WO2024102456A1 - Compositions and methods for controlled release of therapeutic agents from articles - Google Patents

Abstract

The present disclosure relates to articles that are therapeutic coverings and wraps comprising a substrate and a releasable therapeutic agent in contact with or attached to one another. The articles comprising therapeutic coverings and wraps are useful for treatment of atopic dermatitis and/or are useful for treatment of wounds. The substrate can comprise a textile having hydroxyl groups in the textile yarn or filament such as cotton, rayon, silk, or combinations thereof. The therapeutic agent interacts with or is attached to the substrate via non-covalanet interactions, or alternatively via a covalent linkage that can release the therapeutic agent. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

Description

ATTORNEY DOCKET NO.330304-2010 COMPOSITIONS AND METHODS FOR CONTROLLED RELEASE OF THERAPEUTIC AGENTS FROM ARTICLES CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This Application claims the benefit of U.S. Provisional Application No. 63/423,929, filed on November 9, 2022, which is incorporated herein by reference in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH [0002] This disclosure was made with U.S. Government support under grant number R43AT011486, awarded by the National Institutes of Health. The U.S. government has certain rights in the disclosure. BACKGROUND [0003] Wounds are commonplace from childhood to old age. Wounds are a significant problem among the geriatric and nursing home population, especially at the end of life. Pressure ulcers alone exact a significant human and financial toll, costing on average more than $1,200 per patient per month to treat. CDC data indicates that from about 2% to 28% of nursing home residents have pressure ulcers. Diabetic ulcers similarly result in significant morbidity and costs, with diabetics accounting for approximately 82,000 amputations annually in the U.S., averaging $30,000 per amputation. Other wounds plaguing the nursing home and end of life population are ulcers resulting from arterial and venous insufficiency, as well as traumatic wounds, and non-healing surgical wounds. [0004] Any penetration of the skin carries with it the risk of potential infection. This risk pertains to simple wounds incurred by accident or negligence; to surgical procedures performed under controlled conditions which utilize different biomaterials for the closure and dressing of incisions and/or wounds; and to a diverse range of in-vivo implantable textile fabrics, configured textile articles, and textile-containing mechanical appliances and devices which are surgically introduced into the body for diagnostic, therapeutic and/or prosthetic purposes. [0005] Standard wound care involves debridement, cleansing and covering the wound with any of a variety of commercially available dressings. There are many special dressings available which are designed to keep wounds moist or absorb exudates. Some specialty dressings have silver impregnated in the dressing to prevent infection. Typically, dressings are attached either with self-adhesive or tape, or in some cases are applied with a compression wrap. Recent high-tech approaches are available for wound care using thermal wound treatments and vacuum pumps. While these can be effective, they are very expensive ATTORNEY DOCKET NO.330304-2010 and healing times are still measured in weeks or months. As such, it is desired to have an inexpensive wound treatment method and composition which reduces the time required for wounds to heal. [0006] The rational use of antimicrobial agents against infection, particularly for simple wound treatment, has been advocated generally and has been previously reviewed in detail [Rodgers, K. G., Emer. Med. Clin. N. Am. 10: 753 (1992)]. Similarly, the major concerns regarding the ever-growing incidence of infections resulting from biocompatible textiles, articles and devices implanted in the body—espite recent advances in sterile procedures used in the clinical/surgical setting—have been considered and reviewed as the primary purpose and focus of a FDA/EPA/CDC/AAMI joint conference [Proceedings, Infection Control Symposium: Influence Of Medical Device Design, U.S. Dept. of Health and Human Services, Bethesda, Md., January 1995]. Moreover, the use of antibiotics and of mechanisms for delivering antimicrobial agents generally, particularly via slow-release delivery systems over time, to prevent or reduce severity of infection for implanted biodegradable materials has been reviewed [Sasmor et al., J. Vasc. Sur.14: 521 (1993)]. All of these considerations lead to the same conclusion: Infection, with or without the use of antibiotics, must be prevented or be controlled for all implantable biomaterials (including textiles, articles and devices) regardless of need or medical purpose. [0007] A further clinical indication of unmet need is atopic dermatitis. Associated with changes in living environment and eating habits, the number of people suffering from atopic dermatitis has been increasing rapidly. It is one of the representative skin diseases shown in people with a history of allergy disorders. It is a chronic skin disease which has immunologic responses and thus often occurs together with other atopic diseases such as urticaria, metal allergy, allergic asthma, or allergic rhinitis etc, and its main skin symptoms are dryness and itch. In addition, it is believed to have a hereditary component, and often runs in families whose members also have atopic disease. [0008] The pathogenetic mechanism of atopic dermatitis has not been clarified in many aspects and methods for treating atopic dermatitis have not yet been established. Although of unknown etiology, there is genetic predisposition and it is also related to abnormalities in the immune system. In addition, it is known as an inflammatory skin disease with a complex etiology that encompasses dry skin, increased susceptibility to irritation compared with normal human skin, cutaneous infection with bacteria, virus, fungus, etc., emotional factors, environmental factors and the like. Main skin symptoms of atopic dermatitis are severe itching, dryness, rash, redness, weeping crusting, scaling and the like. It has been known that there is no fundamental treatment for atopic dermatitis even with contemporary medical science, ATTORNEY DOCKET NO.330304-2010 and thus the patients just have to avoid atopic dermatitis inducing factors and use therapies or therapeutic agents that help reduce the symptoms although they could not provide fundamental treatment. [0009] Atopic dermatitis is a very common skin disease which affects 0.5-1% of the population as a whole, and 5~10% of children, and starts 2~6 months after birth, particularly, occurs most often within a year after birth, and 85% of children with atopic dermatitis manifest the disease before the age of 5 years. In 50% of atopic patients, it resolves spontaneously by the time the patient reaches age 2, however, the symptoms do not improve in 25% of the patients until they reach adolescence and the rest 25% of the patients has some degree of eczema that occurs throughout their lifetime. [0010] Despite advances in wound care research, there is still a scarcity of articles, products and systems that meet the needs for adequate and effective wound treatment or treatment of atopic dermatitis. These needs and other needs are satisfied by the present disclosure. SUMMARY [0011] In accordance with the purpose(s) of the disclosure, as embodied and broadly described herein, the disclosure, in one aspect, relates to articles that are therapeutic coverings and wraps comprising a substrate and a releasable therapeutic agent in contact with or attached to one another. In various aspects, the articles comprising therapeutic coverings and wraps are useful for treatment of atopic dermatitis. In other aspects, the articles are wound coverings and wraps such as dressings and bandages that are useful for treatment of wounds. [0012] In a further aspect, the substrate comprises a textile having hydroxyl groups in the textile yarn or filament, e.g., a textile comprising a yarn or filament comprising cotton, rayon, silk, or combinations thereof. It is understood that substrates can comprise other materials and is not limited to textile materials. Moreover, a substrate can comprise a composite material, e.g., a bilayer material wherein a first layer comprises a substrate and a releasable therapeutic agent in contact with or attached to one another and a second layer does not. In a further aspect, the therapeutic agent interacts with or is attached to the substrate via non- covalent interactions, e.g., van der Waals forces, ionic interactions, and combinations thereof, or via a covalent linkage that can release the therapeutic agent under normal use with a subject. [0013] In a further aspect, the articles comprising a substrate and a releasable therapeutic agent in contact with or attached to one another provide for tunable release of the therapeutic ATTORNEY DOCKET NO.330304-2010 agent such that the therapeutic agent can be released in a short time frame (or immediate release) on the order of minutes to hours to longer time frames (or delayed release) on the order of hours to days or longer by varying the mode of interaction between the substrate and the releasable therapeutic agent from non-covalent interactions of different types to covalent interactions involving linkers of different length and chemical reactivities to mixtures of chemistries and covalent/non-covalent interactions between the releasable therapeutic agent and substrate. [0014] Disclosed are articles comprising a substrate and a therapeutic agent. [0015] Also disclosed are methods of making the disclosed articles. [0016] Also disclosed are methods of treating a subject using the disclosed articles. [0017] Other systems, methods, features, and advantages of the present disclosure will be or become apparent to one with skill in the art upon examination of the following drawings and detailed description. It is intended that all such additional systems, methods, features, and advantages be included within this description, be within the scope of the present disclosure, and be protected by the accompanying claims. In addition, all optional and preferred features and modifications of the described aspects are usable in all aspects of the disclosure taught herein. Furthermore, the individual features of the dependent claims, as well as all optional and preferred features and modifications of the described aspects are combinable and interchangeable with one another. BRIEF DESCRIPTION OF THE FIGURES [0018] Many aspects of the present disclosure can be better understood with reference to the following drawings. The components in the drawings are not necessarily to scale, emphasis instead being placed upon clearly illustrating the principles of the present disclosure. Moreover, in the drawings, like reference numerals designate corresponding parts throughout the several views. [0019] FIG.1 shows representative data for release of a therapeutic agent from a disclosed substrate comprising a therapeutic agent attached thereto. [0020] FIGs.2A-2B show representative schematic illustrations of a substrate before and after covalent linkage to a therapeutic agent. FIG.2A shows a schematic representation of a substrate comprising a polymer comprising a plurality of hydroxy moieties along the polymer backbone. FIG.2B shows a schematic representation of a substrate comprising a polymer comprising a plurality of hydroxy moieties along the polymer backbone in which some have ATTORNEY DOCKET NO.330304-2010 been covalently linked to a therapeutic agent. The covalent linkage may involve one, two, or three covalent linkages between oxygen (derived from hydroxy moieties) along the polymer backbone to a silyl moiety (with the definitions of substituent groups as disclosed herein below). [0021] Additional advantages of the disclosure will be set forth in part in the description which follows, and in part will be obvious from the description, or can be learned by practice of the disclosure. The advantages of the disclosure will be realized and attained by means of the elements and combinations particularly pointed out in the appended claims. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory only and are not restrictive of the disclosure, as claimed. DETAILED DESCRIPTION [0022] Many modifications and other aspects disclosed herein will come to mind to one skilled in the art to which the disclosed compositions and methods pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that the disclosures are not to be limited to the specific aspects disclosed and that modifications and other aspects are intended to be included within the scope of the appended claims. The skilled artisan will recognize many variants and adaptations of the aspects described herein. These variants and adaptations are intended to be included in the teachings of this disclosure and to be encompassed by the claims herein. [0023] Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. [0024] As will be apparent to those of skill in the art upon reading this disclosure, each of the individual aspects described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several aspects without departing from the scope or spirit of the present disclosure. [0025] Any recited method can be carried out in the order of events recited or in any other order that is logically possible. That is, unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not specifically state in the claims or descriptions that the steps are to be limited to a specific order, it is no way intended that an order be inferred, in any respect. This holds for any possible non-express basis for interpretation, including matters of logic with respect to arrangement of steps or ATTORNEY DOCKET NO.330304-2010 operational flow, plain meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. [0026] All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. Further, the dates of publication provided herein can be different from the actual publication dates, which can require independent confirmation. [0027] While aspects of the present disclosure can be described and claimed in a particular statutory class, such as the system statutory class, this is for convenience only and one of skill in the art will understand that each aspect of the present disclosure can be described and claimed in any statutory class. [0028] It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed compositions and methods belong. It will be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly defined herein. [0029] Prior to describing the various aspects of the present disclosure, the following definitions are provided and should be used unless otherwise indicated. Additional terms may be defined elsewhere in the present disclosure. A. DEFINITIONS [0030] As used herein, “comprising” is to be interpreted as specifying the presence of the stated features, integers, steps, or components as referred to, but does not preclude the presence or addition of one or more features, integers, steps, or components, or groups thereof. Moreover, each of the terms “by”, “comprising,” “comprises”, “comprised of,” “including,” “includes,” “included,” “involving,” “involves,” “involved,” and “such as” are used in their open, non-limiting sense and may be used interchangeably. Further, the term “comprising” is intended to include examples and aspects encompassed by the terms ATTORNEY DOCKET NO.330304-2010 “consisting essentially of” and “consisting of.” Similarly, the term “consisting essentially of” is intended to include examples encompassed by the term “consisting of. [0031] As used herein, the term “and/or” includes any and all combinations of one or more of the associated listed items. Expressions such as “at least one of,” when preceding a list of elements, modify the entire list of elements and do not modify the individual elements of the list. [0032] As used herein, nomenclature for compounds, including organic compounds, can be given using common names, IUPAC, IUBMB, or CAS recommendations for nomenclature. When one or more stereochemical features are present, Cahn-Ingold-Prelog rules for stereochemistry can be employed to designate stereochemical priority, E/Z specification, and the like. One of skill in the art can readily ascertain the structure of a therapeutic agent if given a name, either by systemic reduction of the therapeutic agent structure using naming conventions, or by commercially available software, such as CHEMDRAW^TM (Cambridgesoft Corporation, U.S.A.). [0033] Reference to "a" chemical therapeutic agent refers to one or more molecules of the chemical therapeutic agent rather than being limited to a single molecule of the chemical compound. Furthermore, the one or more molecules may or may not be identical, so long as they fall under the category of the chemical compound. Thus, for example, "a" chemical therapeutic agent is interpreted to include one or more molecules of the chemical, where the molecules may or may not be identical (e.g., different isotopic ratios, enantiomers, and the like). [0034] As used in the specification and the appended claims, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a therapeutic agent,” “a substrate,” or “a wrap,” includes, but is not limited to, two or more such therapeutioc agents, substrates, or wraps, and the like. [0035] Reference to "a/an" therapeutic agent chemical compound, protein, and antibody each refers to one or more molecules of the chemical compound, protein, and antibody rather than being limited to a single molecule of the chemical compound, protein, and antibody. Furthermore, the one or more molecules may or may not be identical, so long as they fall under the category of the chemical compound, protein, and antibody. Thus, for example, "an" antibody is interpreted to include one or more antibody molecules of the antibody, where the antibody molecules may or may not be identical (e.g., different isotypes and/or different antigen binding sites as may be found in a polyclonal antibody). ATTORNEY DOCKET NO.330304-2010 [0036] It should be noted that ratios, concentrations, amounts, and other numerical data can be expressed herein in a range format. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value, and/or to “about” another particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms a further aspect. For example, if the value “about 10” is disclosed, then “10” is also disclosed. [0037] When a range is expressed, a further aspect includes from the one particular value and/or to the other particular value. For example, where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the disclosure, e.g., the phrase “x to y” includes the range from ‘x’ to ‘y’ as well as the range greater than ‘x’ and less than ‘y’. The range can also be expressed as an upper limit, e.g., ‘about x, y, z, or less’ and should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘less than x’, less than y’, and ‘less than z’. Likewise, the phrase ‘about x, y, z, or greater’ should be interpreted to include the specific ranges of ‘about x’, ‘about y’, and ‘about z’ as well as the ranges of ‘greater than x’, greater than y’, and ‘greater than z’. In addition, the phrase “about ‘x’ to ‘y’”, where ‘x’ and ‘y’ are numerical values, includes “about ‘x’ to about ‘y’”. [0038] It is to be understood that such a range format is used for convenience and brevity, and thus, should be interpreted in a flexible manner to include not only the numerical values explicitly recited as the limits of the range, but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of about 0.1% to about 5%, but also include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g., about 0.5% to about 1.1%; about 5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range. [0039] As used herein, the terms “about,” “approximate,” “at or about,” and “substantially” mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, it is understood that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and/or larger or smaller, as desired, reflecting ATTORNEY DOCKET NO.330304-2010 tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In such cases, it is generally understood, as used herein, that “about” and “at or about” mean the nominal value indicated ±10% variation unless otherwise indicated or inferred. In general, an amount, size, formulation, parameter or other quantity or characteristic is “about,” “approximate,” or “at or about” whether or not expressly stated to be such. It is understood that where “about,” “approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself, unless specifically stated otherwise. [0040] The term “contacting” as used herein refers to bringing a disclosed therapeutic agent, compound, chemical, substrate, or material in proximity to another disclosed therapeutic agent, compound, chemical, substrate, or material as indicated by the context. For example, a therapeutic agent contacting a substrate refers to the therapeutic agent being in proximity to the substrate by the therapeutic agent interacting and binding to the substrate via ionic, dipolar and/or van der Waals interactions. In some instances, contacting can comprise both physical and chemical interactions between the indicated components. It is to be understood that chemical interactions can comprise a combination of covalent and non-covalent interactions, including one or more of ionic, dipolar, van der Waals interactions, and the like. For example, a therapeutic agent contacting a substrate is understood to mean that the therapeutic agent in physical and chemical contact with the substrate that can comprise covalent, ionic, and non- covalent interactions. [0041] In a further aspect, the term "contacting" in the specific context of a therapeutic agent contacting a clinically relevant target can refer to bringing a disclosed therapeutic agent in proximity to a tissue, an organ, a cell, a target protein, or other biological entity together in such a manner that the disclosed therapeutic agent or pharmaceutical composition can affect the activity of the a cell, target protein, or other biological entity, either directly; i.e., by interacting with the cell, target protein, or other biological entity itself, or indirectly; i.e., by interacting with another molecule, co-factor, factor, or protein on which the activity of the cell, target protein, or other biological entity itself is dependent. In a more specific instance, “contacting” can refer to bring a therapeutic agent in proximity to or contact with a wound, injury, or skin of a subject. [0042] As used herein, the terms “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where said event or circumstance occurs and instances where it does not. ATTORNEY DOCKET NO.330304-2010 [0043] As used herein, “administering” can refer to an administration of a therapeutic agent that is associated or in contact with a substrate. Administration can be continuous, releasable over specific time intervals, and/or intermittent. In various aspects, a preparation can be administered therapeutically; that is, administered to treat an existing disease or condition. In further various aspects, a preparation can be administered prophylactically; that is, administered for prevention of a disease or condition. [0044] As used herein, “therapeutic agent” can refer to any substance, compound, molecule, and the like, which can be biologically active or otherwise can induce a pharmacologic, immunogenic, biologic and/or physiologic effect on a subject to which it is administered to by local and/or systemic action. A therapeutic agent can be a primary active agent, or in other words, the component(s) of a composition to which the whole or part of the effect of the composition is attributed. A therapeutic agent can be a secondary therapeutic agent, or in other words, the component(s) of a composition to which an additional part and/or other effect of the composition is attributed. The term therefore encompasses those therapeutic agents or chemicals traditionally regarded as drugs, vaccines, and biopharmaceuticals including molecules such as proteins, peptides, hormones, nucleic acids, gene constructs and the like. Examples of therapeutic agents are described in well-known literature references such as the Merck Index (14th edition), the Physicians' Desk Reference (64th edition), and The Pharmacological Basis of Therapeutics (12th edition), and they include, without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of a disease or illness; substances that affect the structure or function of the body, or pro-drugs, which become biologically active or more active after they have been placed in a physiological environment. For example, the term “therapeutic agent” includes therapeutic agents or compositions for use in all of the major therapeutic areas including, but not limited to, adjuvants; anti-infectives such as antibiotics and antiviral agents; analgesics and analgesic combinations, anorexics, anti-inflammatory agents, anti-epileptics, local and general anesthetics, hypnotics, sedatives, antipsychotic agents, neuroleptic agents, antidepressants, anxiolytics, antagonists, neuron blocking agents, anticholinergic and cholinomimetic agents, antimuscarinic and muscarinic agents, antiadrenergics, antiarrhythmics, antihypertensive agents, hormones, and nutrients, antiarthritics, antiasthmatic agents, anticonvulsants, antihistamines, antinauseants, antineoplastics, antipruritics, antipyretics; antispasmodics, cardiovascular preparations (including calcium channel blockers, beta-blockers, beta-agonists and antiarrythmics), antihypertensives, diuretics, vasodilators; central nervous system stimulants; cough and cold preparations; decongestants; diagnostics; hormones; bone growth stimulants and bone resorption inhibitors; immunosuppressives; muscle relaxants; psychostimulants; sedatives; tranquilizers; proteins, ATTORNEY DOCKET NO.330304-2010 peptides, and fragments thereof (whether naturally occurring, chemically synthesized or recombinantly produced); and nucleic acid molecules (polymeric forms of two or more nucleotides, either ribonucleotides (RNA) or deoxyribonucleotides (DNA) including both double- and single-stranded molecules, gene constructs, expression vectors, antisense molecules and the like), small molecules (e.g., doxorubicin) and other biologically active macromolecules such as, for example, proteins and enzymes. The agent may be a biologically active agent used in medical, including veterinary, applications and in agriculture, such as with plants, as well as other areas. The term therapeutic agent also includes without limitation, medicaments; vitamins; mineral supplements; substances used for the treatment, prevention, diagnosis, cure or mitigation of disease or illness; or substances which affect the structure or function of the body; or pro- drugs, which become biologically active or more active after they have been placed in a predetermined physiological environment. [0045] As used herein, “kit” means a collection of at least two components constituting the kit. Together, the components constitute a functional unit for a given purpose. Individual member components may be physically packaged together or separately. For example, a kit comprising an instruction for using the kit may or may not physically include the instruction with other individual member components. Instead, the instruction can be supplied as a separate member component, either in a paper form or an electronic form which may be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. [0046] As used herein, “instruction(s)” means documents describing relevant materials or methodologies pertaining to a kit. These materials may include any combination of the following: background information, list of components and their availability information (purchase information, etc.), brief or detailed protocols for using the kit, troubleshooting, references, technical support, and any other related documents. Instructions can be supplied with the kit or as a separate member component, either as a paper form or an electronic form which may be supplied on computer readable memory device or downloaded from an internet website, or as recorded presentation. Instructions can comprise one or multiple documents and are meant to include future updates. [0047] As used herein, “attached” can be used in lieu of and interchangeably with “contacting”, and “attached” refers to covalent or non-covalent interaction between two or more molecules. Non-covalent interactions can include ionic bonds, electrostatic interactions, van der Walls forces, dipole-dipole interactions, dipole-induced-dipole interactions, London GLVSHUVLRQ^ IRUFHV^^ K\GURJHQ^ ERQGLQJ^^ KDORJHQ^ ERQGLQJ^^ HOHFWURPDJQHWLF^ LQWHUDFWLRQV^^ ʌ-ʌ^ ATTORNEY DOCKET NO.330304-2010 interactions, cation-ʌ^LQWHUDFWLRQV^^DQLRQ-ʌ^LQWHUDFWLRQV^^SRODU^ʌ-interactions, and hydrophobic effects. [0048] As used herein, the term “subject” can be a vertebrate, such as a mammal, a fish, a bird, a reptile, or an amphibian. Thus, the subject of the herein disclosed methods can be a human, non-human primate, horse, pig, rabbit, dog, sheep, goat, cow, cat, guinea pig or rodent. The term does not denote a particular age or sex. Thus, adult and juvenile subjects, whether male or female, are intended to be covered. In one aspect, the subject is a mammal. A patient refers to a subject afflicted with a disease or disorder. The term “patient” includes human and veterinary subjects. [0049] As used herein, the terms "treating" and "treatment" can refer generally to obtaining a desired pharmacological and/or physiological effect. The effect can be, but does not necessarily have to be, prophylactic in terms of preventing or partially preventing a disease, symptom or condition thereof, such as an infection. The effect can be therapeutic in terms of a partial or complete cure of a disease, condition, symptom or adverse effect attributed to the disease, disorder, or condition. The term "treatment" as used herein can include any treatment of a wound, including a wound without apparent infection, infection, or injury in a subject, particularly a human and can include any one or more of the following: (a) preventing the disease or condition from occurring in a subject which may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease or condition, i.e., arresting its development; and (c) relieving the disease or condition, i.e., mitigating or ameliorating the disease and/or its symptoms or conditions. The term "treatment" as used herein can refer to therapeutic treatment alone, prophylactic treatment alone, or both therapeutic and prophylactic treatment. Those in need of treatment (subjects in need thereof) can include those already with the disorder and/or those in which the disorder is to be prevented. As used herein, the term "treating", can include inhibiting the disease, disorder or condition, e.g., impeding its progress; and relieving the disease, disorder, or condition, e.g., causing regression of the disease, disorder and/or condition. Treating the disease, disorder, or condition can include ameliorating at least one symptom of the particular disease, disorder, or condition, even if the underlying pathophysiology is not affected, e.g., such as treating the pain of a subject by administration of an analgesic agent even though such agent does not treat the cause of the pain. [0050] As used herein, “dose,” “unit dose,” or “dosage” can refer to physically discrete units, e.g., mg therapeutic agent per gram substrate or mg therapeutic agent per unit area of substrate, suitable for use in treating a subject, each unit containing a predetermined quantity ATTORNEY DOCKET NO.330304-2010 of a disclosed therapeutic agent thereof calculated to produce the desired response or responses in association with its administration. [0051] As used herein, “therapeutic” can refer to treating, healing, and/or ameliorating a disease, disorder, condition, or side effect, or to decreasing in the rate of advancement of a disease, disorder, condition, or side effect. [0052] As used herein, the term “effective amount” refers to an amount that is sufficient to achieve the desired modification of a physical property of the composition or material. For example, an “effective amount” of a therapeutic agent refers to an amount that is sufficient to achieve the desired improvement or outcome associated with the referenced component, e.g., achieving the desired clinical result and/or rate of therapeutic agent release. The specific level in terms of wt% or mol% in a composition required as an effective amount will depend upon a variety of factors including the amount and type of substrate, amount and type of mode of the interaction between the substrate and therapeutic agent, chemical structure of the linker, if present, and type of therapeutic agent. In a further aspect, “effective amount” can refer to the amount of a disclosed therapeutic agent or pharmaceutical composition provided herein that is sufficient to effect beneficial or desired biological, emotional, medical, or clinical response of a cell, tissue, system, animal, or human. An effective amount can be administered in one or more administrations, applications, or dosages. The term can also include within its scope amounts effective to enhance or restore to substantially normal physiological function. [0053] As used herein, the term “therapeutically effective amount” refers to an amount that is sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms but is generally insufficient to cause adverse side effects. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration; the route of administration; the rate of excretion of the specific therapeutic agent employed; the duration of the treatment; drugs used in combination or coincidental with the specific therapeutic agent employed and like factors within the knowledge and expertise of the health practitioner and which may be well known in the medical arts. In the case of treating a particular disease or condition, in some instances, the desired response can be inhibiting the progression of the disease or condition. This may involve only slowing the progression of the disease temporarily. However, in other instances, it may be desirable to halt the progression of the disease permanently. This can be monitored by routine diagnostic methods known to one of ordinary skill in the art for any particular disease. The ATTORNEY DOCKET NO.330304-2010 desired response to treatment of the disease or condition also can be delaying the onset or even preventing the onset of the disease or condition. [0054] For example, it is well within the skill of the art to start doses of a therapeutic agent at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose can be divided into multiple doses for purposes of administration. Consequently, single dose compositions can contain such amounts or submultiples thereof to make up the daily dose. The dosage can be adjusted by the individual physician in the event of any contraindications. It is generally preferred that a maximum dose of the pharmacological agents of the invention (alone or in combination with other therapeutic agents) be used, that is, the highest safe dose according to sound medical judgment. It will be understood by those of ordinary skill in the art however, that a patient may insist upon a lower dose or tolerable dose for medical reasons, psychological reasons or for virtually any other reasons. [0055] A response to a therapeutically effective dose of a disclosed therapeutic agent and/or pharmaceutical composition, for example, can be measured by determining the physiological effects of the treatment or medication, such as the decrease or lack of disease symptoms following administration of the treatment or pharmacological agent. Other assays will be known to one of ordinary skill in the art and can be employed for measuring the level of the response. The amount of a treatment may be varied for example by increasing or decreasing the amount of a disclosed therapeutic agent and/or pharmaceutical composition, by changing the disclosed therapeutic agent and/or pharmaceutical composition administered, by changing the route of administration, by changing the dosage timing and so on. Dosage can vary, and can be administered in one or more dose administrations daily, for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. [0056] As used herein, the term "prophylactically effective amount" refers to an amount effective for preventing onset or initiation of a disease or condition. [0057] As used herein, the term "prevent" or "preventing" refers to precluding, averting, obviating, forestalling, stopping, or hindering something from happening, especially by advance action. It is understood that where reduce, inhibit or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed. ATTORNEY DOCKET NO.330304-2010 [0058] The term "pharmaceutically acceptable" describes a material that is not biologically or otherwise undesirable, i.e., without causing an unacceptable level of undesirable biological effects or interacting in a deleterious manner. [0059] The term "pharmaceutically acceptable salts", as used herein, means salts of the active principal agents which are prepared with acids or bases that are tolerated by a biological system or tolerated by a subject or tolerated by a biological system and tolerated by a subject when administered in a therapeutically effective amount. When therapeutic agents of the present disclosure contain relatively acidic functionalities, base addition salts can be obtained by contacting the neutral form of such therapeutic agents with a sufficient amount of the desired base, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable base addition salts include, but are not limited to; sodium, potassium, calcium, ammonium, organic amino, magnesium salt, lithium salt, strontium salt or a similar salt. When therapeutic agents of the present disclosure contain relatively basic functionalities, acid addition salts can be obtained by contacting the neutral form of such therapeutic agents with a sufficient amount of the desired acid, either neat or in a suitable inert solvent. Examples of pharmaceutically acceptable acid addition salts include, but are not limited to; those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydriodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, maleic, malonic, benzoic, succinic, suberic, fumaric, lactic, mandelic, phthalic, benzenesulfonic, p-tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as arginate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like. [0060] The term "pharmaceutically acceptable ester" refers to esters of therapeutic agents of the present disclosure which hydrolyze in vivo and include those that break down readily in the human body to leave the parent therapeutic agent or a salt thereof. Examples of pharmaceutically acceptable, non-toxic esters of the present disclosure include C 1 -to-C 6 alkyl esters and C 5 -to-C 7 cycloalkyl esters, although C 1 -to-C 4 alkyl esters are preferred. Esters of disclosed therapeutic agents can be prepared according to conventional methods. Pharmaceutically acceptable esters can be appended onto hydroxy groups by reaction of the therapeutic agent that contains the hydroxy group with acid and an alkylcarboxylic acid such as acetic acid, or with acid and an arylcarboxylic acid such as benzoic acid. In the case of therapeutic agents containing carboxylic acid groups, the pharmaceutically acceptable esters are prepared from therapeutic agents containing the carboxylic acid groups by reaction of the ATTORNEY DOCKET NO.330304-2010 therapeutic agent with base such as triethylamine and an alkyl halide, for example with methyl iodide, benzyl iodide, cyclopentyl iodide or alkyl triflate. They also can be prepared by reaction of the therapeutic agent with an acid such as hydrochloric acid and an alcohol such as ethanol or methanol. [0061] The term "pharmaceutically acceptable amide" refers to non-toxic amides of the present disclosure derived from ammonia, primary C 1 -to-C 6 alkyl amines and secondary C 1 -to-C 6 dialkyl amines. In the case of secondary amines, the amine can also be in the form of a 5- or 6-membered heterocycle containing one nitrogen atom. Amides derived from ammonia, C 1 -to-C 3 alkyl primary amides and C 1 -to-C 2 dialkyl secondary amides are preferred. Amides of disclosed therapeutic agents can be prepared according to conventional methods. Pharmaceutically acceptable amides can be prepared from therapeutic agents containing primary or secondary amine groups by reaction of the therapeutic agent that contains the amino group with an alkyl anhydride, aryl anhydride, acyl halide, or aroyl halide. In the case of therapeutic agents containing carboxylic acid groups, the pharmaceutically acceptable amides are prepared from therapeutic agents containing the carboxylic acid groups by reaction of the therapeutic agent with base such as triethylamine, a dehydrating agent such as dicyclohexyl carbodiimide or carbonyl diimidazole, and an alkyl amine, dialkylamine, for example with methylamine, diethylamine, and piperidine. They also can be prepared by reaction of the therapeutic agent with an acid such as sulfuric acid and an alkylcarboxylic acid such as acetic acid, or with acid and an arylcarboxylic acid such as benzoic acid under dehydrating conditions such as with molecular sieves added. The composition can contain a therapeutic agent of the present disclosure in the form of a pharmaceutically acceptable prodrug. [0062] The term "pharmaceutically acceptable prodrug" or "prodrug" represents those prodrugs of the therapeutic agents of the present disclosure which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit/risk ratio, and effective for their intended use. Prodrugs of the present disclosure can be rapidly transformed in vivo to a parent therapeutic agent having a structure of a disclosed compound, for example, by hydrolysis in blood. A thorough discussion is provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, V.14 of the A.C.S. Symposium Series, and in Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press (1987). [0063] As used herein, the term "derivative" refers to a therapeutic agent having a structure derived from the structure of a parent therapeutic agent (e.g., a therapeutic agent disclosed ATTORNEY DOCKET NO.330304-2010 herein) and whose structure is sufficiently similar to those disclosed herein and based upon that similarity, would be expected by one skilled in the art to exhibit the same or similar activities and utilities as the claimed compounds, or to induce, as a precursor, the same or similar activities and utilities as the claimed compounds. Exemplary derivatives include salts, esters, amides, salts of esters or amides, and N-oxides of a parent compound. [0064] As used herein, nomenclature for compounds, including organic compounds, can be given using common names, IUPAC, IUBMB, or CAS recommendations for nomenclature. When one or more stereochemical features are present, Cahn-Ingold-Prelog rules for stereochemistry can be employed to designate stereochemical priority, E/Z specification, and the like. One of skill in the art can readily ascertain the structure of a therapeutic agent if given a name, either by systemic reduction of the therapeutic agent structure using naming conventions, or by commercially available software, such as CHEMDRAW™ (Cambridgesoft Corporation, U.S.A.). [0065] Unless otherwise specified, temperatures referred to herein are based on atmospheric pressure (i.e., one atmosphere). [0066] Described herein are articles comprising wound coverings and wraps such as dressings and bandages, comprising a substrate and a releasable therapeutic agent in contact with one another. Also described herein are methods of administering the articles to a subject in need thereof. In various aspects, the subject can have a wound, injury, or infection. Other compositions, compounds, methods, features, and advantages of the present disclosure will be or become apparent to one having ordinary skill in the art upon examination of the following drawings, detailed description, and examples. It is intended that all such additional compositions, compounds, methods, features, and advantages be included within this description, and be within the scope of the present disclosure. B. DISCLOSED ARTICLES COMPRISING A SUBSTRATE AND A THERAPEUTIC AGENT [0067] In one aspect, the disclosure relates to articles comprising a substrate and a releasable therapeutic agent in contact with or attached to one another. [0068] In a further aspect, the substrate comprises a textile having hydroxyl groups in the textile yarn or filament, e.g., a textile, such as a fabric, comprising a yarn or filament comprising cotton, rayon, silk, or combinations thereof. A schematic illustration of a substrate is given in FIG.2A, which shows a polymer backbone, e.g., a cellulose backbone as found in a textile comprising cotton, rayon, silk, or combinations thereof. In some instances, the active therapeutic agent, e.g., glycyrrhetinic acid, is covalently linked to the substrate as ATTORNEY DOCKET NO.330304-2010 schematically shown in FIG. 2B. As shown in FIG. 2B, a substrate comprising a polymer comprising a plurality of hydroxy moieties along the polymer backbone in which some have been covalently linked to a therapeutic agent in which the covalent linkage may comprise one, two, or three covalent linkages between oxygen (derived from hydroxy moieties) along the polymer backbone to a silyl moiety (with the definitions of substituent groups as disclosed herein below). [0069] In a further aspect, the textile is a woven fabric, a knitted fabric, a non-woven fabric, or combinations thereof. It is understood that substrates can comprise other materials and is not limited to textile materials. Moreover, a substrate can comprise a composite material, e.g., a bilayer material wherein a first layer comprises a substrate and a releasable therapeutic agent in contact with or attached to one another and a second layer does not. In a further aspect, the therapeutic agent interacts with or is attached to the substrate via non-covalent interactions, e.g., van der Waals forces, ionic interactions, and combinations thereof, or via a covalent linkage that can release the therapeutic agent under normal use with a subject. [0070] In a further aspect, the articles comprising a substrate and a releasable therapeutic agent in contact with or attached to one another provide for tunable release of the therapeutic agent such that the therapeutic agent can be released in a short time frame (or immediate release) on the order of minutes to hours to longer time frames (or delayed release) on the order of hours to days or longer by varying the mode of interaction between the substrate and the releasable therapeutic agent from non-covalent interactions of different types to covalent interactions involving linkers of different length and chemical reactivities to mixtures of chemistries and covalent/non-covalent interactions between the releasable therapeutic agent and substrate. [0071] In one aspect, the disclosure relates to articles comprising medical or therapeutic wraps, coverings, and devices comprising a substrate and a releasable therapeutic agent in contact with or attached to one another that can be used of treatment of inflammation, atopic dermatitis and other clinical conditions associated with the skin and muscle. [0072] In one aspect, the disclosure relates to articles comprising wound coverings, dressings and bandages comprising a substrate and a releasable therapeutic agent in contact with or attached to one another. [0073] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate. In a still further aspect, the substrate comprises one or more hydroxyl groups. In a yet further aspect, the therapeutic agent is in contact with or attached to the ATTORNEY DOCKET NO.330304-2010 substrate via non-covalent bonds comprising hydrogen bond interactions with the one or more hydroxyl groups of the substrate. In an even further aspect, the therapeutic agent is in contact with or attached to the substrate via covalent bonds comprising a covalent bond with one or more oxygen atom derived from the one or more hydroxyl groups associated with the substrate. [0074] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below:

Cotton or Rayon Glycyrrhetinic acid (cellulose) In the foregoing, a specific therapeutic agent is depicted, glycyrrhetinic acid, but other therapeutic agents as described in the present disclosure capable of hydrogen bonding interactions with the substrate can be used in addition to or in lieu of glycyrrhetinic acid. Exemplary, but non-limiting therapeutic agents that could be used in addition to or in lieu of glycyrrhetinic acid in the article depicted above include penicillins (e.g., amoxicillin, flucoxacillin, and the like); cephalosporins (e.g., cefepime, cefalexin, and the like); streptomycin; neomycin; kanamycin; paromomycin; vancomycin; ciprofloxacin; linezolid; and combinations thereof. In the aspect shown above, the substrate can be a fabric or textile material comprising cotton, rayon, silk, and other substrate materials comprising one or more hydroxyl groups as described in the present disclosure such as synthetic fibers (e.g., polyester or polyamides) that are blends comprising cotton, rayon, silk, and other materials comprising one or more hydroxyl group. The article depicted above can be prepared by the disclosed methods. [0075] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below: ATTORNEY DOCKET NO.330304-2010

Substrate Glycyrrhetinic acid . In the foregoing, a specific therapeutic agent is depicted, glycyrrhetinic acid, but other therapeutic agents as described in the present disclosure capable of hydrogen bonding interactions with the substrate can be used in addition to or in lieu of glycyrrhetinic acid. Exemplary, but non-limiting therapeutic agents that could be used in addition to or in lieu of glycyrrhetinic acid in the article depicted above include penicillins (e.g., amoxicillin, flucoxacillin, and the like); cephalosporins (e.g., cefepime, cefalexin, and the like); streptomycin; neomycin; kanamycin; paromomycin; vancomycin; ciprofloxacin; linezolid; and combinations thereof. In the aspect shown above, the substrate can be a fabric or textile material comprising cotton, rayon, silk, and other substrate materials comprising one or more hydroxyl groups as described in the present disclosure such as synthetic fibers (e.g., polyester or polyamides) that are blends comprising cotton, rayon, silk, and other materials comprising one or more hydroxyl group. Articles comprising the therapeutic agent in contact or attached to a substrate having the structure shown in the formula above can be prepared by the disclosed methods. [0076] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below: ATTORNEY DOCKET NO.330304-2010

. In the foregoing, a specific therapeutic agent is depicted, glycyrrhetinic acid, but other therapeutic agents as described in the present disclosure capable of hydrogen bonding interactions with the substrate can be used in addition to or in lieu of glycyrrhetinic acid. Exemplary, but non-limiting therapeutic agents that could be used in addition to or in lieu of glycyrrhetinic acid in the article depicted above include penicillins (e.g., amoxicillin, flucoxacillin, and the like); cephalosporins (e.g., cefepime, cefalexin, and the like); streptomycin; neomycin; kanamycin; paromomycin; vancomycin; ciprofloxacin; linezolid; and combinations thereof. In the aspect shown above, the substrate can be a fabric or textile material comprising cotton, rayon, silk, and other substrate materials comprising one or more hydroxyl groups as described in the present disclosure such as synthetic fibers (e.g., polyester or polyamides) that are blends comprising cotton, rayon, silk, and other materials comprising one or more hydroxyl group. Articles comprising the therapeutic agent in contact or attached to a substrate having the structure shown in the formula above can be prepared by the disclosed methods. [0077] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below:

, wherein A is OH or a moiety having a structure shown in the formula:

; wherein Y is a moiety having a structure shown in the formula: ATTORNEY DOCKET NO.330304-2010

; wherein Z is selected from O, NH, and S; wherein m is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8.9, 10, 11, 12, 13, 14, 15, 16, 17, and 18; wherein n is an integer selected from 1, 2, and 3; and wherein q is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8.9, and 10. [0078] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below:

, wherein A is OH or a moiety having a structure shown in the formula:

wherein Y is a moiety having a structure shown in the formula:

wherein Z is selected from O, NH, and S; wherein m is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8.9, 10, 11, 12, 13, 14, 15, 16, 17, and 18; wherein n is an integer selected from 1, 2, and 3; and wherein q is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8.9, and 10. [0079] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below: ATTORNEY DOCKET NO.330304-2010

. In the foregoing, a specific therapeutic agent is depicted, glycyrrhetinic acid, but other therapeutic agents as described in the present disclosure capable of hydrogen bonding interactions with the substrate can be used in addition to or in lieu of glycyrrhetinic acid. Exemplary, but non-limiting therapeutic agents that could be used in addition to or in lieu of glycyrrhetinic acid in the article depicted above include penicillins (e.g., amoxicillin, flucoxacillin, and the like); cephalosporins (e.g., cefepime, cefalexin, and the like); streptomycin; neomycin; kanamycin; paromomycin; vancomycin; ciprofloxacin; linezolid; and combinations thereof. In the aspect shown above, the substrate can be a fabric or textile material comprising cotton, rayon, silk, and other substrate materials comprising one or more hydroxyl groups as described in the present disclosure such as synthetic fibers (e.g., polyester or polyamides) that are blends comprising cotton, rayon, silk, and other materials comprising one or more hydroxyl group. Articles comprising the therapeutic agent in contact or attached to a substrate having the structure shown in the formula above can be prepared by the disclosed methods. [0080] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below: ATTORNEY DOCKET NO.330304-2010

. In the foregoing, a specific therapeutic agent is depicted, glycyrrhetinic acid, but other therapeutic agents as described in the present disclosure capable of hydrogen bonding interactions with the substrate can be used in addition to or in lieu of glycyrrhetinic acid. Exemplary, but non-limiting therapeutic agents that could be used in addition to or in lieu of glycyrrhetinic acid in the article depicted above include penicillins (e.g., amoxicillin, flucoxacillin, and the like); cephalosporins (e.g., cefepime, cefalexin, and the like); streptomycin; neomycin; kanamycin; paromomycin; vancomycin; ciprofloxacin; linezolid; and combinations thereof. In the aspect shown above, the substrate can be a fabric or textile material comprising cotton, rayon, silk, and other substrate materials comprising one or more hydroxyl groups as described in the present disclosure such as synthetic fibers (e.g., polyester or polyamides) that are blends comprising cotton, rayon, silk, and other materials comprising one or more hydroxyl group. Articles comprising the therapeutic agent in contact or attached to a substrate having the structure shown in the formula above can be prepared by the disclosed methods. [0081] In a further aspect, the disclosed articles comprise a therapeutic agent in contact or attached to a substrate having the structure shown in the formula below: ATTORNEY DOCKET NO.330304-2010

. In the foregoing, a specific therapeutic agent is depicted, glycyrrhetinic acid, but other therapeutic agents as described in the present disclosure capable of hydrogen bonding interactions with the substrate can be used in addition to or in lieu of glycyrrhetinic acid. Exemplary, but non-limiting therapeutic agents that could be used in addition to or in lieu of glycyrrhetinic acid in the article depicted above include penicillins (e.g., amoxicillin, flucoxacillin, and the like); cephalosporins (e.g., cefepime, cefalexin, and the like); streptomycin; neomycin; kanamycin; paromomycin; vancomycin; ciprofloxacin; linezolid; and combinations thereof. In the aspect shown above, the substrate can be a fabric or textile material comprising cotton, rayon, silk, and other substrate materials comprising one or more hydroxyl groups as described in the present disclosure such as synthetic fibers (e.g., polyester or polyamides) that are blends comprising cotton, rayon, silk, and other materials comprising one or more hydroxyl group. Articles comprising the therapeutic agent in contact or attached to a substrate having the structure shown in the formula above can be prepared by the disclosed methods. C. SUBSTRATES [0082] In various aspects, the present disclosure comprises a therapeutic agent in contact or attached to a substrate. In a further aspect, the substrate can be a textile material or a fabric comprising a yarn, a fiber and/or a filament comprising one or more hydroxyl groups. In a still further aspect, the fabric can be a woven fabric, a knit fabric, a non-woven fabric, and combinations thereof. [0083] In a further aspect, the textile material or the fabric can comprise a yarn, a fiber, and/or a filament comprising plant fibers, animal fibers or synthetic fibers. In a still further aspect, the textile material or the fabric can comprise a yarn, a fiber, and/or a filament comprising cotton, rayon staple, flax, wool, viscose, silk and/or synthetic fibers. In a yet further aspect, the textile material or the fabric can comprise a yarn, a fiber, and/or a filament comprising polyamide, polyester, polypropylene, polyacrylics, and combinations thereof provided that comprise one ATTORNEY DOCKET NO.330304-2010 or more hydroxyl group or moiety in the polymer backbone or within a graft or sidechain linked to the polymer backbone. [0084] In a further aspect, the textile material is selected from cotton, silk, polyester, wool, rayon, nylon, pre-printed textile fabric, woven-fabric, dyed-woven fabric, raw fiber, non-woven fabric, silk, synthetic textile or bandage cloth, woven fabric or non- woven fabric and yarn, and combinations thereof. D. THERAPEUTIC AGENTS [0085] In various aspects, the present disclosure comprises a therapeutic agent in contact or attached to a substrate. In a further aspect, the therapeutic agent is an antimicrobial therapeutic agent, antibiotic therapeutic agent, antibacterial therapeutic agent, antifungal therapeutic agent, an anti-inflammatory therapeutic agent such as a non-steroidal anti- inflammatory agent (“NSAID”) or a steroid, an anti-pain therapeutic agent, analgesic therapeutic agent, an antiallegic therapeutic agent, an anesthetic therapeutic agent, an antihistamine therapeutic agent, and combinations thereof. [0086] In a further aspect, the therapeutic agent is an an antimicrobial therapeutic agent, antibiotic therapeutic agent, antibacterial therapeutic agent, and/or antifungal therapeutic agent. [0087] In a further aspect, the therapeutic agent is an antimicrobial therapeutic agent, antibiotic therapeutic agent, and/or antibacterial therapeutic agent and is selected from the group consisting of chloramphenicol, tetracyclines, synthetic and semi-synthesic penicillins, beta-lactames, quinolones, fluoroquinolnes, macrolide antibiotics, peptide antibiotics, cyclosporines and combinations thereof. In a still further aspect, the therapeutic agent is an antimicrobial therapeutic agent, antibiotic therapeutic agent, and/or antibacterial therapeutic agent and is selected from the group consisting of cefadroxil, cefazolin, cephalexin, cephalothin, cephapirin, cephacelor, cephprozil, cephadrine, cefamandole, cefonicid, ceforanide, cefuroxime, cefixime, cefoperazone, cefotaxime, cefpodoxime, ceftaxidime, ceftibuten, ceftizoxime, ceftriaxone, cefepime, cefmetazole, cefotetan, cefoxitin, loracarbef, imipenem, erythromycin (and erythromycin salts such as estolate, ethylsuccinate, gluceptate, lactobionate, stearate), azithromycin, clarithromycoin, dirithromycin, troleanomycin, penicillin V, peniciliin salts, and complexes, methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, amoxicillin, amoxicillin and clavulanate potassium, ampicillin, bacampicillin, carbenicillin indanyl sodium (and other salts of carbenicillin) mezlocillin, piperacillin, piperacillin and taxobactam, ticarcillin, ticarcillin and clavulanate potassium, clindamycin, vancomycin, novobiocin, aminosalicylic acid, capreomycin, cycloserine, ethambutol HC 1 and other salts, ATTORNEY DOCKET NO.330304-2010 ethionamide, and isoniazid, ciprofloxacin, levofloxacin, lomefloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, sulfacytine, suflamerazine, sulfamethazine, sulfamethixole, sulfasalazine, sulfisoxazole, sulfapyrizine, sulfadiazine, sulfmethoxazole, sulfapyridine, metronidazole, methenamine, fosfomycin, nitrofurantoin, trimethoprim, clofazimine, co- triamoxazole, pentamidine, and trimetrexate, and combinations thereof. In an yet further aspect, the therapeutic agent is an antimicrobial therapeutic agent, antibiotic therapeutic agent, and/or antibacterial therapeutic agent and is selected from the group consisting of azoleaic acid, erythromycin, bacitracin, zinc bacitracin, polymyxin, neomycin, chloramphenicol, tetracycline, minocycline, clindamycin, doxycycline, undecylenic acid and salts thereof, propionic acid and salts thereof, caprylic acid and salts thereof, ciprofloxacin, cephalosporins, benzoic acid, ciclopirox olamine, clotrimazole, econazole nitrate, metronidazole, miconazol nitrate, ketaconazole, oxiconazole, tolnaftate and combinations thereof. [0088] In a further aspect, the therapeutic agent is an antimicrobial therapeutic agent, antibiotic therapeutic agent, and/or antibacterial therapeutic agent and is selected from the group consisting of glycyrrhetinic acid or derivative thereof; a penicillin or derivative thereof, such as amoxicillin and/or flucoxacillin; a cephalosporin such as cefepime and/or cefalexin; streptomycin; neomycin; kanamycin; paromomycin; vancomycin; ciprofloxacin; linezolid; and combinations thereof. [0089] In a further aspect, the therapeutic agent is an an antifungal therapeutic agent. In a yet further aspect, the therapeutic agent is an antifungal therapeutic agent and is selected from the group consisting of amphotericin B, flucytosine, fluconazole, griseofulvin, miconazole nitrate, terbinafine hydrochloride, ketoconazole, itraconazole, undecylenic acid and chloroxylenol, ciclopirox, clotrimazole, butenafine hydrochloride, nystatin, naftifine hydrochloride, oxiconazole nitrate, selenium sulfide, econazole nitrate, terconazole, butoconazole nitrate, carbol- fuchsin, clioquinol, methylrosaniline chloride, sodium thiosulfate, sulconazole nitrate, terbinafine hydrochloride, tioconazole, tolnaftate, undecylenic acid and undecylenate salts (calcium undecylenate, copper undecylenate, zinc undecylenate) The following are representative examples of some antivirals that may be used in the invention: Acyclovir, Amantadine, Amprenavir, Cidofovir, Delavirdine, Didanosine, Famciclovir, Foscarnet, Ganciclovir, Indinavir, Interferon, Lamivudine, Nelfinavir, Nevirapine, Palivizumab, Penciclovir, Ribavirin, Rimantadine, Ritonavir, Saquinavir, Stavudine, Trifluridine, Valacyclovir, Vidarabine, Zalcitabine, Zidovudine The following are representative examples of agents for the treatment of cancer that may be used in accordance with the invention: carboplatin, busulfan, cisplatin, thiotepa, melphalan hydrochloride, cyclophosphamide, ATTORNEY DOCKET NO.330304-2010 ifosfamide, chlorambucil, mechlorethamine hydrochloride, carmustine, lomustine, streptozocin, polifeprosan 20, dexrazoxane, dronabinol, granisetron hydrochloride, fluconazole, erythropoietin, octreotide acetate, pilocarpine hydrochloride, etidronate disodium, pamidronate disodium, allopurinol sodium, amifostine, filgrastim, mesna, ondansetron hydrochloride, dolasetron mesylate, leucovorin calcium, sargramostim, levamisole hydrochloride, doxorubicin hydrochloride, idarubicin hydrochloride, mitomycin, daunorubicin citrate, plicamycin, daunorubicin hydrochloride, bleomycin sulfate, mitoxantrone hydrochloride, valrubicin, dactinomycin, fludarabine phosphate, cytarabine, mercaptopurine, thioguanine, methotrexate sodium, cladribine, floxuridine, capecitabine, anastrozole, bicalutamide, tamoxifen citrate, testolactone, nilutamide, methyltestosterone, flutamide, toremifene citrate, goserelin acetate, estramustine phosphate sodium, ethinyl estradiol, esterified estrogen, leuprolide acetate, conjugated estrogens, megestrol acetate, aldesleukin, medroxyprogesterone acetate, dacarbazine, hydroxyurea, etoposide phosphate, megestrol acetate, paclitaxel, etoposide, teniposide, trastuzumab, rituximab, vinorelbine tartrate, denileukin diftitox, gemcitabine hydrochloride, vincristine sulfate, vinblastine sulfate, asparaginase, edrophonium chloride, bacillus calmette and guerin, irinotecan hydrochloride, pegaspargase, docetaxel, interferon alfa-2a, recombinant, tretinoin, porfimer sodium, interferon alfa-2b, recombinant, procarbazine hydrochloride, topotecan hydrochloride, altretamine, fluorouracil, prednisolone sodium phosphate, cortisone acetate, dexamethasone, dexamethasone sodium sulfate, dexamethasone acetate, hydrocortisone sodium phosphate, hydrocortisone, prednisolone, methylprednisolone sodium succinate, betamethasone sodium phosphate, betamethasone acetate, letrozole, mithramycin, mitotane, pentostatin, perfosfamide, raloxifene, and combinations thereof. [0090] In a further aspect, the therapeutic agent is a prodrug or compound that can release a therapeutically useful peroxide, e.g., a benzoyl peroxide. [0091] In a further aspect, therapeutic agent is an NSAID. In a still further aspect, the NSAID is selected from piroxicam, aspirin, carprofen, diclofenac, fenoprofen, flufenamic acid, flurbiprofen, ibufenac, ibuprofen, indomethacin, isoxicam, ketoprofen, meclofenamic acid, naproxen, oxaprozin, pranoprofen, tenoxicam, zomepirac, diflunisal, sulindac and tolmetin and combinations thereof. In a yet further aspect, the NSAID can be a salicylic acid derivative, such as, but not limited to, aspirin, sodium salicylate, choline magnesium trislicylate, salsalate, diflunisal, salicylsalicylic acid, sulfasalazine, olsalazine. In a still further aspect, the NSAID can be a para-aminophenol derivative such as acetaminophen. In an even further aspect, the NSAID can be an indole and indole acetic acid such as indomethacin, sulindac, etodolac. In a yet further aspect, the NSAID can be an aryl acetic acid such as tolmetin, diclofenac, ketorolac. ATTORNEY DOCKET NO.330304-2010 In a still further aspect, the NSAID can be an arylpropionic acid such as ibuprofen, naproxen, flubiprofen, ketoprofen, fenoprofen, oxaprozin. In an even further aspect, the NSAID can be an anthranilic acid or fenamate such as mefenamic acid or meclofenamic acid. In a yet further aspect, the NSAID can be an enolic acids such as an oxicam, including, but not limited to, piroxicam or tenoxicam, or a pyrazolidinedione, including, but not limited to phenylbutazone or oxyphenthratrazone. In a still further aspect, the NSAID can be an alkenone such as nabumetone. [0092] The disclosed therapeutic agents encompass their pharmaceutical salts and derivatives or analogues, including bioisosteric equivalents. [0093] In various aspects, it is contemplated herein that the disclosed therapeutic agents further comprise their biosteric equivalents. The term “bioisosteric equivalent” refers to therapeutic agents or groups that possess near equal molecular shapes and volumes, approximately the same distribution of electrons, and which exhibit similar physical and biological properties. Examples of such equivalents are: (i) fluorine vs. hydrogen, (ii) oxo vs. thia, (iii) hydroxyl vs. amide, (iv) carbonyl vs. oxime, (v) carboxylate vs. tetrazole. Examples of such bioisosteric replacements can be found in the literature and examples of such are: (i) Burger A, Relation of chemical structure and biological activity; in Medicinal Chemistry Third ed., Burger A, ed.; Wiley-Interscience; New York, 1970, 64-80; (ii) Burger, A.; “Isosterism and bioisosterism in drug design”; Prog. Drug Res.1991, 37, 287-371; (iii) Burger A, “Isosterism and bioanalogy in drug design”, Med. Chem. Res.1994, 4, 89-92; (iv) Clark R D, Ferguson A M, Cramer R D, “Bioisosterism and molecular diversity”, Perspect. Drug Discovery Des.1998, 9/10/11, 213-224; (v) Koyanagi T, Haga T, “Bioisosterism in agrochemicals”, ACS Symp. Ser. 1995, 584, 15-24; (vi) Kubinyi H, “Molecular similarities. Part 1. Chemical structure and biological activity”, Pharm. Unserer Zeit 1998, 27, 92-106; (vii) Lipinski C A.; “Bioisosterism in drug design”; Annu. Rep. Med. Chem. 1986, 21, 283-91; (viii) Patani G A, LaVoie E J, “Bioisosterism: A rational approach in drug design”, Chem. Rev. (Washington, D.C.) 1996, 96, 3147-3176; (ix) Soskic V, Joksimovic J, “Bioisosteric approach in the design of new dopaminergic/serotonergic ligands”, Curr. Med. Chem.1998, 5, 493-512 (x) Thornber C W, “Isosterism and molecular modification in drug design”, Chem. Soc. Rev.1979, 8, 563-80. [0094] In further aspects, bioisosteres are atoms, ions, or molecules in which the peripheral layers of electrons can be considered substantially identical. The term bioisostere is usually used to mean a portion of an overall molecule, as opposed to the entire molecule itself. Bioisosteric replacement involves using one bioisostere to replace another with the expectation of maintaining or slightly modifying the biological activity of the first bioisostere. The bioisosteres in this case are thus atoms or groups of atoms having similar size, shape ATTORNEY DOCKET NO.330304-2010 and electron density. Preferred bioisosteres of esters, amides or carboxylic acids are therapeutic agents containing two sites for hydrogen bond acceptance. In one embodiment, the ester, amide or carboxylic acid bioisostere is a 5-membered monocyclic heteroaryl ring, such as an optionally substituted 1H-imidazolyl, an optionally substituted oxazolyl, 1H- tetrazolyl, [1,2,4]triazolyl, or an optionally substituted [1,2,4]oxadiazolyl. [0095] In various aspects, it is contemplated herein that the disclosed therapeutic agents further comprise their isotopically labelled or isotopically-substituted variants, i.e., therapeutic agents identical to those described, but for the fact that one or more atoms are replaced by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature. Examples of isotopes that can be incorporated into therapeutic agents of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine and chlorine, such as ² H, ³ H, ¹³ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O, ³⁵ S, ¹⁸ F and ³⁶ Cl, respectively. Therapeutic agents further comprise prodrugs thereof, and pharmaceutically acceptable salts of said therapeutic agents or of said prodrugs which contain the aforementioned isotopes and/or other isotopes of other atoms are within the scope of this invention. Certain isotopically labelled therapeutic agents of the present invention, for example those into which radioactive isotopes such as ³H and ¹⁴C are incorporated, are useful in drug and/or substrate tissue distribution assays. Tritiated, i.e., ³H, and carbon-14, i.e., ¹⁴C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with heavier isotopes such as deuterium, i.e., ²H, can afford certain therapeutic advantages resulting from greater metabolic stability, for example increased in vivo half-life or reduced dosage requirements and, hence, may be preferred in some circumstances. Isotopically labelled therapeutic agents of the present invention and prodrugs thereof can generally be prepared by carrying out the procedures below, by substituting a readily available isotopically labelled reagent for a non- isotopically labelled reagent. [0096] In various aspects, the disclosed therapeutic agents can possess at least one center of asymmetry, they can be present in the form of their racemates, in the form of the pure enantiomers and/or diastereomers or in the form of mixtures of these enantiomers and/or diastereomers. The stereoisomers can be present in the mixtures in any arbitrary proportions. In various aspects, provided this is possible, the disclosed therapeutic agents can be present in the form of the tautomers. [0097] Thus, methods which are known per se can be used, for example, to separate the disclosed therapeutic agents which possess one or more chiral centers and occur as racemates into their optical isomers, i.e., enantiomers or diastereomers. The separation can be effected by means of column separation on chiral phases or by means of recrystallization ATTORNEY DOCKET NO.330304-2010 from an optically active solvent or using an optically active acid or base or by means of derivatizing with an optically active reagent, such as an optically active alcohol, and subsequently cleaving off the residue. [0098] In various aspects, the disclosed therapeutic agents can be in the form of a co-crystal. The term “co-crystal” means a physical association of two or more molecules which owe their stability through non-covalent interaction. One or more components of this molecular complex provide a stable framework in the crystalline lattice. In certain instances, the guest molecules are incorporated in the crystalline lattice as anhydrates or solvates, see e.g., “Crystal Engineering of the Composition of Pharmaceutical Phases. Do Pharmaceutical Co-crystals Represent a New Path to Improved Medicines?” Almarasson, O., et. al., The Royal Society of Chemistry, 1889-1896, 2004. Preferred co-crystals include p-toluenesulfonic acid and benzenesulfonic acid. [0099] The term “pharmaceutically acceptable co-crystal” means one that is compatible with the other ingredients of the formulation and not deleterious to the recipient thereof. [0100] In a further aspect, the disclosed therapeutic agents can be isolated as solvates and, in particular, as hydrates of a disclosed compound, which can be obtained, for example, by crystallization from a solvent or from aqueous solution. In this connection, one, two, three or any arbitrary number of solvate or water molecules can combine with the therapeutic agents according to the invention to form solvates and hydrates. [0101] The disclosed therapeutic agents can be used in the form of salts derived from inorganic or organic acids. Pharmaceutically acceptable salts include salts of acidic or basic groups present in the disclosed compounds. Suitable pharmaceutically acceptable salts include base addition salts, including alkali metal salts, e.g., sodium or potassium salts; alkaline earth metal salts, e.g., calcium or magnesium salts; and salts formed with suitable organic ligands, e.g., quaternary ammonium salts, which may be similarly prepared by reacting the drug therapeutic agent with a suitable pharmaceutically acceptable base. The salts can be prepared in situ during the final isolation and purification of the therapeutic agents of the present disclosure; or following final isolation by reacting a free base function, such as a secondary or tertiary amine, of a disclosed therapeutic agent with a suitable inorganic or organic acid; or reacting a free acid function, such as a carboxylic acid, of a disclosed therapeutic agent with a suitable inorganic or organic base. [0102] Acidic addition salts can be prepared in situ during the final isolation and purification of a disclosed compound, or separately by reacting moieties comprising one or more nitrogen ATTORNEY DOCKET NO.330304-2010 groups with a suitable acid. In various aspects, acids which may be employed to form pharmaceutically acceptable acid addition salts include such inorganic acids as hydrochloric acid, sulphuric acid and phosphoric acid and such organic acids as oxalic acid, maleic acid, succinic acid and citric acid. In a further aspect, salts further include, but are not limited, to the following: hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzensulfonate, p- toluenesulfonate, butyrate, camphorate, camphorsulfonate, digluconate, glycerophosphate, hemisulfate, heptanoate, hexanoate, fumarate, hydrochloride, 2-hydroxyethanesulfonate (isethionate), nicotinate, 2-naphthalenesulfonate, oxalate, pectinate, persulfate, 3- phenylpropionate, picrate, pivalate, propionate, succinate, tartrate, thiocyanate, phosphate, glutamate, bicarbonate, undecanoate, and pamoate (i.e., 1,1'-methylene-bis-(2-hydroxy-3- naphthoate)) salts. Also, basic nitrogen-containing groups can be quatemized with such agents as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chloride, bromides, and iodides; dialkyl sulfates like dimethyl, diethyl, dibutyl, and diamyl sulfates, long chain halides such as decyl, lauryl, myristyl and stearyl chlorides, bromides and iodides, aralkyl halides like benzyl and phenethyl bromides, and others. [0103] Basic addition salts can be prepared in situ during the final isolation and purification of a disclosed compound, or separately by reacting carboxylic acid moieties with a suitable base such as the hydroxide, carbonate or bicarbonate of a pharmaceutical acceptable metal cation or with ammonia, or an organic primary, secondary or tertiary amine. Pharmaceutical acceptable salts include, but are not limited to, cations based on the alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium, aluminum salts and the like, as well as nontoxic ammonium, quaternary ammonium, and amine cations, including, but not limited to ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, and the like. Other representative organic amines useful for the formation of base addition salts include diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like. In further aspects, bases which may be used in the preparation of pharmaceutically acceptable salts include the following: ammonia, L-arginine, benethamine, benzathine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)-ethanol, ethanolamine, ethylenediamine, N- methyl-glucamine, hydrabamine, 1H-imidazole, L-lysine, magnesium hydroxide, 4-(2- hydroxyethyl)-morpholine, piperazine, potassium hydroxide, 1-(2-hydroxyethyl)-pyrrolidine, secondary amine, sodium hydroxide, triethanolamine, tromethamine and zinc hydroxide. ATTORNEY DOCKET NO.330304-2010 E. METHODS OF MAKING THE DISCLOSED ARTICLES [0104] In various aspects, the disclosed articles can be prepared by the methods disclosed herein. [0105] In a further aspect, a disclosed article comprising:

Cotton or Rayon Glycyrrhetinic acid (cellulose) , can be prepared by incubating a substrate, e.g., fabric or textile material as disclosed herein, with a solution of the therapeutic agent, e.g., glycyrrhetinic acid as shown above, in a suitable solvent, e.g., water or dichloromethane, at a suitable concentration, e.g., about 100-350 mg of an activated form of therapeutic agent per milliliter of solvent, e.g., an acyl halide analogue of the therapeutic agent such as the acyl chloride analogue of glycyrrheticinic acid. In some instances, the solvent can further comprise a catalyst, e.g., 0.1 w/v% DMSO. The solution of therapeutic agent can then be applied to the substrate in an amount of 100-^^^^^^/^RI^WKH^ solution per square centimeter of substrate, or in an amount of therapeutic agent of from about 1 mg per cm² of substrate to about 100 mg per cm² of substrate. In a still further aspect, the substrate can be washed prior to incubation with the solution comprising the therapeutic agent, e.g., washed with water and/or a detergent, then washed with isopropanol, then dried under a vacuum at a temperature of about 20 °C to about 30 °C. The solution and substrate can be incubated together for a suitable period of time at a suitable temperature. In a further aspect, the article depicted above can be prepared by exposing the substrate to a solution comprising the therapeutic agent, and incubated for a suitable period of time, such as from about 1 minute to about 24 hours, at a suitable temperature, such as from about 10 °C to about 40 °C. In a yet further aspect, the article depicted above can be prepared by exposing the substrate to a solution comprising the therapeutic agent, and incubated for a suitable period of time, such as from about 1 minute to about 24 hours, at a suitable temperature, such as a gradual temperature ramp from about -10 °C to about 25 °C In a still further aspect, the temperature during incubation can be gradual temperature ramp from about -10 °C to about 30 °C. Following incubation, the substrate is removed from the solution and washed with a suitable solvent, e.g., dichloromethane, and vacuum dried at a suitable temperature, e.g., about 25 °C. ATTORNEY DOCKET NO.330304-2010 Appropriate storage conditions can be determined by the skilled artisan, e.g., storage in an airtight or evacuated container can improve stability of the foregoing article. [0106] In a further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1:1 to about 1:10. In a still further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1:2 to about 1:7. In a yet further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1:1 to about 1:3. [0107] In a further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 100 mg therapeutic agent to about 1 cm² of substrate. In a still further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 50 mg therapeutic agent to about 1 cm² of substrate. In a yet further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 25 mg therapeutic agent to about 1 cm² of substrate. In an even further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 10 mg therapeutic agent to about 1 cm² of substrate. [0108] In a further aspect, a disclosed article comprising:

Substrate Glycyrrhetinic acid , can be prepared by incubating a substrate, e.g., fabric or textile material as disclosed herein, with a solution of the therapeutic agent, e.g., glycyrrhetinic acid as shown above, in a suitable solvent, e.g., water and/or DMSO, a suitable concentration, e.g., about 100-350 mg of therapeutic agent per milliliter of solvent. The solution of therapeutic agent can then be applied to the substrate in an amount of 100-^^^^^ ^/^ RI^ WKH^ VROXWLRQ^ SHU^ VTXDUH^ FHQWLPHWHU^ RI^ substrate, or in an amount of therapeutic agent of from about 1 mg per cm² of substrate to about 100 mg per cm² of substrate. In various aspects, the therapeutic agent may be formed into a paste by grinding with water and then spread onto the substrate. In a still further aspect, the substrate can be washed prior to incubation with the solution comprising the therapeutic agent, e.g., washed with water and/or a detergent, then washed with isopropanol, then dried under a vacuum at a temperature of about 20 °C to about 30 °C. The solution and substrate can be incubated together for a suitable period of time at a suitable temperature. In a further aspect, the article depicted above can be prepared by exposing the substrate to a solution comprising the therapeutic agent, and incubated for a suitable period of time, such as from about 1 minute to about 24 hours, at a suitable temperature, such as from about 10 °C to about 40 °C. In a still further aspect, the temperature during incubation can be from about 20 °C to about 30 °C.

[0109] In a further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :10. In a still further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :2 to about 1 :7. In a yet further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :3 to about 1 :5.

[0110] In a further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 100 mg therapeutic agent to about 1 cm² of substrate. In a still further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 50 mg therapeutic agent to about 1 cm² of substrate. In a yet further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 25 mg therapeutic agent to about 1 cm² of substrate. In an even further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 10 mg therapeutic agent to about 1 cm² of substrate.

[0111] In a further aspect, a disclosed article comprising:

can be prepared by incubating a substrate, e.g., fabric or textile material as disclosed herein, with a solution of the therapeutic agent, e.g., glycyrrhetinic acid as shown above, in a suitable solvent, e.g., DMSO, a suitable concentration, e.g., about 100-350 mg of therapeutic agent per milliliter of solvent comprising about 0.01 v/v% ammonia to about 1% v/v% ammonia. The solution of therapeutic agent can then be applied to the substrate in an amount of 100-1000 pL of the solution per square centimeter of substrate, or in an amount of therapeutic agent of from about 1 mg per cm² of substrate to about 100 mg per cm² of substrate. In a still further aspect, the substrate can be washed prior to incubation with the solution comprising the therapeutic agent, e.g., washed with water, then washed with isopropanol, then dried under a vacuum at a temperature of about 20 °C to about 30 °C, and then rinsed with a 1% aqueous ammonia solution, followed by draining excess ammonia before incubating with the solution comprising the therapeutic agent. The solution and substrate can be incubated together for a suitable period of time at a suitable temperature. In a further aspect, the article depicted above can be prepared by exposing the substrate to a solution comprising the therapeutic agent, and incubated for a suitable period of time, such as from about 1 minute to about 24 hours, at a suitable temperature, such as from about 10 °C to about 40 °C. In a still further aspect, the temperature during incubation can be from about 20 °C to about 30 °C.

[0112] In a further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :10. In a still further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :2 to about 1 :7. In a yet further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :3 to about 1 :5. [0113] In a further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 100 mg therapeutic agent to about 1 cm² of substrate. In a still further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 50 mg therapeutic agent to about 1 cm² of substrate. In a yet further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 25 mg therapeutic agent to about 1 cm² of substrate. In an even further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 10 mg therapeutic agent to about 1 cm² of substrate.

[0114] In a further aspect, a disclosed article comprising:

comprising a substrate, e.g., fabric or textile material as disclosed herein, can be prepared by incubating as shown in the reaction schemes as disclosed herein.

[0115] In a further aspect, a disclosed method of making a disclosed article is provided in the following reaction scheme:

wherein A is hydroxy or a moiety having a structure represented by the formula: ; wherein X is a halogen; wherein Y is a moiety having a structure

represented by the formula: wherein n is an integer selected from 1 , 2, and 3; wherein m is an an

integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, and 18; and wherein q is an integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, and 10.

[0116] In a further aspect, the above generalized reaction scheme can be carried out as shown below, although other methods and conditions are suitable as determined by the skilled artisan:

Briefly, sequence for preparation of the article comprising the composition shown above invoves: (a) reaction of the substrate with a suitable alkoxy silyl amine; (b) reaction the substrate comprising a covalently linked alkoxy silyl amine with a suitable linker; and (c) reaction of the material generated in the previous step with an activated form of the therapeutic agent. In a still further aspect, the substrate can be washed prior to incubation with the solution comprising the alkoxy silyl amine, e.g., washed with water, then washed with isopropanol, then dried under a vacuum at a temperature of about 20 °C to about 30 °C. A silyl amine solution comprising the suitable alkoxy silyl amine, e.g., 3-(triethoxysilyl) propane-1 -amine, is prepared in a suitable solvent, e.g., THF, at an appropriate concentration, e.g., 1 part alkoxy silyl amine with 2 parts solvent. The substrate is immersed in the silyl amine solution and allowed to react, e.g., heating at about 60 °C to about 90 °C for a suitable period of time, e.g., about 1 hr to about 6 hours. The substrate is removed from the silyl amine solution, and allowed to dry, e.g., at room temperature, with protection from light. A suitable linker solution is prepared comprising a suitable linker, e.g., aconitic anhydride acyl chloride, in a suitable solvent, e.g., dichloromethane. The linker solution can further comprise a suitable catalyst, e.g., DMSO in about 0.1 v/v% to about 1 % v/v%. The linker solution is added in a sufficient amount to provide, on a weight basis, a substrate: linker ratio of about 1 :1 to about 1 :10, and in a particular instance about 1 :4 to about 1 :6. The reaction can be carried out under an inert atmosphere, e.g., nitrogen or argon. The substrate is separated from the linker solution, and washed, e.g., washed with excess solvent such as used to prepare the linker solution. The substrate can then be dried under a vacuum at ambient temperature. In the last step, the substrate comprising the alkoxy silyl amine and linker is reacted with a suitable therapeutic agent that is chemically activated, e.g., an acyl chloride derivative of the therapeutic agent. In the reaction depicted above, the therapeutic agent is glycyrrhetinic acyl chloride. In this last step, an activated therapeutic agent solution is prepared, e.g., glycyrrhetinic acyl chloride in dichloromethane as a solvent. The activated therapeutic agent solution can further comprise a catalytic amount of a second agent, e.g., DMSO in about 0.1 v/v% to about 1% v/v%. The reaction is carried out under an inert atmosphere, e.g., nitrogen or argon. The activated therapeutic agent solution is added in a sufficient amount to provide, on a weight basis, a substrate: activated therapeutic agent ratio of about 1 :1 to about 1 :10, and in a particular instance a ratio of about 1 :4 to about 1 :6. The reacted substrate comprising a covalently linked alkoxy silyl amine linked to a linker group and further comprising a releasable therapeutic agent is then washed and dried under a vacuum at ambient temperature, e.g., about 20 °C to about 30 °C. The therapeutic agent, e.g., glycyrrhetinic acid as shown above, in an amount of therapeutic agent of from about 1 mg per cm² of substrate to about 25 mg per cm² of substrate.

[0117] In a further aspect, a disclosed method of making a disclosed article is provided in the following reaction scheme:

wherein A is hydroxy or a moiety having a structure represented by the formula: wherein X is a halogen; wherein Y is a moiety having a structure

represented by the formula: wherein n is an integer selected from 1 , 2, and 3; wherein m is an an

integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 , 12, 13, 14, 15, 16, 17, and 18; and wherein q is an integer selected from 1 , 2, 3, 4, 5, 6, 7, 8, 9, and 10.

[0118] In a further aspect, the above generalized reaction scheme can be carried out as shown below, although other methods and conditions are suitable as determined by the skilled artisan:

Briefly, sequence for preparation of the article comprising the composition shown above invoves: (a) reaction of the substrate with a suitable alkoxy silyl amine; (b) reaction the substrate comprising a covalently linked alkoxy silyl amine with a suitable linker; and (c) reaction of the material generated in the previous step with an activated form of the therapeutic agent. In a still further aspect, the substrate can be washed prior to incubation with the solution comprising the alkoxy silyl amine, e.g., washed with water, then washed with isopropanol, then dried under a vacuum at a temperature of about 20 °C to about 30 °C. A silyl amine solution comprising the suitable alkoxy silyl amine, e.g., 3-(triethoxysilyl) propane-1 -amine, is prepared in a suitable solvent, e.g., THF, at an appropriate concentration, e.g., 1 part alkoxy silyl amine with 2 parts solvent. The substrate is immersed in the silyl amine solution and allowed to react, e.g., heating at about 60 °C to about 90 °C for a suitable period of time, e.g., about 1 hr to about 6 hours. The substrate is removed from the silyl amine solution, and allowed to dry, e.g., at room temperature, with protection from light. A suitable linker solution is prepared comprising a suitable linker, e.g., aconitic anhydride acyl chloride, in a suitable solvent, e.g., dichloromethane. The linker solution can further comprise a suitable catalyst, e.g., DMSO in about 0.1 v/v% to about 1 % v/v%. The linker solution is added in a sufficient amount to provide, on a weight basis, a substrate: linker ratio of about 1 :1 to about 1 :10, and in a particular instance about 1 :4 to about 1 :6. The reaction can be carried out under an inert atmosphere, e.g., nitrogen or argon. The substrate is separated from the linker solution, and washed, e.g., washed with excess solvent such as used to prepare the linker solution. The substrate can then be dried under a vacuum at ambient temperature. In the last step, the substrate comprising the alkoxy silyl amine and linker is reacted with a suitable therapeutic agent that is chemically activated, e.g., an acyl chloride derivative of the therapeutic agent. In the reaction depicted above, the therapeutic agent is glycyrrhetinic acyl chloride. In this last step, an activated therapeutic agent solution is prepared, e.g., glycyrrhetinic acyl chloride in dichloromethane as a solvent. The activated therapeutic agent solution can further comprise a catalytic amount of a second agent, e.g., DMSO in about 0.1 v/v% to about 1% v/v%. The reaction is carried out under an inert atmosphere, e.g., nitrogen or argon. The activated therapeutic agent solution is added in a sufficient amount to provide, on a weight basis, a substrate: activated therapeutic agent ratio of about 1 :1 to about 1 :10, and in a particular instance a ratio of about 1 :4 to about 1 :6. The reacted substrate comprising a covalently linked alkoxy silyl amine linked to a linker group and further comprising a releasable therapeutic agent is then washed and dried under a vacuum at ambient temperature, e.g., about 20 °C to about 30 °C. The therapeutic agent, e.g., glycyrrhetinic acid as shown above, in an amount of therapeutic agent of from about 1 mg per cm² of substrate to about 25 mg per cm² of substrate.

[0119] In a further aspect, the ratio of substrate to alkoxy silyl amine on a weight basis can be from about 1 :1 to about 1 :10. In a still further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :0 to about 1 :7. In a yet further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :6. In an even further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :2 to about 1 :6.

[0120] In a further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :10. In a still further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :0 to about 1 :5. In a yet further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :0 to about 1 :3. In an even further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :2.

[0121] In a further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 100 mg therapeutic agent to about 1 cm² of substrate. In a still further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 50 mg therapeutic agent to about 1 cm² of substrate. In a yet further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 25 mg therapeutic agent to about 1 cm² of substrate. In an even further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 10 mg therapeutic agent to about 1 cm² of substrate.

[0122] In a further aspect, a disclosed article comprising:

comprising a substrate, e.g., fabric or textile material as disclosed herein, can be prepared by incubating as shown in the following reaction scheme:

Briefly, sequence for preparation of the article comprising the composition shown above invoves: (a) reaction of the substrate with a suitable alkoxy silyl amine; (b) reaction the substrate comprising a covalently linked alkoxy silyl amine with a suitable linker; and (c) reaction of the material generated in the previous step with an activated form of the therapeutic agent. In a still further aspect, the substrate can be washed prior to incubation with the solution comprising the alkoxy silyl amine, e.g., washed with water, then washed with isopropanol, then dried under a vacuum at a temperature of about 20 °C to about 30 °C. A silyl amine solution comprising the suitable alkoxy silyl amine, e.g., 3-(triethoxysilyl) propane- 1 -amine, is prepared in a suitable solvent, e.g., THF, at an appropriate concentration, e.g., 1 part alkoxy silyl amine with 2 parts solvent. The substrate is immersed in the silyl amine solution and allowed to react, e.g., heating at about 60 °C to about 90 °C for a suitable period of time, e.g., about 1 hr to about 6 hours. The substrate is removed from the silyl amine solution, and allowed to dry, e.g., at room temperature, with protection from light. A suitable linker solution is prepared comprising a suitable linker, e.g., maleic anhydride acyl chloride, in a suitable solvent, e.g., dichloromethane. The linker solution can further comprise a suitable catalyst, e.g., DMSO in about 0.1 v/v% to about 1 % v/v%. The linker solution is added in a sufficient amount to provide, on a weight basis, a substrate: linker ratio of about 1 :1 to about 1 :10, and in a particular instance about 1 :4 to about 1 :6. The reaction can be carried out under an inert atmosphere, e.g., nitrogen or argon. The substrate is separated from the linker solution, and washed, e.g., washed with excess solvent such as used to prepare the linker solution. The substrate can then be dried under a vacuum at ambient temperature. In the last step, the substrate comprising the alkoxy silyl amine and linker is reacted with a suitable therapeutic agent that is chemically activated, e.g., an acyl chloride derivative of the therapeutic agent. In the reaction depicted above, the therapeutic agent is glycyrrhetinic acyl chloride. In this last step, an activated therapeutic agent solution is prepared, e.g., glycyrrhetinic acyl chloride in dichloromethane as a solvent. The activated therapeutic agent solution can further comprise a catalytic amount of a second agent, e.g., DMSO in about 0.1 v/v% to about 1% v/v%. The reaction is carried out under an inert atmosphere, e.g., nitrogen or argon. The activated therapeutic agent solution is added in a sufficient amount to provide, on a weight basis, a substrate: activated therapeutic agent ratio of about 1 :1 to about 1 :10, and in a particular instance a ratio of about 1 :6 to about 1 :8. The reacted substrate comprising a covalently linked alkoxy silyl amine linked to a linker group and further comprising a releasable therapeutic agent is then washed and dried under a vacuum at ambient temperature, e.g., about 20 °C to about 30 °C. The therapeutic agent, e.g., glycyrrhetinic acid as shown above, in an amount of therapeutic agent of from about 1 mg per cm² of substrate to about 25 mg per cm² of substrate.

[0123] In a further aspect, the ratio of substrate to alkoxy silyl amine on a weight basis can be from about 1 :1 to about 1 :10. In a still further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :0 to about 1 :7. In a yet further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :6. In an even further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :2 to about 1 :6.

[0124] In a further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :10. In a still further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :0 to about 1 :5. In a yet further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :0 to about 1 :3. In an even further aspect, the ratio of substrate to therapeutic agent on a weight basis can be from about 1 :1 to about 1 :2.

[0125] In a further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 100 mg therapeutic agent to about 1 cm² of substrate. In a still further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 50 mg therapeutic agent to about 1 cm² of substrate. In a yet further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 25 mg therapeutic agent to about 1 cm² of substrate. In an even further aspect, the amount of therapeutic agent to the substrate is about 1 mg therapeutic agent to about 1 cm² of substrate to about 10 mg therapeutic agent to about 1 cm² of substrate.

[0126] In a further aspect, a disclosed article comprising:

comprising a substrate, e.g., fabric or textile material as disclosed herein, can be prepared by incubating as described above with omission of the reaction step comprising reaction with the alkoxy silyl amine.

A. METHODS OF TREATING A SUBJECT

[0127] In various aspects, present disclosure relates to use of the disclosed articles for methods of treatment of a subject. In a further aspect, the subject is a patient diagnosed with having atopic dermatitis. In a still further aspect, the subject is a patient diagnosed with having a wound, injury to their skin, an infection, an inflammation, topical pain, and combinations thereof. In a further aspect, the present disclosure relates to use of the disclosed articles for methods of treatment of a subject have a clinical condition involving or comprising a microbial infection and/or an inflammatory aspect.

[0128] In a further aspect, the present disclosure relates to use of the disclosed articles for methods of treatment of a subject having atopic dermatitis. In a yet further aspect, the present disclosure relates to use of the disclosed articles for methods of treatment of a subject having atopic dermatitis, wherein the subject has one or more skin excoriations. In a still further aspect, the present disclosure relates to use of the disclosed articles for methods of treatment of a subject having atopic dermatitis, wherein the method comprises administering a disclosed article comprising a substrate contacting or attached to glycyrrhetinic acid.

[0129] In a further aspect, the present disclosure relates to use of the disclosed articles for methods of treatment of a subject having psoriasis.

[0130] In a further aspect, the present disclosure relates to use of the disclosed articles for methods of treatment of a subject having acne.

[0131] In a further aspect, the foregoing method can further comprise co-administration, e.g., simultaneously or sequentially, a further therapeutic agent associated with treatment of atopic dermatitis, e.g., nemolizumab or an equivalent thereof, an IL-13 antagonist, an anti-OX40 antagonist, a anti-TSLP antibody, a ceramide derivative, acetylcholine receptor antagonist, a corticosteroid, an antihistamine, a calcineurin inhibitor, a phosphodiesterase inhibitor, an antimicrobial agent, and other therapeutic agents as known to the skilled artisan. In a still further aspect, the further therapeutic agent can be administered by a suitable route of administration for that agent and the disclosed article is separately administered to the skin or excoriation. In a yet further aspect, the article can further comprise poly-gamma-glutamic acid is used at a concentration of 0.001 to 5 % by weight, and preferably 0.01 to 3 % by weight.

[0132] In a further aspect, the subject has an active infection associated with a bacterium, a fungus, a microbial organism, and combinations thereof. In a still further aspect, the subject has an active infection associated with Pseudomonas aeruginosa, Vancomycin Resistant Enterococci, Klebsiella pneumoniae, Streptococcus pneumoniae, Salmonella sp., Escherichia coli, extensively drug resistant tuberculosis, Acinetobacter baumannii, Neisseria gonorrhaeae, Clostridium difficile, and Candida sp. related infections. In a yet further aspect, the subject has an active infection associated with a macrofungi, such as Ganoderma lucidum (GL) and Pycnoporus sanguineus (PY). In an even further aspect, the subject has an active infection associated with a microfungi, such as Hypocrea rufa (Hr), Phoma foveata (PH), Curvularia sp. (Cur), Fusarium sp. and Pestalotiopsis sp. In a still further aspect, the subject has an active infection associated with an actinomycetes such as Streptomyces species such as Streptomyces sp. (unidentified) Streptomyces cacaoi, and Streptomyces parvulus. In a yet further aspect, the subject has an active infection associated with Pseudomonas sp., Chromobacterium sp., Serratia marcescens, and combinations thereof. In an even further aspect, the subject has an active infection associated with MRSA, VRSA, P. aeruginosa, Vancomycin Resistant Enterococci, Klebsiella pneumoniae, Streptococcus pneumoniae, Salmonella sp., Escherichia coli, extensively drug resistant tuberculosis, Acinetobacter baumannii, Neisseria gonorrhaeae, Clostridium difficile, Candida sp. related infections, and combinations thereof. In a still further aspect, the subject has an active infection associated with Streptococcus pyogenes, Streptococcus aglactiae, Streptococcus pneumonia, Staphylococcus aureus, Neisseria gonorhoeae, Haemophilus influenza, Vibrio cholera, E. coli, Salmonella typhimurium, Shigella dysenteriae, Shigella dysenteriae, Proteus mirabilis, Pseudomonas aeruginosa, Bacillus anthracis, Bacillus anthracis spores, Bacillus cereus, Bacillus cereus spores, Bacillus subtilus, Bacillus subtilus spores, Yersinia enterocolitica, or Yersinia pseudotuberculosis. In a yet further aspect, the subject has an active infection associated with a fungus such as Candida albicans, Candida tropicalis, and combinations thereof. [0133] From the foregoing, it will be seen that aspects herein are well adapted to attain all the ends and objects hereinabove set forth together with other advantages which are obvious, and which are inherent to the structure.

[0134] While specific elements and steps are discussed in connection to one another, it is understood that any element and/or steps provided herein is contemplated as being combinable with any other elements and/or steps regardless of explicit provision of the same while still being within the scope provided herein.

[0135] It will be understood that certain features and subcombinations are of utility and may be employed without reference to other features and subcombinations. This is contemplated by and is within the scope of the claims.

[0136] Since many possible aspects may be made without departing from the scope thereof, it is to be understood that all matter herein set forth or shown in the accompanying drawings and detailed description is to be interpreted as illustrative and not in a limiting sense.

[0137] It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and is not intended to be limiting. The skilled artisan will recognize many variants and adaptations of the aspects described herein. These variants and adaptations are intended to be included in the teachings of this disclosure and to be encompassed by the claims herein.

[0138] Now having described the aspects of the present disclosure, in general, the following Examples describe some additional aspects of the present disclosure. While aspects of the present disclosure are described in connection with the following examples and the corresponding text and figures, there is no intent to limit aspects of the present disclosure to this description. On the contrary, the intent is to cover all alternatives, modifications, and equivalents included within the spirit and scope of the present disclosure.

B. EXAMPLES

[0139] The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices and/or methods claimed herein are made and evaluated, and are intended to be purely exemplary of the disclosure and are not intended to limit the scope of what the inventors regard as their disclosure. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric.

1. EXAMPLE 1

[0140] Glycyrrhetinic acid was solubilized in DMSO to a obtain clear solution. For example, 800 mg of Glycyrrhetinic acid was solubilized in 3 mb of DMSO. A cotton fabric was washed with water and isopropanol and dried in a high vacuum at room temperature, then the Glycyrrhetinic acid DMSO solution, 375 pb was applied to the dried fabric, 2 cm², then dried using a stream of air at 25 °C to a constant weight.

[0141] The amount of therapeutic agent incorporated into the fabric as follows: a 2 square cm fabric was incubated in 3.0 mb phosphate buffer pH 5.5 and at specific times 50 pb of the buffer was removed and analyzed using bC-MS. The bC-MS method utilized an Agilent 1200 bC equipped with 6120 single quad mass spectrometers (detector-UV -Vis 254 nm), using a mobile phase comprising acetonitrile and water, with a gradient of 20% acetonitrile in water to 100% acetonitrile over 11 minutes. The bC-MS column was Infinity poroschell 120EC-C18, 2.1 internal diameter, 75mm length; 2.7-micron particle size.

[0142] The rate of release of therapeutic agent under the foregoing conditions is shown in

FIG. 1.

[0143] It will be apparent to those skilled in the art that various modifications and variations can be made in the present disclosure without departing from the scope or spirit of the disclosure. Other aspects of the disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the disclosure disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the disclosure being indicated by the following claims.

Claims

ATTORNEY DOCKET NO.330304-2010

wherein Y is a moiety having a structure shown in the formula:

wherein Z is selected from O, NH, and S; wherein m is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8.9, 10, 11, 12, 13, 14, 15, 16, 17, and 18; wherein n is an integer selected from 1, 2, and 3; and wherein q is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8.9, and 10; or combinations of one or more of the foregoing structures. 2. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the following formula:

. 3. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the following formula:

ATTORNEY DOCKET NO.330304-2010

. 4. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the following formula:

. 5. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the following formula:

. 6. The article of claim 5, wherein the substrate and therapeutic agent comprise a structure having the following formula: ATTORNEY DOCKET NO.330304-2010

. 7. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the following formula:

. 8. The article of claim 7, wherein the substrate and therapeutic agent comprise a structure having the following formula:

. 9. A method of treating a subject comprising administering to the subject an article of claim 1. 10. The method of claim 9, wherein the subject is diagnosed with clinical condition selected from an inflammatory disorder, a wound, an infection, and combinations thereof. 11. The method of claim 10, wherein the clinical condition is atopic dermatitis. 12. The method of claim 3, wherein the clinical condition is psoriasis. 13. The method of claim 10, wherein the clinical condition is acne. 14. The method of claim 10, wherein the clinical condition is a wound.