Rhamnolipids for standard of care wound healing

Abstract

The technology presented herein, in general, relates to the use of biosurfactants, such as rhamnolipids, for treating wounds. More particularly, the present technology is directed to a composition comprising a mixture of particular rhamnolipids in combination with Standard of Care medical devices and therapies for use in eliminating, reducing, or controlling wound infection.

Description

Attorney Docket No. 68680W001RHAMNOLIPIDS FOR STANDARD OF CARE WOUND HEALINGCROSS-REFERENCE TO RELATED APPLICATIONSThis application claims priority to United States Provisional Application No. 63 / 726724, filed December 2, 2024. The entire contents of this provisional application are hereby incorporated by reference.FIELD OF THE INVENTION

[0001] The present technology, in general, relates to the use of biosurfactants, such as rhamnolipids, for improving the standard of care for treating and healing wounds. More particularly, the present technology relates to methods for treating wounds by applying to the wound a composition comprising a mixture of particular rhamnolipids in combination with standard of care wound treatments, wherein application of the composition improves wound healing.BACKGROUND OF THE INVENTION

[0002] The wound-healing process consists of a progression through a number of highly integrated and overlapping phases, including: hemostasis (e.g. vascular constriction, platelet aggregation, degranulation, and fibrin formation (thrombus)); inflammation (e.g., neutrophil infiltration, monocyte infiltration and differentiation to macrophage, and lymphocyte infiltration); proliferation (e.g., re-epithelialization, angiogenesis, collagen synthesis, and ECM formation); and tissue remodeling or resolution (e.g., collagen remodeling, and vascular maturation and regression).Attorney Docket No. 68680W001

[0003] These phases, and their associated biophysiological functions, must occur in the proper sequence, at specific times and durations. Optimal wound healing in adult humans generally involves at least the following the events: (1 ) rapid hemostasis; (2) appropriate inflammation; (3) mesenchymal cell differentiation, proliferation, and migration to the wound site; (4) suitable angiogenesis; (5) prompt re-epithelialization (regrowth of epithelial tissue over the wound surface); and (6) proper synthesis, crosslinking, and alignment of collagen to provide strength to the healing tissue.

[0004] Current Standards of Care can often fail to fully improve and / or treat wound(s) and frequently have little or no impact on improving the healing process. In addition to the lack of improving the overall healing process, current Standards of Care often fail to have any impact or address in any way the potential for or existence of wound infection.

[0005] There is therefore an ongoing need for improved Standard of Care wound healing interventions and related therapies to reduce and / or control infection. There is also a need for new wound healing compositions in combination with medical devices, and related methods of use for advanced wound care intervention, that accelerate wound closure and / or reduce microbial count and / or penetrate any established biofilm in or on a wound and eliminate any concomitant infection

[0006] There has also been a recent trend to formulate products with ingredients that are based on renewable raw materials. Such ingredients are considered “green” or “natural”, since they are derived from renewable and / or sustainable sources. As a result, they are more environmentally friendly than ingredients derived from fossil fuels or other non-renewable sources. An ingredient having a high Biorenewable Carbon Index (BCI),Attorney Docket No. 68680W001 such as greater than 80, indicates that the ingredient contains carbons that are derived primarily from plant, animal or marine-based sources.

[0007] Rhamnolipids are interface-active glycolipids produced by various bacterial species and are an example of a “green” ingredient, since they can be prepared by means of fermentation based on renewable raw materials. It would be desirable to provide compositions that include active ingredients derived from renewable sources, such as rhamnolipids, that can be used to facilitate the treatment and healing of wounds and improve current Standards of Care wound healing interventions and therapies. Providing wound healing / treatment compositions comprising rhamnolipid would satisfy sustainability goals of ensuring sustainable consumption through the use of bio-based antibacterial materials.

[0008] Applicants have determined that particular mixtures of rhamnolipid salts, in combination with medical devices and wound healing therapies, can meet the above objectives while also advancing UN Sustainability Goals (“SDG”). The rhamnolipid salt mixtures of the present technology contribute to better health and well-being by delivering equal or better efficacy in the treatment of wounds. The rhamnolipid salt mixtures are advantageously bio-based, renewably sourced actives obtained from a bacterial fermentation process that generates biodegradable waste products that are less impactful on the environment. These benefits further SDG #3 (Good Health and Well-being) and SDG #12 (Responsible Consumption and Production).Attorney Docket No. 68680W001SUMMARY OF THE INVENTION

[0009] One aspect of the present technology is directed to particular rhamnolipid compositions used in combination with various Standard of Care interventions and therapies and methods for improving the wound healing process through accelerated wound closure and / or the improved reduction in microbial count and inhibition and / or removal of pathogenic biofilms (e.g., prevention, control or elimination of infection). The methods of the present disclosure comprise applying a composition to a wound, wherein the composition comprises at least one rhamnolipid, and wherein application of the composition improves wound healing / closure and / or the inhibition and / or removal of pathogenic biofilms during healing and closure of the wound. In some embodiments, the wound being treated is an acute wound, including an incision, a laceration, an abrasion, an avulsion, a puncture, a penetration, or a burn wound. In other embodiments, the composition applied to the wound comprises mono-rhamnolipid, di-rhamnolipid, or a combination of both mono- and di-rhamnolipids. In further embodiments, in response to the application of the rhamnolipid compositions presented herein the rate or time to wound closure is accelerated, together with the prevention, treatment, or removal of associated pathogenic biofilms.

[0010] In another aspect, the present technology is directed to a rhamnolipid composition in combination with Standard of Care medical devices and therapies for use in eliminating, reducing, or controlling wound infection, wherein the composition comprises a mixture of mono-rhamnolipids and di-rhamnolipids having a mono- rhamnolipids:di-rhamnolipids weight ratio of about 40:60 to about 60:40, preferably about 40:60 to about 48:52. In addition, the rhamnolipid composition comprises, based on theAttorney Docket No. 68680W001 total weight of rhamnolipids present in the composition: an amount of 010-010 monorhamnolipid of about 29% to about 40% by weight, preferably 29% to about 37% by weight; an amount of C10-C10 di-rhamnolipid of about 35% to about 50% by weight, preferably about 35% to about 45%; an amount of 08-010 mono-rhamnolipid of about 2% to about 5% by weight; an amount of 08-010 di-rhamnolipid of about 2% to about 5% by weight; an amount of 010-012 mono-rhamnolipid of about 2% to about 6% by weight; and an amount of 010-012 di-rhamnolipid of about 8% to about 14% by weight. The composition further comprises at least one acceptable carrier, and optionally one or more additives, in an amount to total 100% by weight of the composition.DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] While the present technology will be described in connection with one or more preferred embodiments, it will be understood by those skilled in the art that the technology is not limited to only those particular embodiments. To the contrary, the presently described technology includes all alternatives, modifications, and equivalents as may be included within the spirit and scope of the appended claims.

[0012] Generally, the present disclosure is directed to compositions in combination with Standard of Care wound healing medical devices and therapies, and methods for treating a wound, including eliminating and controlling pathogenic infection (e.g., S. aureus, P. aeruginosa, C. albicans, E. coli, S. pyogenes, and E. faecal is). The methods disclosed herein comprise applying a composition to a wound, wherein the composition comprises at least one rhamnolipid, and wherein application of the composition to the wound improves wound healing and / or the inhibition and / or removal of pathogenic biofilms.Attorney Docket No. 68680W001Wounds treated herein include, for example, acute wounds including incisions, lacerations, abrasions, avulsions, punctures, penetrations, or burns.

[0013] As defined herein, a “rhamnolipid” is a glycolipid that has a lipid portion that includes one or more, typically linear, saturated or unsaturated B-hydroxy-carboxylic acid moieties and a saccharide portion of one or two units of rhamnose.

[0014] The saccharide portion and the lipid portion are linked via a B-glycosidic bond between the 1 -OH group of a rhamnose moiety of the saccharide portion and the 3-OH group of a B-hydroxy-carboxylic acid of the lipid portion. Thus, the carboxylic acid of one carboxylic acid moiety defines the end of the rhamnolipid. Where more than one rhamnose-moiety is included in a rhamnolipid, each of the rhamnose moieties not linked to the lipid portion is linked to another rhamnose moiety via a 1 ,4B-glycosidic bond. In embodiments where two or more B-hydroxy-carboxylic acids are present in a rhamnolipid, the B-hydroxy-carboxylic acid moieties are selected independently from each other. B- hydroxy carboxylic acid moieties may in some embodiments be identical. In some embodiments, they are different from each other.

[0015] The present technology generally relates to a wound care / treatment composition that comprises a particular mixture of rhamnolipids in their salt form. The rhamnolipids may have the following structure (I):Attorney Docket No. 68680W001In this formula, R9is a hydrogen atom (H) or an aliphatic group that has a main chain of one to about 46, such as one to about 42, one to about 40, one to about 38, one to about 36, one to about 34, one to about 30, one to about 28, including e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 15, 16, 17, 18, 19, 20, 21 , 22, 23, 24, 25, 26, 27 or 28 carbon atoms and one to about three, including two, oxygen atoms. In some embodiments, the main chain of the respective aliphatic group carries a terminal carboxylic acid group and / or an internal ester group. As an illustrative example in this regard, R9may be of the formula - CH(R5)— -CH2- COOR6. In these illustrative moieties, R5may be an aliphatic moiety with a main chain that has a length from 1 to about 19, such as from 1 to about 17, from 1 to about 15, from 1 to about 13, about 2 to about 13, about 3 to about 13 or about 4 to about 13, including e.g. 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 or 12 carbon atoms. R4in formula (I) is a hydrogen atom (H), or a rhamnopyranosyl moiety. R6is a hydrogen atom.

[0016] The term "aliphatic" means, unless otherwise stated, a straight or branched hydrocarbon chain, which may be saturated or mono- or poly-unsaturated and include heteroatoms. The term "heteroatom" as used herein means an atom of any element other than carbon or hydrogen. Herein, an unsaturated aliphatic group contains one or moreAttorney Docket No. 68680W001 double bonds (alkenyl moieties). The branches of the hydrocarbon chain may include linear chains as well as non-aromatic cyclic elements. The hydrocarbon chain, which may, unless otherwise stated, be of any length, and contain any number of branches. Typically, the hydrocarbon (main) chain includes 1 to about 5, to about 10, to about 15 or to about 20 carbon atoms. Examples of alkenyl moieties are straight-chain or branched hydrocarbon moieties that contain one or more double bonds. Alkenyl moieties generally contain about two to about twenty carbon atoms and one or more, for instance two, double bonds, such as about two to about ten carbon atoms, and one double bond. Examples of alkyl groups are methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, the n isomers of these radicals, isopropyl, isobutyl, isopentyl, sec-butyl, tert-butyl, neopentyl, 3,3-dimethylbutyl. Both the main chain as well as the branches may furthermore contain heteroatoms as for instance N, O, S, Se or Si or a carbon atom may be replaced by one of these heteroatoms. An aliphatic moiety may be substituted or unsubstituted with one or more functional groups. Substituents may be any functional group, as for example, but not limited to, amino, amido, carbonyl, carboxyl, hydroxyl, nitro, thio and sulfonyl.

[0017] In a more particular embodiment, the rhamnolipid salts in said structure have the structure (II):Attorney Docket No. 68680W001wherein x is 1 or 2, y is 4, 6 or 8, z is 4, 6, or 8, and M is H, or a metal, such as alkali metals Li, Na, or K, alkali earth metals Mg or Ca, or transition metals Mn, Fe, Cu, or Zn. In the cases of the alkali earth and transition metals, multiple rhamnolipid salt moieties may associate with each metal.

[0018] The mixture of rhamnolipids preferably comprises mono (where x=1 ) and di (where x=2) rhamnolipids where y and z are 6 and M is H or Na. The mono-rhamnolipid may be referred to as Rha-C10-C10, with a formula of C26H48O9. The IUPAC Name is 3- [3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxydecanoyloxy]decanoic acid. The di-rhamnolipid may be referred to as RhaRha-C10-C10, with a formula of C32H58O13. The IUPAC name is 3-[3-[ 4, 5-dihydroxy-6-methyl-3-(3,4,5-trihydroxy-6- methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid. In general, the mixture of rhamnolipids disclosed herein comprises various types of mono and di rhamnolipids and the mixture specifically encompasses all possible combinations of mono and di rhamnolipids as disclosed herein. Further, unless otherwise stated, an amount of an individual mono or di-rhamnolipid as disclosed herein means that the respective mono orAttorney Docket No. 68680W001 di-rhamnolipid can be present in the mixture of rhamnolipids in the indicated amount, and the mixture of rhamnolipids disclosed herein specifically includes all possible combinations of amounts of mono and di-rhamnolipids as disclosed herein. Generally preferred mixtures of rhamnolipids are SEP-RM rhamnolipid compositions as described below.

[0019] Rha-C10-C10 may be present in the mixture in an amount of about 29% to about 40%, alternatively about 30% to about 40%, alternatively about 29% to about 37%, alternatively about 35% to about 37% by weight based on the total weight of rhamnolipids. RhaRha-C10-C10 may be present in the mixture in an amount of about 35% to about 50%, alternatively about 35% to about 45%, alternatively about 36% to about 40%, alternatively about 36% to about 38% by weight based on the total weight of rhamnolipids.

[0020] In addition to Rha-C10-C10 and RhaRha-C10-C10, the mixture of rhamnolipids may comprise RhaRha-C10-C12 in an amount of about 8% to about 14%, alternatively about 9% to about 12%, alternatively about 10% to about 12.5% by weight based on the total weight of rhamnolipids, and Rha-C10-C12 in an amount of about 2% to about 6% by weight, alternatively about 2% to about 5%, alternatively about 3.5% to about 5% by weight based on the total weight of rhamnolipids. The mixture of rhamnolipids may also comprise RhaRha-C10-C12:1 in an amount of about 2% to about 5% by weight, alternatively about 3% to about 5% by weight, based on the total weight of rhamnolipids, an amount of RhaRha-C8-C10 in the range of about 2% to about 5% by weight, alternatively about 2% to about 4% by weight, based on the total weight of rhamnolipids, and an amount of Rha-C8-C10 in the range of about 2% to about 5% by weight, alternatively about 2% to about 4% by weight, based on the total weight of rhamnolipids.Attorney Docket No. 68680W001The mixture of rhamnolipids may also comprise Rha-Rha 012-012 in an amount of about 0.1 % to about 0.5% by weight, alternatively about 0.2% to about 0.4% by weight, alternatively about 0.2% to about 0.3% by weight, alternatively about 0.25% to about 0.3% by weight, based on the total weight of rhamnolipids present in the composition.

[0021] The mixture of rhamnolipids may comprise a mixture of mono-rhamnolipids and di-rhamnolipids. The mono-rhamnolipids may be present in an amount of about 40% to about 50%, preferably about 42% to about 48%, based on the total weight of rhamnolipids in the mixture. The di-rhamnolipids may be present in an amount of about 50% to about 60% by weight, preferably about 52% to about 58%, based on the total weight of rhamnolipids. The ratio of mono-rhamnolipids:di-rhamnolipids can be from about 40:60 to about 60:40, alternatively about 40:60 to about 50:50, alternatively about 40:60 to about 48:52, preferably about 42:58 to about 48:52.

[0022] The terms “active”, “% active”, and “% active weight” refer to the amount of the active ingredient without regard to the amount of water or other solvent that may be present with the ingredient.

[0023] As used herein, “effective amount” refers to an amount of an active ingredient or composition that, when administered to a wound, is capable of accelerating or otherwise facilitating the healing process, including the inhibition of biofilm formation during wound closure. The actual amount may vary depending on a number of factors, including, but not limited to, the severity of the wound, the age and health status of the subject, and the form of administration.

[0024] The mono-rhamnolipid may comprise one or more mono-rhamnolipid-mono- lipidic congeners, including for example: Rha-C8:2; Rha-C8; Rha-C10; Rha-C12:2; Rha-Attorney Docket No. 68680W001012; Rha-C14:2; or combinations thereof. The mono-rhamnolipid may also comprise one or more mono-rhamnolipid-di-lipidic congeners, including for example: Rha-C8-C8; Rha- C8-C10:1 ; Rha-C10:1 -C8; Rha-C8-C10; Rha-C10-C8; Rha-C10-C10:1 ; Rha-C10-C10; Rha-C8-C12; Rha-C12-C8; Rha-C10-C12:1 ; Rha-C12:1 -010; Rha-C10-12; Rha-012- C10; Rha-C10-014:1 ; Rha-C12-C12:1 ; Rha-C10-C14; Rha-C12-C12; Rha-C12-C14; Rha-C14-C14; Rha-C14-C16; Rha-C16-C16; Rha-C10-C10-CH3; Decenoyl-Rha-010- 010; or combinations thereof.

[0025] The di-rhamnolipid may comprise one or more di-rhamnolipid-mono-lipidic congeners, including for example: Rha-Rha-C8; Rha-Rha-C10; Rha-Rha-C12:1 ; Rha- Rha-C12; Rha-Rha-C14; or combinations thereof. The di-rhamnolipid may also comprise one or more di-rhamnolipid-di-lipidic congeners, including for example: Rha-Rha-C8-C8; Rha-Rha-C8-C10; Rha-Rha-C10-C8; Rha-Rha-C10-010:1 ; Rha-Rha-C10-010; Rha- Rha-C8-C12:1 ; Rha-Rha-C12:1 -08; Rha-Rha-C10-012:1 ; Rha-Rha-C12:1 -C10; Rha- Rha-C10-C12; Rha-Rha-C12-010; Rha-Rha-C10-C14:1 ; Rha-Rha-C12-C12:1 ; Rha- Rha-C12:1 -C12; Rha-Rha-C12-C12; Rha-Rha-C12-C14; Rha-Rha-C14-C12; Rha-Rha- 014-014; Rha-Rha-C14-C16; Rha-Rha-C16-C14; Rha-Rha-C16-016; Rha-Rha-014- C14-C14; Rha-Rha-C10-C10-CH3; Decenoyl-Rha-Rha-C10-C10; or combinations thereof.

[0026] In one aspect, the present technology provides a wound care composition, and methods of use, wherein the composition comprises a mixture of rhamnolipids in an amount of 0.1 % to 99% by weight, based on the total weight of the composition, wherein the mixture of rhamnolipids comprises mono-rhamnolipids and di-rhamnolipids in a weight ratio 40:60 to 60:40 mono-rhamnolipids:di-rhamnolipids, alternatively 40:60 to 50:50Attorney Docket No. 68680W001 mono-rhamnolipids:di-rhamnolipids, alternatively about 40:60 to about 48:52, alternatively 42:58 to 48:52 mono-rhamnolipids:di-rhamnolipids.

[0027] A further aspect of the present technology provides a method for treating a wound comprising administering to the wound an effective amount of a composition comprising a mixture of rhamnolipids, thereby accelerating or otherwise facilitating healing, wherein the mixture of rhamnolipids comprises mono-rhamnolipids and dirhamnolipids in a weight ratio of 40:60 to 60:40 mono-rhamnolipids:di-rhamnolipids, alternatively 40:60 to 50:50 mono-rhamnolipids:di-rhamnolipids, alternatively 40:60 to 48:52 mono-rhamnolipids:di-rhamnolipids, alternatively 42:58 to 48:52 mono- rhamnolipids:di-rhamnolipids.

[0028] In some embodiments, the present technology provides a method for treating a wound, as described above, in which the mixture of rhamnolipids comprises mono- rhamnolipids and di-rhamnolipids in a weight ratio of 42:58 to 48:52, an amount of Rha- C10-C10 mono-rhamnolipid of about 29% to about 40% by weight, and an amount of RhaRha-C10-C10 di-rhamnolipid of about 35% to 50% by weight, based on the total weight of the rhamnolipids in the mixture of rhamnolipids.

[0029] The rhamnolipids may be produced from a rhamnolipid-producing microorganism that has the capacity to synthesize / produce rhamnolipids under suitable conditions. Such microorganisms include, but are not limited to, bacteria, particularly bacteria of the phyla Pseudomonadota, Actinobacteria, Fimicutes, and Proteobacteria. The rhamnolipids are naturally derived and therefore have a BCI of 100. In a particular embodiment, the rhamnolipid-producing microorganism for producing the rhamnolipids is Pseudomonas aeruginosa. Methods of culturing the rhamnolipid-producing bacteria andAttorney Docket No. 68680W001 the production of rhamnolipids from fermentation are known in the art from, for example U.S. Patent No 1 1 ,142,782 and U.S. Patent No. 10,144,943, incorporated herein by reference in their entirety. Methods of purifying the rhamnolipids are also known in the art from, for example, U.S. Patent No 9,884,883 and U.S. Patent No. 10,829,507, incorporated herein by reference in their entirety.

[0030] The mixture of rhamnolipid salts can be used alone, as the sole active ingredient in the wound care I treatment composition. When used alone, the mixture of rhamnolipids may be in the range of about 0.01 % to about 99% by active weight, based on the total weight of the composition, alternatively about 0.02% to about 25%, alternatively about 0.1 % to about 10%, alternatively about 0.2% to about 6% by active weight, based on the total weight of the composition. The mixture of rhamnolipid salts may also be used as a co-active in combination with another active ingredient, such as antibiotics, vitamins (e.g., vitamins E, A, and C), and Hyaluronic Acid. When used in combination, the mixture of rhamnolipids may be in the range of about 0.01 % to about 99% by active weight, based on the total weight of the composition, alternatively about 0.02% to about 25%, alternatively about 0.1 % to about 10%, alternatively about 0.2% to about 6% by active weight, by active weight based on the total weight of the composition. The combination of the mixture of rhamnolipid salts and another co-active ingredient may help to alleviate the irritation potential of the co-active without reducing or inhibiting its activity. Combining the mixture of rhamnolipid salts with another co-active ingredient may also allow for the reduction of the other co-active ingredient, which can also help to reduce the overall irritation potential.Attorney Docket No. 68680W001

[0031] The wound care I treatment compositions can be formulated into any treatment form commonly used for dermatological I topical applications. For example, the compositions can be in the form of an aqueous solution, suspension, cream, lotion, gel, paste, spray, cream, foam or emollient, or impregnated onto pads, wipes, bandages and / or dressings.

[0032] The wound care / treatment compositions of the present technology also include at least one carrier suitable for wound care I treatment to bring the total percentage of the composition to 100%. As will be appreciated by at least those skilled in the art, a variety of carriers, vehicles, diluents, and the like are suitable for use in the practice of the present technology. Thus, it will also be appreciated that the terms “carrier”, “vehicle”, and “diluent” are to be considered non-exhaustive and interchangeable with respect to the present technology and in describing the various formulations, applications, uses, and compositions thereof.

[0033] Water is a suitable carrier, and can be de-ionized water, hard water, soft water, distilled water, tap water or combinations thereof. Water can be used alone as the carrier, or in combination with other carriers suitable for personal care, such as for example, alcohols such as ethanol, isopropanol, or benzyl alcohol; glycols such as propylene glycol, or polyethylene glycol. Other carriers can include, but are not limited to solvents, emulsifiers, or solubilizers.

[0034] When the treatment form is a cream, gel, or paste, the wound care I treatment compositions can include, but are not limited to, vegetable gums, starches, celluloses, waxes, silicone, silica, or clays, as carrier ingredients. When the treatment form is a spray, the composition may include a propellant.Attorney Docket No. 68680W001

[0035] In addition to the rhamnolipid active and carrier, the wound care I treatment compositions of the present technology can include optional ingredients as known in the art. Such other components or additives can include, but are not limited to, surfactants, pH adjustment agents, skin conditioners, antioxidants, preservatives, fragrances, pigments, dyes, and other excipients (e.g., anesthetics such as Benzocaine, and other antibiotics, such as topical antimicrobials, as well as fibrous materials compatible with nonwoven bandages). Fibrous materials may consist of cellulose, cotton, viscose, or other materials known in the art that may be used to help obtain hemostasis or may be used in the creation of an in situ dressing.

[0036] The wound care I treatment compositions of the present technology can have pH values in the range of about 4.0 to about 8.5, alternatively, about 5.0 to about 8.0, ideally 5.5 to 7.0.

[0037] The wound care / treatment compositions of the present technology may be used by applying the composition to the wound of a subject in an amount effective to treat, and / or otherwise facilitate wound healing. “Applying” can refer to any commonly used method of application, such as, but not limited to, spreading a cream, gel, or ointment containing the wound care / treatment composition on the surface of the wound and allowing the cream, gel, or ointment to remain on the wound; spraying a liquid containing the wound care / treatment composition on the surface of the wound and, if desired, surrounding tissue (e.g., liquid, foam, cream emulsion, or fibrous); wiping the wound with a wipe impregnated with the wound care / treatment composition and allowing the composition to remain on the wound and, if desired, surrounding tissue; applying a pad or bandage impregnated with the wound care / treatment composition and allowingAttorney Docket No. 68680W001 the pad or bandage to remain on the surface of the wound and, if desired, surrounding tissue; or an aqueous or non-aqueous liquid wash intended to treat the surface of the wound and, if desired, the surrounding tissue.

[0038] Dosage forms and treatment regimens using the wound care / treatment compositions of the present technology can vary with the type and intensity of the wound. In one or more embodiments, methods of treatment in accordance with the present technology may use a one, two, three, four, or more daily dosage regime. The daily dosage regimen can continue for 1 -6 days, alternatively one, two, three, four, five, six, or more weeks according to the condition and response of the patient.

[0039] Methods of the present disclosure comprise combining a rhamnolipid-containing wound care I treatment composition with Standard of Care medical devices and therapies and applying the composition to a wound to eliminate, reduce, or control wound infection, and facilitate wound healing / closure and / or reduce the formation of pathogenic biofilms during wound closure.ITEMS OF THE INVENTIONThe invention further relates to the following items:1 A rhamnolipid composition for use in methods for facilitating wound healing / closure and / or inhibiting or reducing biofilm formation during wound closure, wherein the composition comprises a mixture of mono-rhamnolipids and di-rhamnolipids having a mono-rhamnolipids:di-rhamnolipids weight ratio of about 40:60 to about 60:40; and wherein application of the composition to a wound accelerates wound closure. The rhamnolipid composition also comprises, basedAttorney Docket No. 68680W001 on the total weight of rhamnolipids present in the composition, an amount of C10- C10 mono-rhamnolipid of about 29% to about 40% by weight, an amount of C10- C10 di-rhamnolipid of about 35% to about 50% by weight, an amount of C8-C10 mono-rhamnolipid of about 2% to about 5% by weight; an amount of C8-C10 di- rhamnolipid of about 2% to about 5% by weight; an amount of C10-C12 mono- rhamnolipid of about 2% to about 6% by weight; and an amount of C10-C12 di- rhamnolipid of about 8% to about 14% by weight. The composition also further comprises at least one acceptable carrier, and optionally one or more additives, in an amount to total 100% by weight of the composition.2. The composition of the preceding item, wherein the mixture of rhamnolipids comprises an amount of total mono rhamnolipid of about 40% to about 50% by weight, preferably about 40% to about 48% by weight, such as about 42 % to about 48% by weight, or about 43% to about 47% by weight, or about 43% to about 45% by weight, based on the total weight of rhamnolipids present in the composition.3 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of total di-rhamnolipid of about 50% to about 60% by weight, preferably about 52% to about 60% by weight, such as about 52% to about 58% by weight, or about 53% to about 57% by weight, or about 55% to about 57% by weight, based on the total weight of rhamnolipids present in the composition.4 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the mono-rhamnolipid C8-C10 congener inAttorney Docket No. 68680W001 the range of about 2% to about 4% by weight, based on the total weight of rhamnolipids present in the composition.5 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the mono-rhamnolipid C10-C10 congener in the range of about 29% to about 37% by weight, preferably about 32% to about 37% by weight, such as about 34% to about 37% by weight, or about 35% to about 37% by weight, based on the total weight of rhamnolipids present in the composition.6 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the mono-rhamnolipid C10-C12 congener in the range of about 2% to about 5% by weight, preferably about 3.5% to about 5% by weight, based on the total weight of rhamnolipids present in the composition.7 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the di-rhamnolipid C8-C10 congener in the range of about 2% to about 4% by weight, based on the total weight of rhamnolipids present in the composition.8 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the di-rhamnolipid C10-C10 congener in the range of about 35% to about 45% by weight, preferably about 36% to about 40% by weight, such as about 36% to about 38% by weight, based on the total weight of rhamnolipids present in the composition.Attorney Docket No. 68680W0019 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the di-rhamnolipid C10-C12.1 congener in the range of about 2% to about 5% by weight, preferably about 3% to about 5% by weight, such as about 3% to about 4% by weight, based on the total weight of rhamnolipids present in the composition.10 The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the di-rhamnolipid C10-C12 congener in the range of about 9% to about 12% by weight, preferably in the range of about 10% to about 12% by weight, or about 10% to about 12.5% by weight, based on the total weight of rhamnolipids present in the composition.1 1. The composition of any one of the preceding items, wherein the mixture of rhamnolipids comprises an amount of the di-rhamnolipid C12-C12 congener in the range of about 0.1 % to about 0.5% by weight, preferably about 0.2% to about 0.4% by weight, such as about 0.2% to about 0.3% by weight, or about 0.25% to about 0.3% by weight, based on the total weight of rhamnolipids present in the composition.12. The composition of any one of the preceding items, wherein the mixture of rhamnolipids is a SEP-RM Rhamnolipid composition.13. The composition of any one of the preceding items, wherein the mixture of rhamnolipids is a SEP-RM Rhamnolipid composition obtained by a solvent extraction process including a bleaching step after acidulation and before the solvent extraction.Attorney Docket No. 68680W00114. A bandage or pad impregnated with the composition of any one of the preceding items, wherein the bandage or pad improves the rate of healing of a wound and / or reduces infection of the wound.15. A patch containing the composition of any one of the preceding items 1 -13, wherein the patch is formed from a silicone-based gel.16. The patch of item 15 wherein the patch provides one or more of (i) controlled release of the composition from the patch; (ii) wound healing improvement compared to a patch without the composition; (iii) wound moisture retention; (iv) wound coverage; and (v) prevention or reduction of wound infection.17. A patch containing the composition of any one of the preceding items 1 -13, wherein the patch is formed from a hydrogel material, or wherein the patch is formed from a urethane material.18. The patch of item 18 wherein the patch provides one or more of (i) controlled release of the composition from the patch; (ii) breathability; (iii) wound moisturization; (iv) wound coverage; and (v) prevention or reduction of wound infection; and wherein the patch comprises a fibrous material or nonwoven material.19. A gel comprising the composition of any one of claims 1 -13.20. Use of the gel of item 19 for one or more of (i) wound bed preparation; (ii) prevention or reduction of wound infection; and (iii) wound moisture retention.21 . An ointment comprising the composition of any one of items 1 -13.Attorney Docket No. 68680W00122. Use of the ointment of item 21 for one or more of (i) wound bed preparation;(ii) prevention or reduction of wound infection; (iii) wound moisture retention; and (iv) film formation on or in a wound.23. A foam comprising the composition of any one of items 1 -13.24. Use of the foam of item 23 for one or more of (i) cleansing a wound; and (ii) prevention or reduction of wound infection.25. A disposable negative pressure contact pad containing or impregnated with the composition of any one of items 1 -13.26. The disposable negative pressure contact pad of item 25, wherein the disposable negative pressure contact pad comprises at least one of (i) silicone; (ii) silver;(iii) alginates; or (iv) collagen.27. A disposable foam dressing or pad containing or impregnated with the composition of any one of items 1 -13.28. Use of the disposable foam dressing or pad of item 28 for absorbing exudate and / or controlling wound infection.29. A medical device for treating a wound, wherein the medical device comprises a coating formed on at least a portion of the medical device, and the coating comprises the composition of any one of items 1 -13.30. The medical device of item 29, wherein the coating is an antimicrobial coating and / or provides lubricity to the medical device.31. A method of debriding a wound, wherein the method comprises washing the wound with a cleansing composition comprising the composition of any one of itemsAttorney Docket No. 68680W0011 -13, and / or applying a gel or ointment to the wound wherein the ointment or gel comprises the composition of any one of items 1 -13.32. The method of item 31 , wherein washing the wound accomplishes one or more of (i) penetrating and removing biofilm; (ii) removing wound debris; (iii) removing hyperkeratotic, infected, and / or nonviable tissue; and (iv) destroying and removing pathogens.33. The method of item 31 or 32, wherein the gel is a hydrogel and accomplishes one or more of (i) penetrating and moisturizing debris in the wound; (ii) penetrating and removing biofilm; and (iii) controlling wound infection.34. The method of any one of items 31 -33, wherein the ointment accomplishes one or more of (i) penetrating and moisturizing debris in the wound; (ii) forming a film on or in a wound; and (iii) controlling wound infection.EXAMPLES

[0040] The presently described technology and its advantages will be better understood by reference to the following examples. These examples are provided to describe specific embodiments of the present technology. By providing these examples, the inventors do not limit the scope and spirit of the present technology.Experimental Procedures***Test MaterialsRhamnolipid Compositions

[0041] Rhamnolipids are produced, as understood in the art, through the fermentation of rhamnolipid producing bacteria such as Pseudomonas aeruginosa. The rhamnolipidsAttorney Docket No. 68680W001 may be produced from a rhamnolipid-producing microorganism that has the capacity to synthesize / produce rhamnolipids under suitable conditions. Such microorganisms include, but are not limited to, bacteria, particularly bacteria of the phyla Pseudomonadota, Actinobacteria, Fimicutes, and Proteobacteria. The rhamnolipids are naturally derived and therefore have a BCI of 100. In a particular embodiment, the rhamnolipid-producing microorganism for producing the rhamnolipids is Pseudomonas aeruginosa. Methods of culturing the rhamnolipid-producing bacteria and the production of rhamnolipids from fermentation are known in the art from, for example U.S. Patent No 1 1 ,142,782 and U.S. Patent No. 10,144,943, incorporated herein by reference in their entirety. Methods of purifying the rhamnolipids are also known in the art from, for example, U.S. Patent No 9,884,883 and U.S. Patent No. 10,829,507, incorporated herein by reference in their entirety.

[0042] Fermentation whole broth then undergoes multiple purification steps. The specific combination of steps depends on the rhamnolipid actives and purity requirements of the target application. Certain rhamnolipid mixtures used herein are purified by a solvent extraction process. As used herein, the acronym SEP-RM refers to Solvent Extraction Purified Rhamnolipid Mixture (or composition), in accordance with the current specification.

[0043] For example, the SEP-RM Rhamnolipid compositions used herein are prepared in accordance with at least the following processing steps: (1 ) fermentation of appropriate Rhamnolipid producing bacterium; (2) biomass separation; (3) sterilization; (4) clarification (e.g. filtration); (5) acidulation; (6) bleaching; (7) washing; (8) solvent extraction; (9) neutralization and dilution; and (10) final polishing step(s). As discussedAttorney Docket No. 68680W001 below, the solvent extraction process / step is intended to yield a higher purity rhamnolipid mixture / composition for personal care applications. The additional solvent extraction steps provide a rhamnolipid composition having a lighter color and milder odor profile that are preferred for the personal care market.

[0044] At the end of fermentation, the whole broth typically contains rhamnolipids along with biomass and other by-products of fermentation. To separate the biomass solids, the broth can be centrifuged. The resulting centrifuged broth is then subjected to sterilization (e.g., high temperature sterilization), after which, the centrifuged sterilized broth is clarified by filtration to remove suspended solids.

[0045] Further purification is achieved by treating the clarified broth with acid, which converts the rhamnolipid to a water-insoluble form that settles to the bottom and separates from the bulk aqueous phase. This dense acidulated rhamnolipid is then isolated (and referred to as Acidulated, Concentrated Clarified Broth (ACCB). ACCB is then treated with bleaching agent, then water washed to remove residual bleaching agent and other water-soluble impurities. At this point, the decolorized washed ACCB is concentrated (e.g., > about 45% actives, or between about 35% to about 55% actives) and purer (e.g., > about 75% purity, or between about 65% to about 85% purity).

[0046] Solvent Extraction Process - To achieve better purity, color, and odor, the decolorized Acidulated, Concentrated Clarified Broth (ACCB) undergoes a solvent extraction process. This is generally performed by dissolving the decolorized, washed ACCB in organic solvent, preferably ethyl acetate. The rag layer that typically forms is separated from the bulk solution. Activated carbon is then added to the rhamnolipid solution in ethyl acetate for further decolorization and deodorization. The slurry is filteredAttorney Docket No. 68680W001 and the resulting solution is stripped under vacuum to remove ethyl acetate. The highly concentrated ACCB obtained as residue is then neutralized and diluted (e.g., from between about 20% to about 30% actives, preferably about 25% actives) to give crude SEP-RM. As a final polishing step, crude SEP-RM is then washed with ethyl acetate to extract the antifoam and yield the final product as optically clear SEP-RM at about 25% active and about 85% purity.Mono-Rhamnolipid:Di-Rhamnolipid Ratio and Congener Distribution

[0047] The mono-rhamnolipid:di-rhamnolipid ratio, and congener distribution for SEP- RM rhamnolipid compositions of the present disclosure can be determined using HPLC (High Performance Liquid Chromatography). As understood by the person of ordinary skill in the art, HPLC will separate rhamnolipid congeners by chain length and number of rhamnose moieties (with the more polar congeners eluting first). Fractions are collected and analyzed by mass spec to identify each peak. The congener distribution is reported as area percent (with actives being calculated relative to known standards).

[0048] The HPLC congener distribution for SEP-RM rhamnolipid compositions of the present technology may comprise mono-rhamnolipid C8-C10 congener in an amount of about 2% to about 5% by weight, di-rhamnolipid C8-C10 congener in an amount of about 2% to about 5% by weight, mono-rhamnolipid C10-C10 congener in an amount of about 29% to about 40% by weight, preferably about 35% to about 40% by weight, di- rhamnolipid C10-C10 congener in an amount of about 35% to about 50 weight, preferably about 35% to about 45% by weight, mono-rhamnolipid C10-C12 congener in an amount of about 2% to about 6% by weight, di-rhamnolipid C10-C12 congener in an amount of about 8% to about 14% by weight, with total mono-rhamnolipid congeners in an amountAttorney Docket No. 68680W001 of about 40% to about 48% by weight, and total di-rhamnolipid congeners in an amount of about 52% to about 60% by weight, based on the total weight of the congeners in the composition.

[0049] The HPLC congener distribution for an exemplary SEP-RM rhamnolipid composition of the present disclosure, is presented below:Optional Bleaching Step

[0050] The SEP-RM rhamnolipid composition provided herein can be processed either with, or without a bleaching step (occurring after acidulation, and before the solvent extraction step(s)). For the SEP-RM rhamnolipid compositions of the present disclosure, the mono-rhamnolipid:di-rhamnolipid ratio, and the associated congener distribution, areAttorney Docket No. 68680W001 unaffected by whether a bleaching step is included, or not included, in the purification process.

[0051] The mixture of rhamnolipids comprises a mixture of mono-rhamnolipids and dirhamnolipids. In some embodiments, the mono-rhamnolipids may be present in an amount of about 10% to about 90%, alternatively about 15% to about 90%, alternatively about 20% to about 90%, alternatively about 30% to about 90%, alternatively about 40% to about 90%, alternatively about 10% to about 80%, alternatively about 20% to about 80%, alternatively about 30% to about 80%, alternatively about 40% to about 80%, alternatively about 10% to about 70%, alternatively about 15% to about 70%, alternatively about 20% to about 70%, alternatively about 30% to about 70% by weight, based on the total weight of rhamnolipids in the mixture and as measured by high-performance liquid chromatography (HPLC).

[0052] In some embodiments, the mono-rhamnolipids may be present in an amount of about 10% to about 60%, alternatively about 15% to about 60%, alternatively about 20% to about 60%, alternatively about 25% to about 60%, alternatively about 30% to about 60%, alternatively about 25% to about 50%, alternatively about 10% to about 48%, alternatively about 15% to about 48%, alternatively about 20% to about 48%, alternatively about 25% to about 48%, alternatively about 30% to about 48% by weight, based on the total weight of rhamnolipids in the mixture, as determined by HPLC.

[0053] In some embodiments, the di-rhamnolipids may be present in an amount of about 10% to about 90%, alternatively about 15% to about 90%, alternatively about 20% to about 90%, alternatively about 30% to about 90%, alternatively about 40% to about 90%, alternatively about 50% to about 90%, alternatively about 10% to about 80%,Attorney Docket No. 68680W001 alternatively about 20% to about 80%, alternatively about 30% to about 80%, alternatively about 40% to about 80%, alternatively about 50% to about 80%, alternatively about 10% to about 75%, alternatively about 15% to about 75%, alternatively about 20% to about 75%, alternatively about 30% to about 75%, alternatively about 40% to about 75%, alternatively about 50% to about 75% by weight, based on the total weight of rhamnolipids in the mixture, as determined by HPLC.

[0054] In some embodiments, the di-rhamnolipids may be present in an amount of about 40% to about 70%, alternatively about 50% to about 70%, alternatively about 52% to about 90%, alternatively about 52% to about 85%, alternatively about 52% to about 80%, alternatively about 52% to about 75%, alternatively about 52% to about 70%, based on the total weight of rhamnolipids in the mixture, as determined by HPLC.

[0055] The ratio of mono-rhamnolipids:di-rhamnolipids can be from about 10:90 to about 90:10, alternatively 10:90 to about 60:40, alternatively about 15:85 to about 60:40, alternatively about 20:80 to about 60:40, alternatively about 25:75 to about 60:40, alternatively about 30:70 to about 60:40, alternatively about 10:90 to about 48:52, alternatively about 15:85 to about 48:52, alternatively about 20:80 to about 48:52, alternatively about 25:75 to about 48:52, alternatively about 30:70 to about 48:52. In preferred embodiments, the ratio of mono-rhamnolipids:di-rhamnolipids is about 25:75 to about 60:40, alternatively about 25:75 to about 50:50, or about 25:72 to about 48:52.

[0056] The mixture of rhamnolipids preferably comprises mono (where x=1 ) and di (where x=2) rhamnolipids where y and z are 6 and M is H or Na. The mono-rhamnolipid may be referred to as Rha-C10-C10, with a formula of C26H48O9. The IUPAC Name is 3- [3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxydecanoyloxy]decanoicAttorney Docket No. 68680W001 acid. The di-rhamnolipid may be referred to as RhaRha-C10-C10, with a formula of C32H58O13. The IUPAC name is 3-[3-[ 4, 5-dihydroxy-6-methyl-3-(3,4,5-trihydroxy-6- methyloxan-2-yl)oxyoxan-2-yl]oxydecanoyloxy]decanoic acid.

[0057] Rha-C10-010 may be present in the mixture in an amount of about 5% to about 85%, alternatively about 5% to about 50%, alternatively about 5% to about 38%, alternatively about 10% to about 38%, alternatively about 15% to about 38%, alternatively about 20% to about 38%, alternatively about 25% to about 37.5%, alternatively about 29% to about 37.5%, by weight based on the total weight of rhamnolipids. RhaRha-C10- C10 may be present in the mixture in an amount of about 5% to about 85%, alternatively about 10% to about 80%, alternatively about 20% to about 80%, alternatively about 30% to about 80%, alternatively about 35% to about 75%, alternatively about 35% to about 65%, alternatively about 35% to about 60%, alternatively about 35% to about 55%, alternatively about 35.5% to about 50%, alternatively about 36% to about 45%, alternatively about 40% to about 60% by weight based on the total weight of rhamnolipids.

[0058] In addition to Rha-C10-C10 and RhaRha-C10-C10, the mixture of rhamnolipids may comprise RhaRha-C10-C12 in an amount of about 3% to about 15%, alternatively about 3% to about 12%, alternatively about 3% to about 12.5% by weight based on the total weight of rhamnolipids, and Rha-C10-C12 in an amount of about 0.2% to about 6% by weight, alternatively about 0.4% to about 5% by weight based on the total weight of rhamnolipids. The mixture of rhamnolipids may also comprise RhaRha-C10-C12:1 in an amount of about 0.04% to about 4% by weight, alternatively about 0.05% to about 4% by weight, alternatively about 0.05% to about 3% by weight, based on the total weight of rhamnolipids, an amount of RhaRha-C8-C10 in the range of about 0.2% to about 5% byAttorney Docket No. 68680W001 weight, alternatively about 0.6% to about 4% by weight, based on the total weight of rhamnolipids, and an amount of Rha-C8-C10 in the range of about 0.2% to about 5% by weight, alternatively about 0.6% to about 4% by weight, based on the total weight of rhamnolipids. In some embodiments, the mixture of rhamnolipids may also comprise an amount of RhaRha-C12-C12 in the range of about 3% to about 10% by weight, based on the total weight of rhamnolipids in the mixture.

[0059] In some embodiments, the mixture of rhamnolipids comprises a mixture of mono-rhamnolipids and di-rhamnolipids in a weight ratio of mono-rhamnolipids:di- rhamnolipids in the range of about 25:75 to about 60:40, alternatively about 25:75 to about 50:50, or alternatively about 25:75 to about 45:55.

[0060] The mono-rhamnolipid may comprise one or more mono-rhamnolipid-mono- lipidic congeners, including for example: Rha-C8-:2; Rha-C8; Rha-C10; Rha-C12:2; Rha- C12; Rha-C14:2; or combinations thereof. The mono-rhamnolipid may also comprise one or more mono-rhamnolipid-di-lipidic congeners, including for example: Rha-C8-C8; Rha- C8-C10:1 ; Rha-C10:1 -C8; Rha-C8-C10; Rha-C10-C8; Rha-C10-C10:1 ; Rha-C10-C10; Rha-C8-C12; Rha-C12-C8; Rha-C10-C12:1 ; Rha-C12:1 -010; Rha-C10-12; Rha-C12- C10; Rha-C10-C14:1 ; Rha-C12-C12:1 ; Rha-C10-C14; Rha-C12-C12; Rha-C12-C14; Rha-014-014; Rha-C14-C16; Rha-C16-C16; Rha-C10-C10-CH3; Decenoyl-Rha-010- C10; or combinations thereof.

[0061] The di-rhamnolipid may comprise one or more di-rhamnolipid-mono-lipidic congeners, including for example: Rha-Rha-C8; Rha-Rha-C10; Rha-Rha-C12:1 ; Rha- Rha-C12; Rha-Rha-C14; or combinations thereof. The di-rhamnolipid may also comprise one or more di-rhamnolipid-di-lipidic congeners, including for example: Rha-Rha-C8-C8;Attorney Docket No. 68680W001Rha-Rha-C8-C10; Rha-Rha-C10-C8; Rha-Rha-010-010:1 ; Rha-Rha-C10-010; Rha- Rha-C8-C12:1 ; Rha-Rha-C12:1 -08; Rha-Rha-C10-012:1 ; Rha-Rha-C12:1 -C10; Rha- Rha-010-012; Rha-Rha-C12-C10; Rha-Rha-C10-C14:1 ; Rha-Rha-C12-C12:1 ; Rha- Rha-C12:1 -C12; Rha-Rha-C12-012; Rha-Rha-C12-014; Rha-Rha-014-012; Rha-Rha- 014-014; Rha-Rha-014-016; Rha-Rha-016-014; Rha-Rha-016-016; Rha-Rha-014- 014-014; Rha-Rha-010-010-CH3; Decenoyl-Rha-Rha-010-010; or combinations thereof.Example 1

[0062] This study determined how certain rhamnolipid compositions impacted the development and / or inhibition of biofilm during wound healing / closure.

[0063] The objective of the study was to evaluate various concentrations (e.g., 1 % and 3%) of a SEP-RM Rhamnolipid gel in an advanced wound care prototype. The animal model used was the male BKS.Cg-Dock7m + / + Lepr db / J (Jax Stock # 000642; Genotype: Homozygous genotype, Wildtype for Dock7<m>, Homozygous for Lepr<db>) diabetic mouse delayed wound healing model. The study design, using SEP-RM Rhamnolipid, is summarized below in Table 1 .Table 1 : Diabetic Mouse Wound Model Study DesignAttorney Docket No. 68680W001mg = milligram; mL = milliliter*n=3 (sacrificed during inflammatory phase, Day 3-5)** n=3 sacrificed during proliferative phase, Day 1 1 -18

[0064] As indicated in Table 1 , wound creation, on Day 0, included a skin biopsy (10 mm disc) removed from the dorsal right side of the mouse model. The study included 6 treatment groups, including: 2 x control groups (without rhamnolipid); 2 x 1 % SEP-RM rhamnolipid (dose level = 0.1 mg; dose concentration = 10 mg / mL, 1 %; and dose volume = 100 uL); and 2 x 3% SEP-RM rhamnolipid (dose level = 0.2 mg; dose concentration = 20 mg / mL, 20%; and dose volume = 100 uL). The douse route was topical (to the area of the skin biopsy), at days 0, 3, 7, 10, 14, 17, and 21 . The study end was set at 24 days.

[0065] The Control group included Control Gel Collagen (Coloplast 7690 Woun'dres Collagen Hydrogel), with ambient storage. Rhamnolipid treatment group 1 comprised 1% SEP-RM rhamnolipid in Collagen (Coloplast 7690 Woun'dres Collagen Hydrogel), withAttorney Docket No. 68680W001 ambient storage. Rhamnolipid treatment group 2 comprised 3% SEP-RM rhamnolipid in Collagen (Coloplast 7690 Woun'dres Collagen Hydrogel), with ambient storage. The wound dressing comprised 3M Tegaderm™ dressing, with ambient storage.

[0066] As indicated above, the test system included species Mus muscuus (strain = BKS.Cg-Dock7m + / + Leprdb / J). The source was Jackson Laboratories (Stock# 000642; Genotype: Homozygous genotype, Wildtype for Dock7<m>, Homozygous for Lepr<db>). The age of the animals upon arrival was 8 weeks, and before use the animals were held for a minimum of 3 days for environmental acclimation.

[0067] With respect to the environment, animal holding rooms’ environmental controls were set to maintain temperatures between 20 - 26eC (68 - 792F) with a relative humidity range of 30% - 70%. A 12-hour light / 12-hour dark cycle was maintained, except when interrupted to accommodate study procedures. Ten or greater air changes per hour were also maintained in the animal holding and procedure rooms.

[0068] With respect to diet, the test animals were provided Teklad Global 18% Protein Rodent Diet 2918 ad libitum daily. The test animals were also provided filtered tap water during the acclimation period and Innovive bottled water throughout the study period, ad libitum.

[0069] Light anesthesia inhalant isoflurane on O2 (1 - 4%, to effect) was used to facilitate wound creation, and for treatments, wound assessments, wound measurements, photography, and reapplication of dressings. Isoflurane overdose or carbon dioxide asphyxiation was used, to effect, for terminal tissue collections.Attorney Docket No. 68680W001

[0070] All animals had a wound created on Day 0 while anesthetized, and after received analgesics. With respect to pre-wound care, all test animals had their dorsum shaved prior to study start. All animals recieved a subcutaneous injection of Buprenorphine-SR analgesia (1.0 mg / kg) on Day 0, ~ 1 hour prior to wounding, and an additional dose 48-72 hours later, if needed.

[0071] With respect to wound creation, sterile techniques were used. The test animals were lightly anesthetized using isoflurane on O2 (1 - 4%, to effect) and placed on their abdomen. Using sterile, disposable skin biopsy punches a 10 mm disc skin biopsy was removed from the dorsal right side of each test animal. A 3D Printed biofilm (S. aureus) was placed in the wounds of animals in groups 2A and 3A only. The wound was covered with Tegaderm™ and the biofilm was allowed to incorporate into the wound until treatment initiation (Day 3). From Day 0 until study conclusion all wounds were covered with a Tegaderm™ dressing as outlined above. Tegaderm™ was left on for the duration of the study.

[0072] Bioburden was assessed during the study period utilizing a MolecuLight i:x™ device at each dressing change, and at study end by Colony Forming Units (CFU) quantification of harvested wounds.

[0073] With respect to the dose regimen, topical administration of SEP-RM rhamnolipid treatment was performed twice per week, on Study Days 0 (non-infected groups only), 3, 7, 10, 14, 17, and 21 while animals were under light anesthesia inhalant isoflurane on O2 (1-4%, to effect). Treatment administration for the infected groups began on Study Day 3 and continued twice per week outlined above. The test animals were observed for anyAttorney Docket No. 68680W001 adverse reactions to each dose, at each session, prior to being placed back into their respective home cages.

[0074] At the time of wound measurements and assessment, on Days 0, 3, 7, 10, 14, 17, and 21 , animals, while lightly anesthetized via isoflurane on 02 (1 - 4%, to effect), had wounds imaged with the MolecuLight i:x™ device which detected wounds with elevated bacterial loads of >104 CFU / g at up to 0.8mm below the skin surface.

[0075] Results utilizing the diabetic mouse wound model study describe above are presented in U.S. Provisional Patent Application Nos.: 63 / 724,979; 63 / 724,975; and 63 / 724,974. The content of each of these U.S. Provisional Patent Applications is incorporated herein by reference in their entirety.

[0076] Wound care devices, systems and methods that may be used with the SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 10,828,203; U.S. Pat. No. 8,497,407; U.S. Pat. No. 9,271 ,876; U.S. Pat. No. 8,530,022; U.S. Pat. No. 8,519,211 ; U.S. Pat. No. 8,263,100; U.S. Pat. No. 10,143,595; U.S. Pat. No. 9,492,549; U.S. Pat. No. 10,543,133; U.S. Pat. No. 9,877,872; U.S. Pat. No. 10,231 ,874; U.S. Pat. No. 10,130,519; U.S. Pat. No. 11 ,559,437; U.S. Pat. No. 10,624,931 ; U.S. Pat. No. 1 1 ,464,809; U.S. Pat. No. 10,265,344; U.S. Pat. No. 10,994,913; U.S. Pat. No. 10,279,974; U.S. Pat. No. 11 ,207,353; U.S. Pat. No. 8,084,665; U.S. Pat. No. 8,541 ,481 ; U.S. Pat. No. 8,546,637; U.S. Pat. No. 9,017,771 ; U.S. Pat. No. 9,273,233; U.S. Pat. No. 9,242,022; U.S. Pat. No. 9,572,942; U.S. Pat. No. 8,581 ,017; U.S. Pat. No. 9,604,031 ; U.S. Pat. No. 9,457,169; U.S. Pat. No. 8,541 ,481 ; U.S. Pat. No. 7,947,366; U.S. Pat. No. 9,289,450; U.S. Pat. No. 7,612,248; U.S. Pat. No. 8,1 10,718; U.S. Pat. No. 7,442,849; U.S. Pat. No. 9,713,659; U.S. Pat. No. 10,456,509; U.S. Pai.Attorney Docket No. 68680W001No. 7,641 ,893; U.S. Pat. No. 8,197,803; U.S. Pat. No. 8,491 , 881 ; U.S. Pat. No. 8,784,793; U.S. Pat. No. 9,962,461 ; U.S. Pat. No. 8,461 ,410; U.S. Pat. No. 5,536,656; and European Pat. No. EP0617938, the disclosures of each of which are incorporated herein by reference for all purposes.Example 2

[0077] Wound care devices, systems and methods that may be used in combination with the SEP-RM Rhamnolipid mixtures and compositions set forth herein include various collagen hydrogels.

[0078] In one embodiment, the collagen hydrogel hydrates dry wounds and eschar, as well as promotes a moist wound environment and autolytic debridement.

[0079] For example, the SEP-RM Rhamnolipid mixtures and compositions set forth herein can be formulated together with a collagen hydrogel comprising collagen admixed with a number of other ingredients, including, for example, panthenol, allantoin, carbomer, imidazolidinyl urea, tetra sodium EDTA, triethanolamine, methylparaben, and propylparaben.

[0080] Example formulations that may be used or formulated with the SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 6,468,521 , U.S. Pat. No. 5,738,860, and U.S. Pat. No. 6,201 ,164, the disclosures of each of which are incorporated herein by reference for all purposes.Example 3Attorney Docket No. 68680W001

[0081] Wound care devices, systems and methods that may be used in combination with the SEP-RM Rhamnolipid mixtures and compositions set forth herein include various other hydrogels.

[0082] In one embodiment, the hydrogel is an antimicrobial hydrogel that is effective in assisting the debridement and desloughing process in dry necrotic wounds, while maintaining a moist wound environment for optimal wound healing. In this embodiment, the hydrogel can contain an antimicrobial compound (e.g., an antimicrobial silver compound) that is an effective barrier to bacterial penetration by inhibiting the growth of broad spectrum of microorganisms.

[0083] For example, the SEP-RM Rhamnolipid mixtures and compositions set forth herein can be formulated together with a hydrogel comprising, for example, water, guar gum CAS# 9000-30-0, propylene glycol CAS# 57-55-6, silver carbonate CAS# 534-16-7 ( < 1 % ), mono potassium phosphate CAS# 7778-77-0, and Sodium Chloride CAS# 7647-14-5.

[0084] Example hydrogel formulations that may be used or formulated together with the SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 10,111 ,959, the disclosures of which is incorporated herein by reference for all purposes.Example 4

[0085] Wound care devices, systems and methods that may be used in combination with the SEP-RM Rhamnolipid mixtures and compositions set forth herein include various dressings, including, for example, foam dressings.Attorney Docket No. 68680W001

[0086] In at least one embodiment, the dressing comprises: a soft silicone wound contact layer; a flexible absorbent pad of polyurethane foam; and an outer polyurethane film which is breathable but waterproof. In this embodiment, the SEP-RM Rhamnolipid mixtures and compositions set forth herein can be admixed or co-formulated with the soft silicone wound contact layer, and / or the flexible absorbent pad of polyurethane foam.

[0087] In one aspect of this embodiment, the flexible absorbent pad of polyurethane contains silver sulphate (e.g., 1.2 mg / cm2silver) to create an effective bacterial barrier and to inactivate a wide range of wound related pathogens (e.g., bacteria and fungi).

[0088] Example devices, systems, and formulations that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 10,828,203; U.S. Pat. No. 8,497,407; U.S. Pat. No. 9,271 ,876; U.S. Pat. No. 8,530,022; U.S. Pat. No. 8,519,21 1 ; U.S. Pat. No. 8,263,100; U.S. Pat. No. 10,143,595, the disclosures of each of which are incorporated herein by reference for all purposes.Example 5

[0089] Wound care devices, systems and methods that may be used in combination with the SEP-RM Rhamnolipid mixtures and compositions set forth herein include various dressings, including, for example, transparent perforated and non-absorbent dressing. The dressing has an open mesh structure that allows exudate to pass, for example, into a secondary absorbent dressing. This can reduce frequent dressing changes closest to the wound and allows for changing the secondary dressing with minimized disturbance of the wound.Attorney Docket No. 68680W001

[0090] In this particular embodiment, the transparent perforated and non-absorbent dressing comprises: a soft silicone wound contact layer; and a transparent and flexible polyamide net with open mesh structure.

[0091] Example devices, systems, and formulations of this embodiment that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 9,492,549, the disclosures of which are incorporated herein by reference for all purposes.Example 6

[0092] Wound care devices, systems and methods that may be used in combination with the SEP-RM Rhamnolipid mixtures and compositions set forth herein include various dressings, including, for example, thin transparent, adhesive, breathable soft silicone film dressings.

[0093] The thin transparent, adhesive, breathable soft silicone film dressing described in this embodiment is configured to protect fragile and sensitive skin and minimize risk of skin breakdown during wound healing and closure. It can be used as secondary dressing, fixating e.g. gauze or nonwoven swabs or as a landing zone for aggressive tapes to secure devices to skin. It also can be used as a protective dressing over IV sites when the IV device is secured through adhesive tape or sutures.

[0094] The thin transparent, adhesive, breathable soft silicone film dressing described in this embodiment comprises, for example: a silicone coated paper frame; a breathable and waterproof polyurethane film; a soft silicone wound contact layer; and an embossed polypropylene film release liner.Attorney Docket No. 68680W001

[0095] Example devices, systems, and formulations of this embodiment that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 9,492,549, the disclosures of which are incorporated herein by reference for all purposes.Example 7

[0096] Wound care devices, systems and methods that may be used in combination with the SEP-RM Rhamnolipid mixtures and compositions set forth herein include various dressings, including, for example, transparent, breathable and adhesive film dressings.

[0097] The transparent, breathable and adhesive film dressing of this embodiment is configured for protection of intact skin and superficial wounds and can also be used for fixation of medical devices such as other wound dressings, tubes and cannulas.

[0098] The transparent, breathable and adhesive film dressing described in this embodiment comprises: a transparent polyurethane film coated with a solvent-based polyacrylic adhesive; and an application frame and tabs of siliconized paper. The adhesive area can also be covered with a printed release liner.Example 8

[0099] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with self-adhesive and absorbent wound dressings.

[0100] The self-adhesive and absorbent wound dressings of this embodiment comprises: an absorbent wound pad with an integrated non-adherent wound contactAttorney Docket No. 68680W001 layer; an adhesive border with water based acrylic adhesive; and an outer breathable nonwoven providing a physical protection to the wound.

[0101] In this embodiment, the adhesive is skin friendly and free from organic solvents. Also, the outer breathable nonwoven can be formulated using polyester nonwoven, viscose, polyolefin nonwoven, or combinations thereof.

[0102] The self-adhesive and absorbent wound dressings set forth in this embodiment are generally designed for use on low to moderately exuding wounds, such as surgical wounds, cuts and abrasions.Example 9

[0103] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a gelling fiber dressing.

[0104] The gelling fiber dressing of this embodiment comprises a nonwoven dressing made from highly absorbent polyvinyl alcohol (PVA) fibers. When in contact with wound exudate, the gelling fiber dressing is configured to transform into a gel that facilitates moist wound healing and ease of removal during dressing change. Further, the gelling fiber dressing is configured to absorb and retain wound exudate.

[0105] In another embodiment, the gelling fiber dressing is coated on both sides with silver sulphate. In contact with liquid, the gelling fiber releases silver ions and inactivates a variety of wound related pathogens such as bacteria, fungi and molds. In this embodiment, gelling fiber dressing can prevent and reduce the formation of bacterial biofilm, and can be used as an effective barrier against microbial penetration of the dressing.Attorney Docket No. 68680W001Example 10

[0106] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a non-adhesive foam wound dressing.

[0107] The non-adhesive foam wound dressing comprises a sodium carboxymethylcellulose wound contact layer. In some embodiments, the non-adhesive foam wound dressing comprises: an outer polyurethane film configured to provide a bacterial and viral barrier; and a soft, multi-layered, absorbent central pad comprising a polyurethane foam and a sodium carboxymethylcellulose wound contact layer. In this embodiment, the non-adhesive foam wound dressing is configured to absorb and retain moisture, exudate, and bacteria. In this capacity, the non-adhesive foam wound dressing of this embodiment provides a moist wound healing environment, aiding autolytic debridement and removing dead-space between the wound and dressing interface

[0108] The non-adhesive foam wound dressing of this embodiment can be used for the management of exuding and non-exuding wounds, and for the protection of intact skin. Further, the non-adhesive foam wound dressing of this embodiment can also be used on intact skin as part of a pressure injury prevention protocol. For example, the non-adhesive foam wound dressing of this embodiment can be used for the management of: leg ulcers; pressure injuries; diabetic foot ulcers; surgical wounds; and traumatic wounds.

[0109] Example devices, systems, and formulations of this embodiment that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 10,543,133, the disclosures of which are incorporated herein by reference for all purposes.Attorney Docket No. 68680W001Example 11

[0110] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a multi-layer dressing. The multi-layer dressing of this example can comprise a laminate of adhesive coated polyurethane films to polyurethane foam containing silver sulphadiazine (e.g., 5%).

[0111] Example devices, systems, and formulations that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 9,877,872, U.S. Pat. No. 10,231 ,874, U.S. Pat. No. 10,130,519, U.S. Pat. No. 11 ,559,437, the disclosures of each of which are incorporated herein by reference for all purposes.Example 12

[0112] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with an umbilical tissue dressing.

[0113] The umbilical tissue dressing of this example comprises cryopreserved umbilical tissue and is configured to improve the closure rates of challenging wounds, including those wounds with exposed structures or hardware. The umbilical tissue dressing of this example is suitable, for example, as a cover for tendon, ligament, bone, nerve repair or soft tissue sites.

[0114] Example devices, systems, and formulations that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 10,624,931 , or U.S. Pat. No. 11 ,464,809, the disclosures of each of which are incorporated herein by reference for all purposes.Attorney Docket No. 68680W001Example 13

[0115] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a human placental tissue dressing. In this example, the human placental tissue dressing comprises an intact extracellular matrix (ECM), growth factors, and native placental cells.

[0116] Example devices, systems, and formulations that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 10,265,344, U.S. Pat. No. 10,994,913, U.S. Pat. No. 10,279,974, and U.S. Pat. No. 11 ,207,353, the disclosures of each of which are incorporated herein by reference for all purposes.Example 14

[0117] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a transparent film dressing.

[0118] In one embodiment of this example, the transparent film dressings are made of semi-permeable films and can be considered selective filters. In this capacity, they are occlusive to liquids, bacteria, and viruses, yet water vapor, oxygen, and carbon dioxide can easily be exchanged. The transparent film dressings of this embodiment allow moisture vapor and gas exchange, essential to maintaining normal skin function under the dressing.

[0119] Example devices, systems, and formulations that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 8,084,665, U.S. Pat. No. 8,541 ,481 , U.S. Pat. No., 8, 546, 637,Attorney Docket No. 68680W001U.S. Pat. No. 9,017,771 , U.S. Pat. No. 9,273,233, U.S. Pat. No. 9,242,022, U.S. Pat. No. 9,572,942, U.S. Pat. No. 8,581 ,017, U.S. Pat. No. 9,604,031 , U.S. Pat. No. 9,457,169, U.S. Pat. No. 8,541 ,481 , U.S. Pat. No. 7,947,366, U.S. Pat. No. 9,289,450, U.S. Pat. No. 7,612,248, U.S. Pat. No. 8,1 10,718, U.S. Pat. No. 7,442,849, U.S. Pat. No. 9,713,659, and U.S. Pat. No. 10,456,509, the disclosures of each of which are incorporated herein by reference for all purposes.Example 15

[0120] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a barrier film dressing.

[0121] In one embodiment of this example, the barrier film comprises a polymeric- cyanoacrylate solution configured for the protection of intact or damaged skin. Upon application to skin, the liquid dries rapidly to form a primary long-lasting waterproof, highly durable film barrier. The barrier film is elastomeric, adhering to the contours of the skin and providing a uniform film. The barrier film is also transparent and possesses good oxygen and moisture vapor permeability.

[0122] In one aspect of this example, the polymer-cyanoacrylate can be dispersed in a non-stinging solvent. The barrier film is colorless, non-cytotoxic and has a low dermatitis potential. The barrier film adheres to dry, moist or wet skin surfaces and remains intact during conditions of continuous or repeated exposure to moisture or caustic irritants. In another aspect, the barrier film will wear off the skin and does not require removal.

[0123] Example devices, systems, and formulations that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, forAttorney Docket No. 68680W001 example, in U.S. Pat. No. 7,641 ,893, U.S. Pat. No. 8,197,803, U.S. Pat. No. 8,491 , 881 , U.S. Pat. No. 8,784,793, and U.S. Pat. No. 9,962,461 , the disclosures of each of which are incorporated herein by reference for all purposes.Example 16

[0124] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a collagen matrix-based dressing.

[0125] In one embodiment of this example, the collagen matrix-based dressing comprises collagen and oxidized regenerated cellulose, and optionally an anti-microbial agent (e.g., silver).

[0126] Example devices, systems, and formulations of this embodiment that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 8,461 ,410, the disclosures of which are incorporated herein by reference for all purposes.Example 17

[0127] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a skin construct.

[0128] In one embodiment of this example, the skin construct is a bi-layered construct comprising an epidermal and a dermal layer. The epidermal layer can be formed by human keratinocytes and has a well differentiated stratum cerneum. The dermal layer can be composed of human fibroblasts in a bovine Type I collagen lattice.Attorney Docket No. 68680W001

[0129] In one embodiment, while the skin construct contains matrix proteins and cytokines found in human skin, it does not contain Langerhans cells melanocytes macrophages lymphocytes blood vessels or hair follicles. In one embodiment, the skin construct is manufactured under aseptic conditions from human neonatal male foreskin tissue.

[0130] Example devices, systems, and formulations of this embodiment that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in U.S. Pat. No. 5,536,656, the disclosures of which are incorporated herein by reference for all purposes.Example 18

[0131] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a hydrocolloid dressing.

[0132] In one embodiment of this example, the hydrocolloid dressing comprises a cross-linked honeycomb matrix made from a mix of sodium carboxymethylcellulose, gelatin, pectin and adhesive polymers.

[0133] Example devices, systems, and formulations of this embodiment that may be used or formulated with SEP-RM Rhamnolipid mixtures and compositions set forth herein are described, for example, in European Pat. No. EP0617938, the disclosures of which are incorporated herein by reference for all purposes.Example 19

[0134] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with an absorbent wound dressing.Attorney Docket No. 68680W001

[0135] In one embodiment of this example, the absorbent wound dressing comprises: a wound contact layer; a non-woven distribution layer; an absorbent core; a non-woven clothing protection (on the back side of the dressing); and an adhesive. The wound contact layer can be a polyethylene film. The non-woven distribution layer can be polypropylene fibers. The absorbent core can be a cellulose with an embedded superabsorber (e.g., sodium polyacrylate). The non-woven clothing protection can be polypropylene fibers, and the adhesive can be synthetic. The wound contact layer and the non-woven clothing protection completely envelop the non-woven distribution layer and absorbent core and are adhered along all four edges by means of a hotmelt adhesive.

[0136] The absorbent wound dressing of this example can be used for the treatment of heavily exuding wounds such as pressure sores, arterial ulcers, venous leg ulcers, diabetic ulcers, postoperative wounds healing by second intention, laparotomy wounds, on fistulae, and superficial 2nd degree burns.Example 20

[0137] The SEP-RM Rhamnolipid mixtures and compositions set forth herein can also be used, admixed, formulated, or otherwise combined with a collagen powder.

[0138] In one embodiment of this example, the collagen powder is 100% hydrolyzed collagen prepared from TYPE I collagen. In this embodiment, the collagen powder interacts with the wound, forming a gel that provides a moist wound-healing environment, reduces inflammation, and promotes cellular re-generation.

[0139] The present technology is now described in such full, clear and concise terms as to enable a person skilled in the art to which it pertains, to practice the same. It is toAttorney Docket No. 68680W001 be understood that the foregoing describes preferred embodiments of the present technology and that modifications may be made therein without departing from the spirit or scope of the present technology as set forth in the appended claims. Further, the examples are provided to not be exhaustive but illustrative of several embodiments that fall within the scope of the claims.

[0140] Additionally, any references noted in the detailed description section of the instant application are hereby incorporated by reference in their entireties, unless otherwise noted.

Claims

1. Attorney Docket No. 68680W001Claims1. A composition for use during the treatment or management of wound healing, the composition comprising:(a) a mixture of rhamnolipids, wherein the mixture of rhamnolipids comprises: mono-rhamnolipids and di-rhamnolipids in a weight ratio of about 40:60 to about 60:40 mono-rhamnolipids:di-rhamnolipids; an amount of C10-C10 mono-rhamnolipid of about 29% to about 40% by weight, based on the total weight of rhamnolipids present in the composition; an amount of C10-C10 di-rhamnolipid of about 35% to about 50% by weight, based on the total weight of rhamnolipids present in the composition; an amount of 08-010 mono-rhamnolipid of about 2% to about 5% by weight, based on the total weight of rhamnolipids present in the composition; an amount of 08-010 di-rhamnolipid of about 2% to about 5% by weight, based on the total weight of rhamnolipids present in the composition; an amount of C10-C12 mono-rhamnolipid of about 2% to about 6% by weight, based on the total weight of rhamnolipids present in the composition; and an amount of 010-012 di-rhamnolipid of about 8% to about 14% by weight, based on the total weight of rhamnolipids present in the composition;Attorney Docket No. 68680W001(b) at least one acceptable carrier, and optionally one or more additives, in an amount to total 100% by weight of the composition.

2. The composition of claim 1 , wherein the mixture of rhamnolipids further comprises an amount of C10-C12:1 di-rhamnolipid of about 2% to about 5% by weight, based on the total weight of rhamnolipids present in the composition.

3. The composition of claim 1 , wherein the mixture of rhamnolipids further comprises an amount of C12-C12 di-rhamnolipid of about 0.2% to about 0.4% by weight, based on the total weight of rhamnolipids present in the composition.

4. The composition of claim 1 , wherein the mixture of rhamnolipids comprises an amount of total mono-rhamnolipid of about 40% to about 50% by weight, based on the total weight of rhamnolipids present in the composition.

5. The composition of claim 1 , wherein the mixture of rhamnolipids comprises an amount of total di-rhamnolipid of about 50% to about 60% by weight, based on the total weight of rhamnolipids present in the composition.

6. The composition of any one of claims 1 to 5, wherein the mixture of rhamnolipids is in an amount of about 0.1 % to about 10%, based on the total weight of the composition.

7. The composition of any one of claims 1 to 6, wherein the wound being treated is an incision, laceration, abrasion, or burn.

8. The composition of any one of claims 1 to 7, wherein the at least one acceptable carrier is water alone or in combination with an alcohol or glycol.Attorney Docket No. 68680W0019. The composition of claim 8, wherein the alcohol is ethanol, isopropanol, or benzyl alcohol.

10. The composition of claim 8, wherein the glycol is propylene glycol or polyethylene glycol.1 1 . The composition of any one of claims 1 to 10, wherein the method comprises topical administration of the composition.

12. A method for the treatment of a wound, comprising: applying to a wound a composition comprising:(a) a mixture of rhamnolipids, wherein the mixture of rhamnolipids comprises: mono-rhamnolipids and di-rhamnolipids in a weight ratio of about 40:60 to about 50:50 mono-rhamnolipids:di-rhamnolipids; an amount of C10-C10 mono-rhamnolipid of about 29% to about 37% by weight, based on the total weight of rhamnolipids present in the composition; an amount of C10-C10 di-rhamnolipid of about 35% to about 50% by weight, based on the total weight of rhamnolipids present in the composition; an amount of C8-C10 mono-rhamnolipid of about 2% to about 5% by weight, based on the total weight of rhamnolipids present in the composition; an amount of C8-C10 di-rhamnolipid of about 2% to about 5% by weight, based on the total weight of rhamnolipids present in the composition;Attorney Docket No. 68680W001 an amount of C10-C12 mono-rhamnolipid of about 2% to about 6% by weight, based on the total weight of rhamnolipids present in the composition; and an amount of C10-C12 di-rhamnolipid of about 8% to about 14% by weight, based on the total weight of rhamnolipids present in the composition;(b) at least one acceptable carrier, and optionally one or more additives, in an amount to total 100% by weight of the composition.

13. The method of claim 12, wherein the mixture of rhamnolipids further comprises an amount of C10-C12:1 di-rhamnolipid of about 2% to about 5% by weight, based on the total weight of rhamnolipids present in the composition.

14. The method of claim 12 or 13, wherein the mixture of rhamnolipids further comprises an amount of C12-C12 di-rhamnolipid of about 0.2% to about 0.4% by weight, based on the total weight of rhamnolipids present in the composition.

15. The method of any one of claims 12-14, wherein the mixture of rhamnolipids comprises an amount of total mono-rhamnolipid of about 40% to about 48% by weight, based on the total weight of rhamnolipids present in the composition.

16. The method of any one of claims 12-15, wherein the mixture of rhamnolipids comprises an amount of total di-rhamnolipid of about 52% to about 60% by weight, based on the total weight of rhamnolipids present in the composition.

17. The method of any one of claims 12-16, wherein the mixture of rhamnolipids is in an amount of about 0.1 % to about 10%, based on the total weight of the composition.Attorney Docket No. 68680W00118. The method of any one of claims 12-17, wherein the at least one acceptable carrier is water alone or in combination with an alcohol or glycol.

19. The method of claim 18, wherein the alcohol is ethanol, isopropanol, or benzyl alcohol.

20. The method of claim 18, wherein the glycol is propylene glycol or polyethylene glycol.

21. A wound healing system, wherein the system comprises a wound healing dressing admixed, formulated, or combined with the composition of any one of claims 1 -6.

22. The wound healing system of claim 21 , wherein the wound healing dressing is a collagen hydrogel.

23. The wound healing system of claim 22, wherein the collagen hydrogel comprises collagen admixed with panthenol, allantoin, carbomer, imidazolidinyl urea, tetra sodium EDTA, triethanolamine, methylparaben, and propylparaben.

24. The wound healing system of claim 21 , wherein the wound healing dressing is a guar gum-based hydrogel.

25. The wound healing system of claim 24, wherein the hydrogel is an antimicrobial hydrogel.

26. The wound healing system of claim 24, wherein the hydrogel comprises water, guar gum, propylene glycol, silver carbonate, mono potassium phosphate, and sodium chloride.

27. The wound healing system of claim 21 , wherein the wound healing dressing is a foam dressing.Attorney Docket No. 68680W00128. The wound healing system of claim 27, wherein the foam dressing comprises: a soft silicone wound contact layer; a flexible absorbent pad of polyurethane foam; and an outer polyurethane film.

29. The wound healing system of claim 21 , wherein the wound healing dressing is a nonabsorbent dressing.

30. The wound healing system of claim 29, wherein the non-absorbent dressing comprises: a silicone wound contact layer; and a transparent and flexible polyamide net with open mesh structure.31 . The wound healing system of claim 21 , wherein the wound healing dressing is a film dressing.

32. The wound healing system of claim 31 , wherein the film dressing comprises: a silicone coated paper frame; a breathable and waterproof polyurethane film; a soft silicone wound contact layer; and an embossed polypropylene film release liner.

33. The wound healing system of claim 31 , wherein the film dressing comprises: a transparent polyurethane film coated with a solvent-based polyacrylic adhesive; and an application frame and tabs of siliconized paper.

34. The wound healing system of claim 21 , wherein the wound healing dressing is a self- adhesive absorbent wound dressing.

35. The wound healing system of claim 34, wherein the self-adhesive absorbent wound dressing comprises: an absorbent wound pad with an integrated non-adherent woundAttorney Docket No. 68680W001 contact layer; an adhesive border with water based acrylic adhesive; and an outer breathable nonwoven configured to provide a physical protection to the wound.

36. The wound healing system of claim 35, wherein the outer breathable nonwoven comprises polyester nonwoven, viscose, polyolefin nonwoven, or combinations thereof.

37. The wound healing system of claim 21 , wherein the wound healing dressing is a gelling fiber.

38. The wound healing system of claim 37, wherein the gelling fiber comprises highly absorbent polyvinyl alcohol (PVA) fibers.

39. The wound healing system of claim 37, wherein the gelling fiber comprises silver sulphate.

40. The wound healing system of claim 21 , wherein the wound healing dressing is a nonadhesive foam.

41. The wound healing system of claim 40, wherein the non-adhesive foam comprises: an outer polyurethane film configured to provide a bacterial and viral barrier; and a multilayered central pad comprising a polyurethane foam and a sodium carboxymethylcellulose wound contact layer.

42. The wound healing system of claim 21 , wherein the wound healing dressing is a multilayer dressing.Attorney Docket No. 68680W00143. The wound healing system of claim 42, wherein the multi-layer dressing comprises a laminate, wherein the laminate comprises adhesive coated polyurethane films laminated to a polyurethane foam containing silver sulphadiazine.

44. The wound healing system of claim 21 , wherein the wound healing dressing is an umbilical tissue dressing.

45. The wound healing system of claim 21 , wherein the wound healing dressing is a human placental tissue dressing.

46. The wound healing system of claim 45, wherein the human placental tissue dressing comprises: an intact extracellular matrix (ECM); growth factors; and native placental cells.

47. The wound healing system of claim 21 , wherein the wound healing dressing is a transparent film dressing.

48. The wound healing system of claim 47, wherein the transparent film dressing comprises semi-permeable films, wherein the semi-permeable films are occlusive to liquids, bacteria, and viruses.

49. The wound healing system of claim 48, wherein the semi-permeable films exchange vapor, oxygen, and carbon dioxide.

50. The wound healing system of claim 21 , wherein the wound healing dressing is a barrier film.Attorney Docket No. 68680W00151 . The wound healing system of claim 50, wherein the barrier film comprises a polymeric- cyanoacrylate solution configured to dry rapidly upon application to form a waterproof film barrier.

52. The wound healing system of claim 50, wherein the barrier film is transparent and permeable to oxygen and moisture vapor.

53. The wound healing system of claim 21 , wherein the wound healing dressing is a collagen matrix.

54. The wound healing system of claim 53, wherein the collagen matrix comprises: collagen; oxidized regenerated cellulose; and optionally an anti-microbial agent.

55. The wound healing system of claim 54, wherein the anti-microbial agent is a silver compound.

56. The wound healing system of claim 21 , wherein the wound healing dressing is a skin construct.

57. The wound healing system of claim 56, wherein the skin construct is a bi-layered construct comprising an epidermal layer and a dermal layer.

58. The wound healing system of claim 57, wherein the epidermal layer comprises: human keratinocytes; and a differentiated stratum cerneum.

59. The wound healing system of claims 57 or 58, wherein the dermal layer comprises human fibroblasts in a bovine Type I collagen lattice.Attorney Docket No. 68680W00160. The wound healing system of claim 21 , wherein the wound healing dressing is a hydrocolloid dressing.

61. The wound healing system of claim 60, wherein the hydrocolloid dressing comprises a cross-linked honeycomb matrix, the matrix comprising sodium carboxymethylcellulose, gelatin, pectin and adhesive polymers.

62. The wound healing system of claim 21 , wherein the wound healing dressing is an absorbent wound dressing comprising: a wound contact layer; a non-woven distribution layer; an absorbent core; a non-woven clothing protection; and an adhesive.

63. The wound healing system of claim 62, wherein the wound contact layer comprises a polyethylene film.

64. The wound healing system of claim 62, wherein the non-woven distribution layer comprises polypropylene fibers.

65. The wound healing system of claim 62, wherein the absorbent core comprises a cellulose embedded with sodium poly-acrylate.

66. The wound healing system of claim 21 , wherein the system comprises the application of a collagen powder.

67. The wound healing system of claim 66, wherein the collagen powder comprises hydrolyzed collagen prepared from TYPE I collagen.

68. The wound healing system of claim 66, wherein the collagen powder forms a gel upon interaction with a wound.

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