Nitric oxide precursor and multi-component composition for forming the same

Abstract

A nitric oxide precursor for providing nitric oxide is provided. In a particularly contemplated embodiment, the nitric oxide precursor comprises the reaction product of a (preferably primary) thiol-containing compound and a nitrosating compound. The thiol-containing compound and the nitrosating compound typically react in the presence of a solvent and optionally a catalyst / reducing equivalent to form the nitric oxide precursor, which then rapidly decomposes to form nitric oxide.

Description

Technical Field

[0001] Related Applications This application claims priority to co-pending U.S. Provisional Patent Application No. 63 / 341,320, filed May 12, 2022, which is incorporated herein by reference.

[0002] The present invention generally relates to compositions and methods for nitric oxide precursors that can release nitric oxide, particularly nitric oxide precursors comprising reaction products of (preferably primary) thiol-containing compounds and nitrosating compounds.

Background Art

[0003] A variety of products and articles, including for example medical devices, instruments, and apparatuses, must be sterilized prior to use to prevent biocontamination of wound sites, samples, organisms, or the like. Similarly, many detergents reduce the microbial count to some extent, but most detergent compositions may not have a bactericidal component, which may be desirable for some applications. Additionally, certain formulations are known in the art for masking the malodorous by-products of microbial metabolism, but such formulations typically lack a bactericidal component.

[0004] Several sterilization processes are used that include the step of contacting the product or article with a sterilant. Examples of such sterilants include dinitrogen tetraoxide, nitric oxide, steam, ethylene oxide, hydrogen peroxide, dry heat, and the like. Conventional methods of forming nitric oxide use the catalytic and enzymatic generation of nitric oxide from NO-donor compounds such as nitrite compounds or diazenium dioate. Such conventional methods for forming nitric oxide typically require expensive reactants and in most cases must be utilized within a controlled system that allows for safe operation and the generation of nitric oxide. These and other drawbacks have hindered the mainstream commercialization of sterilization or sanitation compositions capable of generating nitric oxide by consumers and experts.

[0005] More recently, as described in WO 2022 / 164894, nitric oxide-releasing compositions and devices have been developed in which a tertiary nitrosothiol compound is covalently bound to a polymer (SNAP-PDMS) and irradiation of the tertiary nitrosothiol compound results in decomposition of the compound to form nitric oxide. Additional polymeric compounds containing various nitrosothiols that release nitric oxide upon irradiation are described in U.S. Patent No. 9,884,943 and WO 2020 / 018488. Such compounds and compositions offer various advantages in certain use cases, but the release of nitric oxide is relatively slow and typically requires energy directed at the compound. Thus, currently known compositions and methods are unable to produce substantial amounts of nitric oxide in a bolus or on demand. SUMMARY OF THE INVENTION PROBLEM TO BE SOLVED BY THE INVENTION

[0006] Accordingly, there remains an opportunity for improved compositions capable of generating nitric oxide for a variety of medical and consumer purposes, particularly where nitric oxide is rapidly generated in substantial amounts. MEANS FOR SOLVING THE PROBLEM

[0007] Nitric oxide precursors for providing nitric oxide are provided herein. The nitric oxide precursor comprises, consists essentially of, consists of, or is the reaction product of a thiol-containing compound and a nitrosating compound. In particularly preferred embodiments, the thiol is a primary thiol. The thiol-containing compound and the nitrosating compound are reacted in the presence of a solvent to form a nitric oxide precursor. The nitric oxide precursor is capable of decomposing to form nitric oxide. If necessary, a catalyst / reducing equivalent may be added to enhance the formation of the nitric oxide precursor. In various embodiments, the nitric oxide precursor comprises a (preferably primary) nitrosothiol that is capable of rapidly decomposing to form nitric oxide. It is contemplated herein that the nitric oxide precursor can be decomposed to form nitric oxide on demand, depending on when the thiol-containing compound and the nitrosating compound react in the presence of a solvent. Viewed from a different perspective, the contemplated nitric oxide precursor will have significant chemical instability such that it decomposes to nitric oxide immediately after its formation. As described in further detail below, the on-demand formation of the nitric oxide precursor is suitable for various applications that require such control for forming nitric oxide.

[0008] The nitric oxide precursor may be widely used in a variety of medical and consumer applications. The properties of the nitric oxide precursor can be adjusted based on the selection of the thiol-containing compound and the nitrosating compound to suit a particular application. Non-limiting examples of suitable adjustments include nitric oxide generating ability and nitric oxide release rate. As described in further detail below, the nitric oxide precursor may be formed in situ from a multi-component composition. This in situ formation of the nitric oxide precursor may be adjusted to suit a particular application by adjusting the properties of the formation and stability of the nitric oxide precursor such that nitric oxide can be generated, for example, rapidly and in a controlled manner. This controlled release of nitric oxide is useful for sterilizing and sanitizing medical and consumer devices.

[0009] In particular, the multi-component composition may be utilized to form a solution that produces nitric oxide in a controlled and predictable manner from the parent material / solution phase. These compositions can form small molecule nitric oxide donors that can be used in the formulation and application related to disinfection, sanitization, and aseptic cleaning in a wide variety of objects and devices and in several applications, and may include a first component containing a thiol-containing compound and a second component containing a nitrosated compound.

[0010] In some embodiments, the multi-component composition includes a first component containing a thiol-containing compound and a second component containing a nitrosated compound, and the first component and the second component are separated from each other. At least one of the first component and the second component may include a solvent.

[0011] In other embodiments, the multi-component composition includes a first component containing a thiol-containing compound having a particle size of from about 1 nm to about 10 mm, and a second component containing a nitrosated compound having a particle size of from about 1 nm to about 10 mm.

[0012] In various embodiments, the thiol-containing compound includes cysteine or its derivatives, thiol-derivatized polymers or fillers, or combinations thereof. In an exemplary embodiment, cysteine or its derivatives include cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-n-acetylpenicillamine, bucillamine, or combinations thereof. Preferably, the thiol-containing compound includes a primary thiol group, although secondary and tertiary thiols are also contemplated herein. In these and other embodiments, the nitrosating compound includes a nitrous acid compound. The nitrous acid compound may include sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, t-butyl nitrite, amyl nitrite, pentyl nitrite, nitrite salts, ion-pair nitrous acid compounds, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrous acid compounds, or combinations thereof. Further, if necessary, a reducing equivalent may be used to enhance the reaction between the thiol compound and the nitrosating compound. In particular, contemplated reducing equivalents include transition metals, other thiols, NADH, ascorbic acid, and the like.

[0013] The inventors contemplate that the reaction product can be formed within a predetermined time, for example, within 1 hour or less, after which the nitric oxide precursor can exhibit decomposition into nitric oxide. In various embodiments, the decomposition into nitric oxide can be sustained over a predetermined period of time, for example, from about 1 second to 1 minute, or from about 1 minute to about 10 minutes, or from about 10 minutes to 1 hour, or from about 1 hour to 6 hours, or from about 6 hours to 24 hours, or from 1 day to about 10 days, and even longer periods. Without being bound by theory, the in-situ formation of the reaction product is thought to result in a controlled decomposition of the nitric oxide precursor (e.g., (primary) nitrosothiol) into nitric oxide within a predetermined time.

[0014] Viewed from different perspectives, the intended multi-component composition may be formulated as a detergent composition or a cleaning composition. The detergent or cleaning composition may be formulated as a liquid, powder, single-phase or multi-phase unit dose, pouch, tablet, gel, paste, bar, or wafer. In these and other embodiments, the detergent or cleaning composition may further contain a cleaning agent. The cleaning agent may contain a detergent, an enzyme, or a combination thereof. Non-limiting examples of suitable cleaning agents include Alconox powder.

[0015] Also provided herein is a method for sterilizing or sanitizing a device or object. The method includes the step of applying the above-described nitric oxide precursor to the device or object. In embodiments where the nitric oxide precursor is included in a multi-component composition, the method includes the step of applying the above-described multi-component composition to the device or object. As will be understood, the step of applying the nitric oxide precursor may include the step of applying a thiol-containing compound and a nitrosating compound that will react in situ to form the nitric oxide precursor.

[0016] Also provided herein is a multi-component system for providing nitric oxide. The system includes a first compartment containing a first component. As described above, the first component includes a thiol-containing compound. The system further includes a second compartment containing a second component. Again, as described above, the second component includes a nitrosating compound. The system further includes a mixing chamber in fluid communication with the first and second compartments for combining the first and second compartments.

Brief Description of the Drawings

[0017]

Figure 1

Figure 2

Figure 3

Figure 4

[0018] Unless otherwise indicated in the examples or elsewhere, all quantities in this description indicating amounts of materials or conditions of reactions and / or uses are to be understood as being modified by the word "about" when describing the broadest scope of the invention. In various embodiments, the terms "about" and "approximately" when referring to a specified measurable value (parameters, amounts, time durations, and the like, etc.) mean the specified value as well as variations from the specified value, provided that such variations are appropriate for the embodiments in which they are disclosed, for example, variations of ±10% or less, or ±5% or less, or ±1% or less, or ±0.1% or less from the specified value. Thus, the values to which the modifier "about" or "approximately" refers are themselves also specifically disclosed.

[0019] Implementations within the recited numerical limits are generally preferred. Also, unless the contrary is explicitly stated, percent, "parts by", and ratio values are by weight, a description of a group or class of materials appropriate or preferred for a given purpose in connection with the present invention implies that any two or more mixtures of the elements of the group or class are equally appropriate or preferred, a description of a component in chemical terms refers to the component upon addition to any combination specified in that description, does not necessarily exclude chemical interactions between the components of a mixture once mixed, the first definition of an acronym or other abbreviation applies to all subsequent uses of the same abbreviation in this specification, with modifications as necessary to the normal grammatical variations of the initially defined abbreviation, and unless the contrary is explicitly stated, measured values of properties are determined by the same techniques as those already or later referenced for the same property.

[0020] As used in this specification and the appended claims, it should also be noted that the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. For example, references to a component in the singular are to be construed as including a plurality of components.

[0021] As used herein, "embodiment" means that a particular feature, structure, or characteristic is included in at least one manifestation, example, or realization of the present invention. Further, the particular features, structures, or characteristics may be combined in any suitable manner as will be apparent to those skilled in the art. Combinations of features of various embodiments mean that all are within the scope of the present invention without the need to explicitly describe all possible permutations by way of example. Thus, any of the embodiments recited in the claims can be used in any combination.

[0022] As used herein, the term "weight percent" (and thus the related abbreviation "wt%") typically refers to weight percent expressed with respect to the weight of the dry matter. Thus, it should be understood that wt% can be calculated based on the total weight of the composition or from the ratio between two or more components / parts of a mixture (e.g., the total weight of the dry matter).

[0023] As used herein, the term "substantially" refers to the complete or nearly complete extent or degree of an action, characteristic, property, state, structure, item, or result. By way of any example, an object "substantially" encapsulated is considered to mean that the object is nearly completely encapsulated such that the object is completely encapsulated or has the same overall result as if the object were completely encapsulated.

[0024] The drawings are semi-schematic, not to scale, and some dimensions are shown for clarity only and are exaggerated in the drawings. Similarly, the views in the drawings generally show similar orientations for ease of description, but the depiction in the drawings is arbitrary. In general, the functionalized polymer material can operate in any orientation. As used herein, when a first element or layer is "over", "overlying", "under", or "underlying" a second element or layer, the first element or layer may be directly above the second element or layer, or intervening elements or layers may be present between the elements or layers in a relationship where a straight line can be drawn through the interior or overlying the form. When it is said that a first element or layer is "on" a second element or layer, the first element or layer is directly above and in contact with the second element or layer. Further, spatially related terms such as "upper", "over", "lower", "under", and the like may be used herein to simplify the description of the relationship of one element or form to another element or form (s) shown in the figures. It will be understood that the spatially related terms include various orientations of the functionalized polymer material during use or operation in addition to the orientation shown in the figures. For example, if the functionalized polymer material in the figure changes orientation, an element described as "under" another element or form is considered to face "above" the other element or form. Thus, the exemplary term "under" can encompass either an above or below orientation. The functionalized polymer material may face another (rotated 90 degrees or other orientation), and the spatially related descriptions used herein can be interpreted accordingly as well.

[0025] All publications and patent applications cited herein are incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict or contradiction between the definitions or uses of terms in the incorporated references and the definitions of terms presented herein, the definitions of terms presented herein shall apply and the definitions of terms in the references shall not apply.

[0026] The following detailed description is, in fact, merely exemplary and is not intended to limit the subject embodiments or the application and use of such embodiments. Further, no limitation is imposed by any theory presented, described, or suggested in the prior art field, background, brief summary, or the following detailed description.

[0027] Nitric oxide precursors for providing nitric oxide are provided herein. The nitric oxide precursor comprises, consists essentially of, consists of, or is the reaction product of a thiol-containing compound and a nitrosating compound. In a preferred embodiment, the thiol-containing compound comprises a primary thiol. The thiol-containing compound and the nitrosating compound are reacted in the presence of a solvent to form a nitric oxide precursor. In some embodiments, the solvent is supplied with the thiol-containing compound and / or the nitrosating compound, or is supplied separately, or is supplied by the moisture in air (which can be attracted by a desiccant). As will be appreciated, the reaction can be enhanced by various reducing equivalents such as transition metals, thiols, ascorbic acid, NADH, etc. The nitric oxide precursor thus formed is capable of decomposing to form nitric oxide. An exemplary reaction scheme is shown below.

[0028]

Chemical formula

[0029] In various embodiments, the nitric oxide precursor comprises a nitrosothiol capable of decomposing to form nitric oxide. There, nitric oxide and air are intended to react, resulting in a mixture containing various oxides of nitrogen. In particular, the addition of nitric oxide to air, or the addition of air to nitric oxide, results in the formation of nitrogen dioxide when nitric oxide reacts with oxygen in the air. The concentration of each nitrogen oxide species present in the mixture can vary depending on temperature, pressure, and the initial concentration of nitric oxide.

[0030] Nitric oxide is lipophilic and has the ability to disrupt the lipid membranes of microorganisms, regulate cell and tissue responses, control aggregation and biological integration, and confer antibacterial properties. Furthermore, nitric oxide can inactivate thioproteins, thereby destroying the functional proteins of microorganisms. Nitrogen dioxide is more water-soluble than nitric oxide. Finally, nitric oxide and nitrogen dioxide are effective DNA-damaging agents, causing strand breaks and other damage, as a result making it impossible for cells to function.

[0031] As used herein, the terms "nitric oxide" or "NO" mean the NO free radical. As is well known, NO is chemically unstable and readily reacts with oxygen to form various oxides collectively called NOx. As used herein, the term NOx is an abbreviation for nitrogen oxides or oxides of nitrogen, which are oxides formed by nitrogen, each showing its positive oxidation number from +1 to +5. The terms "nitrogen oxides", "oxides of nitrogen", and "NOx" as used herein all refer to the following gases containing nitrogen and oxygen in various amounts: nitric oxide (NO), nitrogen dioxide (NO 2 ), nitrogen trioxide (NO 3 ), dinitrogen trioxide (N 2 O 3 ), dinitrogen tetroxide (N 2 O 4 ), dinitrogen pentoxide (N 2 O 5 ), and nitrous oxide (N 2It means a gas having one or more of (O). As used herein, the term "nitric oxide precursor" means a compound or composition capable of generating or releasing NO.

[0032] Nitric oxide precursors may be widely used in a variety of medical and consumer applications. The properties of nitric oxide precursors can be adjusted based on the selection of thiol-containing compounds and nitrosated compounds to suit a particular application. Non-limiting examples of suitable adjustments include nitric oxide generating ability and the rate of nitric oxide release from the nitric oxide precursor. As described in more detail below, nitric oxide precursors may be formed in situ from multi-component compositions. This in situ formation of nitric oxide precursors may be adjusted to suit a particular application by adjusting the properties of the formation and stability of the nitric oxide precursors so that nitric oxide can be generated, for example, in a rapid and controlled manner. This controlled release of nitric oxide is useful for sterilizing and sanitizing medical and consumer devices.

[0033] From a different perspective, the inventors contemplate forming nitric oxide for various medical and consumer applications using a nitric oxide precursor and a multi-component composition. In various embodiments, the device or object may be treated with a multi-component composition in the form of a liquid, powder, film, coating, etc. Non-limiting examples of suitable uses of the multi-component composition (e.g., as a liquid, powder, film, or coating) include: cleaning agents or cleaning solutions for sanitizing or sterilizing objects treated with a solution (e.g., sports equipment such as hockey gloves and cycling gloves, surgical instruments being cleaned, the inner lumen of an endoscope, the surface of medical devices, and the like); cleaning agents or cleaning powders for sanitizing or sterilizing objects treated with a powder; sanitary containers for sanitizing sanitary devices (e.g., desiccants and the like); medical device containers for sanitizing medical devices (e.g., stethoscopes, otoscopes, and the like), medical devices (e.g., portable ultrasonic devices, communication devices, and the like); components of devices exposed to moisture to resist the growth of blue or white mold (e.g., washing machines, boat compartments, and the like); sports equipment (e.g., yoga mats, contact surfaces of strength training equipment, contact surfaces of cardio equipment, and the like); liners for sports equipment bags for sanitizing sports equipment (e.g., shoes, hockey equipment, ski equipment, face masks, goggles, helmets, and the like); food packages for preserving food products (e.g., meat, fruits, vegetables, cheese, their components, and the like); components of vehicles for sanitizing vehicles (e.g., headliners, seat cushion liners, carpet liners, and the like); and those within drawers of cabinets, desks, boxes, etc. for eliminating the smell of mold. In some or all of the above examples, the nitric oxide precursor is preferably not supplied as a pre-formed compound, and it should be understood that the nitric oxide precursor is generated in situ by reacting a thiol-containing compound with a nitrosating compound in the presence of a solvent (derived from the moisture in the air, which may be supplied individually or used as a solvent for the thiol-containing compound and / or the nitrosating compound).

[0034] Accordingly, as introduced above, multi-component compositions for providing nitric oxide are also provided. The multi-component compositions may be utilized to form solutions that produce nitric oxide in a controlled and predictable manner from a parent material / solution phase. These compositions can be used in a wide variety of objects and devices and in several applications, for the formulation and application related to disinfection, sanitization, and sterilizing washes, to form small molecule nitric oxide donors (preferably, but not necessarily, primary nitrosothiols) that can be used. The compositions may include a first component containing a thiol-containing compound and a second component containing a nitrosating compound.

[0035] In some embodiments, the multi-component composition includes a first component containing a thiol-containing compound and a second component containing a nitrosating compound, where the first component and the second component are separated from each other. At least one of the first component and the second component may include a solvent. Alternatively, the first and second components are separated from each other, the solvent is provided separately, or the first and second components are placed in a solvent. In other embodiments, the multi-component composition includes a first component containing a thiol-containing compound having a particle size of from about 1 nm to about 10 mm, or from about 1 nm to about 1 mm, or from about 1 nm to about 500 μm, or from about 10 nm to about 500 μm. Similarly, the multi-component composition further includes a second component containing a nitrosating compound having a particle size of from about 1 nm to about 10 mm, or from about 1 nm to about 1 mm, or from about 1 nm to about 500 μm, or from about 10 nm to about 500 μm. Irrespective of the arrangement configuration, it should be understood once again that the nitric oxide precursor is formed in situ and then subjected to decomposition to form nitric oxide.

[0036] Regarding multi-component compositions, the inventors contemplate that after the formation of the reaction product, within a predetermined time, for example, within 1 hour, or within 30 minutes, or within 5 minutes, or within 1 minute, or within 10 seconds, or within 1 second, or within 0.1 second, the nitric oxide precursor may exhibit decomposition into nitric oxide. From a different perspective, the multi-component composition may exhibit decomposition into nitric oxide within a predetermined time after the formation of the nitric oxide precursor, for example, from about 0.01 second to about 1 hour, or from about 0.01 second to about 30 minutes, or from about 1 second to about 5 minutes, or from about 1 second to about 1 minute. In various embodiments, the decomposition into nitric oxide may be sustained over a predetermined time, for example, from about 1 minute to about 1 year, or from about 1 hour to about 6 months, or from about 24 hours to about 3 months, or from about 1 week to about 8 weeks. From a different perspective, the decomposition into nitric oxide may be sustained over a period of at least 1 minute, or at least 1 hour, or at least 24 hours, or at least 1 week. Without being bound by theory, the in-situ formation of the reaction product is thought to result in a controlled decomposition of the nitric oxide precursor (e.g., nitrosothiol) into nitric oxide within a predetermined time over a predetermined time.

[0037] As can be readily understood, the decomposition rate of the nitric oxide precursor will depend on a variety of factors that can be fine-tuned to achieve the desired decomposition profile. Among the numerous factors, the decomposition rate can be modified by selecting the type of nitrosothiol, the molar ratio of the thiol-containing compound and the nitrosated compound, the presence / amount of a reducing equivalent or other catalyst that affects the in-situ formation of the nitric oxide precursor, the pH of the solution, and the availability of the solvent. For example, it should be understood that primary nitrosothiols have a substantially faster decomposition rate than secondary or tertiary nitrosothiols. Further, the in-situ formation of nitrosothiol may be accelerated in the presence of various reducing equivalents such as, for example, thiol, NADH, transition metals, ascorbic acid, etc. (such reducing agents can be present in trace amounts to equimolar ratios, or even in excess molar amounts relative to the thiol-containing agent). Similarly, an acidic pH (e.g., pH < 4.0) generally acts favorably on the stability of nitrosothiol, while a basic pH (e.g., pH > 7.0) acts favorably on the decomposition of nitrosothiol. Still further, when the solvent is water from humid air, the degree of humidity will determine the in-situ formation rate of the nitric oxide precursor.

[0038] Regardless of the reaction conditions, in some embodiments, the rate at which the nitric oxide precursor decomposes to form nitric oxide is greater than the in-situ formation rate, e.g., 1.5 times greater, or 2.5 times greater, or 5 times greater, or 10 times greater, or even greater than that. In other embodiments, the rate at which the nitric oxide precursor decomposes to form nitric oxide is less than the in-situ formation rate, e.g., one 1.5th, or one 2.5th, or one 5th, or one 10th, or even less than that. Further, depending on the particular formulation and nitric oxide precursor, in some embodiments, the nitric oxide released within 1 hour is at least 25%, or at least 50%, or at least 70%, or at least 80%, or at least 90%, or at least 95% of all the releasable nitric oxide in the formulation. In further embodiments, the nitric oxide released within 24 hours is at least 25%, or at least 50%, or at least 70%, or at least 80%, or at least 90%, or at least 95% of all the releasable nitric oxide in the formulation, and in still other embodiments, the nitric oxide released within 7 days is at least 25%, or at least 50%, or at least 70%, or at least 80%, or at least 90%, or at least 95% of all the releasable nitric oxide in the formulation. In additional embodiments, the nitric oxide released within 1 month is at least 25%, or at least 50%, or at least 70%, or at least 80%, or at least 90%, or at least 95% of all the releasable nitric oxide in the formulation.

[0039] The inventors herein contemplate blending a nitric oxide precursor into a matrix (embedded in a polymer or powder or within or on a solid support) to create a wide range of NO-donating / generating entities, or to create a solution that generates NO in a controlled and predictable manner from the matrix / solution phase, by blending small molecule nitric oxide precursors into polymers, into solution phases, or into powders, and that can be used to generate nitric oxide. Herein, the inventors describe methods for synthesizing novel small molecule NO donors that can be used for this purpose, as well as formulations and applications of these NO-generating moieties that can be used as disinfectants, sanitizers, and sterilizing washes in a wide variety of objects and situations.

[0040] Small molecule nitrosothiols (particularly primary nitrosothiols) formed in situ from nitric oxide precursors such as thiol-containing compounds (e.g., cysteine, N-acetylcysteine, and glutathione) and nitrosating compounds (e.g., organic nitrite compounds or inorganic nitrites) may be formed in both organic and aqueous phases. Solutions containing cleaning agents (e.g., enzymes, surfactants, etc.) may be combined with specific thiol-containing compounds and appropriate nitrosating compounds under controlled conditions to form nitrosothiols. These nitrosothiols can then rapidly decompose to produce nitric oxide. These two-component systems (thiol-containing compounds and nitrosating compounds) may be combined with various carriers and cleaning agents, such as powders or solution components (e.g., silica gel, sodium polyacrylate, Alconox soap, protease, etc.) and used to reprocess endoscopes and probes and to sterilize other objects.

[0041] Non-limiting examples of suitable embodiments include silica gel desiccants combined with cysteine and sodium nitrite as a dry powder that can generate nitric oxide when the mixture adsorbs moisture from humid air. Another example is combining a thiol-containing compound and a sodium nitrite solution together and pouring this solution onto an object, e.g., shoes, to eliminate odors caused by bacteria.

[0042] Returning to the thiol-containing compounds utilized to form the reaction products, there are a wide variety of possible thiol-containing compounds that can be used depending on the design constraints of the desired application examples of the multi-component composition. Among the numerous options, primary thiols are typically preferred. The thiol-containing compounds can include, but are not limited to, one or more of 1,2-ethanedithiol, 2,3-dimercaptopropanol, pyrithione, dithioerythritol, 3,4-dimercaptotoluene, 2,3-butanedithiol, 1,3-propanedithiol, 2-hydroxypropanethiol, 1-mercapto-2-propanol, dithioerythritol, and dithiothreitol. Other exemplary thiol-containing compounds include alpha-lipoic acid, methanethiol (CH 3 SH [m-mercaptan]), ethanethiol (C 2 H 5 SH [e-mercaptan]), 1-propanethiol (C 3 H 7 SH [n-P mercaptan]), 2-propanethiol (CH 3 CH(SH)CH 3 [2C3 mercaptan]), butanethiol (C 4 H 9 SH ([n-butyl mercaptan]), tert-butyl mercaptan (C(CH 3 ) 3 SH [t-butyl mercaptan]), pentanethiol (C 5 H 11SH [pentyl mercaptan]), coenzyme A, lipoamide, glutathione, cysteine, cystine, 2-mercaptoethanol, dithiothreitol, dithioerythritol, 2-mercaptoindole, transglutaminase, (11-mercaptoundecyl) hexa(ethylene glycol), (11-mercapto-undecyl) tetra(ethylene glycol), (11-mercaptoundecyl) tetra (ethylene glycol) functionalized gold nanoparticles, 1,1′,4′,1″-terphenyl-4-thiol, 1,11-undecanedithiol, 1,16-hexadecanedithiol, 1,2-ethanedithiol, 1,3-propanedithiol, 1,4-benzenedimethanethiol, 1,4-butanedithiol, 1,4-butane-dithiol diacetate, 1,5-pentanedithiol, 1,6-hexanedithiol, 1,8-octanedithiol, 1,9-nonanethiol, adamantanethiol, 1-butanethiol, 1-decanethiol, 1-dodecanethiol, 1-heptanethiol, 1-heptanethiol, 1-hexadecanethiol, 1-hexanethiol, 1-mercapto-(triethylene glycol), 1-mercapto-(triethylene glycol) methyl ether functionalized gold nanoparticles, 1-mercapto-2-propanol, 1-nonanethiol, 1-octadecanethiol, 1-octanethiol, 1-octanethiol, 1-pentadecanethiol, 1-pentanethiol, 1-propanethiol, 1-tetradecanethiol, 1-undecanethiol, 11-(1H-pyrrol-1-yl) undecane-1-thiol, 11-amino-1-undecane-thiol hydrochloride, 11-bromo-1-undecanethiol, 11-mercapto-1-undecanol, 11-mercapto-1-undecanol, 11-mercaptoundecanoic acid, 11-mercaptoundecanoic acid, 11-mercaptoundecyl trifluoroacetate, 11-mercaptoundecyl phosphate, 12-mercaptododecanoic acid, 12-mercaptododecanoic acid, 15-mercaptopentadecanoic acid, 16-mercaptohexadecanoic acid, 16-mercaptohexadecanoic acid, 1H,1H,2H,2H-perfluorodecanethiol, 2,2′-(ethylenedioxy) di-ethanethiol, 2,3-Butanedithiol, 2-Butanethiol, 2-Ethylhexanethiol, 2-Methyl-1-propanethiol, 2-Methyl-2-propanethiol, 2-Phenylethanethiol, 3,3,4,4,5,5,6,6,6-Nonafluoro-1-hexanethiol purum, 3-(Dimethoxymethylsilyl)-1-propanethiol, 3-Chloro-1-propanethiol, 3-Mercapto-1-propanol, 3-Mercapto-2-butanol, 3-Mercapto-N-nonylpropionamide, 3-Mercaptopropionic acid, 3-Mercaptopropyl-functionalized silica gel, 3-Methyl-1-butanethiol, 4,4′-Bis(mercapto-methyl)biphenyl, 4,4′-Dimercaptostilbene, 4-(6-Mercaptohexyloxy)benzyl alcohol, 4-Cyano-1-butanethiol, 4-Mercapto-1-butanol, 6-(Ferrocenyl)hexanethiol, 6-Mercapto-1-hexanol, 6-Mercaptohexanoic acid, 8-Mercapto-1-octanol, 8-Mercaptooctanoic acid, 9-Mercapto-1-nonanol, Biphenyl-4,4′-dithiol, Butyl 3-mercaptopropionate, Copper(I) 1-butanethiolate, Cyclohexanethiol, Cyclopentanethiol, Decanethiol-functionalized silver nanoparticles, Dodecanethiol-functionalized gold nanoparticles, Dodecanethiol-functionalized silver nanoparticles, Hexa(ethylene glycol) mono-11-(acetylthio)undecyl ether, Mercaptosuccinic acid, Methyl 3-mercaptopropionate, Octanethiol-functionalized gold nanoparticles, PEG dithiol, S-(11-Bromoundecyl)thioacetate, S-(4-Cyanobutyl)thioacetate, Thiophenol, Triethylene glycol mono-11-mercapto-undecyl ether, Trimethylolpropane tris(3-mercaptopropionate), [11-(Methylcarbonylthio)undecyl]tetra(ethylene glycol), m-Carborane-9-thiol, p-Terphenyl-4,4″-dithiol, tert-Dodecyl mercaptan, or tert-Nonyl mercaptan is included.,

[0043] In certain embodiments, the thiol-containing compound includes cysteine or its derivatives, thiol-derivatized polymers or fillers, or combinations thereof. In embodiments where cysteine or its derivatives are utilized, cysteine or its derivatives may include cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitrosoglutathione, buserelin, or combinations thereof. It should be understood that the thiol-containing compound may be included as part of a peptide or other polymer as long as the thiol-containing compound is compatible with the components of the multi-component composition. In embodiments where cysteine or its derivatives are utilized as part of a peptide, the peptide may include any combination of amino acids as long as the peptide includes cysteine or its derivatives as at least one of the constituent components of the peptide. Non-limiting examples of suitable cysteine or its derivatives are described in the academic paper cited as Langmuir 2006, 22, 25, 10830-10836, entitled "S-Nitrosothiol Detection via Amperometric Nitric Oxide Sensor with Surface Modified Hydrogel Layer Containing Immobilized Organoselenium Catalyst", which is incorporated herein by reference in its entirety.

[0044] In various embodiments, the thiol-containing compound has a weight average molecular weight of 500,000 g / mol or less, or 100,000 g / mol or less, or 10,000 g / mol or less, or 1,000 g / mol or less, or 500 g / mol or less. From a different perspective, the thiol-containing compound may have a weight average molecular weight of from about 10 g / mol to about 500,000 g / mol, or from about 10 g / mol to about 100,000 g / mol, or from about 10 g / mol to about 1,000 g / mol, or from about 10 g / mol to about 500 g / mol. For example, cysteine has a weight average molecular weight of 121 g / mol, glutathione has a weight average molecular weight of 307.33 g / mol, butyl mercaptan has a weight average molecular weight of 90.19 g / mol, and serum albumin has a weight average molecular weight of 66 kDa. Without being bound by theory, it is believed that the reaction kinetics for forming the reaction product are improved by utilizing a thiol-containing compound having a lower weight average molecular weight. This improved reaction kinetics results in a rapid generation of nitric oxide obtained from the in-situ formation of the reaction product. Furthermore, primary nitrosothiol compounds generally decompose more rapidly than secondary or tertiary nitrosothiols to form nitric oxide.

[0045] Returning to the nitrosating compound utilized to form the reaction product, the nitrosating compound may be any compound that serves as a source of a nitroso group and generally will be a compound of the formula NOX (wherein X is an organic or inorganic anion or an OR 2 group, where R 2(where X is an organic group). Thus, X may be an organic anion derived from a carboxylic acid, for example an alkane carboxylic acid containing 2 to 7 carbon atoms, and this type of nitrosating agent includes acetyl nitrite and propionyl nitrite. When X is an inorganic anion, this may be derived from, for example, a mineral acid, for example a halide ion, such as chloride or bromide or sulfate ion, or may be derived from a Lewis acid, for example a borofluoride ion. Other inorganic anions include hydroxides and sulfonates. Thus, this type of nitrosation compound includes nitrosyl chloride, nitrosyl sulfate, nitrosyl borofluoride, nitrous acid, and Fremy's salt (potassium nitrosyl disulfonate). When X is a group of the formula OR2, the organic group R2 may be, for example, a lower alkyl group, for example one containing 1 to 9 carbon atoms, for example ethyl, n-propyl, isopropyl, n-butyl, t-butyl, or isopentyl.

[0046] In certain embodiments, the nitrosation compound includes a nitrite compound. The nitrite compound may include sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, t-butyl nitrite, amyl nitrite, pentyl nitrite, nitrites, ion pair nitrite compounds, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrite compounds, or combinations thereof. Also, nitric oxide gas may be used as a nitrosating agent.

[0047] In various embodiments, the nitrosation compound has a weight average molecular weight of 10,000 g / mol or less, or 1,000 g / mol or less, or 500 g / mol or less, or 250 g / mol or less. From a different perspective, the nitrosation compound may have a weight average molecular weight of from about 10 g / mol to about 10,000 g / mol, or from about 10 g / mol to about 1,000 g / mol, or from about 10 g / mol to about 500 g / mol, or from about 10 g / mol to about 250 g / mol. For example, NaNO 2has a weight average molecular weight of 69 g / mol, and butyl nitrite has a weight average molecular weight of 103 g / mol. Without being bound by theory, the reaction kinetics for forming the reaction product may be improved by utilizing a nitrosated compound having a lower weight average molecular weight. As described above, this improved reaction kinetics results in a rapid generation of nitric oxide obtained from the in-situ formation of the reaction product.

[0048] As introduced above, the thiol-containing compound and the nitrosated compound may react in the presence of a solvent to form a reaction product (e.g., (primary) nitrosothiol). When utilized, the solvent may be included in various amounts. The solvent may be aqueous, organic, non-organic, or a combination thereof. In certain embodiments, the solvent is an aqueous solvent such as water or a mixture of water and methanol. In other embodiments, the solvent may include an organic solvent such as tetrahydrofuran. Other non-limiting examples of suitable solvents include aromatics, aliphatics, ketones such as methyl ethyl ketone, isobutyl ketone, ethyl amyl ketone, acetone, alcohols such as methanol, ethanol, n-butanol, isopropanol, esters such as ethyl acetate, glycols such as ethylene glycol, propylene glycol, ethers such as tetrahydrofuran, ethylene glycol monobutyl ether, or combinations thereof.

[0049] In various embodiments, the thiol-containing compound and the nitrosating compound react in the presence of an acid. The acid may be utilized to improve the formation and / or stability of the reaction product, for example, when using a thiol-containing compound that includes cysteine. In certain embodiments, the acid may include hydrochloric acid. Other non-limiting examples of suitable acids include citric acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, acetic acid, hydroxyacetic acid, propionic acid, hydroxypropionic acid, a-ketopropionic acid, butyric acid, mandelic acid, valeric acid, succinic acid, tartaric acid, malic acid, oxalic acid, fumaric acid, adipic acid, maleic acid, sorbic acid, benzoic acid, succinic acid, glutaric acid, adipic acid, α-hydroxy acid, ethylenediaminetetraacetic acid (EDTA), phosphonic acid, octylphosphonic acid, acrylic acid, polyacrylic acid, aspartic acid, polyaspartic acid, p-hydroxybenzoic acid, iminodiacetic acid, or combinations thereof. It should be understood that the acid may be included as any component of the composition (e.g., carrier, solvent, etc.) or as part of a reactant of the reaction product.

[0050] In other embodiments, the reaction product is formed in the substantial absence of an acid, for example, when using a thiol-containing compound that includes glutathione. The inventors contemplate that a multi-component composition substantially free of acid exhibits improved compatibility with a device or an object. As used herein, the phrase "substantially free of" refers to either the complete absence of an acid or its minimal amount as an impurity, an unintended by-product of another component, or an amount having a negligible effect on the composition. In certain embodiments, "substantially free of" means that the acid is present in the composition in an amount less than 0.5 wt%, less than 0.25 wt%, less than 0.1 wt%, less than 0.05 wt%, or less than 0.01 wt%, or even 0 wt% based on the total weight of the composition.

[0051] In still other embodiments, the reaction product is formed in the presence of a reducing equivalent, and suitable reducing equivalents include various metals and transition metals, dithionates, thiosulfates, hydrazine, oxalic acid, ascorbic acid, formic acid, NADH, NADPH, and the like. As will be readily appreciated, these reducing equivalents can be provided separately, provided in a solvent, or mixed with a thiol-containing compound and / or a nitrosating compound.

[0052] In these and other embodiments, the multi-component composition further includes a carrier. The carrier may include silica gel, sodium polyacrylate, or a combination thereof. However, it should be understood that any other carrier may be utilized. Such carriers are well known to those skilled in the art and are described in textbooks such as Remington's Pharmaceutical Sciences, Mack Publishing Co., Easton, Pa., 1985, which is hereby incorporated by reference in its entirety.

[0053] The multi-component composition may include a thiol-containing compound in an amount of from about 1 to about 80 weight percent, or from about 1 to about 70 weight percent, or from about 50 to about 80 weight percent, based on the total weight of the composition. The multi-component composition may include a nitrosating compound in an amount of from about 1 to about 75 weight percent, or from about 1 to about 10 weight percent, or from about 10 to about 75 weight percent, based on the total weight of the composition. The multi-component composition may include a carrier in an amount of from about 10 to about 95 weight percent, or from about 10 to about 80 weight percent, or from about 80 to about 95 weight percent, based on the total weight of the composition. The multi-component composition may include a solvent in an amount of from about 1 to about 99 weight percent, based on the total weight of the composition.

[0054] In an exemplary embodiment, the multi-component composition may be formulated as a detergent composition or a cleaning composition. As used herein, the terms "detergent composition" or "cleaning composition" include compositions and formulations designed to clean soiled materials. Such compositions include, but are not limited to, object cleaning compositions, medical device cleaning compositions, hard surface cleaning compositions, dishware cleaning compositions, laundry cleaning compositions and detergents, spray products, dry cleaning agents or compositions, unit dose formulations, delayed delivery formulations, detergents contained on or in porous substrates or non-woven sheets, detergents contained on or in water-soluble films, and other suitable forms that may be apparent to those skilled in the art in view of the teachings herein. The multi-component composition may have a form selected from liquids, powders, single-phase or multi-phase unit doses, two-layer paper carriers, pouches, tablets, gels, pastes, bars, or flakes.

[0055] In these and other embodiments, the detergent or cleaning composition further comprises a cleaning agent. The cleaning agent includes a detergent, an enzyme, or a combination thereof. Non-limiting examples of suitable cleaning agents include Alconox powder. In embodiments where the cleaning agent includes a detergent, the detergent may include surfactants such as amine oxides, alkylbenzene sulfonates, alkyl ether sulfates, fatty alcohol ethoxylates, alkyl glycosides, alkoxylated fatty acid alkyl esters, amine oxides, fatty acid alkanolamides, hydroxy mixed ethers, sorbitan fatty acid esters, polyhydroxy fatty acid amides, and alkoxylated alcohols.

[0056] In embodiments where the cleaning agent contains an enzyme, the enzyme may include one or more enzymes capable of exhibiting catalytic activity in a cleaning agent, such as protease, amylase, lipase, cellulase, hemicellulase, mannanase, pectin-cleaving enzyme, tannase, xylanase, xanthanase, β-glucosidase, carrageenase, peroxidase, oxidase, oxidoreductase, and mixtures thereof. In certain embodiments, the enzyme includes protease, amylase (e.g., α-amylase), cellulase, lipase, hemicellulase, pectinase, mannanase, β-glucanase, or combinations thereof. The properties of the enzyme should be compatible with the multi-component composition (i.e., pH-optimum, compatibility with other enzyme and non-enzyme components, etc.). When utilized, the enzyme should be present in an effective amount.

[0057] When utilized, the protease may be of animal, plant, or microbial origin, including chemically or genetically engineered variants. Microbial origin is preferred. It may be an alkaline protease, such as a serine protease or a metalloprotease. The serine protease may be, for example, of the Si family, such as trypsin, or of the S8 family, such as subtilisin. The protease of the metalloprotease may be, for example, from the M4, M5, M7, or M8 family, such as thermolysin.

[0058] When used, suitable lipases and cutinases include those derived from bacteria or fungi. Chemically modified or variants designed by protein engineering are included. Examples include lipases from Thermomyces described in EP 258 068 and EP 305 216, such as from T. lanuginosus (formerly known as Humicola lanuginosa), cutinases from Humicola described in WO 96 / 13580, such as from H. insolens, Pseudomonas lipases, such as from P. alcaligenes or P. pseudoalcaligenes (EP 218 272), P. cepacia (EP 331 376), P. stutzeri (GB 1,372,034), P. fluorescens, Pseudomonas sp., strain SD 705 (WO 95 / 06720 and WO 96 / 27002), P. wisconsinensis (WO 96 / 12012), Bacillus lipases, such as from B. subtilis (Dartois et al., 1993, Biochemica et Biophysica Acta, 1131: 253-360), B. stearothermophilus (JP 64 / 744992), or B. pumilus (WO 91 / 16422).

[0059] Other examples are lipase variants such as those described in WO 92 / 05249, WO 94 / 01541, EP 407 225, EP 260 105, WO 95 / 35381, WO 96 / 00292, WO 95 / 30744, WO 94 / 25578, WO 95 / 14783, WO 95 / 22615, WO 97 / 04079, WO 97 / 07202, WO 00 / 060063, WO2007 / 087508, and WO 2009 / 109500, which are incorporated herein by reference in their entirety.

[0060] When utilized, suitable amylases include those derived from bacteria or fungi. Variants that are chemically modified or designed by protein engineering are included. Amylases include, for example, α-amylases obtained from a particular strain of Bacillus, such as Bacillus licheniformis, which are described in more detail in GB 1,296,839. Examples of useful amylases are variants described in WO 94 / 02597, WO 94 / 18314, WO 96 / 23873, and WO 97 / 43424, which are incorporated herein by reference in their entirety.

[0061] When utilized, suitable cellulases include those derived from bacteria or fungi. Variants that are chemically modified or designed by protein engineering are included. Suitable cellulases include cellulases from the genera Bacillus, Pseudomonas, Humicola, Fusarium, Thielavia, Acremonium, such as those produced by Humicola insolens, Myceliophthora thermophila, and Fusarium oxysporum, which are disclosed in U.S. Patent No. 4,435,307, U.S. Patent No. 5,648,263, U.S. Patent No. 5,691,178, U.S. Patent No. 5,776,757, and WO 89 / 09259, which are incorporated herein by reference in their entirety.

[0062] When utilized, suitable peroxidases / oxidases include those derived from plants, bacteria, or fungi. Chemically modified or variants designed by protein engineering are included. Examples of useful peroxidases include those from Coprinus, such as peroxidases from C. cinereus, and their variants, as described in WO 93 / 24618, WO 95 / 10602, and WO 98 / 15257, which are incorporated herein by reference in their entirety.

[0063] The detergent or cleaning composition may further contain additives such as builders, bleaches, electrolytes, non-aqueous solvents, pH regulators, fragrances, perfume carriers, optical brighteners, dyes, hydrotropes, foam inhibitors, silicone oils, soil redeposition inhibitors, anti-greying agents, anti-shrinkage agents, anti-wrinkle agents, dye transfer inhibitors, antibacterial substances, bactericides, fungicides, antioxidants, preservatives, corrosion inhibitors, antistatic agents, bittering agents, ironing aids, hydrophobizing and impregnating agents, swelling and slip agents, softening components, and UV absorbers.

[0064] The detergent or cleaning composition may contain a thiol-containing compound in an amount of from about 0.01 to about 40% by weight, or from about 0.01 to about 5% by weight, or from about 5 to about 10% by weight, or from about 10 to about 40% by weight, based on the total weight of the composition. The detergent or cleaning composition may contain a nitrosating compound in an amount of from about 0.1 to about 40% by weight, or from about 0.1 to about 10% by weight, based on the total weight of the composition. The detergent composition or cleaning composition may contain a cleaning agent in an amount of from about 1 to about 99% by weight, based on the total weight of the composition. The detergent composition or cleaning composition may contain a solvent in an amount of from about 1 to about 99% by weight, based on the total weight of the composition.

[0065] In various embodiments, the detergent or cleaning composition described herein can be filled into a water-soluble envelope and thus can be part of a water-soluble package. The water-soluble envelope may be formed of a water-soluble film material. Such a water-soluble package can be manufactured by a vertical form-fill-seal (VFFS) method or by a thermoforming method.

[0066] The envelope can be made of one layer or two or more layers of a water-soluble film material. The water-soluble film material of the first layer and, if present, the other layers can be the same or different. The water-soluble envelope is made, for example, from a water-soluble film material selected from the group comprising polymers or polymer mixtures. The water-soluble envelope may contain polyvinyl alcohol or a polyvinyl alcohol copolymer. Polymers selected from the group comprising acrylic acid-containing polymers, polyacrylamides, oxazoline polymers, polystyrene sulfonates, polyurethanes, polyesters, polyether polyacetic acids, and / or mixtures of the above polymers can be added to the film material suitable for manufacturing the water-soluble envelope.

[0067] The thermoforming method generally includes the steps of forming a first layer from a water-soluble film material to create a convex portion for receiving the composition therein, filling the convex portion with the composition, covering the convex portion filled with the composition with a second layer of the water-soluble film material, and sealing the first and second layers together at least around the convex portion. The water-soluble package containing the liquid detergent and the water-soluble envelope can have one or more chambers. The water-soluble package can have substantially dimensionally stable spherical and pillow-shaped forms having a basic form of a circle, an ellipse, a square, or a rectangle. The chambers may be separated from each other.

[0068] Methods for sterilizing or sanitizing a device or object are also provided herein. The method includes the step of applying the above-described nitric oxide precursor to the device or object. In embodiments where the nitric oxide precursor is included in a multi-component composition, the method includes the step of applying the above-described multi-component composition to the device or object.

[0069] Multi-component systems for providing nitric oxide are also provided herein. The system includes a first compartment containing a first component. As described above, the first component includes a thiol-containing compound. The system further includes a second compartment containing a second component. Also as described above, the second component includes a nitrosating compound. The system further includes a mixing chamber in fluid communication with the first and second compartments for combining the first and second compartments.

[0070] Methods for forming a nitric oxide precursor are provided herein. The method includes the step of combining a thiol-containing compound and a nitrosating compound in the presence of a solvent to form a nitric oxide precursor.

[0071] In one exemplary embodiment, the combining step includes (a) combining the thiol-containing compound and the solvent to form a first solution, (b) combining the nitrosating compound and the solvent to form a second solution, and (c) combining the first solution and the second solution to form a nitric oxide precursor.

[0072] In another exemplary embodiment, the combining step includes (a) combining the thiol-containing compound, the solvent, and a detergent to form a first solution, and (b) combining the nitrosating compound and the first solution to form a nitric oxide precursor. In these and other embodiments, if an acid is utilized, the acid may similarly be combined with the first solution.

[0073] In yet another embodiment, the combining step comprises: (a) combining a thiol-containing compound, a nitrosating compound, and a carrier, each in particulate form (i.e., substantially free of solvent), to form a first mixture; and (b) combining a solvent and the first mixture to form a nitric oxide precursor.

Example

[0074] The following examples are included to demonstrate various embodiments as contemplated herein. The techniques disclosed in the examples that follow represent techniques discovered by the inventor(s) to function well in the practice of the invention and, accordingly, can be considered to constitute a desired mode for its practice. However, one skilled in the art should understand that, in light of the present invention, many modifications can be made in the specific embodiments disclosed and still obtain a similar or analogous result without departing from the spirit and scope of the invention. All percentages are by weight and all measurements are performed at 23 °C unless otherwise indicated.

[0075] [Example 1] Exemplary GNSO desiccant powder 100 mg of reduced glutathione, 150 mg of NaNO 2 , and 2.5 g of sodium polyacrylate were mixed as dry powders. When exposed to water vapor, NO was generated. When the mixture was dried (i.e., the time for removing water vapor and drying the hydrophilic polymer), NO release stopped. When water vapor was reintroduced, NO was generated again. The formation of nitric oxide is shown in Figure 1.

[0076] [Example 2] Exemplary NOCys desiccant powder 100 mg of cysteine, 300 mg of NaNO 2 , and 2 g of sodium polyacrylate were mixed as dry powders. Approximately 125 mg of this mixture was placed in a Tyvek envelope and heat-sealed. The packet was exposed to water vapor and released NO. The formation of nitric oxide is shown in Figure 2.

[0077] [Example 3] Exemplary GSNO and Alconox detergent 100 mg of glutathione was dissolved in 4 mL of water together with 130 mg of Alconox powder. NaNO 2 34.5 mg and 100 μL of 1 M HCl were added to the solution. This soap released NO. See FIGS. 3 and 4A.

[0078] [Example 4] Exemplary NOCys and Alconox detergent 50 mg of cysteine was dissolved in 4 mL of water together with 130 mg of Alconox powder. NaNO 2 34.5 mg and 100 μL of 1 M HCl were added to the solution. This soap released NO. See FIGS. 3 and 4B.

[0079] [Example 5] Exemplary GSNO protease detergent 100 mg of glutathione was dissolved in 4 mL of water. NaNO 2 34.5 mg was added to the solution. This detergent immediately turned a deep ruby color and released NO. See FIGS. 3 and 4C.

[0080] [Example 6] Exemplary NOCys protease detergent 50 mg of cysteine was dissolved in 4 mL of water. NaNO 2 34.5 mg and 100 μL of 1 M HCl were added to the solution. This detergent changed color to red-pink and released NO. See FIGS. 3 and 4D.

[0081] [Example 7] Exemplary GSNO two-component solution A 0.01 M glutathione solution was prepared in water. A 0.1 M NaNO 2 solution was prepared in water. 5 mL of each solution was combined and turned bright red. The solution was poured into stinky sports shoes and tested after 12 hours. After 12 hours, no odor remained in the shoes.

[0082] The appended claims are not limited to representing specific compounds, compositions, or methods described in the detailed description, and it should be understood that they may vary among specific embodiments encompassed within the scope of the appended claims. With respect to any Markush group relied upon herein to describe a particular feature or aspect of various embodiments, various, special, and / or unexpected results may be obtained from each element of each Markush group independently of all other Markush groups. Each element of a Markush group may be relied upon individually and / or in combination, and each of those elements provides appropriate support with respect to specific embodiments within the scope of the appended claims.

[0083] Furthermore, any ranges and sub-ranges relied upon when describing various embodiments of the present invention, independently and collectively, are included within the scope of the appended claims, and it is understood that all ranges, including whole and / or partial values therein, are described and contemplated even if such values are not explicitly written herein. One of ordinary skill in the art will readily understand that the recited ranges and sub-ranges fully describe and enable various embodiments of the present invention, and that such ranges and sub-ranges may be further delineated into related halves, thirds, quarters, fifths, etc. By way of example only, the range of "0.1 to 0.9" may be further delineated into the lower third, i.e., 0.1 to 0.3, the middle third, i.e., 0.4 to 0.6, and the upper third, i.e., 0.7 to 0.9, and these are individually and collectively within the scope of the appended claims and may be relied upon individually and / or collectively to provide appropriate support for particular embodiments within the scope of the appended claims. Further, with respect to language that defines or modifies a range, such as "at least", "greater than", "less than", "less than or equal to", and the like, it is to be understood that such language includes sub-ranges and / or upper or lower limits. As another example, the range of "at least 10" inherently includes sub-ranges such as at least 10 to 35, at least 10 to 25, 25 to 35, etc., and each sub-range may be relied upon individually and / or collectively to provide appropriate support for particular embodiments within the scope of the appended claims. Finally, individual numbers within the disclosed ranges may be relied upon and provide appropriate support for particular embodiments within the scope of the appended claims. For example, the range of "1 to 9" includes various individual integers, such as 3, and individual numbers including a decimal point (or fraction), such as 4.1, which may be relied upon to provide appropriate support for particular embodiments within the scope of the appended claims.

[0084] The present invention has been described herein by way of example, and it should be understood that the terminology used is of a descriptive nature and not of a limiting nature. Many modifications and variations of the present invention are possible in light of the above teachings. The present invention may be practiced otherwise than as particularly described within the scope of the appended claims. All combinations of independent and dependent claims, both single and multiple dependent, are explicitly contemplated herein.

Claims

**Claim 1** A method for sterilizing or sanitizing an article with nitric oxide, comprising: contacting the article with a reaction mixture comprising a solvent, a thiol-containing compound, and a nitrosating compound; wherein the thiol-containing compound and the nitrosating compound react in situ on or near the article to form a nitrosothiol compound; while the article is in contact with the reaction mixture, the nitrosothiol compound decomposes to form nitric oxide; and nitric oxide is formed in an amount sufficient to sterilize or sanitize the article. A method. **Claim 2** The method according to claim 1, wherein the nitrosothiol compound comprises a primary nitrosothiol. **Claim 3** The method according to claim 1, wherein the nitrosothiol compound decomposes to nitric oxide within 1 hour after formation of the nitric oxide precursor. **Claim 4** The method according to claim 1, wherein the thiol-containing compound comprises cysteine or a derivative thereof, a thiol-derivatized polymer or filler, or a combination thereof. **Claim 5** The method according to claim 1, wherein the thiol-containing compound comprises cysteine or a derivative thereof. **Claim 6** The method according to claim 5, wherein cysteine or a derivative thereof comprises cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-n-acetylpenicillamine, buserelin, or a combination thereof. **Claim 7** The method according to claim 1, wherein the nitrosating compound comprises a nitrite compound. **Claim 8** The method according to claim 7, wherein the nitrite compound comprises sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, t-butyl nitrite, amyl nitrite, pentyl nitrite, nitrite salts, ion-pair nitrite compounds, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrite compounds, or a combination thereof. **Claim 9** The method according to claim 1, wherein the nitrosothiol compound is formed in the presence of an acid. **Claim 10** The method according to claim 9, wherein the acid comprises hydrochloric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, acetic acid, hydroxyacetic acid, propionic acid, hydroxypropionic acid, a-ketopropionic acid, butyric acid, mandelic acid, valeric acid, succinic acid, tartaric acid, malic acid, oxalic acid, fumaric acid, adipic acid, maleic acid, sorbic acid, benzoic acid, succinic acid, glutaric acid, adipic acid, α-hydroxy acid, ethylenediaminetetraacetic acid (EDTA), phosphonic acid, octylphosphonic acid, acrylic acid, polyacrylic acid, aspartic acid, polyaspartic acid, p-hydroxybenzoic acid, iminodiacetic acid, or a combination thereof.

11. The method according to claim 9, wherein the thiol-containing compound comprises cysteine.

12. The method according to claim 1, wherein the nitrosothiol compound is formed in the absence of an acid.

13. The method according to claim 12, wherein the thiol-containing compound comprises glutathione.

14. The method according to claim 1, wherein the reaction mixture is formulated as a purification composition or a desiccant composition in which the solvent is provided as the moisture of air.

15. A multi-component composition for providing nitric oxide, the multi-component composition comprising a first component comprising a thiol-containing compound, a second component comprising a nitrosated compound and the first component and the second component are separated from each other, at least one of the first component and the second component further comprises a solvent, the thiol-containing compound and the nitrosated compound have a composition such that the thiol-containing compound and the nitrosated compound react in the presence of the solvent to form a nitric oxide precursor that decomposes to form nitric oxide. Multi-component composition.

16. The multi-component composition according to claim 15, wherein at least one of the first component and the second component further comprises a carrier.

17. The multi-component composition according to claim 16, wherein the carrier comprises silica gel, sodium polyacrylate, or a combination thereof.

18. The multi-component composition according to claim 15, wherein at least one of the first component and the second component further comprises a purifying agent.

19. The multi-component composition according to claim 18, wherein the purifying agent comprises a detergent, an enzyme, or a combination thereof.

20. The multi-component composition according to claim 15, wherein the nitric oxide precursor comprises a primary nitrosothiol.

21. The multi-component composition according to claim 15, wherein the nitric oxide precursor decomposes to form nitric oxide within 1 hour after the formation of the nitric oxide precursor.

22. The multi-component composition according to claim 15, wherein the thiol-containing compound comprises cysteine or a derivative thereof, a thiol-derivatized polymer or filler, or a combination thereof.

23. The multi-component composition according to claim 22, wherein the thiol-containing compound comprises cysteine or a derivative thereof.

24. The multi-component composition according to claim 23, wherein cysteine or a derivative thereof comprises cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-n-acetylpenicillamine, buserelin, or a combination thereof.

25. The multi-component composition according to claim 15, wherein the nitrosated compound comprises a nitrous acid compound.

26. The multi-component composition according to claim 25, wherein the nitrous acid compound comprises sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, t-butyl nitrite, amyl nitrite, pentyl nitrite, nitrite, ion-pair nitrous acid compounds, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrous acid compounds, or a combination thereof.

27. The multi-component composition according to claim 15, further comprising an acid.

28. The multi-component composition according to claim 27, wherein the acid comprises hydrochloric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, acetic acid, hydroxyacetic acid, propionic acid, hydroxypropionic acid, a-ketopropionic acid, butyric acid, mandelic acid, valeric acid, succinic acid, tartaric acid, malic acid, oxalic acid, fumaric acid, adipic acid, maleic acid, sorbic acid, benzoic acid, succinic acid, glutaric acid, adipic acid, α-hydroxy acid, ethylenediaminetetraacetic acid (EDTA), phosphonic acid, octylphosphonic acid, acrylic acid, polyacrylic acid, aspartic acid, polyaspartic acid, p-hydroxybenzoic acid, iminodiacetic acid, or a combination thereof.

29. The multi-component composition according to claim 27, wherein the thiol-containing compound comprises cysteine.

30. The multi-component composition according to claim 15, wherein the composition is substantially free of acid.

31. The multi-component composition according to claim 30, wherein the thiol-containing compound comprises glutathione.

32. A multi-component composition for providing nitric oxide, wherein the multi-component composition comprises a first component comprising a thiol-containing compound having a particle size of from about 1 nm to about 10 mm, a second component comprising a nitrosated compound having a particle size of from about 1 nm to about 10 mm and the thiol-containing compound and the nitrosated compound have a composition such that the thiol-containing compound and the nitrosated compound react in the presence of a solvent to decompose to form a nitric oxide precursor that forms nitric oxide. Multi-component composition. **Claim 33** The multi-component composition according to claim 32, wherein the first component and the second component are substantially homogeneously dispersed. **Claim 34** The multi-component composition according to claim 32, wherein at least one of the first component and the second component further comprises a carrier. **Claim 35** The multi-component composition according to claim 34, wherein the carrier comprises silica gel, sodium polyacrylate, or a combination thereof. **Claim 36** The multi-component composition according to claim 32, wherein at least one of the first component and the second component further comprises a scavenger. **Claim 37** The multi-component composition according to claim 36, wherein the scavenger comprises a detergent, an enzyme, or a combination thereof. **Claim 38** The multi-component composition according to claim 32, wherein the nitric oxide precursor comprises a primary nitrosothiol. **Claim 39** The multi-component composition according to claim 32, wherein the nitric oxide precursor decomposes to form nitric oxide within 1 hour after formation of the nitric oxide precursor. **Claim 40** The multi-component composition according to claim 32, wherein the thiol-containing compound comprises cysteine or a derivative thereof, a thiol-derivatized polymer or filler, or a combination thereof. **Claim 41** The multi-component composition according to claim 40, wherein the thiol-containing compound comprises cysteine or a derivative thereof. **Claim 42** The multi-component composition according to claim 41, wherein cysteine or a derivative thereof comprises cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-n-acetylpenicillamine, buseramine, or a combination thereof. **Claim 43** The multi-component composition according to claim 32, wherein the nitrosated compound comprises a nitrite compound. **Claim 44** The multi-component composition according to claim 43, wherein the nitrite compound comprises sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, t-butyl nitrite, amyl nitrite, pentyl nitrite, nitrite salts, ion-pair nitrite compounds, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrite compounds, or combinations thereof.

45. The multi-component composition according to claim 32, further comprising an acid.

46. The multi-component composition according to claim 45, wherein the acid comprises hydrochloric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, acetic acid, hydroxyacetic acid, propionic acid, hydroxypropionic acid, a-ketopropionic acid, butyric acid, mandelic acid, valeric acid, succinic acid, tartaric acid, malic acid, oxalic acid, fumaric acid, adipic acid, maleic acid, sorbic acid, benzoic acid, succinic acid, glutaric acid, adipic acid, α-hydroxy acids, ethylenediaminetetraacetic acid (EDTA), phosphonic acids, octylphosphoric acid, acrylic acid, polyacrylic acid, aspartic acid, polyaspartic acid, p-hydroxybenzoic acid, iminodiacetic acid, or combinations thereof.

47. The multi-component composition according to claim 45, wherein the thiol-containing compound comprises cysteine.

48. The multi-component composition according to claim 32, wherein the composition is substantially free of acid.

49. The multi-component composition according to claim 48, wherein the thiol-containing compound comprises glutathione.

50. A multi-component system for providing nitric oxide, the system comprising a first compartment comprising a first component comprising a thiol-containing compound, a second compartment comprising a second component comprising a nitrosating compound, a mixing chamber in fluid communication with the first and second compartments for combining the first and second compartments and the thiol-containing compound and the nitrosating compound having a composition such that the thiol-containing compound and the nitrosating compound react in the presence of a solvent to decompose to form a nitric oxide precursor that decomposes to form nitric oxide. multi-component system.

51. The multi-component composition according to claim 50, wherein the nitric oxide precursor decomposes to form nitric oxide within 1 hour after formation of the nitric oxide precursor.

52. The multi-component composition according to claim 50, wherein the nitric oxide precursor comprises a primary nitrosothiol.

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