WO2020040785A1

WO2020040785A1 - Formulations for generating oxygen

Info

Publication number: WO2020040785A1
Application number: PCT/US2018/047916
Authority: WO
Inventors: Erik Edwards; Anthony Duong; Jeff BOYCE; David Marshall
Original assignee: Avent Inc
Current assignee: Avent Inc
Priority date: 2018-08-24
Filing date: 2018-08-24
Publication date: 2020-02-27
Anticipated expiration: 2021-02-24

Abstract

A composition for generating oxygen upon exposure to a trigger is provided. The oxygen delivery composition releases or delivers oxygen to a tissue of a mammal and includes a silicone, a hydrophilic polymeric additive, and a solid oxygen producing compound. A container for the delivery of oxygen to a tissue of a mammal utilizing a solid oxygen producing compound is also provided, as well as a method of delivering oxygen to a tissue of a mammal. An oxygen delivery composition may produce at least 5 milliliters of oxygen per gram of oxygen delivery composition over a time period of at least 24 hours.

Description

Formulations for Generating Oxygen

Statement of Government Support

This invention was made with government support under contract No. N00014-16-C-3025 awarded by the Department of the Navy, Office of Naval Research. 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 applications for which current oxygen delivery solutions may be used. 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 or in a remote location.

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 often arises in military or disaster relief settings in which there may be a significant time lapse between the injury event and

transportation of the patient to a treatment facility. Flowever, many wounds would benefit from a more accessible oxygen delivery source that is able to continuously deliver oxygen over an extended period of time.

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 for oxygen delivery have 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 could maintain the oxygen production over a sustained period of time.

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. Pumps are one elegant way to address this issue, however, they either require external fuel or battery sources to provide oxygen, or provide oxygen over a very short period of time, or require the responder to carry a tank into the field.

Therefore, at least for transport and storage in medical emergency situations, it would be beneficial to have an oxygen delivery composition that can produce a large volume of oxygen per gram of the oxygen delivery composition. It would be a further advantage to have an oxygen delivery composition that does not require an additional fuel or energy source. It would be a further advantage if an oxygen delivery composition could be stored in an easily transportable container until needed for the delivery of oxygen. It would also be advantageous to have an oxygen delivery composition that could remain inactive in a container, such as in solid form, until contacted with a trigger to produce oxygen. 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 an oxygen delivery composition for delivering oxygen to a tissue of a mammal. The oxygen delivery composition comprises a silicone, a solid oxygen producing compound, and a hydrophilic polymeric additive configured to induce hydrogel-like behavior in the silicone. The oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 24 hours when contacted by a trigger.

In one embodiment, the silicone is present in the oxygen delivery

composition in an amount of at least about 30% by weight of the oxygen delivery composition. Additionally, or alternatively, the hydrophilic polymeric additive is present in the oxygen delivery composition in an amount of at least about 10% by weight of the oxygen delivery composition. Further yet, in an embodiment, the solid oxygen producing compound is present in the oxygen delivery composition in an amount of at least about 25% by weight of the oxygen delivery composition. In one embodiment, the silicone and the hydrophilic polymeric additive are present in the oxygen delivery composition in a ratio of silicone to hydrophilic polymeric additive that is from about 5: 1 to about 1 :1.

In one embodiment, the hydrophilic polymeric additive comprises a polyethylene glycol. Additionally or alternatively, the silicon comprises a

polydimethylsiloxane. In a further embodiment, the solid oxygen producing composition comprises a sodium percarbonate.

In an embodiment, the oxygen delivery composition further comprises a catalyst. In one further embodiment, the trigger is water, saline, or a wound exudate.

In a further embodiment, the trigger is configured to produce oxygen at low temperatures. In an additional or alternative embodiment, the oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of oxygen delivery composition over a period of at least 72 hours.

The present disclosure may also be generally directed to a container for delivering oxygen to a tissue of a mammal. The container holds an oxygen delivery composition located in or on the container. The oxygen delivery composition located in or on the container comprises a silicone, a solid oxygen producing compound, and a hydrophilic polymeric additive. The oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 24 hours when contacted by a trigger. In a further embodiment, the oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 72 hours when contacted by a trigger.

An embodiment of the container for delivering oxygen to a tissue of a mammal includes a container that is configured to maintain the oxygen delivery composition separate from the trigger until the trigger is introduced to the oxygen delivery composition. In an embodiment, the container comprises a first

compartment and a second compartment. The oxygen delivery composition is located in the first compartment and the trigger is located in the second

compartment. In a further embodiment, the first compartment and the second compartment are separated by a releasable seal, where the first compartment and the second compartment form a combined third compartment when the seal is released.

In one embodiment, the container has at least one opening for introducing a trigger to the oxygen delivery composition, and in an additional or alternative embodiment, the container contains at least one opening for releasing oxygen from the container.

In an additional or alternative embodiment, the container is a gauze.

Furthermore, in an embodiment, the oxygen delivery composition is printed or impregnated on the gauze. Thus, in an embodiment, the trigger is introduced to the oxygen delivery composition upon application of the gauze to a wound.

The present disclosure may also be generally directed to a method of delivering oxygen to a tissue of a mammal. The method comprises forming an oxygen delivery composition and contacting the oxygen delivery composition with a trigger. The oxygen delivery composition comprises a silicone, a solid oxygen producing compound, and a hydrophilic polymeric additive. In the method, the oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 24 hours after being contacted by a trigger.

In one embodiment, the method further comprises storing the oxygen delivery composition in or on a container for at least one day prior to contacting the oxygen delivery composition with a trigger.

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 is a schematic showing an oxygen delivery composition according to an embodiment of the present disclosure;

Fig. 2 is a graph showing oxygen release by an oxygen delivery

composition according to an embodiment of the present disclosure over time;

Fig. 3 is a graph showing oxygen release by an oxygen delivery

composition according to an embodiment of the present disclosure over time; Fig. 4 is a graph showing oxygen release by an oxygen delivery

composition according to an embodiment of the present disclosure over time;

Fig. 5 is a graph showing oxygen release by an oxygen delivery

composition according to an embodiment of the present disclosure over time;

Fig. 6 is a graph showing oxygen release by an oxygen delivery

composition according to an embodiment of the present disclosure over time;

Fig. 7 is a graph showing oxygen release by an oxygen delivery

composition according to an embodiment of the present disclosure over time;

Fig. 8 illustrates a container according to an embodiment of the present disclosure;

Fig. 9 illustrates a container according to an embodiment of the present disclosure;

Fig. 10 illustrates a container according to an embodiment of the present disclosure; and

Fig. 11 illustrates a container according to an embodiment of the present disclosure inside of a cover or wound dressing.

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 an oxygen delivery composition that produces oxygen upon contact with a trigger. Particularly, an oxygen delivery composition of the present disclosure may be beneficial for use with injured tissue or limbs that require sustained access to oxygen over a period of time, such as in medical or military scenarios where access to medical care may be delayed for several days. Further, the oxygen delivery composition of the present disclosure does not require a separate battery or fuel cell to produce or deliver oxygen, or to deliver oxygen from a container according to the present disclosure. Instead, the oxygen producing compound may produce or deliver oxygen by simply contacting the oxygen producing compound with a trigger. In one embodiment, the trigger may be water or saline, or alternatively a wound exudate from a wound or damaged tissue, which may or may not be modified to operate at low temperatures or to affect the rate of oxygen production.

Particularly, the present inventors have unexpectedly found that an oxygen delivery composition that includes a silicone, a solid oxygen producing compound, and a hydrophilic polymeric additive configured to induce hydrogel-like behavior in the silicone may be formed into a solid matrix and stored until needed to produce oxygen, at which time, a trigger may be applied to the oxygen delivery composition for the generation and delivery of oxygen to a tissue of a mammal. Moreover, the present inventors have unexpectedly found that the oxygen delivery composition may include a solid matrix that is formed according to the present disclosure, such that the matrix may have a high oxygen generating capacity per mass of the oxygen delivery composition and is also surprisingly able to generate oxygen over a sustained period of time, such as at least about three days. For instance, by carefully selecting the silicone, solid oxygen producing compound, and the hydrophilic polymeric additive configured to induce hydrogel-like behavior in the silicone, a matrix may be formed that allows a highly efficient volume of oxygen to be produced, while also stabilizing the composition for delivery over a sustained period of time. Furthermore, the oxygen delivery composition may be used at low temperatures, such as temperatures below the freezing point. In order to utilize the oxygen delivery composition at lower temperatures a salt may be used in the triggering material to depress the freezing point of the trigger solution. Further yet, the present disclosure has unexpectedly found that a small amount of the oxygen delivery composition, such as in an amount of about 5% or less, may be directly applied to the tissue of a mammal and still provide sufficient oxygen without any previously known downfalls.

For instance, in one embodiment, the oxygen delivery composition of the present disclosure may be capable of producing, or be capable of delivering, upon contact with a trigger, an amount of from about 1 milliliter or greater of oxygen per gram of oxygen delivery composition, such as about 5 milliliters or greater, such as about 7.5 milliliters or greater, such as about 10 milliliters or greater, such as about 12.5 milliliters or greater, such as about 15 milliliters or greater, such as about 17.5 milliliters, such as about 20 milliliters or greater, such as about 22.5 milliliters or greater, such as about 25 or greater, such as about 27.5 milliliters or greater, such as about 30 milliliters or greater, and such as about 50 milliliters or less, such as about 45 milliliters or less, such as about 40 milliliters or less, such as about 35 milliliters or less, such as about 30 milliliters or less of oxygen per gram of oxygen delivery composition. In one embodiment, the oxygen delivery composition may be capable of producing and/or delivering an amount of oxygen of from about 5 milliliters to about 35 milliliters, such as about 7.5 milliliters to about 32.5 milliliters, such as about 10 milliliters to about 30 milliliters of oxygen per gram of oxygen delivery composition.

Additionally, an oxygen delivery composition according to an embodiment of the present disclosure may be capable of delivering or producing oxygen over a sustained period of time after being contacted with a trigger. For instance, an oxygen delivery composition according to the present disclosure may be capable of delivering or producing oxygen for 12 hours or greater, such as 24 hours or greater, such as 36 hours or greater, such as 48 hours or greater, such as 60 hours or greater, such as 72 hours or greater, and such as 120 hours or less, such as 108 hours or less, such as 96 hours or less, such as 84 hours or less. In one embodiment, an oxygen delivery composition according to the present disclosure may be capable of delivering or producing oxygen over a time period of from about 24 hours to about 108 hours, such as about 48 hours to about 96 hours, such as about 60 hours to about 84 hours.

Therefore, a feature of the oxygen delivery composition of the present disclosure is that it may have the ability to generate oxygen for delivery of the oxygen to a wound or tissue, as well as 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. In one embodiment, the oxygen delivery composition of the present disclosure may be used in conjunction with a wound dressing, such as a cover as generally shown in Fig. 11 , in order to deliver oxygen to a tissue of a mammal.

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 the wounded tissue demands high oxygen levels, the overall oxygen needs of a wound differ 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 the subcutaneous tissue is highly dependent on appropriate oxygen transport through the blood at a sufficient bulk flow rate.

During tissue injury, blood supply decreases due to disruption of blood vessels. As a consequence, there is a marked decrease in oxygen delivery. Although the 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 oxygen concentration near an oxygen tension of about 40 mmHg, which is the average oxygen tension found in healthy, well-perfused tissues. 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, advancements have been made in the scientific field 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 at a faster and more efficient way 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 silicone, a solid oxygen producing compound, and a hydrophilic polymeric additive configured to induce hydrogel-like behavior in the silicone. These components may be combined to form a solid matrix. The present disclosure may also include a method of delivering oxygen to a tissue of a mammal as well as a container, which in one embodiment may include a gauze that has been printed or impregnated with the oxygen delivery composition, for delivering generated oxygen to the mammal, without needing an external power source.

For instance, an oxygen delivery composition according to the present disclosure may generally include a silicone, a solid oxygen producing compound, and a hydrophilic polymeric additive configured to induce the silicone to behave as a hydrogel, as well as other optional components, such as a catalyst, that may be discussed further below or as may be known in the art. The oxygen delivery composition may be in the form of a matrix generally formed by the silicone and that includes the hydrophilic polymeric additive configured to induce hydrogel-like behavior in the silicone and the solid oxygen producing compound within the matrix. Such a matrix may be in the form of a solid, in one embodiment, or may be in a semi-solid, or an alternative form. Regardless, the present inventors have unexpectedly found that when the oxygen delivery composition is carefully formed according to the present disclosure, a composition that is capable of delivering a large volume of oxygen per mass of the composition ( e.g a high efficiency composition), is formed that may additionally or alternatively be capable of delivering a consistent amount of oxygen over a sustained period of time.

In an embodiment, the silicone may be any silicone or siloxane. As may be generally understood, a silicone or silicone polymer may refer to a polymer that includes repeating siloxane units {e.g., Si-O-Si units). A silicone polymer may of course be substituted or unsubstituted as known in the art. Furthermore, the silicone may be, or may include, a polyalkysiloxane and/or a polydialkylsiloxanes.

In this regard, the alkyl may be a Ci or greater alkyl chain, such as a C₂ or greater alkyl chain, such as a C₃ or greater alkyl chain, such as a C₄ or greater alkyl chain, such as a C₅ or greater alkyl chain, such as a C_& or greater alkyl chain, such as a C₇ or greater alkyl chain, such as a C₈ or greater alkyl chain, such as a C₉ or greater alkyl chain, such as a C₁-C₉ alkyl group, and/or where the alkyl chain may be a Ci₂ or less alkyl chain, such as a Cio or less alkyl chain, such as a C₈ or less alkyl chain, such as a C₈ or less alkyl chain, such as a C₄ or less alkyl chain, such as a C₃ or less alkyl chain. However, it should be understood that even longer alkyl chains may be employed in certain embodiments. In one particular embodiment, however, the alkyl group may be a methyl such that the siloxane is a polydimethylsiloxane.

A silicone or siloxane, as discussed above, or a further silicone or siloxane, may be generally formed as known in the art. However, varying degrees of crosslinking may be achieved based upon the silicone used as well as the method of curing used to cure the silicone to form the matrix. As may be generally known in the art, a silicone may be cured using various methods. During curing, a plurality of crosslinking bonds may be formed between silicone polymers to form a solid, or semi-solid matrix. Particularly, the present inventors have found that by selecting the amount of crosslinking in the silicone matrix, such as by controlling the method of curing used or by selecting a silicone polymer that is capable of forming the desired amount of crosslinks, oxygen delivery compositions with greater oxygen producing capabilities and/or greater sustained oxygen delivery may be obtained.

For instance, in one embodiment, a silicone with a lower crosslink density may be desired. Particularly, the present disclosure has found that, in some embodiments, a lower crosslink density may result in faster release of the oxygen from the system. In such an embodiment where a lower crosslink density is desired, a silicone according to the present disclosure may formed by utilizing a one-part, or single part, cure method, either alone or in combination with selecting a silicone polymer with low crosslinking potential as discussed above. In a one-part cure, a silicone matrix as discussed above may be formed by curing the silicone in the presence of a crosslinking compound. The crosslinking compound may be introduced to or exposed to compounds, such as atmospheric water for example, that cause the crosslinking compound to hydrolyze, forming a crosslinking compound with a hydroxy functional group and/or a silanol group. The hydroxy or silanol functionality on the crosslinking compound may then condense with the silicone polymer, forming crosslinking bridges between silicone polymers, or react with a further crosslinking compound, continuing the reaction until the system is fully cured.

In an embodiment that utilizes a one-part cure, the crosslinking compound may be a composition with alkoxy, acetoxy, or oxime silane functionality, and in a further embodiment, an acetoxy crosslinking compound is preferred. However, other crosslinking compounds as known in the art may be used.

In an additional or alternative embodiment, a higher degree of crosslinking may be desired. Without intending to be bound by theory, the present inventors have found that a silicone matrix with a higher degree of crosslinking may slow the rate of oxygen released from the oxygen delivery composition, and further, that a silicone matrix with a higher degree of crosslinking may further slow the overall release of oxygen from the oxygen delivery composition, such as by slowing the introduction of the trigger to the matrix as will be discussed in greater detail below. Such an embodiment may be desirable, for instance, where oxygen production over a longer period of time is needed, or in a situation in which the oxygen delivery composition is prone to releasing oxygen too quickly, though a higher degree of crosslinking may also be desirable in other circumstances.

Thus, in an embodiment where a higher degree of crosslinking is desired, the silicone may be cured using a two-part cure, either alone or in combination with selecting a silicone polymer with high crosslinking potential as discussed above. A two-part cure is generally an addition reaction that is catalyzed by platinum. The platinum catalyst is combined with a silicone polymer having vinyl functionality and a crosslinking compound. The platinum catalyst catalyzes an addition reaction between the two part compound of the crosslinking compound and the vinyl functional silicone polymer, forming ethyl bridges between the silicone polymer and the crosslinking compound, and eventually crosslinking bonds between silicone polymers. The reaction is allowed to proceed to completion, forming a silicone matrix according to the present disclosure. However, it should be noted, that in certain circumstances, either a one-part cure or a two-part cure may be used to form a matrix having a higher degree or lower degree of crosslinking depending upon the silicone or siloxane selected, but may also contribute to higher and lower degrees of crosslinking utilizing a similar silicone or siloxane.

Regardless of the curing method chosen, a silicone matrix according to the present disclosure may be generally shown for instance, in Fig. 1 of the present disclosure. An oxygen delivery composition 100 of the present disclosure may be in the form of a solid matrix after the silicone 102 has been cured. The oxygen delivery composition 100 may include a solid oxygen producing compound 104, which will be discussed in greater detail below, and a hydrophilic polymeric additive configured to induce hydrogel-like behavior in the silicone 106, which will also be discussed in greater detail below, included within the solid matrix formed by the cured silicone 102. As shown in Fig. 1 , the silicone 102 may include crosslinking 108, and as discussed above, the degree of crosslinking may be increased or decreased based upon the desired properties of the composition. While the crosslinking in Fig. 1 is shown as symmetrical, the crosslinking may be varied and only connect adjacent or nonadjacent silicone polymers 102 as may be generally known in the art. The oxygen delivery composition may also include a catalyst 110 within the solid matrix, which will be discussed in greater detail below.

Regardless of the curing method used, the present disclosure has also found that the size of the matrix may also impact the oxygen release properties of the oxygen delivery composition. Particularly, after the matrix is formed, the matrix may be divided or broken into particles of a variety of sizes. Without intending to be bound by theory, the present disclosure has found that a matrix that is larger in size slows the release of oxygen from the system, potentially due to the increased barrier that the trigger must travel through to reach the oxygen producing compound, as well as the increased diffusion barrier the oxygen must travel through to be released from the matrix. Therefore, the oxygen delivery composition according to the present disclosure may be broken or divided into a desired size or sizes based upon the desired rate of release of oxygen. For instance, in one embodiment, a matrix or plurality of matrix particles according to the present disclosure may have a relatively small size if a faster release of oxygen is desired or a larger size may be selected if a slower, or longer term composition is desired.

Thus, in an embodiment, the oxygen delivery composition according to the present disclosure may be a solid matrix, or a plurality of matrix particles formed by breaking or dividing the cured silicone matrix into particles have a single or a mixture of desired sizes. Further, it is understood that a matrix or an oxygen delivery composition according to the present disclosure may be referring to a single matrix or a plurality of matrix particles. For instance, the present disclosure may refer to an amount in grams of the oxygen delivery composition needed to yield an amount of oxygen upon contact with a trigger. The weight in grams of the composition may be in reference to a single matrix having the desired weight, or may be in reference to a plurality of matrix particles having the recited weight in aggregate. For instance, when a slower releasing composition is desired, a single or a few larger matrix particles may be used, or alternatively, for a faster releasing composition, a larger number of small matrix particles may be used.

Flowever, in a preferred embodiment, a matrix or some or all of the matrix particles according to the present disclosure may each have an average size measured by the average volume of the matrix or individual matrix particle. The average volume of the matrix or matrix particle may be about 1 millimeter³ or greater, such as about 2 millimeters³ or greater, such as about 3 millimeters³ or greater, such as about 4 millimeters³ or greater, such as about 5 millimeters³ or greater, such as about 10 millimeters³ or greater, such as about 15 millimeters³ or greater, such as about 20 millimeters³ or greater, such as about 25 millimeters³ or greater, such as about 30 millimeters³ or greater, such as about 50 millimeters³ or greater, such as about 75 millimeters³ or greater, such as about 100 millimeters³ or greater, such as about 125 millimeters³ or greater in volume, and the matrix or matrix particle may have a size of from about 175 millimeters³ or less, such as about 150 millimeters³ or less, such as about 140 millimeters³ or less, such as about 130 millimeters³ or less, such as about 125 millimeters³ or less, such as about 100 millimeters³ or less, such as about 75 millimeters³ or less, such as about 50 millimeters³ or less, such as about 25 millimeters³ or less, such as about 20 millimeters³ or less, such as about 10 millimeters³ or less. In one embodiment a matrix or matrix particle according to the present disclosure may have a volume of from about 1 millimeter³ to about 150 millimeters³, such as from about 2

millimeters³ to about 130 millimeters³, such as from about 5 millimeters³ to about 125 millimeters³.

Regardless of the volume or range of volumes selected, as not all of the particles need to be the same size, in an embodiment, the matrix or matrix particles having the selected size(s) may be used as the oxygen delivery

composition, and a weight of matrix or matrix particles having the desired size(s) may be selected based upon the weight needed to yield a desired volume of oxygen as discussed above. Thus, an oxygen delivery composition may be formed from a matrix or matrix particles with a size or sizes selected based upon desired oxygen release characteristics of the composition, and then an amount of the matrix or matrix particles having the desired size and release properties may be selected based upon the volume of oxygen that is desired to be produced.

While the method of curing the silicone has been discussed separately from the size of the matrix or matrix particles, it is to be understood that the rate and length of oxygen production/delivery may be influenced by both factors

simultaneously. For instance, referring to Fig. 2 of the present disclosure, a two- part cured silicone, a commercial example of which may be Sylgard 184, and a one-part cured silicone, a commercial example of which may be SS-101 , were each used to form an oxygen delivery composition having a 2: 1 :2 ratio of silicone to polyethylene glycol to sodium percarbonate. Further, the oxygen delivery compositions were tested using the same amount in grams of the oxygen delivery composition, but a variety of matrix or matrix particle sizes were evaluated. As shown in Fig. 2, the one-part cured silicone generally has a higher rate of oxygen release in milliliters per gram (ml_/g) both as to the initial rate and the total amount of oxygen released. However, the oxygen generating composition having a larger average size (125 mm³) of both the one-part and two-part cured silicone resulted in a slower release of oxygen as compared to the oxygen delivery composition having a smaller average size (3 mm³).

As discussed above, an oxygen delivery composition according to the present disclosure may also include a hydrophilic polymeric additive, such as polyethylene glycol, that is able to induce hydrogel-like behavior in the silicone.

The present disclosure has found that hydrophilic polymeric materials selected according to the present disclosure are capable of interacting with the silicone in a manner, such as by exerting a pressure on the silicone due to swelling of the hydrophilic polymer, that induces the silicon to act in a similar manner as a hydrogel, for instance. Additionally, hydrogel-like behavior may be induced by cross-linking hydrophilic polymeric particle or chains within the silicone matrix. In such a manner, the silicone matrix may be induced to retain water in the polymeric structure. Particularly, the hydrophilic polymeric additive is able to interact with, or induce the silicone to act, as a hydrogel without needing a hydrogel to be added to the composition. For instance, a hydrophilic polymeric additive, such as polyethylene glycol, may be introduced to the silicone matrix, to induce hydrogel- like behavior in the silicone in order to increase the absorbency of the matrix for the trigger. In such a manner, the matrix may be better able to increase or improve the diffusion of the trigger into the matrix, and/or retain the trigger in the matrix at least until the solid oxygen producing compound is fully reacted.

While a variety of hydrophilic polymeric additives may be used, in one embodiment, the hydrophilic polymeric additive can be a polyalkylene ether.

Polyalkylene ethers may include polyalkylene glycols, such as, polyethylene glycols, polypropylene glycols polytetramethylene glycols, polyepichlorohydrins, etc.), polyoxetanes, polyphenylene ethers, polyether ketones, and so forth.

Particularly suitable are polyethylene glycols, polypropylene glycols and

polytetramethylene glycols. The polyalkylene ethers may be prepared by polycondensation reactions from diols or polyols.

In a further embodiment the hydrophilic polymeric additive may be a carboxyl containing water-absorbent polymer, such as a polymer derived from one or more ethylenically unsaturated carboxylic acids, ethylenically unsaturated carboxylic acid anhydrides or salts thereof. Additionally, the polymers can include comonomers known in the art for use in water-absorbent resin particles or for grafting onto the water-absorbent resins, including comonomers such as

acrylamide, a vinyl pyrrolidone, a vinyl sulphonic acid or a salt thereof,

acrylamidopropane sulfonic acid (AMPS), salts thereof, or phosphonic acid containing monomers, a cellulosic monomer, a modified cellulosic monomer, a polyvinyl alcohol, a starch hydrolyzate, the hydrolyzates of acrylamide copolymers, or crosslinked products of hydrolyzates of acrylamide copolymers. Examples of ethylenically unsaturated carboxylic acid and carboxylic acid anhydride monomers include, but are not limited to, acrylic acids, such as acrylic acid, methacrylic acid, ethacrylic acid, alpha-chloro acrylic acid, alpha-cyano acrylic acid, beta- methyl acrylic acid (crotonic acid), alpha-phenyl acrylic acid, beta-aryloyloxy propionic acid, sorbic acid, alpha-chloro sorbic acid, angelic acid, cinnamic acid, p-chloro cinnamic acid, beta-styd acrylic acid (1 -carboxy-4-phenyl butadiene-1 ,3), itaconic acid, citraconic acid, mesaconic acid, glutaconic acid, maleic acid, fumaric acid and maleic acid anhydride. In some embodiments, the carboxyl containing water- absorbent polymers are derived from acrylic acid, methacrylic acid, or a salt thereof, with preferred embodiments including polyacrylic acids and crosslinked products of polyacrylic acids.

Furthermore, an oxygen delivery composition according to the present disclosure may also include a solid oxygen producing compound. In one

embodiment, the oxygen producing compound according to the present disclosure may be a solid peroxygen species such as a peroxide or a percarbonate.

Particularly, solid peroxygen species according to the present disclosure may include solid percarbonates and/or sold peroxides. In one example, the solid peroxygen species may be sodium percarbonate, calcium peroxide, or a

combination thereof. Regardless, the solid oxygen producing compound may be other solid compounds known in the art that are capable of reacting with a trigger, such as water to produce oxygen, and that can be used in conjunction with a matrix as previously discussed. For instance, a solid oxygen producing compound according to the present disclosure may react with the trigger to decompose into hydrogen peroxide, and further decompose into oxygen and non-toxic or biocompatible byproducts. Of course, a container, which may be discussed in greater detail below, may also include a filter such that byproducts that may be produced are caught by the filter instead of being transferred to a tissue of a mammal with the produced oxygen.

Regardless of the solid oxygen producing compound selected, the solid oxygen producing compound may be contained in the oxygen delivery composition sufficient to produce a volume of oxygen according to the present disclosure. For instance, the solid oxygen producing compound may be present in the oxygen delivery composition in an amount of from about 0.25% to about 60% by weight of the oxygen delivery composition, such as from about 2.5% to about 58%, such as from about 5% to about 55%, such as from about 10% to about 52.5%, such as from about 20% to about 50%, such as from about 30% to about 45%, such as from about 37.5% to about 42.5% by weight of the oxygen delivery composition, or any ranges therebetween. In an additional or alternative embodiment, such as an embodiment utilizing a gauze as a container, the oxygen delivery composition may be used in an amount of about 5% by weight of the oxygen delivery composition or less, such as from about 0.25% to about 5%, such as from about 0.5% to about 4.5%, such as from about 1 % to about 4%, or any ranges therebetween. For instance, in an embodiment that will be discussed in greater detail below, a gauze may be used as the container for the oxygen generating composition, and it may be desired to utilize an oxygen delivery composition having an amount of oxygen producing compound of about 5% or less, such as the ranges discussed above, so that the oxygen delivery composition may directly contact the tissue of a mammal. Particularly, the present disclosure has unexpectedly found that when the oxygen producing compound is used in an amount of about 5% or less by weight of the oxygen delivery composition, the oxygen delivery composition may be able to produce a sufficient amount of oxygen and is also able to directly contact the tissue of a mammal without any of the known shortcomings discussed above in regards to solid peroxides.

Similarly, the silicone may be present in the composition in an amount sufficient to maintain the structural stability or consistency of the matrix, for example. For instance, in an embodiment, the silicone may be present in the oxygen delivery composition in an amount of from about 30% to about 60% by weight of the oxygen delivery composition, such as from about 35% to about 55%, such as from about 40% to about 50% by weight of the oxygen delivery composition. In one embodiment, the silicone is present in the oxygen delivery composition in an amount of at least about 30% by weight.

Further, the hydrophilic polymeric additive may be present in the

composition in an amount sufficient to aid in diffusing the trigger through the matrix. In one embodiment, the hydrophilic polymeric additive may be present in the oxygen delivery composition in an amount of from about 5% to about 40% by weight of the oxygen delivery composition, such as from about 10% to about 30% by weight of the oxygen delivery composition, such as from about 15% to about 25% by weight of the oxygen delivery composition.

Moreover, the silicone and the hydrophilic polymeric additive may be present in the oxygen delivery composition in a ratio of from about 5:1 to about 1 :2, such as from about 4:1 to about 1 :1 , such as from about 2:1 to about 1 :1. Similarly, in one embodiment, the silicone, the hydrophilic polymeric additive, and the solid oxygen producing compound may be present in the composition in a ratio of about 2: 1 :2.

Further, the composition may also include any other additive known in the art such as solvents, surfactants, catalysts, and the like, for example.

In one embodiment, the oxygen delivery composition further includes a catalyst. While catalysts generally known in the field may be used, metals, alkali metal, or salts thereof, are preferred, and in a further embodiment, the catalyst may be manganese chloride, silver, platinum or potassium iodide. Particularly, a catalyst should be selected that catalyzes the decomposition of the solid oxygen producing compound into hydrogen peroxide and eventually free oxygen when contacted by the trigger.

For instance, referring to Figs. 3 and 4 of the present disclosure, the release of oxygen from the oxygen delivery composition may be enhanced by including a catalyst in the silicone matrix. For instance, as shown in Fig. 3 for a 2-part cured silicone and Fig. 4 for a 1 -part cure silicone, potassium iodide and manganese chloride catalyze the rapid release of the majority of the oxygen within about 48 hours from the time the trigger is introduced. Similarly, silver is an effective catalyst, however, in one embodiment, the present inventors have found that if the silver particles are too small, the silver may inhibit the ability of the oxygen delivery composition to product oxygen. Therefore, in an embodiment, if a silver catalyst is used, the silver may have a particle size of from about 50 nanometers or larger, such as about 100 nanometers or larger, such as about 500 nanometers or larger, such as from about 1 micrometer or larger, such as from about 2.5 micrometers or larger, such as about 2 micrometers or larger, such as from about 2.5 micrometers or larger, such as from about 3 micrometers or larger, or about 5 micrometers or smaller, such as about 4 micrometers or smaller, such as about 3.5 micrometers or smaller, such as about 3 micrometers or smaller.

In a composition that uses a catalyst according to the present disclosure, the catalyst may be present in the oxygen delivery composition in an amount of about 0.05% by weight or greater of the oxygen delivery composition, such as about 0.1 % by weight or greater, such as from about 0.5% by weight or greater, such as about 0.75% by weight or greater, such as about 1 % by weight or greater, such as about 1.5% by weight or greater, such as about 2% by weight or greater, or such as about 3% by weight or less, such as about 2% by weight or less, such as about 1.5% by weight or less, such as about 1.25% by weight or less, such as about 1 % by weight or less, such as about 0.75% by weight or less, such as about 0.5% by weight or less, such as about 0.25% by weight or less of the oxygen delivery composition. However, in one embodiment where silver is used, the catalyst may be present in an amount ranging from about 0.5% to about 2%, such as from about 0.75% to about 1.5%, such as from about 0.9% to about 1.25% by weight of the oxygen delivery composition. In a further embodiment that uses potassium iodide and/or manganese chloride, or a similar catalyst, the amount of catalyst may be about 0.5% by weight or less, such as about 0.25% by weight or less, such as about 0.15% by weight or less of the oxygen delivery composition.

The oxygen delivery composition according to the present disclosure may also include a solvent. While any suitable solvent may be used, in one

embodiment the solvent may include at least one organic solvent. While any suitable organic solvent capable of dispersing or dissolving the components may be suitable, solvents may include: alcohols, dimethylformamide, dimethyl sulfoxide, aromatic hydrocarbons, ethers, ketones and aldehydes, acids, or a combination thereof, for example. In one embodiment, the solvent may be an aldehyde or a ketone such as acetone or methyl ethyl ketone, for example. A solvent may be selected such that the solvent remains in the oxygen delivery composition, or the solvent may be removed prior to or after curing has occurred in forming the matrix. Moreover, the oxygen delivery composition is configured to produce or deliver a volume of oxygen over a sustained period of time when exposed to a trigger. While any trigger generally known in the field may be used, in one embodiment, the trigger may be water, saline, a wound exudate, or other salt containing solutions. Nonetheless, other triggers may be selected that are able to diffuse through the matrix to contact the oxygen producing compound in order to cause the oxygen producing compound to degrade into free oxygen.

Furthermore, the present disclosure has also found that an oxygen delivery composition according to the present disclosure may be used, and may maintain an ability to produce oxygen, at low temperatures. For instance, the oxygen delivery composition may be effective even at temperatures as low as -28°C, so as to be effective in cold weather environments. In such an embodiment, the oxygen delivery composition may be the same as any of the embodiments discussed above, however, the trigger may be altered in order to lower the freezing point of the trigger.

For instance, referring to Figs. 5 and 6, oxygen generating compositions according to the present disclosure were tested utilizing a standard trigger, as discussed above, as the control. Additionally, a trigger, namely, water in this example, was modified with percentages by weight of the total weight of the trigger, of calcium chloride and ethylene glycol. As shown in the figures, the modified triggers were effective in beginning the decomposition of the solid oxygen producing compound with marginal tradeoffs in terms of oxygen producing rates and volumes. In these examples, it is predicted that a trigger that includes about 90% water and about 10% calcium chloride would be able to operate at

approximately 5.6°C below freezing and only shows a decrease of about 18%-20% in the volume and/or rate of oxygen produced, as compared to a trigger that is 100% water. Similarly, based on these examples, it is predicted that a trigger that is about 20% ethylene glycol and about 80% water would be able to operate at approximately 7.5°C below freezing and only shows a decrease of about 20% in the volume and/or rate of oxygen produced as compared to a trigger that is 100% water. Moreover, Fig. 6 illustrates that a composition according to the present disclosure may have a trigger modified with ethylene glycol and produce oxygen over a sustained period of time even at an estimated freezing point depression of 29.85°C. Furthermore, Fig. 7 illustrates that even when utilizing a full scale model, the efficiency and production rates of the present disclosure are maintained.

Particularly, 100 grams of an oxygen delivery composition according to the present disclosure produced roughly 3L of oxygen over 72 hours, in duplicate.

The present disclosure also contemplates a container for housing the oxygen delivery composition during storage and/or providing a container wherein the oxygen delivery composition is introduced to the trigger. The storage container may be the same as the reaction container, or it may be a separate container. For instance, in one embodiment, the oxygen delivery composition is placed in a container formed from a non-reactive material, such as polyethylene, after the oxygen delivery composition has been formed. The container may be a bottle, as generally shown in Fig. 9, or a packet, as generally shown in Fig. 10, or any other, packet, bottle, jug, jar, cup, bag, or other container that may generally be known in the art. The oxygen delivery composition may remain in the storage container during introduction to the trigger, or may be transferred or placed into a separate container for generating and/or delivering oxygen just prior to introduction to the trigger.

Additionally or alternatively, the container 200 may be a gauze or substrate, as shown in Fig. 8, such as a wound dressing, known in the art. For ease and clarity,“gauze” will be used refer to all such substrates as discussed above in regards to a wound dressing. In such an embodiment the gauze may have the oxygen delivery composition 212 printed on the gauze after the oxygen delivery composition 212 has been formed. For instance, the oxygen delivery composition 212 may be formed as discussed above, and is then printed or otherwise impregnated into the gauze. In such an embodiment, the gauze may then be applied to a wound, and the wound exudate may serve as the trigger, releasing oxygen to the wound. The staggered configuration of the oxygen delivery composition 212 on the gauze allows oxygen, or other solute, to diffuse between the oxygen delivery composition 212. Further, in an embodiment, the various dots of oxygen delivery composition 212 may contain varying amounts of the oxygen producing compound, allowing for further tuning of the oxygen delivery rate. Of course, other shapes may be printed or otherwise impregnated on the gauze as known in the art, such as an“x” or square shape, to name a few, or a different pattern other than the shown staggered configuration of circles, may be used, or a combination thereof, to further modify the oxygen delivery rate or amount of oxygen generating composition on the gauze. Further, in an embodiment that utilizes gauze container applied directly to a wound, the oxygen delivery

composition may contain an amount of about 5% by weight or less of the oxygen producing composition, as discussed above.

Referring to Fig. 9, in an embodiment where the container 200 may be a bottle, or any other suitable container, such as a cup, balloon/balloon bag, jar, jug or the like, the oxygen delivery composition 212 may be stored in the container or may be placed there shortly before contact with the trigger, but not for so long that the oxygen generating composition may be contacted with atmospheric humidity.

In an embodiment where the oxygen delivery composition is stored in the container, the container may have, or be configured to use, seals or sealing type devices to maintain the oxygen delivery composition in an unreacted state, such as by eliminating or minimizing exposure to atmospheric humidity prior to the introduction of the trigger.

Regardless, in an embodiment that utilizes a bottle type container 200 such as Fig. 9, a trigger (not shown) may be added to the bottle before or after introduction of the oxygen delivery composition. The trigger (not shown) may be added via a syringe 202 which utilizes a port 204 at one end of the container 200. The port may be configured to only allow introduction of a substance when an appropriate syringe or device is connected, or may be a one-way port, or any other port as generally known in the art. Generally, an adapter, such as a general adapter 210, or any other adapter as known in the art may be used to supply one or more ports to the container 200. Alternatively, the ports may be formed as part of the container 200 itself. The container 200 may also have an oxygen port 206, which may be the same or different than the port 204 used for the trigger, or which may be located on the same or a different adapter 210 as the port 204, or which may be located directly on the container 200. The oxygen port 206 may have appropriate tubing, hoses, connections, or the like, generally referred to as a delivery configuration 208, attached thereto in order to allow oxygen generated in the container to be delivered to a wound or tissue of a mammal. In one

embodiment, the container 200 and or the delivery configuration 208, may include a filter (not shown) as generally known in the art. Alternatively, a container may have a configuration such as that generally shown in Fig. 10. In such a configuration, the container 300 may be a packet 302. The packet may have at least two compartments 304 separated by a releasable seal 306. Of course, as discussed above, the packet may only have a single compartment for storing the oxygen delivery composition, and the oxygen delivery composition may be emptied from the packet into a separate container for introduction to the trigger, in one embodiment. However, in an embodiment such as Fig. 10, one of the compartments 304 may include a filter or filtration membrane 308, such that a delivery configuration, which may include ports, hoses, tubes and the like and which may be the same or different than discussed above, may be connected to the filtration membrane 308 for delivery of generated oxygen to a tissue of a mammal. When it is desired to generate and deliver oxygen, the releasable seal 306 may be broken, such as, in one example, by squeezing one of the compartments 304 that may contain a liquid trigger. In such an embodiment, the liquid trigger may breach the releasable seal 306 and contact the oxygen delivery composition located in the other compartment 304. In such a manner, the container may be configured to store or contain the oxygen delivery composition and the trigger, as well as provide a container for the generation of oxygen, and delivery of the oxygen to a tissue of a mammal, providing a compact and simple carrier for the generation of oxygen.

Moreover, regardless of the reaction used or the final form of the oxygen delivery composition, the oxygen delivery composition may be utilized in

conjunction with a wound dressing or cover 400, such as generally illustrated in Fig. 11. For instance, a wound dressing 400 according to the present disclosure may generally include a substrate 402. In one embodiment, the substrate 402 may be a material or base material, woven or nonwoven material, film, elastic, self- adhesive material, wrap, cover, combinations thereof, as well as other wound dressing substrates known in the art. Regardless of the substrate 402 used, a wound dressing 400 may be a wound dressing that is able to serve as a tourniquet or compression bandage, or otherwise stabilize an injured limb or other tissue of a mammal.

In a further embodiment, the substrate 402 may include a polymer 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, elastomers, polyethylene polymers, polypropylene polymers, polyethylene and polypropylene copolymers, polyurethanes, as well as other polymers that are known in the art. Particularly, a polyacrylic acid may be included in the substrate in order to improve water absorbance in the final wound dressing. Similarly, an elastomer such as polybutadiene for example, may be included with the substrate to provide greater elasticity to the oxygen delivery composition, or may be included in an outer layer provides greater barrier properties or helps to maintain the generated oxygen in or around the wound. Thus, the wound dressing 400 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 400.

In one embodiment, the substrate 402 can be absorbent and can also have elastic components or properties that provide enhanced compression benefits by applying pressure to immobilize the wound site and minimize minor bleeding. The substrate 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 various wound dressing components that can be used in conjunction with the wound dressing are described in Table 1 below.

Table 1 : Description and Function of Multilayer Wound Dressing

The outer protective layer can provide tensile strength and tear and puncture resistance with adjustable coverage area. The wound dressing 400 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 the generated oxygen from the oxygen delivery composition. The outer protective layer 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 layer of the wound dressing 400, which is the layer of the wound dressing positioned adjacent the wound site may provide air and water vapor transport for wound care. Additionally, the skin contacting layer may also deliver comfort and thermal management while providing absorbency to control minor bleeding and management of wound exudate. Additionally, the skin contacting layer can be tailored such that it is non-stick to skin or mucosa.

The substrate 402 may have one or more layers, such as an inner and outer layer, wherein the configuration allows the wound dressing 400 to provide a soft, lint-free, non-irritating feel against skin and mucosa. Further, it is to be understood that any layers used as part of the wound dressing 400 can be impregnated with nanoparticle metal (e.g., nanoparticle silver) which can provide for protection against microbial contamination.

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 antimicrobials, hemostatic agents, toxin sequestration agents, pain medication, debridement agents, or a combination thereof.

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.

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, 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.

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 sl-

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.

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.

Regardless of the exact configuration of the wound dressing 400 or components included, the wound dressing may be integrated with or may be able to be used with an oxygen delivery composition of the present disclosure for instance, referring again to Fig. 11 , a container 404 may be attached or included in the wound dressing 400 for delivery of oxygen to a tissue of a mammal. Of course, the wound dressing 400 does not need to be connected to the container or have a dedicated area for the container, and may simply have an opening or lining which supports the delivery of oxygen using a container as described herein.

Further, the present disclosure contemplates the use of the oxygen delivery composition in treating an injured limb. In one example of the use of this wound dressing of the present disclosure, a severe limb injury (e.g., avulsion, amputation, laceration, compound fracture, severe burn, degloving, and/or severe abrasion) occurs, for example, an injury requiring the use of a tourniquet, occurs.

Particularly, by utilizing an oxygen delivery composition according to the present disclosure, many of the negative effects associated with using a tourniquet may be counteracted or lessened. A user (e.g., corpsman, medic, first responder, etc.) can remove an oxygen delivery composition and/or a container within which the oxygen delivery composition is disposed, and introduce a trigger to the oxygen delivery composition. In one embodiment, a trigger is introduced separately from the compound. In such an embodiment, a user may place a trigger, such as a water or saline trigger, and an oxygen delivery composition into a container, either together or one at a time, and attach any necessary hosing, tubing and ports. A container according the present disclosure may then be configured to provide oxygen to a wound or tissue of a mammal, in this example, through the use of a hose or tubing attached to, or integrated with, the container as discussed above. Particularly, a distal end of the hose or tubing (e.g., the end of the hose or tubing furthest from the container) may be configured to remain continuously open, or may have a valve or closure, such that the distal end may be placed adjacent to a wound or injured tissue and used to deliver oxygen to the wound or injured tissue.

In a further embodiment, a user may introduce a wound dressing as known in the art, or wound dressing that may be used to house a container such as shown in Fig. 11 , to an injured tissue, such as by applying the wound dressing over or around the wound or injured tissue. A distal end of the hose or tubing may then be placed under all or a portion of the wound dressing, such as a portion of the wound dressing adjacent to a wound or injured tissue in one example, to provide the generated oxygen to the wound or tissue. Of course, a user may first place the distal end of the hose or tube, and may then cover both the wound or injured tissue and the distal end of the hose or tube with a wound dressing. Thus, generated oxygen may be provided to a wound or tissue while the wound dressing also provides an additional benefit or benefits, such as pressure and/or protection from microbes, as discussed above.

In a further embodiment, a user may remove an oxygen delivery

composition according to the present disclosure that includes an embodiment wherein the oxygen delivery composition is disposed or impregnated on a gauze carrier. In such an embodiment, the gauze may be applied to a wound or injured tissue, and a wound exudate may serve as the trigger. Additionally, in an

embodiment, a user may then apply a wound dressing over the gauze.

The embodiments of the invention described above are intended to be exemplary only. 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.

Claims

WHAT IS CLAIMED IS:

1. An oxygen delivery composition for delivering oxygen to a tissue of a

mammal comprising:

a silicone;

a solid oxygen producing compound; and

a hydrophilic polymeric additive;

wherein the oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 24 hours when contacted by a trigger.

2. The oxygen delivery composition of claim 1 , wherein the silicone is present in the oxygen delivery composition in an amount of at least about 30% by weight of the oxygen delivery composition, the solid oxygen producing compound is present in the oxygen delivery composition in an amount of at least about 25% by weight of the oxygen delivery composition, and/or the hydrophilic polymeric additive is present in the oxygen delivery composition in an amount of at least about 10% by weight of the oxygen delivery composition.

3. The oxygen delivery composition of claim 1 or 2, wherein the hydrophilic polymeric additive comprises a polyethylene glycol.

4. The oxygen delivery composition of any of the preceding claims, wherein the silicone comprises a polydimethylsiloxane.

5. The oxygen delivery composition of any of the preceding claims, wherein the solid oxygen producing compound comprises a sodium percarbonate.

6. The oxygen delivery composition of any of the preceding claims, wherein the silicone and the hydrophilic polymeric additive are present in the oxygen delivery composition in a ratio of silicone to hydrophilic polymeric additive that is from about 5: 1 to about 1 :1.

7. The oxygen delivery composition of any of the preceding claims, wherein the trigger is water, saline, or a wound exudate.

8. The oxygen delivery composition of any of the preceding claims, wherein the trigger is configured to produce oxygen at low temperatures.

9. The oxygen delivery composition of any of the preceding claims, wherein the oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 72 hours when contacted by the trigger.

10. A container for delivering oxygen to a tissue of a mammal comprising: an oxygen delivery composition located in or on the container comprising: a silicone;

a solid oxygen producing compound; and

a hydrophilic polymeric additive;

11. The container of claim 10, wherein the container is configured to maintain the oxygen delivery composition separate from the trigger until the trigger is introduced to the oxygen delivery composition.

12. The container of claim 10 or 11 , wherein the container comprises a first compartment and a second compartment, wherein the oxygen delivery composition is located in the first compartment and the trigger is located in the second compartment.

13. The container of claim 12, wherein the first compartment and the second compartment are separated by a releasable seal, wherein the first compartment and the second compartment form a combined third compartment when the seal is released.

14. The container of one of claims claim 10-13, wherein the container has at least one opening for introducing a trigger to the oxygen delivery

composition.

15. The container of one of claims claim 10-14, wherein the container contains at least one opening for releasing oxygen from the container.

16. The container of claim 10, wherein the container is a gauze.

17. The container of claim 16, wherein the oxygen delivery composition is

printed on or impregnated into the gauze.

18. The container of one of claims claim 10-17, wherein the oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 72 hours when contacted by the trigger.

19. A method of delivering oxygen to a tissue of a mammal, the method comprising:

forming an oxygen delivery composition,

the oxygen delivery composition comprising,

a silicone;

a solid oxygen producing compound; and

a hydrogel; and

contacting the oxygen delivery composition with a trigger;

wherein the oxygen delivery composition is configured to produce at least 5 milliliters of oxygen per gram of the oxygen delivery composition over a period of at least 24 hours after being contacted by a trigger.

20. The method of claim 19, further comprising storing the oxygen delivery composition in or on a container for at least one day prior to contacting the oxygen delivery composition with a trigger.