maintaining the bond between the polymer backbone 108 and the hydroperoxide functional groups 106 during the processing of the matrix 104, such that the hydroperoxide functional groups 106 are not exposed or present on an outer surface of the oxygen delivery composition and thus do not contact a surface when the polymeric matrix is applied to the surface.

Moreover, as shown in Fig. 1 , the matrix 104 may further include a catalyst 109. As shown in Fig. 1 , the catalyst 109, which is shown in this exemplary embodiment as manganese, but that may be other catalysts known in the art, may be included in the polymer matrix during processing such that the catalyst 109 remains“contained” in the oxygen delivery composition 111. Thus, as shown in Fig. 1 , the catalyst 109 may remain incorporated with the matrix 104 and the hydroperoxide functional groups 106 may remain bonded to the polymer backbone 108 such that the hydroperoxide functional groups 106 are not decomposed by the catalyst 109 until contacted by a fluid, such as water, for example, as shown in Fig. 1. Further, the matrix 104 contains the hydroperoxide functional groups 106 in the matrix 104 such that the hydroperoxide functional groups 106 do not contact a surface to which the composition is applied, as the hydroperoxide functional groups 106 are contained within the matrix 104. Flowever, the matrix 104 is configured such that when the catalyst 109 is activated by a fluid, the matrix 104 allows the generated oxygen to be released from the matrix 104 and delivered to the surface to be treated. While catalysts generally known in the field may be used, metals are preferred, and in a further embodiment, the catalyst 109 may be manganese, silver, platinum, or copper. Particularly, a catalyst should be selected that catalyzes a reaction of the polymeric hydroperoxide into free oxygen and a polymeric alcohol. Notwithstanding the catalyst selected, as discussed in regards to Fig. 1 , the catalyst may be processed into the polymer matrix containing the hydroperoxide functional groups. In this manner, the catalyst may be contained in the polymeric matrix such that the oxygen delivery composition is stably contained in a lightweight form without needing an external catalyst or oxygen generating source, as the decomposition reaction may begin upon contact with a fluid, for instance, when the composition is brought in contact with a fluid (blood or exudate) from an injured limb.

Further, as discussed above, the decomposition reaction may produce free oxygen and a polymeric alcohol. For example, when the catalyst 109 is contacted by a fluid, the matrix 104 of Fig. 1 may begin a decomposition reaction forming R- OFI + O2. Generally, an exemplary reaction according to Fig. 1 may be:

In one embodiment, the polymeric alcohol produced may be a polyvinyl alcohol. Polyvinyl alcohols and the like are considered to be non-toxic, and are used in biological applications such as eye drops, pharmaceuticals, cosmetics, and dietary supplements. Therefore, a polymeric alcohol need not be removed from solution, or placed behind a barrier, as polymeric alcohols may be non-toxic, for example, to tissue around a wound or injured limb. Instead, the polymer alcohol may simply dissolve as a by-product, and may come into contact with a surface, such as the skin or tissue of an injury. Therefore, the oxygen delivery composition of the present disclosure may be used in situations where solid peroxides cannot be safely used, or that would otherwise require a barrier between the oxygen delivery composition and a surface, or a separate oxygen generating source.

In a further embodiment, the oxygen delivery composition may be

incorporated into a wound dressing. For instance, in one embodiment, the polymer matrix itself may be spun into a bioactive gauze, such as in an embodiment where the polymeric hydroperoxide is processed by a spun-bond or melt-spun process. In such an embodiment, the bioactive gauze itself may be used to form a bandage, or may be further processed to be included in, or on, a pre-made or known wrap, bandage or dressing, for example. Alternatively or additionally, the polymer matrix may be used in conjunction with an existing wound dressing, bandage, wrap, or gauze, such that the polymer matrix may be formed into a bioactive gauze or similar form, and then a bandage, dressing, wrap, or additional gauze may be laid over the bioactive gauze without the two layers being previously incorporated.

In yet a further embodiment, the oxygen delivery composition can be in the form of a particle (e.g. a microparticle or nanoparticle), which may be formed as discussed above, after which the particles can be loaded into a wound dressing. Thus, the microparticles or nanoparticles may be contained in a wound dressing such that they may be activated when the dressing is applied to injured tissue, and may be incorporated into any wound dressing known in the art that may be used for wounds, such as wounds present on severely injured limbs. Additionally, as previously discussed, the particles may be incorporated into any suitable carrier, as the particles themselves serve to prevent the tissue from being contacted by the hydroperoxide functional groups, while still allowing the functional groups to decompose upon exposure to a fluid.

For instance, regardless of the form of the polymer matrix, the polymer matrix may form all or a part of a substrate for a wound dressing, or may be incorporated into a substrate for a wound dressing, or may be incorporated with a substrate for a wound dressing either prior to, or after, application of the polymer matrix to a wound site. For instance, a wound dressing according to the present disclosure may generally include a substrate and the oxygen delivery composition. In one embodiment, the substrate may be a material or base material, such as a bandage, gauze, woven or nonwoven material, film, elastic, self-adhesive material, combinations thereof, as well as other wound dressing substrates known in the art. In one embodiment, the substrate may be separate from the polymer matrix, and may be incorporated with the polymer matrix either prior to application to a wound site, such as an integrated wound dressing that may be applied as a substrate and a polymer matrix together to the wound site, or may be separated from the polymer matrix until after the polymer matrix has been applied to a wound site, and then the substrate may be applied over the polymer matrix. In a further embodiment, the polymer matrix may form all or a part of the substrate, such that the nonwoven or woven material formed from the polymer matrix forms all or a part of the substrate. In a further embodiment, the substrate may server as a carrier for the polymer matrix, and is configured to contain the oxygen delivering composition within the substrate.

In yet a further embodiment, the polymer matrix may include a polymer, that may, or may not, contain any hydroperoxide functional groups, and that may be incorporated into the matrix prior to, or during, processing, or after the initial matrix has been formed. Additional polymers may be selected based upon desired characteristics, such as water absorbency, elasticity, durability, self-adhesion, water-tightness, and the like as is known in the field. For instance, exemplary polymers may include polyacrylic acid polymers, polymethacrylic acid, polyvinyl alcohol, a polyethylene glycol (PEG) functionalized polymer elastomers, polyethylene polymers, polypropylene polymers, polyethylene and polypropylene copolymers, cellulose based polymers, polyurethane polymers, rayon,

polyethylene terephthalate, and combinations thereof, as well as other polymers that are known in the art. Particularly, a polyacrylic acid may be blended with the polymeric hydroperoxide prior to processing to improve water absorption in the final polymer matrix, improving the interaction of the fluid with the catalyst when applied to the wound. Similarly, an elastomer such as polybutadiene for example, may be blended with the polymeric hydroperoxide to provide greater elasticity to the oxygen delivery composition, or may be included in an outer layer that overlies the oxygen delivery composition contained in the polymer matrix.

In an embodiment wherein the composition is in the form of a particle, additional polymers may be incorporated into the wound dressing or carrier to which the particle is applied. Thus, the gauze, wound dressing, bandage, or wrap that is to serve as a carrier for the particles, may also incorporate a polymer that may provide greater absorbency or elasticity, or other polymers as discussed above, in the carrier and thus, the final wound dressing.

In one embodiment, the carrier can be absorbent and can also have elastic properties that provide enhanced compression benefits by applying pressure to immobilize the wound site and minimize minor bleeding. The carrier can thus, in one embodiment, be formed from a multilayer nonwoven composite material that provides properties similar to woven LYCRA™ fabrics, with the durability and cost of a nonwoven material. The components of one wound dressing contemplated by the present disclosure are illustrated in Fig. 2. For example, the wound dressing 300 can include a skin or mucosa contacting inner absorbent layer 107 that may be formed from the polymer matrix or that contains the oxygen delivery composition 111 (see Fig. 1 ), and an outer protective layer 110, where the absorbent layer 107 contacts a wound site and the outer protective layer 110 is exposed to the outside environment upon application of the wound dressing 300 around a wound site. In further optional embodiments, the wound dressing 300 can also include a breathable barrier layer 108 and/or an elastic layer 109. Examples of the various wound dressing 300 components and other components of the oxygen delivery composition 111 that can be used in conjunction with the wound dressing 300 are described in Table 2 below.

Table 2: Description and Function of Multilayer Conformal Cover

The outer protective layer 110 can provide tensile strength and tear and puncture resistance with adjustable coverage area. The wound dressing 300 may therefore also provide adjustable levels of compression force due to the retraction forces inherent in the elastic components of the web, as well as comfort and conformability to control bleeding, physically protect the wounded limb, and preserve injured tissue, in addition to providing an oxygen delivery composition. The outer protective layer 110 further protects against bacteria and solid particle penetration through size exclusion, reducing the risk of infection from the environment and the spread of bacteria from the wound to the surrounding area.

Meanwhile, the skin contacting inner absorbent layer 107 of the wound dressing, which is the layer of the wound dressing positioned adjacent the wound site that may be formed from the polymer matrix itself or that may otherwise contain the oxygen delivery composition, may provide, in addition to oxygen delivery in one embodiment, air and water vapor transport, both for wound care as well as providing sufficient fluid to contact the catalyst and begin decomposition of the hydroperoxide functional groups. Additionally, the inner absorbent layer may also deliver comfort and thermal management while providing absorbency to control minor bleeding and wound exudate management. Additionally, the inner absorbent layer 107 can be tailored such that it does not stick to skin or mucosa.

The combination of the outer protective layer 110 and the inner absorbent layer 107 may be selected to provide a soft, lint-free, non-irritating feel against skin and mucosa in one embodiment. Further, it is to be understood that both the outer protective layer 110 and the inner absorbent layer 107, and any layers positioned there between, can be impregnated with nanoparticle metal (e.g., nanoparticle silver and/or nanoparticle platinum) which can be employed as a catalyst to generate oxygen from the polymeric hydroperoxide or to provide for protection against microbial contamination.

As shown in Fig. 3, a wound dressing 300 has been applied to a wound site 200. The combination of the oxygen delivery composition 111 around the wound site 200 and the application of a wrap or bandage 102 provides a barrier to prevent or reduce the introduction of microbes 112 or other contaminants into the wound and also provides free oxygen that can preserve damaged tissue. In one

embodiment, the oxygen delivery composition 111 may be applied as a bioactive gauze and a wrap or bandage 102 may optionally be applied over the oxygen delivery composition 111 , or alternatively, the wrap or bandage 102 and the oxygen delivery composition 111 may be integrated prior to application as described above to form a wound dressing that may be applied together as an oxygen delivery composition and a wound dressing. In use, the wound dressing may also include, or be used with, a hemostatic agent, a biotoxin sequestrant, a broad spectrum antimicrobial, pain medication, compression, wound exudate absorbency, and a neutral surfactant system to enhance debridement of the wound site once care is rendered at an aid station.

For instance, the wound dressing may further include any of the following, or may be applied over or in conjunction with any of the following:

a. Antimicrobials

Any suitable antimicrobial agent is contemplated for use with a wound dressing of the present disclosure. The use of antimicrobial agents is further demonstrated and described in the following documents, all of which are incorporated by reference to the extent they do not conflict herewith: U.S. Patent Application Publication No. 2007/0048344 to Yahiaoui, et al.: U.S. Patent

Application Publication No. 2007/0048345 to Huang, et al.: U.S. Patent Application Publication No. 2007/0048356 to Schorr et al.. U.S. Patent Application Publication No. 2006/0140994 to Bagwell, et al.: U.S. Patent No. 8,203,029 to Gibbins, et al.: and U.S. Patent No. 8,551 ,517 to Hoffman, et al.

b. Hemostatic Agents

Hemostatic agents are also contemplated for use with a wound dressing of the present disclosure and can be used to deliver blood loss prevention and/or coagulation benefits. Useful hemostatic agents include polyacrylate polymers, modified clays, modified cellulose, chitosan and CaCh in a polyacrylate polymer matrix. The use of these and other hemostatic agents is further demonstrated and described in the following documents, all of which are incorporated by reference to the extent they do not conflict herewith: U.S. Patent No. 7,335,713 to Lang, et al.: and U.S. Patent No. 6,822,135 to Soerens, et al.

c. Toxin Sequestration Agents

Toxin sequestration agents are also contemplated for use with a wound dressing of the present disclosure. Toxin sequestration agents include modified clay technology, as well as any other agents that reduce or eliminate biotoxin interaction with the wound and the surrounding tissue. The use of these and other toxin sequestration agents is further demonstrated and described in the following documents, all of which are incorporated by reference to the extent they do not conflict herewith: U.S. Patent No. 6,551 ,607 to Minerath, III, et al.: U.S. Patent No. 6,521 ,241 to Minerath, III, et al.: U.S. Patent No. 6,485,733 to Huard, et al.: U.S. Patent No. 6,517,848 to Huard et al.: and U.S. Patent No. 8,110,215 to Koenig et al. d. Pain Medication

Pain medications are well known, and any suitable topical, local, or systemic pain medication known in the art can be used in the wound dressing of the present disclosure. Suitable examples include but are not limited to lidocaine, benzocaine, or prilocaine.

e. Debridement Agents

The wound dressing of the present disclosure also contemplates the use of one or more debridement agents. Debridement upon reaching an aid station can be enhanced by using debridement agents. Classes of such debridement agents include structured surfactant technology and agents that allow cleaning and debridement of the wound and the surrounding tissue. The use of these and other debridement agents is further demonstrated and described in the following documents, all of which are incorporated by reference to the extent they do not conflict herewith: U.S. Patent No. 7,268,104 to Krzysik et al.; U.S. Patent No.

7,666,824 to Krzysik, et al.; U.S. Patent No. 8,545,951 to Yahiaoui, et al.: and U.S. Patent No. 6,764,988 to Koenig et al.

In one example of the use of this wound dressing 300 of the present disclosure, a severe limb injury (e.g., avulsion, amputation, laceration, compound fracture, severe burn, degloving, severe abrasion, and/or other injuries possibly requiring the use of a tourniquet) occurs. A user (e.g., corpsman, medic, first responder, etc.) can then remove the wound dressing 300 that includes the oxygen delivery composition 111. The user can then then can apply the wound dressing 300 to the injury, and the fluid from the injury will begin the decomposition reaction such that oxygen is supplied to the injury. As previously discussed, an outer protective layer 110 or wrap/bandage 102 may optionally be applied over the wound dressing 300, or may be incorporated as part of the wound dressing 300 prior to application to an injury.

The embodiments of the invention described above are intended to be exemplary only. The scope of the invention is therefore intended to be limited solely by the scope of the appended claims.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.