Compositions and methods for controlled release of therapeutic agents from articles

Abstract

The present disclosure relates to articles that are therapeutic dressings and wraps comprising a substrate and a releasable therapeutic agent in contact with or attached to one another. Articles comprising therapeutic dressings and wraps are useful for treating atopic dermatitis and / or wounds. The substrate can include a fabric having hydroxyl groups on the textile yarns or filaments, such as cotton, rayon, silk, or a combination thereof. The therapeutic agent interacts with or is attached to the substrate through non-covalent interactions, or alternatively, through covalent bonds that can release the therapeutic agent. This abstract is intended as a scanning tool for searching in a particular technical field and is not intended to limit the disclosure.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No. 63 / 423,929, filed November 9, 2022, which is incorporated herein by reference in its entirety.

[0002] Statement Regarding Federally Sponsored Research This disclosure was made with U.S. government support under Grant No. R43AT011486 awarded by the National Institutes of Health. The U.S. government has certain rights in this disclosure. [Background technology]

[0003] Wounds are common from childhood through old age. They are a significant problem, especially among the elderly and nursing home populations at the end of life. Pressure ulcers alone cause significant human and financial losses, with treatment costs averaging more than $1,200 per patient per month. CDC data indicate that approximately 2% to 28% of nursing home residents have pressure ulcers. Diabetic ulcers similarly cause significant morbidity and expense, with diabetes accounting for approximately 82,000 amputations per year in the United States, averaging $30,000 per amputation. Other wounds plaguing nursing home and end-of-life populations are those resulting from arterial and venous insufficiency, traumatic wounds, and non-healing surgical wounds.

[0004] Any penetration of the skin carries the risk of potential infection, which is relevant for simple wounds caused by accident or negligence, for surgical procedures performed under controlled conditions utilizing different biomaterials for incision and / or wound closure and dressing, and for the diverse range of in vivo implantable textile fabrics, constructed textile articles, and textile-containing mechanical instruments and devices that 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 one of a variety of commercially available bandages. There are many special bandages designed to keep the wound moist or absorb exudate. Some special bandages are impregnated with silver to prevent infection. Typically, bandages are attached with either self-adhesive or tape, or in some cases, applied with a compression wrap. Recent high-tech approaches are available for wound care using burn wound treatment and vacuum pumps. While these can be effective, they are very expensive, and healing times are still measured in weeks or months. Therefore, it is desirable to have an inexpensive wound treatment method and composition that shortens the time required for wounds to heal.

[0006] The rational use of antimicrobial agents against infections, especially for uncomplicated wound treatment, has been generally advocated and previously reviewed in detail [Non-Patent Document 1]. Similarly, despite recent advances in sterilization procedures used in clinical / surgical settings, major concerns regarding the increasing incidence of infections resulting from biocompatible fabrics, articles, and devices implanted within the body have been considered and discussed as the primary objective and focus of the FDA / EPA / CDC / AAMI Joint Meeting [Non-Patent Document 2]. Furthermore, the use of mechanisms for delivering antibiotics and antimicrobial agents in general, particularly via time-dependent sustained-release delivery systems, has been explored to prevent or reduce the severity of infections in implanted biodegradable materials [Non-Patent Document 3]. All of these considerations lead to the same conclusion: Regardless of the use of antibiotics, infections must be prevented or controlled for all implantable biomaterials (including fabrics, articles, and devices), regardless of necessity or medical purpose.

[0007] Another clinical indication with unmet needs is atopic dermatitis. The number of people suffering from atopic dermatitis is rapidly increasing due to changes in living environment and dietary habits. It is one of the most common skin diseases seen in people with a history of allergic disorders. It is a chronic skin disease that involves an immune response and often co-occurs with other atopic diseases, such as urticaria, metal allergies, allergic asthma, or allergic rhinitis, and its main skin symptoms are dryness and itching. In addition, it is believed to have a genetic component, and often belongs to a family history of atopic diseases.

[0008] The etiological mechanism of atopic dermatitis remains unclear in many respects, and no method for treating it has yet been established. Although its etiology is unknown, it is believed to involve genetic predisposition and immune system abnormalities. It is known as an inflammatory skin disease with a complex etiology, including dry skin, increased sensitivity to irritation compared to normal human skin, skin infections caused by bacteria, viruses, fungi, and the like, emotional and environmental factors, and the like. The main skin symptoms of atopic dermatitis include severe itching, dryness, rash, redness, exudative crusts, scaling, and the like. It is known that even modern medicine does not offer a basic treatment for atopic dermatitis, and therefore patients must simply avoid factors that induce atopic dermatitis and use treatments or therapeutic agents that can help alleviate symptoms without providing a basic treatment.

[0009] Atopic dermatitis is a very common skin disease affecting 0.5-1% of the general population and 5-10% of children. It most frequently occurs between 2-6 months of age, especially within the first year of life, with 85% of children with atopic dermatitis developing the disease before the age of 5. In 50% of patients, the condition spontaneously resolves by the time the patient is 2 years old, while in 25% of patients, symptoms do not improve until adolescence, and the remaining 25% will experience some degree of eczema throughout their lives. [Prior art documents] [Non-patent literature]

[0010] [Non-Patent Document 1] Rodgers, KG, Emer. Med. Clin. N. Am. 10:753 (1992) [Non-patent document 2] Proceedings,Infection Control Symposium:Influence Of Medical Device Design,USDept.of Health and Human Services,Bethesda,Md.,January 1995 [Non-patent document 3] Sasmor et al., J. Vasc. Sur. 14:521 (1993) Summary of the Invention [Problem to be solved by the invention]

[0011] Despite advances in wound care research, there remains a lack of articles, products, and systems that meet the need for adequate and effective wound treatment or treatment of atopic dermatitis. These and other needs are met by the present disclosure. [Means for solving the problem]

[0012] In accordance with the object(s) of the present disclosure, as embodied and broadly described herein, the present disclosure relates in one aspect to articles that are therapeutic dressings and wraps, comprising a substrate and a releasable therapeutic agent in contact with or adhered to one another. In various aspects, articles comprising therapeutic dressings and wraps are useful for treating atopic dermatitis. In other aspects, the articles are wound dressings and wraps, such as dressings and bandages, that are useful for treating wounds.

[0013] In a further embodiment, the substrate comprises a textile having hydroxyl groups in the textile yarns or filaments, such as a textile comprising yarns or filaments comprising cotton, rayon, silk, or a combination thereof. It is understood that the substrate can comprise other materials and is not limited to textile materials. Furthermore, the substrate can comprise a composite material, e.g., a bilayer material, in which a first layer comprises a substrate and a releasable therapeutic agent that are in contact with or attached to each other, and a second layer does not. In a further embodiment, 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 covalent bonds that can release the therapeutic agent under normal use with a subject.

[0014] In a further aspect, an article comprising a substrate and a releasable therapeutic agent in contact with or attached to one another provides tunable release of the therapeutic agent, such that the therapeutic agent can be released over a short time frame of minutes to hours (or immediate release) to a long time frame of hours to days or more (or delayed release) by varying the mode of interaction between the substrate and the releasable therapeutic agent from different types of non-covalent interactions to covalent interactions, including linkers of different lengths and chemical reactivities to chemical mixtures, and covalent / non-covalent interactions between the releasable therapeutic agent and the substrate.

[0015] An article is disclosed that includes a substrate and a therapeutic agent.

[0016] Also disclosed are methods of making the disclosed articles.

[0017] Also disclosed are methods of treating a subject using the disclosed articles.

[0018] Other systems, methods, features, and advantages of the present disclosure will be or become apparent to one skilled in the art upon examination of the following figures and detailed description. All such additional systems, methods, features, and advantages are intended to 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 embodiments can be used with all embodiments of the present disclosure taught herein. Furthermore, the individual features of the dependent claims, and all optional and preferred features and modifications of the described embodiments, are combinable and interchangeable with each other.

[0019] 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. [Brief explanation of the drawings]

[0020] [Figure 1] 1 shows representative data for the release of a therapeutic agent from a disclosed substrate that includes an attached therapeutic agent. [Figure 2A] 1 shows a representative schematic of a substrate before and after covalent attachment to a therapeutic agent. 2 shows a schematic of a substrate comprising a polymer containing multiple hydroxy moieties along the polymer backbone. [Figure 2B]

[0023] Figure 1 shows a representative schematic of a substrate before and after covalent attachment to a therapeutic agent. Figure 2 shows a schematic of a substrate comprising a polymer containing multiple hydroxy moieties along the polymer backbone, some of which are covalently attached to a therapeutic agent. The covalent attachment may include one, two, or three covalent bonds between oxygen (from hydroxy moieties) and silyl moieties (with substituent definitions disclosed herein below) along the polymer backbone.

[0021] Additional advantages of the present disclosure will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the present disclosure. The advantages of the present 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 summary and the following detailed description are exemplary and explanatory only and are not restrictive of the present disclosure, as claimed. DETAILED DESCRIPTION OF THE INVENTION

[0022] Numerous modifications and other embodiments of the disclosed compositions and methods 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. It is therefore to be understood that the disclosure is not limited to the particular embodiments disclosed, and that modifications and other embodiments are intended to be included within the scope of the appended claims. Those skilled in the art will recognize many variations and adaptations of the embodiments described herein. These variations and adaptations are within the teachings of the present disclosure and are intended to be encompassed by the scope of 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 skilled in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has distinct components and features that may be readily separated from or combined with the features of any of the other embodiments without departing from the scope or spirit of the disclosure.

[0025] Any recited method may be carried out in the order of events recited or in any other order that is logically possible. That is, unless expressly stated otherwise, it is in no way intended that any method or aspect described herein be construed as requiring that its steps be performed in a particular order. Accordingly, unless a method claim specifically recites in the claim or specification that the steps are to be limited to a particular order, no order is intended to be inferred in any respect. This holds for any possible implicit basis for interpretation, including the obvious meaning derived from the arrangement of steps or operational flow, grammatical construction or punctuation, or logical matters regarding the number or type of aspects described in the specification.

[0026] All publications mentioned herein are incorporated 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 should 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 may be different from the actual publication dates, which can be independently confirmed.

[0027] Although aspects of the present disclosure may be described and claimed in particular statutory classes, such as statutory classes, this is for convenience only, and those skilled in the art will understand that each aspect of the present disclosure may be described and claimed in any statutory class.

[0028] It should also be understood that the terms used herein are for the purpose of describing particular embodiments only and are not intended to be limiting. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art to which the disclosed compositions and methods belong. Terms such as those defined in commonly used dictionaries should be interpreted to have a meaning consistent with their meaning in the context of the present specification and the relevant art, and should not be interpreted in an idealized or overly formal sense unless otherwise explicitly defined herein.

[0029] Prior to describing the various aspects of this disclosure, the following definitions are provided and should be used unless otherwise indicated. Additional terms may be defined elsewhere in this disclosure.

[0030] A.Definition As used herein, "comprising" is to be interpreted as specifying the presence of the features, integers, steps, or components described as referenced, but does not exclude the presence or addition of one or more features, integers, steps, or components, or groups thereof. Furthermore, the terms "by," "comprising," "comprises," "comprised of," "including," "includes," "included," "involving," "involves," "involved," and "such as" are each used in their open, non-limiting sense and may be used interchangeably. Furthermore, the term "comprising" is intended to include examples and embodiments encompassed by the terms "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. When preceding a list of elements, phrases such as "at least one of" modify the entire list of elements and not each individual element 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, stereochemical priority, E / Z specification, etc. can be designated using the Cahn-Ingold-Prelog rules for stereochemistry. One skilled in the art can readily confirm the structure of a therapeutic agent by systematically reducing the therapeutic agent structure using the naming rules, if any, or by commercially available software such as CHEMDRAW™ (Cambridgesoft Corporation, USA).

[0033] Reference to "a" chemotherapeutic agent is not limited to a single molecule of a compound, but refers to one or more molecules of the chemotherapeutic agent. Furthermore, the one or more molecules may or may not be identical, so long as they fall within the category of compounds. Thus, for example, "a" chemotherapeutic agent is understood to include one or more molecules of that chemical agent, which may or may not be identical (e.g., different isotope ratios, enantiomers, etc.).

[0034] As used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, but without limitation, reference to a "therapeutic agent," a "substrate," or a "wrap" includes two or more such therapeutic agents, substrates, or wraps, etc.

[0035] References to "a / an" therapeutic compound, protein, and antibody refer to one or more molecules of the compound, protein, and antibody, rather than being limited to a single molecule of the compound, protein, and antibody, respectively. Furthermore, the one or more molecules may or may not be identical, so long as they fall within the category of compound, protein, and antibody. Thus, for example, "an" antibody is understood to include one or more antibody molecules of the antibody, which may or may not be identical (e.g., different isotypes and / or different antigen binding sites, as may be found in polyclonal antibodies).

[0036] It should be noted that ratios, concentrations, amounts, and other numerical data may be expressed herein in a range format. It is further understood that the endpoints of each of the ranges are significant in relation to the other endpoint, and independently of the other endpoint. It is also understood that, in addition to the value itself, each value is also disclosed herein as "about" that particular value. For example, if a value of "10" is disclosed, "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 is understood that the particular value forms a further aspect. For example, if a value of "about 10" is disclosed, "10" is also disclosed.

[0037] When a range is expressed, a further embodiment includes from the one particular value and / or to the other particular value. For example, when 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; for example, the phrase "from x to y" includes ranges from "x" to "y," as well as ranges from greater than "x" to less than "y." Ranges may also be expressed as upper limits, e.g., "about x, y, z, or less," which should be interpreted to include the specific ranges of "about x," "about y," and "about z," as well as ranges "less than x," "less than y," and "less than z." Similarly, the phrase "about x, y, z, or more" should be interpreted to include the specific ranges of "about x," "about y," and "about z," as well as ranges "more than x," "more than y," and "more than z." Additionally, when "x" and "y" are numerical values, the phrase "about 'x' to 'y'" includes "about 'x' to about 'y'."

[0038] It should be understood that such range formats are used for convenience and brevity and, thus, should be interpreted flexibly to include not only the numerical values ​​explicitly recited as the limits of the range, but also all individual numerical values ​​or subranges subsumed within that range, as if each numerical value and subrange were explicitly recited. To illustrate, a numerical range of "about 0.1% to 5%" should be interpreted not only to include the explicitly recited values ​​of about 0.1% to about 5%, but also to include individual values ​​(e.g., about 1%, about 2%, about 3%, and about 4%) and subranges (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%, as well as other possible subranges) within the indicated range.

[0039] As used herein, the terms "about," "approximately," "nearly," and "substantially" mean that the quantity or value in question may be an exact value or a value that provides an equivalent result or effect 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 may be larger or smaller, as desired, to reflect tolerances, conversion factors, rounding, measurement errors, and other factors known to those skilled in the art, so as to provide an equivalent result or effect. In some situations, a value that provides an equivalent result or effect cannot be reasonably determined. In such cases, "about" and "approximately" are generally understood to mean a nominal value that exhibits a ±10% variation, unless otherwise indicated or implied. In general, a quantity, size, formulation, parameter, or other quantity or characteristic is "about," "approximately," or "nearly," regardless of whether it is expressly described as such. When "about," "approximately," or "nearly" is used in front of a quantitative value, it is understood that the parameter also includes the particular quantitative value itself, unless specifically stated otherwise.

[0040] As used herein, the term "contacting" refers to bringing a disclosed therapeutic agent, compound, chemical, substrate, or material into proximity with another disclosed therapeutic agent, compound, chemical, substrate, or material, as indicated by context. For example, a therapeutic agent contacting a substrate refers to the therapeutic agent being in proximity to the substrate by interacting with and binding to the substrate via ionic, dipolar, and / or van der Waals interactions. In some cases, contacting can include both physical and chemical interactions between the indicated components. It is understood that chemical interactions can include 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 the therapeutic agent being in physical and chemical contact with the substrate, which can include covalent, ionic, and non-covalent interactions.

[0041] In further aspects, the term "contacting" in the particular context of a therapeutic agent contacting a clinically relevant target can refer to bringing the disclosed therapeutic agent into proximity with a cell, target protein, or other biological entity in such a manner that the disclosed therapeutic agent or pharmaceutical composition can affect the activity of the 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, cofactor, factor, or protein on which the activity of the cell, target protein, or other biological entity itself depends. In more specific instances, "contacting" can refer to bringing the therapeutic agent into proximity with or into contact with a wound, injury, or skin of a subject.

[0042] As used herein, the term "optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes both instances in which the event or circumstance occurs and instances in which the event or circumstance does not occur.

[0043] As used herein, "administering" can refer to administration of a therapeutic agent associated with or in contact with a substrate. Administration can be continuous, releasable over a specific time interval, and / or intermittent. In various embodiments, the preparation can be administered therapeutically, i.e., administered to treat an existing disease or condition. In further various embodiments, the preparation can be administered prophylactically, i.e., administered for the prevention of a disease or condition.

[0044] As used herein, a "therapeutic agent" can refer to any substance, compound, molecule, etc. that can be biologically active or otherwise capable of inducing a pharmacological, immunogenic, biological, and / or physiological effect in a subject to which it is administered 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 all or part of the composition's effect is due. A therapeutic agent can be a secondary therapeutic agent, or in other words, the component(s) of a composition to which additional portions of the composition and / or other effects are due. Thus, the term encompasses therapeutic agents or chemical entities traditionally considered to be drugs, vaccines, and biopharmaceuticals, including molecules such as proteins, peptides, hormones, nucleic acids, gene constructs, etc. Examples of therapeutic agents are described in well-known references such as the Merck Index (14th ed.), Physicians' Desk Reference (64th ed.), and The Pharmacological Basis of Therapeutics (12th ed.), and include, without limitation, pharmaceuticals; vitamins; mineral supplements; substances used in the treatment, prevention, diagnosis, cure, or mitigation of disease or illness; substances that affect the structure or function of the body; or prodrugs that become biologically active or more active after being placed in a physiological environment.For example, the term "therapeutic agent" includes adjuvants; anti-infectives such as antibiotics and antivirals; analgesics and analgesic combinations, anorexics, anti-inflammatory drugs, antiepileptics, local and general anesthetics, hypnotics, sedatives, antipsychotics, neuroleptics, antidepressants, anxiolytics, antagonists, neuron blocking drugs, anticholinergic and cholestatic drugs, antimuscarinic and muscarinic drugs, antiadrenergic drugs, antiarrhythmic drugs, antihypertensive drugs, hormones, and nutrients, antiarthritic drugs, antiasthmatic drugs, antiepileptic drugs, antihistamines, antiemetic drugs, antineoplastic drugs, antipruritics, antipyretics; anticonvulsants, cardiovascular preparations (including calcium channel blockers, beta blockers, beta agonists, and antiarrhythmic drugs), antihypertensive drugs, diuretics, vasodilators; central nervous system stimulants; cough and cold medications; Included are therapeutic agents or compositions for use in all major therapeutic areas, including, but not limited to, decongestants; diagnostic agents; hormones; bone growth stimulators and bone resorption inhibitors; immunosuppressants; muscle relaxants; psychostimulants; sedatives; tranquilizers; proteins, peptides, and fragments thereof (whether naturally occurring, chemically synthesized, or recombinantly produced); and nucleic acid molecules (either ribonucleotides (RNA) or deoxyribonucleotides (DNA), including polymeric forms of two or more nucleotides, both double-stranded and single-stranded molecules, gene constructs, expression vectors, antisense molecules, etc.), small molecules (e.g., doxorubicin), and other biologically active macromolecules such as proteins and enzymes. Drugs can be biologically active agents used in medical applications, including veterinary medicine, and in agriculture, such as plants, as well as other areas. The term therapeutic agent also includes, but is not limited to, a pharmaceutical agent; a vitamin; a mineral supplement; a substance used to treat, prevent, diagnose, cure, or mitigate a disease or illness; or a substance that affects the structure or function of the body; or a prodrug that becomes biologically active or more active after being placed in a defined physiological environment.

[0045] As used herein, a "kit" refers to an assemblage of at least two components that comprise the kit. Together, the components constitute a functional unit for a given purpose. The individual member components may be physically packaged together or separately. For example, a kit that includes instructions for using the kit may or may not physically include the instructions with the other individual member components. Alternatively, the instructions may be supplied as separate member components, either in paper form, or in electronic form, such as on a computer-readable memory device, or downloaded from an internet website, or as a recorded presentation.

[0046] As used herein, "instructions(s)" means documents describing relevant materials or methodologies associated with the kit. These materials may include any combination of the following: background information, a list of components and their availability information (such as purchasing information), brief or detailed protocols for using the kit, troubleshooting, references, technical support, and any other relevant documentation. The instructions may be supplied in either paper form, or electronic form, such as on a computer-readable memory device, or downloaded from an internet website or as a recorded presentation, either with the kit or as a separate member component. The instructions may include one or more documents and are meant to include future updates.

[0047] As used herein, "attached" may be used instead of and interchangeably with "contact," and "attached" refers to a covalent or non-covalent interaction between two or more molecules. Non-covalent interactions include ionic bonds, electrostatic interactions, van der Waals forces, dipole-dipole interactions, dipole-induced dipole interactions, London dispersion forces, hydrogen bonding, halogen bonding, electromagnetic interactions, π-π interactions, cation-π interactions, anion-π interactions, polar-π interactions, and the hydrophobic effect.

[0048] As used herein, the term "subject" can be a vertebrate, such as a mammal, fish, bird, reptile, or amphibian. Thus, the subject of the methods disclosed herein 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, it is intended to include adult and juvenile subjects, whether male or female. In one aspect, the subject is a mammal. A patient refers to a subject suffering from a disease or disorder. The term "patient" includes human and veterinary subjects.

[0049] As used herein, the terms "treating" and "treatment" can generally refer to obtaining a desired pharmacological and / or physiological effect. The effect can be, but is not necessarily, preventative in terms of preventing or partially preventing a disease, symptom, or condition, such as an infection. The effect can be therapeutic in terms of partially or completely curing a disease, condition, symptom, or adverse effects resulting from the disease, disorder, or condition. The term "treatment" as used herein can include any treatment of a subject, particularly a human, of an overt infection, infection, or wound, including a wound without injury, and can include any one or more of the following: (a) preventing a disease or condition from occurring in a subject who may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting a disease or condition, i.e., preventing its development; and (c) alleviating a disease or condition, i.e., alleviating or ameliorating a disease and / or its symptoms or condition. As used herein, the term "treatment" can refer to therapeutic treatment alone, prophylactic treatment alone, or both therapeutic and prophylactic treatment. Those in need of treatment (subjects in need of treatment) may include those already with the disorder and / or those in whom a disorder is to be prevented. As used herein, the term "treating" may include inhibiting a disease, disorder, or condition, e.g., preventing its progression, as well as alleviating a disease, disorder, or condition, e.g., causing regression of a disease, disorder, and / or condition. Treating a disease, disorder, or condition may include ameliorating at least one symptom of a particular disease, disorder, or condition even if the underlying pathophysiology is unaffected, such as treating a subject's pain by administering an analgesic even though such an agent does not treat the cause of the pain.

[0050] As used herein, "dose," "unit dose," or "dosage" can refer to a physically discrete unit suitable for use in treating a subject, e.g., mg of therapeutic agent per gram of substrate or mg of therapeutic agent per unit area of ​​substrate, each unit containing a predetermined amount of the disclosed therapeutic agent calculated to produce one or more desired responses associated with its administration.

[0051] As used herein, "therapeutic" can refer to treating, curing, and / or ameliorating a disease, disorder, condition, or side effect, or reducing the rate of progression of a disease, disorder, condition, or side effect.

[0052] As used herein, the term "effective amount" refers to an amount sufficient to achieve a desired modification of the physical properties of a composition or material. For example, an "effective amount" of a therapeutic agent refers to an amount sufficient to achieve a desired improvement or outcome associated with the referenced component, e.g., a desired clinical result and / or therapeutic release rate. The specific level in terms of weight percent or mole percent in a composition required as an effective amount depends on various factors, including the amount and type of substrate, the amount and type of mode of interaction between the substrate and the therapeutic agent, the chemical structure of the linker (if present), and the type of therapeutic agent. In a further aspect, an "effective amount" can refer to an amount of a therapeutic agent or pharmaceutical composition disclosed herein that is sufficient to produce a beneficial or desired biological, emotional, medical, or clinical response in a cell, tissue, system, animal, or human. An effective amount can be administered in one or more administrations, applications, or dosages. The term also includes within its scope an amount effective to enhance or restore substantially normal physiological function.

[0053] As used herein, the term "therapeutically effective amount" refers to an amount sufficient to achieve a desired therapeutic result or to have an effect on undesired symptoms, but generally insufficient to cause adverse side effects. The specific therapeutically effective dose level for any particular patient will depend on various factors, including the disorder being treated and the severity of the disorder; the specific composition used; the patient's age, weight, general health, sex, and diet; the timing of administration; the route of administration; the excretion rate of the specific therapeutic agent used; the duration of treatment; drugs used in combination with or concurrently with the specific therapeutic agent used; and similar factors within the knowledge and expertise of the medical practitioner and well known in the medical field. When treating a particular disease or condition, in some cases, the desired response may be to inhibit the progression of the disease or condition. This may include only temporarily slowing the progression of the disease. However, in other cases, it may be desirable to permanently halt the progression of the disease. This can be monitored by routine diagnostic methods known to those skilled in the art for any particular disease. The desired response to treating a disease or condition may also be to delay or even prevent the onset of the disease or condition.

[0054] For example, it is well within the skill of the art to initiate a dose of a therapeutic agent at a level lower than that required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved. If desired, the effective daily dose can be divided into multiple doses for administration. Consequently, a single-dose composition can contain such amounts or submultiples thereof to make up the daily dose. In the event of any contraindications, the dosage can be adjusted by the individual physician. Generally, it is preferred to use the maximum dose of the pharmacological agent of the present invention (alone or in combination with other therapeutic agents), i.e., the highest safe dose according to sound medical judgment. However, it will be understood by those skilled in the art that a patient may require a lower or tolerable dose for medical reasons, psychological reasons, or virtually any other reason.

[0055] Response to a therapeutically effective dose of the disclosed therapeutic agents and / or pharmaceutical compositions can be measured by determining the physiological effect of the treatment or pharmaceutical, such as, for example, a reduction or absence of disease symptoms after administration of the treatment or pharmacological agent. Other assays for measuring the level of response will be known to those of skill in the art and can be used. The amount of treatment can be varied, for example, by increasing or decreasing the amount of the disclosed therapeutic agents and / or pharmaceutical compositions, by changing the disclosed therapeutic agents and / or pharmaceutical compositions administered, by changing the route of administration, by changing the timing of administration, etc. Dosages can vary and can be administered in one or more doses per day for one or several days. Guidance can be found in the literature for appropriate dosages for a given class of pharmaceuticals.

[0056] As used herein, the term "prophylactically effective amount" refers to an amount effective to prevent the development or onset of a disease or condition.

[0057] As used herein, the terms "prevent" or "preventing" refer to preventing, avoiding, eliminating, forestalling, obstructing, or impeding something from happening, especially by prior action. Where reduce, inhibit, or prevent are used herein, it is understood that the use of the other two words is also expressly disclosed unless specifically indicated otherwise.

[0058] The term "pharmaceutically acceptable" describes a material that is not biologically or otherwise undesirable, i.e., does not cause unacceptable levels of undesirable biological effects or interact in a deleterious manner.

[0059] The term "pharmaceutically acceptable salt" as used herein refers to a salt of an active ingredient prepared with an acid or base that is tolerated by the biological system or tolerated by the subject when administered in a therapeutically effective amount, or that is tolerated by the biological system and tolerated by the subject. When a therapeutic agent of the present disclosure contains a relatively acidic functional group, a base addition salt can be obtained by contacting the neutral form of such a therapeutic agent, either neat or in a suitable inert solvent, with a sufficient amount of the desired base. Examples of pharmaceutically acceptable base addition salts include, but are not limited to, sodium, potassium, calcium, ammonium, organic amino, magnesium salts, lithium salts, strontium salts, or similar salts. When a therapeutic agent of the present disclosure contains a relatively basic functional group, an acid addition salt can be obtained by contacting the neutral form of such a therapeutic agent, either neat or in a suitable inert solvent, with a sufficient amount of the desired acid. Examples of pharmaceutically acceptable acid addition salts include, but are not limited to, those derived from inorganic acids such as hydrochloric acid, hydrobromic acid, nitric acid, carbonic acid, monohydrogencarbonic acid, phosphoric acid, monohydrogenphosphate, dihydrogenphosphate, sulfuric acid, monohydrogensulfuric acid, hydroiodic acid, or phosphorous acid, and the like, as well as salts derived from relatively non-toxic organic acids such as acetic acid, propionic acid, isobutyric acid, maleic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, lactic acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid, etc. Also included are salts of amino acids such as alginate, and salts of organic acids such as glucuronic acid or galacturonic acid.

[0060] The term "pharmaceutically acceptable ester" refers to an ester of a therapeutic agent of the present disclosure that hydrolyzes in vivo and readily decomposes 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 C1-C6 alkyl esters and C5-C7 cycloalkyl esters, with C1-C4 alkyl esters being preferred. Esters of the disclosed therapeutic agents can be prepared according to conventional methods. Pharmaceutically acceptable esters can be added to a hydroxy group by reacting the therapeutic agent with acid and an alkyl carboxylic acid, such as acetic acid, or acid and an aryl carboxylic acid, such as benzoic acid. For therapeutic agents containing a carboxylic acid group, pharmaceutically acceptable esters are prepared from the therapeutic agent by reacting it with triethylamine and a base such as an alkyl halide, e.g., methyl iodide, benzyl iodide, cyclopentyl iodide, or an alkyl triflate. They can also be prepared by reacting 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 the non-toxic amides of the present disclosure derived from ammonia, primary C1-C6 alkylamines, and secondary C1-C6 dialkylamines. In the case of secondary amines, the amine may be in the form of a five- or six-membered heterocycle containing one nitrogen atom. Amides derived from ammonia, C1-C3 alkyl primary amides, and C1-C2 dialkyl secondary amides are preferred. Amides of the 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 reacting the amino group-containing therapeutic agent with an alkyl anhydride, aryl anhydride, acyl halide, or aroyl halide. In the case of therapeutic agents containing carboxylic acid groups, pharmaceutically acceptable amides can be prepared from therapeutic agents containing carboxylic acid groups by reacting the therapeutic agent with a base such as triethylamine, a dehydrating agent such as dicyclohexylcarbodiimide or carbonyldiimidazole, and an alkylamine, dialkylamine, e.g., methylamine, diethylamine, and piperidine. They can also be prepared by reacting a therapeutic agent with an acid, such as sulfuric acid, and an alkylcarboxylic acid, such as acetic acid, or an acid and an arylcarboxylic acid, such as benzoic acid, under dehydrating conditions, for example, with the addition of molecular sieves. The compositions 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" refers to a prodrug of a therapeutic agent of the present disclosure that is, 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, etc., commensurate with a reasonable benefit / risk ratio, and is effective for its intended use. The prodrugs of the present disclosure may be rapidly converted in vivo, for example, by hydrolysis in blood, to the parent therapeutic agent having the structure of the disclosed compound. A thorough discussion is provided in T. Higuchi and V. Stella, Prodrugs as Novel Delivery Systems, Vol. 14 of the ACS 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 herein) and whose structure is sufficiently similar to that disclosed herein that, based on that similarity, one skilled in the art would expect to exhibit the same or similar activity and utility as the claimed compound or to induce the same or similar activity and utility as the compound claimed as a precursor. Exemplary derivatives include salts, esters, amides, salts of esters or amides, and N-oxides of the 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, stereochemical priority, E / Z specification, etc. can be designated using the Cahn-Ingold-Prelog rules for stereochemistry. One skilled in the art can readily confirm the structure of a therapeutic agent by systematically reducing the therapeutic agent structure using the naming rules, if any, or by commercially available software such as CHEMDRAW™ (Cambridgesoft Corporation, USA).

[0065] Unless otherwise indicated, temperatures referred to herein are based on atmospheric pressure (ie, 1 atmosphere).

[0066] Described herein are articles, including wound dressings and wraps, such as dressings and bandages, comprising a substrate and a releasable therapeutic agent in contact with each other. Also described herein are methods of administering the articles to a subject in need thereof. In various aspects, the subject may have a wound, injury, or infection. Other compositions, compounds, methods, features, and advantages of the present disclosure will be, or will become, apparent to one of ordinary skill in the art upon review of the following figures, detailed description, and examples. All such additional compositions, compounds, methods, features, and advantages are intended to be included within this description and be within the scope of the present disclosure.

[0067] B. Disclosed Articles Comprising a Substrate and a Therapeutic Agent In one aspect, the present disclosure relates to an article comprising a substrate and a releasable therapeutic agent in contact with or attached to one another.

[0068] In further embodiments, the substrate comprises a textile, such as a fabric having hydroxyl groups in the textile yarns or filaments, e.g., a fabric comprising yarns or filaments comprising cotton, rayon, silk, or a combination thereof. A schematic diagram of the substrate is shown in Figure 2A, which illustrates the polymer backbone, e.g., the cellulose backbone found in textiles comprising cotton, rayon, silk, or a combination thereof. In some cases, an active therapeutic agent, e.g., glycyrrhetinic acid, is covalently attached to the substrate, as shown schematically in Figure 2B. As shown in Figure 2B, the substrate comprises a polymer comprising multiple hydroxy moieties along the polymer backbone, some of which are covalently attached to the therapeutic agent, and the covalent bond may include one, two, or three covalent bonds between oxygen (from the hydroxy moieties) and a silyl moiety along the polymer backbone (including the definitions of substituents disclosed herein below).

[0069] In further embodiments, the textile is a woven fabric, a knitted fabric, a nonwoven fabric, or a combination thereof. It is understood that the substrate can include other materials and is not limited to woven materials. Furthermore, the substrate can include a composite material, e.g., a bilayer material, in which a first layer includes a substrate and a releasable therapeutic agent that are in contact with or attached to each other, and a second layer does not. In further embodiments, the therapeutic agent interacts with or is attached to the substrate through non-covalent interactions, e.g., van der Waals forces, ionic interactions, and combinations thereof, or through covalent bonds that can release the therapeutic agent under normal use with a subject.

[0070] In a further aspect, an article comprising a substrate and a releasable therapeutic agent in contact with or attached to one another provides tunable release of the therapeutic agent, such that the therapeutic agent can be released over a short time frame of minutes to hours (or immediate release) to a long time frame of hours to days or more (or delayed release) by varying the mode of interaction between the substrate and the releasable therapeutic agent from different types of non-covalent interactions to covalent interactions, including linkers of different lengths and chemical reactivities to chemical mixtures, and covalent / non-covalent interactions between the releasable therapeutic agent and the substrate.

[0071] In one aspect, the present disclosure relates to articles, including medical or therapeutic wraps, dressings, and devices, comprising a substrate and a releasable therapeutic agent in contact with or adhered to one another, that can be used in the treatment of inflammation, atopic dermatitis, and other clinical conditions related to skin and muscle.

[0072] In one aspect, the present disclosure relates to articles including wound dressings, dressings and bandages that include a substrate and a releasable therapeutic agent in contact with or attached to one another.

[0073] In further embodiments, the disclosed articles include a therapeutic agent in contact with or attached to a substrate. In still further embodiments, the substrate includes one or more hydroxyl groups. In still further embodiments, the therapeutic agent is in contact with or attached to the substrate via a non-covalent bond comprising a hydrogen bonding interaction with one or more hydroxyl groups of the substrate. In still further embodiments, the therapeutic agent is in contact with or attached to the substrate via a covalent bond comprising a covalent bond with one or more oxygen atoms derived from one or more hydroxyl groups associated with the substrate.

[0074] In a further aspect, the disclosed articles include a therapeutic agent in contact with or attached to a substrate having the structure shown in the following formula: [ka] While the specific therapeutic agent, glycyrrhetinic acid, is mentioned above, other therapeutic agents described herein that are capable of hydrogen-bonding interactions with the substrate can be used in addition to or in place of glycyrrhetinic acid. Exemplary, but non-limiting, therapeutic agents that can be used in addition to or in place of glycyrrhetinic acid in the above articles include penicillins (e.g., amoxicillin, flucoxacillin, etc.), cephalosporins (e.g., cefepime, cephalexin, etc.), streptomycin, neomycin, kanamycin, paromycin, vancomycin, ciprofloxacin, linezolid, and combinations thereof. In the above embodiments, the substrate can be a fabric or woven material including cotton, rayon, silk, and other substrate materials containing one or more hydroxyl groups as described herein, such as synthetic fibers (e.g., polyester or polyamide) that are blends containing cotton, rayon, silk, and other materials containing one or more hydroxyl groups. The above articles can be prepared by the disclosed methods.

[0075] In a further aspect, the disclosed articles include a therapeutic agent contacted or attached to a substrate having a structure shown in the following formula: [ka] Although the specific therapeutic agent, glycyrrhetinic acid, is described above, other therapeutic agents described herein that are capable of hydrogen-bonding interactions with the substrate can be used in addition to or in place of glycyrrhetinic acid. Exemplary, but non-limiting, therapeutic agents that can be used in addition to or in place of glycyrrhetinic acid in the above articles include penicillins (e.g., amoxicillin, flucoxacillin, etc.), cephalosporins (e.g., cefepime, cephalexin, etc.), streptomycin, neomycin, kanamycin, paromycin, vancomycin, ciprofloxacin, linezolid, and combinations thereof. In the above embodiments, the substrate can be a fabric or woven material including cotton, rayon, silk, and other substrate materials containing one or more hydroxyl groups as described herein, such as synthetic fibers (e.g., polyester or polyamide) that are blends containing cotton, rayon, silk, and other materials containing one or more hydroxyl groups. Articles containing a therapeutic agent in contact with or attached to a substrate having the structure shown in the above formula can be prepared by the disclosed method.

[0076] In a further aspect, the disclosed articles include a therapeutic agent in contact with or attached to a substrate having a structure shown in the following formula: [ka] Although the specific therapeutic agent, glycyrrhetinic acid, is described above, other therapeutic agents described herein that are capable of hydrogen-bonding interactions with the substrate can be used in addition to or in place of glycyrrhetinic acid. Exemplary, but non-limiting, therapeutic agents that can be used in addition to or in place of glycyrrhetinic acid in the above articles include penicillins (e.g., amoxicillin, flucoxacillin, etc.), cephalosporins (e.g., cefepime, cephalexin, etc.), streptomycin, neomycin, kanamycin, paromycin, vancomycin, ciprofloxacin, linezolid, and combinations thereof. In the above embodiments, the substrate can be a fabric or woven material including cotton, rayon, silk, and other substrate materials containing one or more hydroxyl groups as described herein, such as synthetic fibers (e.g., polyester or polyamide) that are blends containing cotton, rayon, silk, and other materials containing one or more hydroxyl groups. Articles containing a therapeutic agent in contact with or attached to a substrate having the structure shown in the above formula can be prepared by the disclosed method.

[0077] In a further aspect, the disclosed articles include a therapeutic agent in contact with or attached to a substrate having a structure shown in the following formula: [ka] wherein A is OH or a moiety having the structure shown in the formula: [ka] Y is a moiety having the structure shown in the formula: [ka] Z is selected from O, NH, and S; 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; n is an integer selected from 1, 2, and 3; and 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 include a therapeutic agent in contact with or attached to a substrate having a structure shown in the following formula: [ka] wherein A is OH or a moiety having the structure shown in the formula: [ka] Y is a moiety having the structure shown in the formula: [ka] Z is selected from O, NH, and S; 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; n is an integer selected from 1, 2, and 3; and 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 include a therapeutic agent contacted or attached to a substrate having a structure shown in the following formula: [ka] Although the specific therapeutic agent, glycyrrhetinic acid, is described above, other therapeutic agents described herein that are capable of hydrogen-bonding interactions with the substrate can be used in addition to or in place of glycyrrhetinic acid. Exemplary, but non-limiting, therapeutic agents that can be used in addition to or in place of glycyrrhetinic acid in the above articles include penicillins (e.g., amoxicillin, flucoxacillin, etc.), cephalosporins (e.g., cefepime, cephalexin, etc.), streptomycin, neomycin, kanamycin, paromycin, vancomycin, ciprofloxacin, linezolid, and combinations thereof. In the above embodiment, the substrate can be a fabric or woven material including cotton, rayon, silk, and other substrate materials containing one or more hydroxyl groups as described herein, such as synthetic fibers (e.g., polyester or polyamide) that are blends containing cotton, rayon, silk, and other materials containing one or more hydroxyl groups. Articles containing a therapeutic agent in contact with or attached to a substrate having the structure shown in the above formula can be prepared by the disclosed method.

[0080] In a further aspect, the disclosed articles include a therapeutic agent contacted or attached to a substrate having a structure shown in the following formula: [ka] Although the specific therapeutic agent, glycyrrhetinic acid, is described above, other therapeutic agents described herein that are capable of hydrogen-bonding interactions with the substrate can be used in addition to or in place of glycyrrhetinic acid. Exemplary, but non-limiting, therapeutic agents that can be used in addition to or in place of glycyrrhetinic acid in the above articles include penicillins (e.g., amoxicillin, flucoxacillin, etc.), cephalosporins (e.g., cefepime, cephalexin, etc.), streptomycin, neomycin, kanamycin, paromycin, vancomycin, ciprofloxacin, linezolid, and combinations thereof. In the above embodiments, the substrate can be a fabric or woven material including cotton, rayon, silk, and other substrate materials containing one or more hydroxyl groups as described herein, such as synthetic fibers (e.g., polyester or polyamide) that are blends containing cotton, rayon, silk, and other materials containing one or more hydroxyl groups. Articles containing a therapeutic agent in contact with or attached to a substrate having the structure shown in the above formula can be prepared by the disclosed method.

[0081] In a further aspect, the disclosed articles include a therapeutic agent contacted or attached to a substrate having a structure shown in the following formula: [ka] Although the specific therapeutic agent, glycyrrhetinic acid, is described above, other therapeutic agents described herein that are capable of hydrogen-bonding interactions with the substrate can be used in addition to or in place of glycyrrhetinic acid. Exemplary, but non-limiting, therapeutic agents that can be used in addition to or in place of glycyrrhetinic acid in the above articles include penicillins (e.g., amoxicillin, flucoxacillin, etc.), cephalosporins (e.g., cefepime, cephalexin, etc.), streptomycin, neomycin, kanamycin, paromycin, vancomycin, ciprofloxacin, linezolid, and combinations thereof. In the above embodiments, the substrate can be a fabric or woven material including cotton, rayon, silk, and other substrate materials containing one or more hydroxyl groups as described herein, such as synthetic fibers (e.g., polyester or polyamide) that are blends containing cotton, rayon, silk, and other materials containing one or more hydroxyl groups. Articles containing a therapeutic agent in contact with or attached to a substrate having the structure shown in the above formula can be prepared by the disclosed method.

[0082] C. Base material In various embodiments, the present disclosure includes a therapeutic agent in contact with or attached to a substrate. In further embodiments, the substrate can be a woven material or fabric comprising yarns, fibers, and / or filaments containing one or more hydroxyl groups. In still further embodiments, the fabric can be a woven fabric, a knit fabric, a nonwoven fabric, or a combination thereof.

[0083] In further embodiments, the textile material or fabric can comprise yarns, fibers, and / or filaments comprising plant, animal, or synthetic fibers. In still further embodiments, the textile material or fabric can comprise yarns, fibers, and / or filaments comprising cotton, rayon staple, flax, wool, viscose, silk, and / or synthetic fibers. In still further embodiments, the textile material or fabric can comprise yarns, fibers, and / or filaments comprising polyamide, polyester, polypropylene, polyacrylic, and combinations thereof, that include one or more hydroxyl groups or moieties within the polymer backbone or within grafts or side chains attached to the polymer backbone.

[0084] In a further aspect, the textile material is selected from cotton, silk, polyester, wool, rayon, nylon, pre-printed textile fabrics, woven fabrics, dyed woven fabrics, greige fibers, nonwoven fabrics, silk, synthetic woven or bandage fabrics, woven or nonwoven fabrics and yarns, and combinations thereof.

[0085] D. Therapeutic Agents In various aspects, the present disclosure includes a therapeutic agent in contact with or attached to the substrate, hi further aspects, the therapeutic agent is an antibacterial therapeutic agent, an antibiotic therapeutic agent, an antibacterial therapeutic agent, an antifungal therapeutic agent, an anti-inflammatory therapeutic agent such as a nonsteroidal anti-inflammatory drug ("NSAID") or a steroid, an anti-pain therapeutic agent, an analgesic therapeutic agent, an anti-allergic therapeutic agent, an anesthetic therapeutic agent, an antihistamine therapeutic agent, and combinations thereof.

[0086] In further embodiments, the therapeutic agent is an antibacterial, antibiotic, antibacterial, and / or antifungal therapeutic agent.

[0087] In further aspects, the therapeutic agent is an antibacterial, antibiotic, and / or antibacterial therapeutic agent selected from the group consisting of chloramphenicol, tetracyclines, synthetic and semi-synthetic penicillins, beta-lactams, quinolones, fluoroquinolones, macrolide antibiotics, peptide antibiotics, cyclosporines, and combinations thereof.In still further embodiments, the therapeutic agent is an antibacterial, antibiotic, and / or antibacterial therapeutic agent, such as cefadroxil, cefazolin, cephalexin, cephalothin, cephapirin, cefacerol, cefprozil, cephadrin, cefamandole, cefonicid, ceforanide, cefuroxime, cefixime, cefoperazone, cefotaxime, cefpodoxime, ceftaxidime, ceftibuten, cef Tizoxime, ceftriaxone, cefepime, cefmetazole, cefotetan, cefoxitin, loracarbef, imipenem, erythromycin (and erythromycin salts, e.g., estolate, ethyl succinate, gluceptate, lactobionate, stearate), azithromycin, clarithromycin, dirithromycin, trolenomycin, penicillin V, penicillin salts salt), and complexes, methicillin, nafcillin, oxacillin, cloxacillin, dicloxacillin, amoxicillin, amoxicillin and potassium clavulanate, ampicillin, bacampicillin, carbenicillin indanyl sodium (and other salts of carbenicillin), mezlocillin, piperacillin, piperacillin and taxobactam, ticarcillin, ticarcillin and potassium clavulanate, clindamycin, vancomycin, novobiocin, aminosalicylic acid, capreomycin, cycloserine, ethambutol HCl and other salts, ethionamide, and isoniazid, Selected from the group consisting of ciprofloxacin, levofloxacin, lomefloxacin, nalidixic acid, norfloxacin, ofloxacin, sparfloxacin, sulfacytine, suflamerazine, sulfamethazine, sulfamethixol, sulfasalazine, sulfisoxazole, sulfapyridine, sulfadiazine, sulfmetoxazole, sulfapyridine, metronidazole, methenamine, fosfomycin, nitrofurantoin, trimethoprim, clofazimine, quatriamoxazole, pentamidine, and trimetrexate, and combinations thereof.In still further aspects, the therapeutic agent is an antibacterial, antibiotic, and / or antibacterial therapeutic agent selected from the group consisting of azoleic acid, erythromycin, bacitracin, zinc bacitracin, polymyxin, neomycin, chloramphenicol, tetracycline, minocycline, clindamycin, doxycycline, undecylenic acid and its salts, propionic acid and its salts, capric acid and its salts, ciprofloxacin, cephalosporins, benzoic acid, cyclopiroxolamine, clotrimazole, econazole nitrate, metronidazole, maconazole nitrate, ketaconazole, oxiconazole, tolnaftate, and combinations thereof.

[0088] In a further aspect, the therapeutic agent is an antibacterial, antibiotic, and / or antibacterial therapeutic agent selected from the group consisting of glycyrrhetinic acid or a derivative thereof, penicillin or a derivative thereof, such as amoxicillin and / or flucoxacillin, cephalosporins, such as cefepime and / or cephalexin, streptomycin, neomycin, kanamycin, paromycin, vancomycin, ciprofloxacin, linezolid, and combinations thereof.

[0089] In a further embodiment, the therapeutic agent is an antifungal therapeutic agent. In yet a further embodiment, 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, methylosaniline chloride, sodium thiosulfinate, sulconazole nitrate, terbinafine hydrochloride, tioconazole, tolnaftate, undecylenic acid and undecylenate salts (calcium undecylenate, copper undecylenate, zinc undecylenate). The following are representative examples of some antiviral drugs that may be used in the present 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 present invention: carboplatin, busulfan, cisplatin, thiotepa, melphalan hydrochloride, cyclophosphamide, ifosfamide, chlorambucil, mechlorethamine hydrochloride, carmustine, lomustine, streptozocin, polifeprosan 20, dexrazoxane, dronabinol, granisetron hydrochloride, fluconazole, erythropoietin, octreotide acetate, pilocarpine hydrochloride, estrogen, erythromycin ... Tidronate disodium, pamidronate disodium, allopurinol sodium, amifostine, filgrastim, mesna, ondansetron hydrochloride, doracetron 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 sodium phosphate, ethinyl estradiol, esterified estrogens, leuprolide acetate, conjugated estrogens, megestrol acetate, aldesleukin, medroxyprogesterone acetate, dacarbazine, hydroxyurea, etoposide phosphate, megestrol acetate, paclitaxel, etoposide, teniposide, trastuzumab, rituximab, vinorelbine tartrate, deniliquin difititox, gemcitabine hydrochloride, vincristine sulfate methylprednisolone sodium succinate, betamethasone sodium phosphate, betamethasone acetate, vinblastine sulfate, asparaginase, edrophonium chloride, bacillus Calmette-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 capable of releasing a therapeutically useful peroxide, such as benzoyl peroxide.

[0091] In a further embodiment, the therapeutic agent is an NSAID. In yet a further embodiment, 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 yet a further embodiment, the NSAID can be a salicylic acid derivative, such as, but not limited to, aspirin, sodium salicylate, choline magnesium trisulciylate, salsalate, diflunisal, salicylsalicylic acid, sulfasalazine, and olsalazine. In yet a further embodiment, the NSAID can be a para-aminophenol derivative such as acetaminophen. In still further embodiments, the NSAID can be an indole or indole acetic acid, such as indomethacin, sulindac, or etodolac. In still further embodiments, the NSAID can be an aryl acetic acid, such as tolmetin, diclofenac, or ketorolac. In still further embodiments, the NSAID can be an aryl propionic acid, such as ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen, or oxaprozin. In still further embodiments, the NSAID can be an anthranilic acid or fenamate, for example, mefenamic acid or meclofenamic acid. In still further embodiments, the NSAID can be an enolic acid, such as an oxicam, including but not limited to, piroxicam or tenoxicam, or a pyrazolidinedione, including but not limited to, phenylbutazone or oxyfentofuratrazone. In still further embodiments, the NSAID can be an alkenone, such as nabumetone.

[0092] The disclosed therapeutic agents include their pharmaceutical salts, and derivatives or analogs, including bioisosteric equivalents.

[0093] In various aspects, it is contemplated herein that the therapeutic agents disclosed herein further include their bioisosteric equivalents. The term "bioisosteric equivalent" refers to a therapeutic agent or group that has approximately the same molecular shape and volume, approximately the same electron distribution, and exhibits similar physical and biological properties. Examples of such equivalents are: (i) fluorine to hydrogen, (ii) oxo to thia, (iii) hydroxyl to amide, (iv) carbonyl to oxime, and (v) carboxylate to tetrazole. Examples of such bioisosteric substitutions can be found in the literature, such as: (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 RD, Ferguson AM, Cramer RD, “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 GA, LaVoie EJ, “Bioisosterism: A rational approach in drug design”, Chem.Rev. (Washington, DC) 1996, 96, 3147-3176, (ix) Soskic V, Joksimovic J, “Bioisosteric approach in the design of new dopaminergic / serotonergic (x) Thornber CW, “Isosterism and molecular modification in drug design”, Chem. Soc. Rev. 1979, 8, 563-80. .

[0094] In a further aspect, a bioisostere is an atom, ion, or molecule whose electron neighbors can be considered substantially identical. The term bioisostere is typically used to refer to a portion of a whole molecule, as opposed to the entire molecule itself. Bioisosteric substitution involves using one bioisostere to replace another with the expectation of maintaining or slightly modifying the biological activity of the first bioisostere. Thus, a bioisostere in this case is an atom or group of atoms with similar size, shape, 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 five-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, the disclosed therapeutic agents also include isotopically labeled or isotopically substituted variants, i.e., therapeutic agents identical to those described, but due to the fact that one or more atoms have been replaced by atoms having an atomic mass or mass number that is different from the atomic mass or mass number typically found in nature. Examples of isotopes that can be incorporated into the therapeutic agents of the present invention include, respectively: 2 H, 3 H, 13 C. 14 C. 15 N, 18 O. 17 O. 35 S, 18 F, and 36 Included within the scope of the present invention are isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, fluorine, and chlorine, such as Cl. Therapeutic agents further include prodrugs thereof, and pharmaceutically acceptable salts of the therapeutic agents or of the prodrugs that contain the aforementioned isotopes and / or other isotopes of other atoms are within the scope of the present invention. Certain isotopically labeled therapeutic agents of the present invention, for example, 3 H and 14 Those in which a radioactive isotope such as C is incorporated are useful in drug and / or substrate tissue distribution assays. 3 H, and carbon 14, i.e., 14 C isotopes are particularly preferred for their ease of preparation and detectability. Additionally, deuterium, i.e., 2 Substitution with heavier isotopes such as H can confer certain therapeutic advantages resulting in greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements, and therefore may be preferred in some circumstances. The isotopically labeled therapeutic agents of the present invention and prodrugs thereof can generally be prepared by carrying out the following procedure by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent.

[0096] In various embodiments, the disclosed therapeutic agents can have at least one asymmetric center and can exist in the form of their racemates, pure enantiomers and / or diastereomers, or mixtures of these enantiomers and / or diastereomers. Stereoisomers can be present in any desired proportion in the mixture. In various embodiments, where this is possible, the disclosed therapeutic agents can exist in the form of tautomers.

[0097] Thus, for example, the disclosed therapeutic agents which have one or more chiral centers and occur as racemates can be separated into their optical isomers, i.e., enantiomers or diastereomers, using methods known per se, such as by column separation on a chiral phase, by recrystallization from an optically active solvent, by using an optically active acid or base, or by derivatization with an optically active reagent such as an optically active alcohol, followed by cleavage of the residue.

[0098] In various embodiments, the disclosed therapeutic agents may be in the form of cocrystals. The term "cocrystal" refers to a physical association of two or more molecules that are responsible for their stability through non-covalent interactions. One or more components of this molecular complex provide a stable framework in the crystal lattice. In certain cases, the guest molecule is incorporated into the crystal lattice as an anhydride or solvate; see, for example, "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. A preferred cocrystal includes 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, particularly hydrates of the disclosed compounds, which can be obtained, for example, by crystallization from a solvent or aqueous solution. In this regard, one, two, three, or any number of solvate or water molecules can combine with a therapeutic agent according to the present 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 can similarly be prepared by reacting the drug therapeutic agent with a suitable pharmaceutically acceptable base. Salts can be prepared in situ during the final isolation and purification of the disclosed therapeutic agents, or after final isolation by reacting a free base functional group (such as a secondary or tertiary amine) of the disclosed therapeutic agent with a suitable inorganic or organic acid, or by reacting a free acid functional group (such as a carboxylic acid) of the disclosed therapeutic agent with a suitable inorganic or organic base.

[0102] Acid addition salts can be prepared in situ during the final isolation and purification of the disclosed compounds, or can be prepared separately by reacting a moiety containing one or more nitrogen groups with a suitable acid. In various embodiments, acids that can be used to form pharmaceutically acceptable acid addition salts include inorganic acids such as hydrochloric acid, sulfuric acid, and phosphoric acid, and organic acids such as oxalic acid, maleic acid, succinic acid, and citric acid. In further embodiments, the salts include the following: hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, butyrate, camphorate, camphorsulfonate, digluconate, methylsulf ... Further salts include, but are not limited to, phosphate, 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. Additionally, basic nitrogen-containing groups can be quaternized with agents such as lower alkyl halides, such as methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides; dialkyl sulfates, such as dimethyl, diethyl, dibutyl, and diamyl sulfate; long chain halides, such as decyl, lauryl, myristyl, and stearyl chlorides; bromides and iodides; and aralkyl halides, such as benzyl and phenethyl bromides.

[0103] Base addition salts can be prepared in situ during the final isolation and purification of the disclosed compounds, or separately, by reacting the carboxylic acid moiety with a suitable base, such as the hydroxide, carbonate, or bicarbonate of a pharmaceutically acceptable metal cation, or with ammonia, or with an organic primary, secondary, or tertiary amine. Pharmaceutically acceptable salts include, but are not limited to, cations based on alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium, and aluminum salts, as well as non-toxic 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 a further aspect, bases that can be used to prepare 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 amines, sodium hydroxide, triethanolamine, tromethamine, and zinc hydroxide.

[0104] E. Methods of Making the Disclosed Articles In various aspects, the disclosed articles can be prepared by the methods disclosed herein.

[0105] In a further aspect, the disclosed article comprises: [ka] A solution of a therapeutic agent, such as an acyl halide analog of a therapeutic agent, such as an acyl chloride analog of glycyrrhetinic acid, can be prepared by incubating a substrate, such as a fabric or textile material as disclosed herein, with a solution of a therapeutic agent, such as glycyrrhetinic acid, in a suitable solvent, such as water or dichloromethane, using a suitable concentration, for example, about 100-350 mg of the active form of the therapeutic agent per milliliter of solvent. In some cases, the solvent can further include a catalyst, for example, 0.1 w / v% DMSO. The solution of the therapeutic agent can then be applied in an amount of 100-1000 μL of solution per square centimeter of substrate, or over 1 cm of substrate. 2 Approximately 1 mg per 1 cm of substrate 2 The substrate can be applied in an amount of about 100 mg per 1000 mg of solution. In still further embodiments, the substrate can be washed, for example, with water and / or detergent, then washed with isopropanol, and then dried under vacuum at a temperature of about 20°C to about 30°C prior to incubation with the solution containing the therapeutic agent. The solution and substrate can be incubated together at a suitable temperature for a suitable period of time. In still further embodiments, the article can be prepared by exposing the substrate to a solution containing the therapeutic agent, which can be incubated at a suitable temperature, such as about 10°C to about 40°C, for a suitable period of time, such as about 1 minute to about 24 hours. In still further embodiments, the article can be prepared by exposing the substrate to a solution containing the therapeutic agent, which can be incubated at a suitable temperature, such as a gradual increase in temperature from about -10°C to about 25°C, for a suitable period of time, such as about 1 minute to about 24 hours. In still further embodiments, the temperature during incubation can be a gradual increase in temperature from about -10°C to about 30°C. After incubation, the substrate is removed from the solution, washed with a suitable solvent, such as dichloromethane, and dried under vacuum at a suitable temperature, such as about 25° C. Suitable storage conditions can be determined by one skilled in the art; for example, storage in an airtight or vacuum container can improve the stability of the aforementioned articles.

[0106] In further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:10. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:2 to about 1:7. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:3.

[0107] In a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 The amount of therapeutic agent is approximately 10 mg per 1000 mg of base material.

[0108] In a further aspect, the disclosed article comprises: [ka] A solution of a therapeutic agent, such as glycyrrhetinic acid, as set forth above, can be prepared by incubating a substrate, such as a textile or textile material as disclosed herein, with a solution of a therapeutic agent, such as glycyrrhetinic acid, in a suitable solvent, such as water and / or DMSO, at 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 in an amount of 100-1000 μL of solution per square centimeter of substrate, or per cm of substrate. 2 Approximately 1 mg per 1 cm of substrate 2The therapeutic agent can be applied to the substrate in an amount of about 100 mg per substrate. In various embodiments, the therapeutic agent can be formed into a paste by grinding it with water and then spreading it on the substrate. In still further embodiments, the substrate can be washed, for example, with water and / or detergent, then with isopropanol, and then dried under vacuum at a temperature of about 20°C to about 30°C prior to incubation with the solution containing the therapeutic agent. The solution and substrate can be incubated together at a suitable temperature for a suitable period of time. In further embodiments, the above-described article can be prepared by exposing the substrate to a solution containing the therapeutic agent, which can be incubated at a suitable temperature, such as about 10°C to about 40°C, for a suitable period of time, such as about 1 minute to about 24 hours. In still further embodiments, the temperature during incubation can be about 20°C to about 30°C.

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

[0110] In a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 The amount of therapeutic agent is approximately 10 mg per 1000 mg of base material.

[0111] In a further aspect, the disclosed article comprises: [ka] Approximately 100-350 mg of therapeutic agent per milliliter of a suitable solvent, e.g., DMSO, containing a suitable concentration, e.g., about 0.01% v / v ammonia to about 1% v / v ammonia, can be prepared by incubating a substrate, e.g., a fabric or textile material as disclosed herein, with a solution of such a therapeutic agent, e.g., glycyrrhetinic acid. The therapeutic agent solution is then applied in an amount of 100-1000 μL of solution per square centimeter of substrate, or over 1 cm of substrate. 2 Approximately 1 mg per 1 cm of substrate 2 The therapeutic agent can be applied to the substrate in an amount of about 100 mg per 1000 mg of solution. In yet a further embodiment, the substrate can be washed prior to incubation with the therapeutic agent-containing solution, e.g., washed with water, then isopropanol, then dried under vacuum at a temperature of about 20°C to about 30°C, then washed with 1% aqueous ammonia, followed by draining off excess ammonia and incubating with the therapeutic agent-containing solution. The solution and substrate can be incubated together at a suitable temperature for a suitable period of time. In a further embodiment, the above-described article can be prepared by exposing the substrate to a therapeutic agent-containing solution and incubating at a suitable temperature, such as about 10°C to about 40°C, for a suitable period of time, such as about 1 minute to about 24 hours. In a still further embodiment, the temperature during incubation can be about 20°C to about 30°C.

[0112] In further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:10. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:2 to about 1:7. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:3 to about 1:5.

[0113] In a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 The amount of therapeutic agent is approximately 10 mg per 1000 mg of base material.

[0114] In a further aspect, the disclosed article comprises: [ka] The substrate, for example, comprises a fabric or textile material disclosed herein and can be prepared by incubating as shown in the reaction schemes disclosed herein.

[0115] In a further aspect, the disclosed method of making the disclosed article is provided in the following reaction scheme: [ka] wherein A is hydroxy or a moiety having a structure represented by the formula: [ka] X is a halogen and Y is a moiety having a structure represented by the formula: [ka] n is an integer selected from 1, 2, and 3; 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; and q is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10.

[0116] In further embodiments, the above generalized reaction scheme can be carried out as shown below, although other methods and conditions are suitable as determined by one skilled in the art. [ka] Briefly, the sequence for preparing an article containing the composition shown above involves: (a) reacting a substrate with a suitable alkoxysilylamine, (b) reacting the substrate containing the covalently bound alkoxysilylamine with a suitable linker, and (c) reacting the material produced in the previous step with an activated form of a therapeutic agent. In yet a further embodiment, the substrate can be washed prior to incubation with the solution containing the alkoxysilylamine, e.g., with water, then isopropanol, and then dried under vacuum at a temperature of about 20°C to about 30°C. A silylamine solution containing a suitable alkoxysilylamine, e.g., 3-(triethoxysilyl)propan-1-amine, is prepared in a suitable solvent, e.g., THF, at an appropriate concentration, e.g., 1 part alkoxysilylamine to 2 parts solvent. The substrate is immersed in the silylamine solution, allowed to react, and heated, e.g., at about 60°C to about 90°C, for a suitable period of time, e.g., about 1 hour to about 6 hours. The substrate is removed from the silylamine solution and allowed to dry, e.g., at room temperature, protected from light. A suitable linker solution is prepared containing a suitable linker, such as aconitic acid acyl chloride anhydride, in a suitable solvent, such as dichloromethane. The linker solution can further contain a suitable catalyst, such as DMSO, at about 0.1% v / v to about 1% v / v. The linker solution is added in an amount sufficient to provide a substrate:linker ratio of about 1:1 to about 1:10, and in certain cases, about 1:4 to about 1:6, by weight. The reaction can be carried out under an inert atmosphere, such as nitrogen or argon. The substrate is separated from the linker solution and washed, for example, with excess solvent, such as that used to prepare the linker solution. The substrate can then be dried under vacuum at ambient temperature. In the final step, the substrate containing the alkoxysilylamine and linker is reacted with a suitable chemically activated therapeutic agent, such as an acyl chloride derivative of the therapeutic agent. In the above reaction, the therapeutic agent is glycyrrhetinic acid acyl chloride. In this final step, an activated therapeutic agent solution is prepared, for example, glycyrrhetinic acid acyl chloride in dichloromethane as a solvent. The activated therapeutic agent solution may further contain a catalytic amount of a second agent, for example, DMSO, at 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 an amount sufficient to provide a substrate:activated therapeutic agent ratio of about 1:1 to about 1:10, and in certain cases, a ratio of about 1:4 to about 1:6, on a weight basis. The reacted substrate, which comprises a covalently bound alkoxysilylamine bonded to a linker group and further contains a releasable therapeutic agent, is then washed and dried under vacuum at ambient temperature, e.g., about 20°C to about 30°C. A therapeutic agent, such as glycyrrhetinic acid, as indicated above, is added to the substrate in an amount sufficient to provide a substrate:activated therapeutic agent ratio of about 1:1 to about 1:10, and in certain cases, a ratio of about 1:4 to about 1:6. 2 Approximately 1 mg per 1 cm of substrate 2 The amount of therapeutic agent is approximately 25 mg per tablet.

[0117] In a further aspect, the disclosed method of making the disclosed article is provided in the following reaction scheme: [ka] wherein A is hydroxy or a moiety having a structure represented by the formula: [ka] X is a halogen and Y is a moiety having a structure represented by the formula: [ka] n is an integer selected from 1, 2, and 3; 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; and 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 one skilled in the art: [ka] Briefly, the sequence for preparing an article containing the composition shown above involves: (a) reacting a substrate with a suitable alkoxysilylamine, (b) reacting the substrate containing the covalently bound alkoxysilylamine with a suitable linker, and (c) reacting the material produced in the previous step with an activated form of a therapeutic agent. In yet a further embodiment, the substrate can be washed prior to incubation with the solution containing the alkoxysilylamine, e.g., with water, then isopropanol, and then dried under vacuum at a temperature of about 20°C to about 30°C. A silylamine solution containing a suitable alkoxysilylamine, e.g., 3-(triethoxysilyl)propan-1-amine, is prepared in a suitable solvent, e.g., THF, at an appropriate concentration, e.g., 1 part alkoxysilylamine to 2 parts solvent. The substrate is immersed in the silylamine solution, allowed to react, and heated, e.g., at about 60°C to about 90°C, for a suitable period of time, e.g., about 1 hour to about 6 hours. The substrate is removed from the silylamine solution and allowed to dry, e.g., at room temperature, protected from light. A suitable linker solution is prepared containing a suitable linker, such as aconitic acid acyl chloride anhydride, in a suitable solvent, such as dichloromethane. The linker solution can further contain a suitable catalyst, such as DMSO, at about 0.1% v / v to about 1% v / v. The linker solution is added in an amount sufficient to provide a substrate:linker ratio of about 1:1 to about 1:10, and in certain cases, about 1:4 to about 1:6, by weight. The reaction can be carried out under an inert atmosphere, such as nitrogen or argon. The substrate is separated from the linker solution and washed, for example, with excess solvent, such as that used to prepare the linker solution. The substrate can then be dried under vacuum at ambient temperature. In the final step, the substrate containing the alkoxysilylamine and linker is reacted with a suitable chemically activated therapeutic agent, such as an acyl chloride derivative of the therapeutic agent. In the above reaction, the therapeutic agent is glycyrrhetinic acid acyl chloride. In this final step, an activated therapeutic agent solution is prepared, for example, glycyrrhetinic acid acyl chloride in dichloromethane as a solvent. The activated therapeutic agent solution may further contain a catalytic amount of a second agent, for example, DMSO, at 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 an amount sufficient to provide a substrate:activated therapeutic agent ratio of about 1:1 to about 1:10, and in certain cases, a ratio of about 1:4 to about 1:6, on a weight basis. The reacted substrate, which comprises a covalently bound alkoxysilylamine bonded to a linker group and further contains a releasable therapeutic agent, is then washed and dried under vacuum at ambient temperature, e.g., about 20°C to about 30°C. A therapeutic agent, such as glycyrrhetinic acid, as indicated above, is added to the substrate in an amount sufficient to provide a substrate:activated therapeutic agent ratio of about 1:1 to about 1:10, and in certain cases, a ratio of about 1:4 to about 1:6. 2 Approximately 1 mg per 1 cm of substrate 2 The amount of therapeutic agent is approximately 25 mg per tablet.

[0119] In further embodiments, the weight ratio of substrate to alkoxysilylamine can be from about 1:1 to about 1:10. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:0 to about 1:7. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:6. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:2 to about 1:6.

[0120] In further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:10. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:0 to about 1:5. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:0 to about 1:3. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:2.

[0121] In a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 The amount of therapeutic agent is approximately 10 mg per 1000 mg of base material.

[0122] In a further aspect, the disclosed article comprises: [ka] Substrates, for example, including fabric or textile materials disclosed herein, can be prepared by incubating as shown in the following reaction scheme: [ka] Briefly, the sequence for preparing an article containing the composition shown above involves: (a) reacting a substrate with a suitable alkoxysilylamine, (b) reacting the substrate containing the covalently bound alkoxysilylamine with a suitable linker, and (c) reacting the material produced in the previous step with an activated form of a therapeutic agent. In yet a further embodiment, the substrate can be washed prior to incubation with the solution containing the alkoxysilylamine, e.g., with water, then isopropanol, and then dried under vacuum at a temperature of about 20°C to about 30°C. A silylamine solution containing a suitable alkoxysilylamine, e.g., 3-(triethoxysilyl)propan-1-amine, is prepared in a suitable solvent, e.g., THF, at an appropriate concentration, e.g., 1 part alkoxysilylamine to 2 parts solvent. The substrate is immersed in the silylamine solution, allowed to react, and heated, e.g., at about 60°C to about 90°C, for a suitable period of time, e.g., about 1 hour to about 6 hours. The substrate is removed from the silylamine solution and allowed to dry, e.g., at room temperature, protected from light. A suitable linker solution is prepared containing a suitable linker, such as maleic anhydride acyl chloride, in a suitable solvent, such as dichloromethane. The linker solution can further contain a suitable catalyst, such as DMSO, at about 0.1% v / v to about 1% v / v. The linker solution is added in an amount sufficient to provide a substrate:linker ratio of about 1:1 to about 1:10, and in certain cases, about 1:4 to about 1:6, by weight. The reaction can be carried out under an inert atmosphere, such as nitrogen or argon. The substrate is separated from the linker solution and washed, for example, with excess solvent, such as that used to prepare the linker solution. The substrate can then be dried under vacuum at ambient temperature. In the final step, the substrate containing the alkoxysilylamine and linker is reacted with a suitable chemically activated therapeutic agent, such as an acyl chloride derivative of the therapeutic agent. In the above reaction, the therapeutic agent is glycyrrhetinic acid acyl chloride. In this final step, an activated therapeutic agent solution is prepared, for example, glycyrrhetinic acid acyl chloride in dichloromethane as a solvent. The activated therapeutic agent solution may further contain a catalytic amount of a second agent, for example, DMSO, at 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 an amount sufficient to provide a substrate:activated therapeutic agent ratio of about 1:1 to about 1:10, and in certain cases, a ratio of about 1:6 to about 1:8, on a weight basis. The reacted substrate, which comprises a covalently bound alkoxysilylamine attached to a linker group and further contains a releasable therapeutic agent, is then washed and dried under vacuum at ambient temperature, e.g., about 20°C to about 30°C. 1 cm of the substrate. 2 Approximately 1 mg per 1 cm of substrate 2 A therapeutic agent, such as glycyrrhetinic acid as set forth above, in a therapeutic amount of about 25 mg per tablet.

[0123] In further embodiments, the weight ratio of substrate to alkoxysilylamine can be from about 1:1 to about 1:10. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:0 to about 1:7. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:6. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:2 to about 1:6.

[0124] In further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:10. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:0 to about 1:5. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:0 to about 1:3. In still further embodiments, the weight ratio of substrate to therapeutic agent can be from about 1:1 to about 1:2.

[0125] In a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2In yet a further embodiment, the amount of therapeutic agent relative to the substrate is about 1 cm 2 Approximately 1 mg of therapeutic agent for approximately 1 cm 2 The amount of therapeutic agent is approximately 10 mg per 1000 mg of base material.

[0126] In a further aspect, the disclosed article comprises: [ka] Substrates, for example, including fabric or textile materials disclosed herein, can be prepared by incubating as described above, omitting the reaction step involving reaction with an alkoxysilylamine.

[0127] A. Methods of Treating a Subject In various aspects, the present disclosure relates to the use of the disclosed articles for a method of treating a subject. In a further aspect, the subject is a patient diagnosed with atopic dermatitis. In yet a further aspect, the subject is a patient diagnosed with a wound, a skin injury, an infection, inflammation, localized pain, and combinations thereof. In a further aspect, the present disclosure relates to the use of the disclosed articles for a method of treating a subject with a clinical condition involving or including a microbial infection and / or inflammatory aspect.

[0128] In a further aspect, the present disclosure relates to the use of the disclosed article for a method for treating a subject with atopic dermatitis.In a still further aspect, the present disclosure relates to the use of the disclosed article for a method for treating a subject with atopic dermatitis, the subject having one or more peeling skin.In a still further aspect, the present disclosure relates to the use of the disclosed article for a method for treating a subject with atopic dermatitis, the method comprising administering the disclosed article, comprising a substrate that is in contact with or adhered to glycyrrhetinic acid.

[0129] In a further aspect, the present disclosure relates to the use of the disclosed articles for a method of treating a subject with psoriasis.

[0130] In a further aspect, the present disclosure relates to the use of the disclosed articles for a method of treating a subject with acne.

[0131] In a further embodiment, the method can further include co-administering, e.g., simultaneously or sequentially, an additional therapeutic agent related to the treatment of atopic dermatitis, such as nemolizumab or its equivalent, an IL-13 antagonist, an anti-OX40 antagonist, an anti-TSLP antibody, a ceramide derivative, an acetylcholine receptor antagonist, a corticosteroid, an antihistamine, a calcineurin inhibitor, a phosphodiesterase inhibitor, an antibacterial agent, and other therapeutic agents known to those skilled in the art. In yet a further embodiment, the additional therapeutic agent can be administered by a suitable route for that agent, and the disclosed article can be administered separately to the skin or peel. In yet a further embodiment, the article can further include poly-gamma-glutamic acid at a concentration of 0.001 to 5% by weight, preferably 0.01 to 3% by weight.

[0132] In further embodiments, the subject has an active infection associated with bacteria, fungi, microorganisms, and combinations thereof. In still further embodiments, the subject has an active infection associated with Pseudomonas aeruginosa, vancomycin-resistant Enterococcus, Klebsiella pneumoniae, Streptococcus pneumoniae, Salmonella species, Escherichia coli, extensively drug-resistant tuberculosis, Acinetobacter baumannii, Neisseria gonorrheae, Clostridium difficile, and Candida species. In still further embodiments, the subject has an active infection associated with macrofungi, such as Ganoderma lucidum (GL) and Pycnoporus sanguineus (PY). In still further embodiments, the subject has an active infection associated with a microfungus, such as Hypocrea rufa (Hr), Phoma foveata (PH), Curvularia species (Cur), Fusarium species, and Pestalotiopsis species. In still further embodiments, the subject has an active infection associated with an actinomycete, such as a Streptomyces species, such as Streptomyces species (unidentified), Streptomyces cacaoi, and Streptomyces parvulus. In still further embodiments, the subject has an active infection associated with a Pseudomonas species, Chromobacterium species, Serratia marcescens, and combinations thereof. In still further aspects, the subject has an active infection associated with MRSA, VRSA, Pseudomonas aeruginosa (P. aeruginosa), vancomycin-resistant Enterococcus, Klebsiella pneumoniae, Streptococcus pneumoniae, Salmonella species, Escherichia coli, extensively drug-resistant tuberculosis, Acinetobacter baumannii, Neisseria gonorrhaeae, Clostridium difficile, and Candida species-associated infections, and combinations thereof.In still further embodiments, the subject has an active infection associated with Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Staphylococcus aureus, Neisseria gonorrhoeae, Haemophilus influenzae, Vibrio cholerae, E. coli, Salmonella typhimurium, Shigella dysenteriae, Proteus mirabilis, Pseudomonas aeruginosa, Bacillus anthracis, Bacillus anthracis spores, Bacillus cereus, Bacillus cereus spores, Bacillus subtilis, Bacillus subtilis spores, Yersinia enterocolitica, or Yersinia pseudotuberculosis. In still further embodiments, 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 the present embodiments are well adapted to attain all ends and objectives hereinabove set forth, together with other advantages which are obvious and which are inherent in the structure.

[0134] Although specific elements and steps are discussed in relation to each other, it is understood that it is contemplated that any element and / or step provided herein can be combined with any other element and / or step, whether or not explicitly provided, 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, which are contemplated by and within the scope of the claims.

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

[0137] It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Those skilled in the art will recognize many variations and adaptations of the embodiments described herein. These variations and adaptations are intended to be included within the teachings of this disclosure and encompassed by the claims herein.

[0138] Having now described aspects of the present disclosure, the following examples generally describe some additional aspects of the present disclosure. While aspects of the present disclosure will be described in conjunction with the following examples and corresponding text and figures, it is not intended that aspects of the present disclosure be limited to this description. On the contrary, the intention is to cover all alternatives, modifications, and equivalents included within the spirit and scope of the present disclosure. [Example]

[0139] B. Working Example The following examples are set 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 otherwise indicated, parts are parts by weight, temperature is in ° C. or is at ambient temperature, and pressure is at or near atmospheric.

[0140] 1. Example 1 Glycyrrhetinic acid was solubilized in DMSO to obtain a clear solution. For example, 800 mg of glycyrrhetinic acid was solubilized in 3 mL of DMSO. After washing a cotton cloth with water and isopropanol and drying under high vacuum at room temperature, 375 μL of the glycyrrhetinic acid DMSO solution was applied to the dried cloth in a 2 cm diameter. 2 and then dried to constant weight at 25°C using a stream of air.

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

[0142] The release rate of the therapeutic agent under the conditions described above is shown in FIG.

[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 embodiments of the present disclosure will be apparent to those skilled in the art from consideration of the specification and practice of the present disclosure disclosed herein. It is intended that the specification and examples be considered as exemplary only, with the true scope and spirit of the present disclosure being indicated by the following claims.

Claims

1. 1. An article comprising a substrate and a therapeutic agent, wherein the substrate and therapeutic agent comprise a structure selected from the following formulas or a combination of one or more of the foregoing structures: 【Chemistry 1】 wherein A is OH or a moiety having the structure shown in the formula: 【Chemistry 2】 Y is a moiety having the structure shown in the formula: 【Transformation 3】 Z is selected from O, NH, and S; 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; n is an integer selected from 1, 2, and 3; q is an integer selected from 1, 2, 3, 4, 5, 6, 7, 8.9, and 10.

2. 10. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the formula: 【Chemistry 4】

3. 10. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the formula: 【Transformation 5】

4. 10. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the formula: 【Transformation 6】

5. 10. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the formula: 【Transformation 7】

6. 6. The article of claim 5, wherein the substrate and therapeutic agent comprise a structure having the formula: 【Transformation 8】

7. 10. The article of claim 1, wherein the substrate and therapeutic agent comprise a structure having the formula: 【Chemistry 9】

8. 8. The article of claim 7, wherein the substrate and therapeutic agent comprise a structure having the formula: 【Chemistry 10】

9. A method of treating a subject, comprising administering to the subject the article of claim 1.

10. 10. The method of claim 9, wherein the subject is diagnosed with a clinical condition selected from an inflammatory disorder, a wound, an infection, and combinations thereof.

11. 11. The method of claim 10, wherein the clinical condition is atopic dermatitis.

12. 4. The method of claim 3, wherein the clinical condition is psoriasis.

13. 11. The method of claim 10, wherein the clinical condition is acne.

14. 11. The method of claim 10, wherein the clinical condition is a wound.

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