Nitric oxide precursors and multi-component compositions for forming nitric oxide precursors

Abstract

Provided herein are nitric oxide precursors for providing nitric oxide. In particularly contemplated aspects, the nitric oxide precursor comprises the reaction product of a thiol-containing compound, preferably a primary thiol, and a nitrosation compound. A thiol-containing compound and a nitrosation compound are typically reacted in the presence of a solvent and optionally a catalyst / reduction equivalent to form a nitric oxide precursor, which will then rapidly decompose to form nitric oxide.

Description

Related Applications

[0001] This application claims priority to co-pending U.S. provisional patent application serial number 63 / 341,320 filed on May 12, 2022, which is incorporated herein by reference. Technical Field

[0002] The present disclosure relates generally to compositions and methods of nitric oxide precursors that can release nitric oxide, particularly nitric oxide precursors comprising the reaction product of a thiol-containing compound, preferably a primary thiol, and a nitrosating compound. Background Art

[0003] Various products and articles, including, for example, medical instruments, medical devices and medical equipment, must be sterilized before use to prevent biological contamination of wound sites, samples, organisms, etc. Similarly, although many detergents can reduce the number of microorganisms to some extent, most detergent compositions do not contain microbicidal components, which are ideal in many uses. In addition, although certain formulations known in the art can mask the malodorous byproducts of microbial metabolism, these formulations generally lack microbicidal components.

[0004] Many sterilization methods have been used, which involve contacting a product or article with a sterilant. Examples of these sterilants include nitrogen tetroxide, nitric oxide, steam, ethylene oxide, hydrogen peroxide, dry heat, etc. The conventional method for forming nitric oxide is to use nitrite / nitrite ester or NO donor compound such as diazeniumdiolate to catalyze and enzymatically generate nitric oxide. This conventional method for forming nitric oxide requires expensive reactants usually, and must be used in a controlled system in most cases, to allow safe operation and to generate nitric oxide. These shortcomings and other shortcomings have hindered the sterilizing composition or disinfecting composition that can generate nitric oxide from being commercialized by consumers and professionals.

[0005] Recently, nitric oxide releasing compositions and devices have been developed in which tertiary nitrosothiol compounds are covalently coupled to polymers (SNAP-PDMS), and illumination of the tertiary nitrosothiol compounds causes the compounds to decompose to form nitric oxide, as described in WO 2022 / 164894. Other polymer compounds containing various nitrosothiols that release nitric oxide under irradiation are described in US 9884943 and WO 2020 / 018488. Although these compounds and compositions provide various advantages in certain application scenarios, the release of nitric oxide is relatively slow, and energy generally needs to be directed to the compounds. Therefore, currently known compositions and methods cannot produce large amounts of nitric oxide at one time or as needed.

[0006] Thus, there remains an opportunity to improve compositions capable of generating nitric oxide for use in a variety of medical and consumer applications, particularly where large amounts of nitric oxide are to be generated rapidly. Summary of the invention

[0007] Provided herein is a nitric oxide precursor for providing nitric oxide. The nitric oxide precursor comprises, consists essentially of, consists of or is the reaction product of a thiol-containing compound and a nitrosated compound. In particularly preferred aspects, the thiol is a primary thiol. The thiol-containing compound and the nitrosated compound react in the presence of a solvent to form a nitric oxide precursor. The nitric oxide precursor can decompose to form nitric oxide. When desired, a catalyst / reduction equivalent can be added to enhance the formation of the nitric oxide precursor. In various embodiments, the nitric oxide precursor comprises a nitrosothiol (preferably a primary nitrosothiol) that can rapidly decompose to form nitric oxide. It is contemplated herein that when desired, the nitric oxide precursor reacts in the presence of a solvent based on a thiol-containing compound and a nitrosated compound, and can decompose on demand to form nitric oxide. From different perspectives, the contemplated nitric oxide precursor will have significant chemical instability, so that it decomposes into nitric oxide immediately after forming the nitric oxide precursor. As described in more detail below, the on-demand formation of a nitric oxide precursor is useful in a variety of applications requiring such control for the formation of nitric oxide.

[0008] Nitric oxide precursors can be widely used in various medical applications 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 specific applications. Non-limiting examples of appropriate adjustment include the generation capacity of nitric oxide and the release rate of nitric oxide. As described in more detail below, nitric oxide precursors can be formed in situ by a multi-component composition. This in situ formation of nitric oxide precursors can also be adjusted by regulating the formation and stability characteristics of nitric oxide precursors to suit specific applications, for example, nitric oxide can be generated quickly in a controlled manner. This controlled nitric oxide release is useful for the sterilization and disinfection of medical devices and consumer devices.

[0009] In particular, multi-component compositions can be used to form solutions that generate nitric oxide from a matrix / solution phase in a controlled and predictable manner. These compositions can include a first component containing a thiol-containing compound and a second component containing a nitrosating compound to form a small molecule nitric oxide donor that can be used in formulations and applications related to sterilizing, disinfecting, and sterilizing washing of various objects and devices, and can be used in many applications.

[0010] In some embodiments, the multi-component composition comprises a first component comprising a thiol-containing compound and a second component comprising a nitrosating compound, wherein the first component and the second component are separated from each other. At least one of the first component and the second component may comprise a solvent.

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

[0012] In various embodiments, the compound containing thiol includes cysteine ​​or its derivatives, polymers or fillers derived from thiol or its combination. In exemplary embodiments, cysteine ​​or its derivatives include cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-N-acetylpenicillamine, Bucillamine or its combination. Preferably, the compound containing thiol includes primary thiol groups, and secondary thiols and tertiary thiols are also expected herein. In these embodiments and other embodiments, nitrosated compounds include nitrite / nitrite. Nitrite / nitrite can include sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, tert-butyl nitrite, isoamyl nitrite, amyl nitrite, nitrite, ion pair nitrite, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrite compound or its combination. Additionally, when desired, reducing equivalents may be used to enhance the reaction between the thiol compound and the nitrosated compound, and particularly contemplated reducing equivalents include transition metals, other thiols, NADH, ascorbic acid, and the like.

[0013] The inventor expects that the nitric oxide precursor can be decomposed into nitric oxide in a predetermined period of time after forming the reaction product, such as 1 hour or less than 1 hour. In various embodiments, decompose into a sustainable predetermined period of time of nitric oxide, such as about 1 second to about 1 minute or about 1 minute to about 10 minutes or about 10 minutes to about 1 hour or about 1 hour to about 6 hours or about 6 hours to about 24 hours or 1 day to about 10 days and even longer time period. Not subject to the constraint of theory, it can be believed that the original position formation of the reaction product makes the nitric oxide precursor (for example, nitroso-group (primary) mercaptan) controlledly decompose into nitric oxide in a predetermined period of time.

[0014] From different perspectives, the multi-component composition of expectation can be formulated as a detergent composition or a cleaning composition. The detergent composition or the cleaning composition can be formulated as a liquid, a powder, a single-phase unit dose or a multi-phase unit dose, a bag, a tablet, a gel, a paste, a rod or a sheet. In these embodiments and other embodiments, the detergent composition or the cleaning composition can also include a detergent. The detergent can include a detergent, an enzyme or a combination thereof. The non-limiting examples of suitable detergents include Alconox powder.

[0015] Also provided herein is a method for sterilizing or cleaning a device or object. The method comprises applying the above-mentioned nitric oxide precursor to a device or object. In an embodiment of a multi-component composition comprising a nitric oxide precursor, the method comprises applying the above-mentioned multi-component composition to a device or object. It should be understood that the step of applying the nitric oxide precursor may also include the step of applying a thiol-containing compound and a nitrosated compound that will react in situ to form a 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 contains a thiol-containing compound. The system also includes a second compartment containing a second component. As described above, the second component contains a nitrosated compound. The system also includes a mixing chamber in fluid communication with the first compartment and the second compartment for combining the first compartment and the second compartment. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 is a graph showing NO release for a non-limiting embodiment of an exemplary nitric oxide precursor.

[0018] Figure 2 is a graph illustrating NO release for another exemplary non-limiting embodiment of a nitric oxide precursor.

[0019] 3 is a photograph showing a non-limiting embodiment of an exemplary multi-component composition comprising a nitric oxide precursor.

[0020] Figure 4 is a graph illustrating NO release for a non-limiting embodiment of the exemplary multi-component composition of FIG. 3 . DETAILED DESCRIPTION

[0021] Except in the examples or otherwise clearly indicated, all numerical values ​​representing the amount of material or the conditions of reaction and / or use in this specification are understood to be modified by the word "about" when describing the widest scope of the present disclosure. In various embodiments, when referring to a specified, measurable value (such as a parameter, amount, duration, etc.), the terms "about" and "approximately" represent the variation including a specific value and a specific value, such as +10% / -10% or less than +10% / -10%, or +5% / -5% or less than +5% / -5%, or +1% / -1% or less than +1% / -1%, or +0.1% / -0.1% or less than +1% / -1% variation of a specific value, as long as these variations are suitable for execution in disclosed embodiments. Therefore, the value referred to by the modifiers "about" or "approximately" is also specifically disclosed per se.

[0022] Practice within the numerical ranges specified is generally preferred. In addition, unless expressly stated to the contrary: percentages, "parts" and ratios are by weight; descriptions of groups or classes of materials suitable or preferred for the intended purpose associated with the present invention indicate that mixtures of any two or more materials in that group or class are also suitable or preferred; descriptions of ingredients in chemical terms refer to the ingredients when added to any combination specified in the description and do not necessarily exclude chemical interactions between the ingredients of the mixture once mixed; the first definition of an acronym or other abbreviation applies to all subsequent uses of the same abbreviation herein and applies mutatis mutandis to normal grammatical variations of the initially defined abbreviation; and, unless expressly stated to the contrary, measurements of properties are determined by the same techniques as previously or later mentioned for determining the same property.

[0023] It must also be noted that, as used in the specification and the appended claims, an element without a quantifier preceding it includes a plural number of elements unless the context clearly dictates otherwise. For example, a component mentioned in the singular is intended to include a plural number of components.

[0024] As used herein, "embodiment" means at least one or more than one manifestation, example, or implementation of the present invention, including a particular feature, structure, or characteristic. In addition, the particular features, structures, or characteristics may be combined in any suitable manner, as will be apparent to one skilled in the art. Combinations of features of different embodiments are all intended to be within the scope of the present invention, without the need to explicitly describe every possible arrangement by example. Thus, any claimed embodiment may be used in any combination.

[0025] As used herein, the term "weight percent" (and the related abbreviation "weight %") generally refers to the weight percent expressed as a dry matter weight. Thus, it should be understood that the weight % 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 dry matter).

[0026] 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. As an arbitrary example, a "substantially" enclosed object means that the object is completely enclosed, or nearly completely enclosed, so as to have the same overall result as if the object were completely enclosed.

[0027] The accompanying drawings are semi-schematic and not drawn to scale, and in particular, some dimensions are enlarged and displayed in the accompanying drawings for clarity of description. Similarly, although the views in the accompanying drawings generally show similar directions for ease of description, such depictions in the accompanying drawings are arbitrary. Generally, functionalized polymer materials can operate in any direction. As used herein, it will be understood that when referring to the "above", "upper layer", "below" or "lower layer" of the first element or first layer of the second element or second layer, the first element or first layer can be directly on the second element or second layer, or there can be an intermediate element or intermediate layer, wherein a straight line can pass through the features in a covering relationship and draw between them. When referring to the first element or first layer "on" the second element or second layer, the first element or first layer is directly on the second element or second layer and in contact with it. In addition, for ease of description, spatially relative terms, such as "upper", "above", "lower", "below", etc., can be used here to describe the relationship between an element or feature and another or more than one element or feature shown in the figure. It should be understood that, outside the orientation shown in the figure, spatially relative terms are intended to include different orientations of functionalized polymer materials in use or operation. For example, if the functionalized polymeric material in the figure is turned over, elements described as being "below" other elements or features would be oriented "above" the other elements or features. Thus, the exemplary term "below" can include an orientation of above or below. The functionalized polymeric material can be oriented in other ways (rotated 90 degrees or at other orientations), and the spatially relative descriptors used herein can likewise be interpreted accordingly.

[0028] All publications and patent applications 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. If a definition or use of a term in an incorporated reference is inconsistent or contrary to the definition of that term provided herein, the definition of that term provided herein applies and the definition of that term in the reference does not apply.

[0029] The following specific embodiments are merely illustrative in nature and are not intended to limit the embodiments of the subject matter or the application and use of the embodiments. In addition, there is no tendency to be bound by any express or implied theory presented in the previous technical field, background technology, summary of the invention or the following detailed description of the invention.

[0030] Provided herein is a nitric oxide precursor for providing nitric oxide. The nitric oxide precursor comprises, consists essentially of, consists of, or is the reaction product of a thiol-containing compound and a nitrosated compound. In a preferred embodiment, the thiol-containing compound comprises a primary thiol. The thiol-containing compound and the nitrosated compound react to form a nitric oxide precursor in the presence of a solvent. In some embodiments, the solvent is supplied together with the thiol-containing compound and / or the nitrosated compound, or supplied separately, or supplied by air humidity (which can be attracted by a desiccant). It should be understood that the reaction can be enhanced by various reduction equivalents, such as transition metals, thiols, ascorbic acid, NADH, etc. The nitric oxide precursor formed can decompose to form nitric oxide. An exemplary reaction schematic diagram is shown below:

[0031] .

[0032] In various embodiments, the nitric oxide precursor comprises a nitrosothiol that can decompose to form nitric oxide. It is expected herein that nitric oxide and air will react to produce a mixture containing various nitrogen oxides. In particular, nitric oxide is added to the air, or air is added to the nitric oxide, and nitrogen dioxide is formed when nitric oxide reacts with the oxygen in the air. The concentration of each nitrogen oxide material present in the mixture can change with the initial concentration of temperature, pressure and nitric oxide.

[0033] Nitric oxide is lipid-soluble and has the ability to disrupt microbial lipid membranes, regulate cell and tissue responses, control coagulation and biointegration, and confer antimicrobial properties. In addition, nitric oxide can inactivate thioproteins, thereby destroying the functional proteins of microorganisms. Nitric oxide is more water-soluble than nitric oxide. Finally, nitric oxide and nitrogen dioxide are potent DNA damaging agents, causing strand breaks and other damage that render cells unable to function.

[0034] As used herein, the term "nitric oxide" or "NO" refers to the NO free radical. As is well known, NO is chemically unstable and easily reacts with oxygen to form various oxides, collectively referred to as NOx. As used herein, the term NOx is an abbreviation for nitrogen oxides or nitrogen oxides, which are oxides formed by nitrogen, wherein nitrogen shows each positive oxidation number from +1 to +5. As used herein, the terms "nitrogen oxides" and "nitrogen oxides" and "NOx" refer to gases having one or more than one of the following gases, all of which contain varying amounts of nitrogen and oxygen: nitric oxide (NO), nitrogen dioxide (NO2), nitrogen trioxide (NO3), dinitrogen trioxide (N2O3), dinitrogen tetroxide (N2O4), dinitrogen pentoxide (N2O5) and dinitrogen monoxide (N2O). As used herein, the phrase "nitric oxide precursor" means a compound or composition capable of generating or releasing NO.

[0035] Nitric oxide precursors can be widely used in various medical applications and consumer applications. The properties of nitric oxide precursors can be adjusted based on the selection of thiol-containing compounds and nitrosated compounds to adapt to specific applications. Non-limiting examples of appropriate adjustment include the ability to generate nitric oxide from the nitric oxide precursor and the rate of releasing nitric oxide from the nitric oxide precursor. As described in more detail below, the nitric oxide precursor can be formed in situ by a multi-component composition. This in situ formation of nitric oxide precursors can also be adjusted by regulating the formation and stability characteristics of the nitric oxide precursor to be suitable for specific applications, for example, nitric oxide can be generated quickly in a controlled manner. This controlled nitric oxide release is useful for the sterilization and disinfection of medical devices and consumer devices.

[0036] From different perspectives, the inventors anticipate utilizing nitric oxide precursors and multi-component compositions to form nitric oxide for various medical and consumer applications. In various embodiments, a device or object may be treated with a multi-component composition, for example 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: detergents or cleaning solutions for disinfecting or sterilizing objects treated with solutions (e.g., sports equipment, such as hockey gloves and bicycle gloves, cleaning surgical equipment, the lumen of an endoscope, the surface of a medical device, etc.); detergents or cleaning powders for disinfecting or sterilizing objects treated with powders; sanitary containers for disinfecting sanitary devices (e.g., desiccants, etc.); medical devices for disinfecting medical instruments (e.g., stethoscopes, otoscopes, etc.), medical devices (e.g., portable ultrasound devices, communication devices, etc.); Containers; components of equipment (such as washing machines, boat cabins, etc.) for resisting mold growth or mildew when exposed to moisture; sports equipment (such as yoga mats, touchable surfaces of strength training equipment, touchable surfaces of aerobic equipment, etc.); sports equipment bag liners for disinfecting sports equipment (such as shoes, hockey equipment, ski equipment, masks, diving goggles, helmets, etc.); food packaging for storing food (such as meat, fruits, vegetables, cheese and its components, etc.); vehicle parts (such as ceiling linings, seat cushion pads, carpet pads, etc.) for disinfecting vehicles; and in drawers such as cabinets, desks, boxes, etc. to eliminate musty odors. In some or all of the above examples, it should be understood that the nitric oxide precursor is preferably not supplied in the form of a formed compound, but is generated in situ by reacting the thiol-containing compound and the nitrosating compound in the presence of a solvent (which can be derived from air humidity, supplied separately, or can be used as a solvent for the thiol-containing compound and / or the nitrosating compound).

[0037] Therefore, as described above, multi-component compositions for providing nitric oxide are also provided. The multi-component compositions can be used to form solutions that generate nitric oxide from a matrix / solution phase in a controlled and predictable manner. These compositions can include a first component that includes a thiol-containing compound and a second component that includes a nitrosated compound to form a small molecule nitric oxide donor (preferably a primary nitrosothiol, but not necessarily a primary nitrosothiol), which can be used in formulations and applications related to sterilization, disinfection and sterilization washing of a variety of objects and devices, and can be used in many applications.

[0038] In some embodiments, the multi-component composition comprises a first component, which comprises a thiol-containing compound, and a second component, which comprises a nitrosated compound, wherein the first component and the second component are separated from each other. At least one of the first component and the second component may comprise a solvent. Alternatively, the first component and the second component are separated from each other, and a solvent is provided separately, or the first component and the second component are placed in a solvent. In other embodiments, the multi-component composition comprises a first component, and the first component comprises a thiol-containing compound having a particle size of about 1nm to about 10mm, or about 1nm to about 1mm, or about 1nm to about 500μm, or about 10nm to about 500μm. Similarly, the multi-component composition also comprises a second component, and the second component comprises a nitrosated compound having a particle size of about 1nm to about 10mm, or about 1nm to about 1mm, or about 1nm to about 500μm, or about 10nm to about 500μm. Regardless of the arrangement, it should be understood again that the nitric oxide precursor will be formed in situ and then undergo decomposition to form nitric oxide.

[0039] For multi-component composition, the inventor expects that after forming reaction product, nitric oxide precursor can be decomposed into nitric oxide within a predetermined time, for example, in 1 hour, or in 30 minutes, or in 5 minutes, or in 1 minute, or in 10 seconds, or in 1 second, or in 0.1 second.From different perspectives, multi-component composition can be decomposed into nitric oxide within a predetermined time after forming nitric oxide precursor, for example, about 0.01 second to about 1 hour, about 0.01 second to about 30 minutes, about 1 second to about 5 minutes, about 1 second to about 1 minute.In various embodiments, decompose into nitric oxide and continue a predetermined time, for example, about 1 minute to about 1 year, or about 1 hour to about 6 months, or about 24 hours to about 3 months, or about 1 week to about 8 weeks.From different perspectives, decompose into nitric oxide and continue at least 1 minute, or at least 1 hour, or at least 24 hours, or at least 1 week. Without being bound by theory, it is believed that the in situ formation of the reaction product provides for controlled decomposition of the nitric oxide precursor (eg, nitrosothiol) to nitric oxide over a predetermined period of time.

[0040] It is easy to understand that the decomposition rate of the nitric oxide precursor will depend on various factors, which can be fine-tuned to achieve the desired decomposition characteristics. Among other factors, the decomposition rate can be changed by selecting the type of nitrosothiol, the molar ratio of the compound containing mercaptan and the nitrosated compound, the presence / amount of the reduction equivalent or other catalyst that affects the in-situ formation of the nitric oxide precursor, the pH value of the solution, and the availability of the solvent. For example, it should be understood that primary nitrosothiol has a decomposition rate that is substantially higher than that of secondary nitrosothiol or tertiary nitrosothiol. In addition, the in-situ formation of nitrosothiol can be accelerated in the presence of various reduction equivalents such as mercaptans, NADH, transition metals, ascorbic acid, etc. (these reducing agents can exist in trace amounts to equal molar ratios, or even exist in molar excess relative to the reagent containing mercaptan). Similarly, acidic pH (such as pH <4.0) is generally conducive to the stability of nitrosothiol, while alkaline pH (such as pH>7.0) is conducive to the decomposition of nitrosothiol. Furthermore, when the solvent is water in humid air, the humidity will determine the rate of in situ formation of the nitric oxide precursor.

[0041] No matter how the reaction conditions are, it is generally expected that, in some embodiments, the rate at which the nitric oxide precursor decomposes to form nitric oxide will be greater than the rate formed in the original position, for example, 1.5 times greater, or 2.5 times greater, or 5 times greater, or 10 times greater, or even more than 10 times greater. In other embodiments, the rate at which the nitric oxide precursor decomposes to form nitric oxide will be less than the rate formed in the original position, for example, 1.5 times less, or 2.5 times less, or 5 times less, or 10 times less, or even more than 10 times less. In addition, according to specific preparations and nitric oxide precursors, it is expected that, in certain embodiments, the nitric oxide released in 1 hour will be 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 releasable nitric oxide in the preparation. In other embodiments, it is expected that the nitric oxide released within 24 hours will be 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 releasable nitric oxide in the preparation, and in other embodiments, it is expected that the nitric oxide released within 7 days will be 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 releasable nitric oxide in the preparation. In other embodiments, it is expected that the nitric oxide released within 1 month will be 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 releasable nitric oxide in the preparation.

[0042] The inventors anticipate that small molecule nitric oxide precursors can be mixed into polymers, solution phases or powders and used to generate nitric oxide to generate a wide variety of NO donors / generating entities by mixing the nitric oxide precursor into a matrix (polymer or powder or embedded in or on a solid support), or to generate solutions that generate NO from a matrix / solution phase in a controlled and predictable manner. Herein we describe methods for synthesizing novel small molecule NO donors that can be used for this purpose and formulations and applications of these NO generating moieties that can be used for sterilizing, disinfecting and sterilizing washing of a wide variety of different objects and in many different situations.

[0043] Nitric oxide precursors, such as small molecule nitrosothiols (particularly primary nitrosothiols), are formed in situ from thiol-containing compounds (such as cysteine, N-acetylcysteine ​​and glutathione) and nitrosated compounds (such as organic nitrites or inorganic nitrites), and nitric oxide precursors can be formed in an organic phase and an aqueous phase. A solution containing a detergent (such as an enzyme, a surfactant, etc.) can be combined with a specific thiol-containing compound and an appropriate nitrosated compound under controlled conditions to form nitrosothiols. The nitrosothiols can then be rapidly decomposed to generate nitric oxide. These two-part systems (thiol-containing compounds and nitrosated compounds) are combined with various carriers and detergents (such as silica gel, sodium polyacrylate, Alconox soap, proteases, etc.) such as powder components or solution components, and can be used for reprocessing of endoscopes and probes and sterilization of other objects.

[0044] Non-limiting examples of suitable embodiments include silica gel desiccant combined with cysteine ​​and sodium nitrite as a dry powder that generates nitric oxide when the mixture absorbs moisture from humid air. Another example is combining a thiol-containing compound with a sodium nitrite solution and pouring the solution into an object such as a shoe to eliminate odors produced by bacteria.

[0045] Returning to the thiol-containing compound used to form the reaction product, there are a variety of possible thiol-containing compounds that can be used depending on the design constraints of the desired application of the multi-component composition. Among other options, primary thiols are generally preferred. The thiol-containing compound can include, but is not limited to, one or more of 1,2-ethanedithiol, 2,3-dimercaptopropanol, pyridinethione, 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 α-lipoic acid, methyl mercaptan (CH3SH [m-thiol]), ethyl mercaptan (C2H5SH [e-thiol]), 1-propanethiol (C3H7SH [n-propyl mercaptan]), 2-propanethiol (CH3CH(SH)CH3 [2C3 mercaptan]), butyl mercaptan (C4H9SH [n-butyl mercaptan]), tert-butyl mercaptan (C(CH3)3SH [tert-butyl mercaptan]), pentanethiol (C5H 11SH [pentyl mercaptan]), coenzyme A, lipoamide, glutathione, cysteine, cystine, 2-mercaptoethanol, dithiothreitol, dithioerythritol, 2-mercaptoindole, transglutaminase, (11-mercaptoundecyl) hexa(ethylene glycol), (11-mercaptoundecyl) tetra(ethylene glycol), (11-mercaptoundecyl) tetra(ethylene glycol) functionalized gold nanoparticles, 1,1′,4′,1″-terphenyl-4-thiol, 1,11-undecanedithiol, 1,16-hexadecandithiol, 1,2-ethanedithiol, 1,3-propanedithiol, 1,4-benzenedithiol, 1,4-butanedithiol, 1,4-butanedithiol diacetate, 1,5-pentanedithiol, 1,6-Hexanedithiol, 1,8-octanedithiol, 1,9-nonanedithiol, adamantanethiol, 1-butanethiol, 1-decanethiol, 1-dodecanethiol, 1-heptanethiol, 1-heptanethiol, 1-hexadecanethiol, 1-hexadecanethiol, 1-hexadecanethiol, 1-mercapto-(triethylene glycol), 1-mercapto-(triethylene glycol) methyl ether functionalized gold nanoparticles, 1-mercapto-2-propanol, 1-nonanethiol, 1-octadecanethiol, 1-octanedithiol, 1-pentadecanethiol, 1-pentanethiol, 1-propanethiol, 1-propanethiol, 1-tetradecanethiol, 1-undecanethiol, 11-(1H-pyrrol-1-yl)undecane-1-thiol, 11-amino-1-undecanethiol hydrochloride, 11-bromo-1- Undecanethiol, 11-mercapto-1-undecanol, 11-mercapto-1-undecanol, 11-mercaptoundecanoic acid, 11-mercaptoundecanoic acid, 11-mercaptoundecanoic acid, 11-mercaptoundecanoic acid, 11-mercaptoundecanoic acid trifluoroacetate, 11-mercaptoundecanoic acid, 12-mercaptododecanoic acid, 12-mercaptododecanoic acid, 15-mercaptopentadecanoic acid, 16-mercaptohexadecanoic acid, 16-mercaptohexadecanoic acid, 1H,1H,2H,2H-perfluorodecanethiol, 2,2′-(ethylenedioxy)diethanethiol, 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, 1-butanethiol copper (I), 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-bromondecyl)thioacetate, S-(4-cyanobutyl)thioacetate, thiophenol, triethylene glycol mono-11-mercaptoundecyl ether, trimethylolpropane tris(3-mercaptopropionate), [11-(methylcarbonylthio)undecyl]tetra(ethylene glycol), m-carborane-9-thiol, p-terphenyl-4,4″-dithiol, tert-dodecylthiol or tert-nonylthiol.

[0046] In certain embodiments, the thiol-containing compound comprises cysteine ​​or a derivative thereof, a polymer or filler derived from a thiol, or a combination thereof. In embodiments using cysteine ​​or a derivative thereof, the cysteine ​​or a derivative thereof may comprise cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-N-acetylpenicillamine, bucillamine, or a combination thereof. It should be understood that the thiol-containing compound may be included as part of a peptide or other macromolecule as long as it is compatible with the components of the multi-component composition. In embodiments using cysteine ​​or a derivative thereof as part of a peptide, the peptide may comprise any combination of amino acids as long as the peptide comprises cysteine ​​or a derivative thereof as at least one constituent of the peptide. Non-limiting examples of suitable cysteine ​​or its derivatives are described in the journal article entitled "S-Nitrosothiol Detection via Amperometric Nitric Oxide Sensor with Surface Modified Hydrogel Layer Containing Immobilized Organoselenium Catalyst", cited as Langmuir 2006, 22, 25, 10830-10836, which is incorporated herein by reference in its entirety.

[0047] In various embodiments, the weight average molecular weight of the thiol-containing compound is no more than 500,000 g / mol, or no more than 100,000 g / mol, or no more than 10,000 g / mol, or no more than 1000 g / mol, or no more than 500 g / mol. From different perspectives, the weight average molecular weight of the thiol-containing compound can be 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 1000 g / mol, or from about 10 g / mol to about 500 g / mol. For example, the weight average molecular weight of cysteine ​​is 121 g / mol, the weight average molecular weight of glutathione is 307.33 g / mol, the weight average molecular weight of butanethiol is 90.19 g / mol, and the weight average molecular weight of serum albumin is 66 kDa. Without being bound by theory, it can be considered that the use of thiol-containing compounds with lower weight average molecular weight can improve the reaction kinetics of forming reaction products. The improved reaction kinetics allow the reaction product to be formed in situ, rapidly generating nitric oxide. In addition, primary nitrosothiol compounds generally decompose faster to generate nitric oxide than secondary or tertiary nitrosothiols.

[0048] Returning to the nitrosating compound used to form the reaction product, the nitrosating compound can be any compound used as a nitroso source, and is generally a compound of the formula NOX, wherein X is an organic anion or an inorganic anion or a group OR2, wherein R2 is an organic group. X can be an organic anion derived from a carboxylic acid, such as an alkane carboxylic acid containing 2 to 7 carbon atoms, and this type of nitrosating agent includes acetyl nitrite / salt and propionyl nitrite / salt. When X is an inorganic anion, it can be derived from, for example, an inorganic acid, such as a halogen ion such as a chloride ion or a bromide ion or a sulfate ion, or derived from a Lewis acid, such as a fluoroborate ion. Other inorganic anions include hydroxide and sulfonate. Therefore, this type of nitrosating compound includes nitrosyl chloride, nitrosyl sulfate, nitrosyl fluoroborate, nitrous acid and Freund's salt (potassium nitrosyl disulfonate). When X is a group of formula OR2, the organic group R2 may be, for example, a lower alkyl group, for example containing 1 to 9 carbon atoms, such as ethyl, n-propyl, isopropyl, n-butyl, tert-butyl or isopentyl.

[0049] In certain embodiments, the nitrosating compound includes nitrite / nitrite ester. Nitrite / nitrite ester can include sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, tert-butyl nitrite, isoamyl nitrite, amyl nitrite, nitrite, ion pair nitrite, silver nitrite, zinc nitrite, ferric nitrite, copper nitrite, transition metal-nitrite compound or its combination. In addition, nitric oxide gas can be used as nitrosating agent.

[0050] In various embodiments, the weight average molecular weight of nitrosated compounds is not more than 10000 g / mol, or not more than 1000 g / mol, or not more than 500 g / mol, or not more than 250 g / mol. From different perspectives, the weight average molecular weight of nitrosated compounds can be about 10 g / mol to about 10000 g / mol, or about 10 g / mol to about 1000 g / mol, or about 10 g / mol to about 500 g / mol, or about 10 g / mol to about 250 g / mol. For example, NaNO2 weight average molecular weight is 69 g / mol, and the weight average molecular weight of butyl nitrite is 103 g / mol. Without being bound by theory, it can be considered that using nitrosated compounds with lower weight average molecular weight can improve the reaction kinetics of forming reaction product. As mentioned above, the improved reaction kinetics makes the reaction product in situ formed, quickly generates nitric oxide.

[0051] As mentioned above, the thiol-containing compound and the nitrosated compound can react in the presence of a solvent to form a reaction product (such as nitroso (primary) thiol). If a solvent is used, the solvent may contain different amounts of solvent. 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 contain an organic solvent, such as tetrahydrofuran. Other non-limiting examples of suitable solvents include aromatic compounds, aliphatic compounds, 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, diethylene glycol monobutyl ether or a combination thereof.

[0052] In various embodiments, the compound containing mercaptan and the nitrosated compound react in the presence of acid. The acid can be used to improve the formation of the reaction product and / or the stability of the reaction product, for example, when using the compound containing mercaptan containing cysteine. In certain embodiments, the acid can include hydrochloric acid. Other non-limiting examples of suitable acid include citric acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, acetic acid, glycolic acid, propionic acid, hydroxypropionic acid, α-ketopropionic acid, butyric acid, mandelic acid, valeric acid, succinic acid, tartaric acid, malic acid, oxalic acid, fumaric acid, adipic acid, toxilic acid, sorbic acid, benzoic acid, succinic acid, glutaric acid, adipic acid, α-hydroxy acid, ethylenediaminetetraacetic acid (EDTA), phosphonic acid, octyl phosphoric acid, acrylic acid, polyacrylic acid, aspartic acid, polyaspartic acid, p-hydroxybenzoic acid, iminoacetic acid (iminoacetic acid) or a combination thereof. It should be understood that the acid may be included as part of any component of the composition (eg, carrier, solvent, etc.) or as part of the reactants of the reaction product.

[0053] In other embodiments, the reaction product is formed under substantially acid-free conditions, such as when a thiol-containing compound containing glutathione is used. The inventors expect that a multi-component composition that is substantially free of acid exhibits better compatibility with a device or object. As used herein, the phrase "substantially free of" means that the acid is completely free, or its amount is very small, only as an impurity, an unexpected by-product of another ingredient, or its amount has a negligible effect on the composition. In certain embodiments, "substantially free of" means that the amount of acid present in the composition is less than 0.5% by weight, less than 0.25% by weight, less than 0.1% by weight, less than 0.05% by weight, or less than 0.01% by weight, or even 0% by weight, based on the total weight of the composition.

[0054] In still other embodiments, the reaction product is formed in the presence of a reducing equivalent, suitable reducing equivalents include various metals and various transition metals, dithionates, thiosulfates, hydrazines, oxalic acid, ascorbic acid, formic acid, NADH, NADPH, etc. It will be readily appreciated that these reducing equivalents may be provided alone, in a solvent, or mixed with the thiol-containing compound and / or the nitrosating compound.

[0055] In these and other embodiments, the multi-component composition further comprises 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 used. These 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 incorporated herein by reference in its entirety.

[0056] Based on the gross weight of the composition, the multi-component composition may include a thiol-containing compound in an amount of about 1 wt % to about 80 wt %, or about 1 wt % to about 70 wt %, or about 50 wt % to about 80 wt %. Based on the gross weight of the composition, the multi-component composition may include a nitrosated compound in an amount of about 1 wt % to about 75 wt %, or about 1 wt % to about 10 wt %, or about 10 wt % to about 75 wt %. Based on the gross weight of the composition, the multi-component composition may include a carrier in an amount of about 10 wt % to about 95 wt %, or about 10 wt % to about 80 wt %, or about 80 wt % to about 95 wt %. Based on the gross weight of the composition, the multi-component composition may include a solvent in an amount of about 1 wt % to about 99 wt %.

[0057] In an exemplary embodiment, the multi-component composition can be formulated as a detergent composition or a cleaning composition. As used herein, the phrase "detergent composition" or "cleaning composition" includes compositions and formulations designed to clean soiled materials. These compositions include, but are not limited to, object cleaning compositions, medical device cleaning compositions, hard surface cleaning compositions, dishwashing cleaning compositions, laundry cleaning compositions and detergents, spray products, dry cleaning agents or dry cleaning compositions, unit dose formulations, delayed release formulations, detergents contained on or in porous substrates or nonwovens, detergents contained on or in water-soluble films, and other suitable forms, which are obvious to those skilled in the art in view of the guidance of this article. The multi-component composition can have a form selected from liquid, powder, single-phase unit dose or multi-phase unit dose, 2-layer paper carrier, bag, tablet, gel, paste, rod or sheet.

[0058] In these and other embodiments, the detergent composition or cleaning composition also comprises a cleaning agent. The cleaning agent comprises a cleaning agent, an enzyme or a combination thereof. The non-limiting examples of suitable cleaning agents include Alconox powder. In the embodiment where the cleaning agent comprises a cleaning agent, the cleaning agent may include a surfactant such as amine oxide, alkylbenzene sulfonate, alkyl ether sulfate, fatty alcohol ethoxylate, alkyl glycoside, alkoxylated fatty acid alkyl ester, amine oxide, fatty acid alkanolamide, hydroxy mixed ether, sorbitan fatty acid ester, polyhydroxy fatty acid amide and alkoxylated alcohol.

[0059] In embodiments where the cleaning agent includes an enzyme, the enzyme may include one or more than one enzyme that can exhibit catalytic activity in the detergent, such as proteases, amylases, lipases, cellulases, hemicellulases, mannanases, pectin lyases, tannases, xylanases, xanthanases, β-glucosidases, carrageenases, perhydrolases, oxidases, oxidoreductases, and mixtures thereof. In certain embodiments, the enzyme includes a protease, an amylase (e.g., α-amylase), a cellulase, a lipase, a hemicellulase, a pectinase, a mannanase, a β-glucanase, or a combination thereof. The properties of the enzyme should be compatible with the multi-component composition (i.e., optimal pH, compatibility with other enzyme components and non-enzyme components, etc.). If an enzyme is used, it should be present in an effective amount.

[0060] When using protease, it can be of animal origin, plant origin or microbial origin, including chemically modified or genetically modified mutants. Preferably, it is of microbial origin. Protease can be an alkaline protease, such as a serine protease or a metalloprotease. For example, the serine protease can be of the Si family, such as trypsin, or of the S8 family, such as subtilisin. For example, the metalloprotease can be a thermolysin from, for example, family M4, family M5, family M7 or family M8.

[0061] When suitable lipases and cutinases are used, they include those of bacterial or fungal origin. The lipases and cutinases include chemically modified or protein engineered mutants. Examples include lipases from Thermomyces, such as T. lanuginosus (formerly known as Humicola lanuginosa) described in EP 258068 and EP 305216, cutinases from Humicola, such as H. insolens described in WO 96 / 13580, Pseudomonas lipases, such as from P. alcaligenes or P. pseudoalcaligenes (EP 218272), P. cepacia (EP331376), P. stutzeri (GB 1372034), P. fluorescens, Pseudomonas species SD 705 strain (WO 95 / 06720 and WO 96 / 27002), Pseudomonas wisconsinensis (WO 96 / 12012), Bacillus lipase, such as from Bacillus subtilis (B. subtilis) (Dartois et al., 1993, Biochemica et Biophysica Acta, 1131: 253-360), Bacillus stearothermophilus (B. stearothermophilus) (JP 64 / 744992) or Bacillus pumilus (B. pumilus) (WO 91 / 16422).

[0062] Other examples are lipase variants as described in WO 92 / 05249, WO 94 / 01541, EP 407225, EP 260105, 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, WO 2007 / 087508 and WO 2009 / 109500, which are incorporated herein in their entirety.

[0063] When suitable amylases are used, amylases include those of bacterial or fungal origin. The amylases include chemically modified or protein engineered mutants. Amylases include, for example, alpha-amylases obtained from bacillus, for example, special strains of 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.

[0064] When using suitable cellulase, cellulase includes cellulase of bacterial origin or fungal origin. The cellulase includes chemically modified or protein engineered mutants. Suitable cellulase includes cellulase from Bacillus, Pseudomonas, Humicola, Fusarium, Thielavia, Acremonium, such as fungal cellulase from Humicola insolens, Myceliophthorathermophila, Fusarium oxysporum, these fungal cellulases are disclosed by U.S. Patent No. 4435307, U.S. Patent No. 5648263, U.S. Patent No. 5691178, U.S. Patent No. 5776757 and WO 89 / 09259, which are incorporated herein by reference in their entirety.

[0065] When suitable peroxidases / oxidases are used, they include peroxidases / oxidases of plant origin, bacterial origin or fungal origin. The peroxidases / oxidases include chemically modified or protein engineered mutants. Examples of useful peroxidases include peroxidases from Coprinus, such as C. cinereus, and variants thereof, as described in WO 93 / 24618, WO 95 / 10602 and WO 98 / 15257, which are incorporated herein by reference in their entirety.

[0066] The detergent composition or cleaning composition may also contain additives such as builders, bleaches, electrolytes, non-aqueous solvents, pH adjusters, fragrances, fragrance carriers, fluorescent agents, dyes, hydrotropes, foam inhibitors, silicone oils, anti-redeposition agents, graying inhibitors, anti-shrinkage agents, anti-wrinkle agents, dye transfer inhibitors, antimicrobial substances, bactericides, fungicides, antioxidants, preservatives, corrosion inhibitors, antistatic agents, bittering agents, ironing aids, hydrophobic agents and impregnation agents, swelling agents and anti-slip agents, softening components and ultraviolet absorbers.

[0067] Based on the gross weight of the composition, the detergent composition or cleaning composition may include an amount of about 0.01 wt % to about 40 wt %, or about 0.01 wt % to about 5 wt %, or about 5 wt % to about 10 wt %, or about 10 wt % to about 40 wt % of the compound containing thiol.Based on the gross weight of the composition, the detergent composition or cleaning composition may include an amount of about 0.1 wt % to about 40 wt %, or about 0.1 wt % to about 10 wt % of the nitrosated compound.Based on the gross weight of the composition, the detergent composition or cleaning composition may include an amount of about 1 wt % to about 99 wt % of the cleaning agent.Based on the gross weight of the composition, the detergent composition or cleaning composition may include an amount of about 1 wt % to about 99 wt % of the solvent.

[0068] In various embodiments, the detergent composition or cleaning composition described herein can be filled into a water-soluble envelope to form part of a water-soluble package. The water-soluble envelope can be formed from a water-soluble film material. Such water-soluble packages can be produced by a vertical form fill seal (VFFS) process or by a thermoforming process.

[0069] The coating may be made of one or two or more layers of water-soluble film material. If there are other layers, the water-soluble film material of the first layer and the water-soluble film material of the other layers may be the same or different. For example, the water-soluble coating material is made of a water-soluble film material selected from a polymer or a polymer mixture. The water-soluble coating may contain polyvinyl alcohol or a polyvinyl alcohol copolymer. The polymer is selected from a polymer containing acrylic acid, polyacrylamide, Oxazoline polymers, polystyrene sulfonates, polyurethanes, polyesters, polyethers, polylactic acid and / or mixtures of the above polymers, which can be added to the membrane material suitable for producing the water-soluble coating.

[0070] The thermoforming process generally comprises the following steps: forming a first layer from a water-soluble film material to form a convex portion for receiving a composition therein, filling the composition into the convex portion, covering the convex portion filled with the composition with a second layer of water-soluble film material, and sealing the first layer and the second layer together at least around the convex portion. The water-soluble package comprising a liquid wash and a water-soluble envelope may have one or more than one chamber. The water-soluble package may have a spherical configuration and a pillow configuration that are substantially dimensionally stable, having a circular, oval, square or rectangular basic shape. The chambers may be isolated from each other.

[0071] Also provided herein is a method for sterilizing or cleaning a device or object. The method comprises applying the above-mentioned nitric oxide precursor to the device or object. In an embodiment where the multi-component composition comprises a nitric oxide precursor, the method comprises applying the above-mentioned multi-component composition to the device or object.

[0072] 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 contains a thiol-containing compound. The system also includes a second compartment containing a second component. As described above, the second component contains a nitrosated compound. The system also includes a mixing chamber in fluid communication with the first compartment and the second compartment for combining the first compartment and the second compartment.

[0073] Provided herein is a method for forming a nitric oxide precursor. The method comprises combining a thiol-containing compound and a nitrosating compound in the presence of a solvent to form a nitric oxide precursor.

[0074] In an exemplary embodiment, the combining step includes (a) combining the thiol-containing compound with a solvent to form a first solution, (b) combining the nitrosated compound with a solvent to form a second solution, and (c) combining the first solution with the second solution to form a nitric oxide precursor.

[0075] In another exemplary embodiment, the combining step includes (a) combining the thiol-containing compound, the solvent, and the 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, when an acid is used, the acid may also be combined with the first solution.

[0076] In yet another embodiment, the combining step includes (a) combining the thiol-containing compound, the nitrosating compound, and the carrier separately in particulate form (ie, substantially free of solvent) to form a first mixture, and (b) combining a solvent with the first mixture to form the nitric oxide precursor.

[0077] Example

[0078] The following examples are included to illustrate various embodiments contemplated herein. It will be appreciated by those skilled in the art that the techniques disclosed in the following examples represent techniques that one or more than one inventor has found to work well in practicing the present invention, and therefore can be considered to constitute an ideal mode for practicing the present invention. However, in light of this disclosure, it will be appreciated by those skilled in the art that many changes may be made to the specific embodiments disclosed without departing from the spirit and scope of the present invention, and still obtaining the same or similar results. Unless otherwise indicated, all percentages are in % by weight, and all measurements are performed at 23°C.

[0079] Example 1: Exemplary GNSO Desiccant Powder

[0080] 100 mg of reduced glutathione, 150 mg of NaNO2 and 2.5 g of sodium polyacrylate were mixed into a dry powder. When it was exposed to water vapor, NO was generated. When the mixture was dried (i.e., the water vapor was removed and the hydrophilic polymer was allowed to dry), the NO release stopped. When the water vapor was reintroduced, NO was generated again. The formation of nitric oxide is as follows Figure 1 shown.

[0081] Example 2: Exemplary NOCys Desiccant Powder

[0082] 100 mg of cysteine, 300 mg of NaNO2 and 2 g of sodium polyacrylate were mixed into a dry powder. Approximately 125 mg of this mixture was placed in a Tyvek package and heat sealed. The package was exposed to water vapor and NO was released. The formation of nitric oxide was as follows Figure 2 shown.

[0083] Example 3: Exemplary GSNO and Alconox Detergents

[0084] Dissolve 100 mg of glutathione and 130 mg of Alconox powder in 4 mL of water. Add 34.5 mg of NaNO2 and 100 µL of 1M HCl to the solution. This soap releases NO. See Figure 3 and Figure 4 A in.

[0085] Example 4: Exemplary NOCys and Alconox Detergents

[0086] Dissolve 50 mg of cysteine ​​and 130 mg of Alconox powder in 4 mL of water. Add 34.5 mg of NaNO2 and 100 µL of 1M HCl to the solution. This soap releases NO. See Figure 3 and Figure 4 B in.

[0087] Example 5: Exemplary GSNO protease detergents

[0088] Dissolve 100 mg of glutathione in 4 mL of water. Add 34.5 mg of NaNO2 to the solution. This detergent immediately turns a deep ruby ​​red and releases NO. See Figure 3 and Figure 4 C in.

[0089] Example 6: Exemplary NOCys protease detergents

[0090] Dissolve 50 mg of cysteine ​​in 4 mL of water. Add 34.5 mg of NaNO2 and 100 µL of 1M HCl to the solution. The detergent turns pink and releases NO. See Figure 3 and Figure 4 D in.

[0091] Example 7: Exemplary GSNO two-component solution

[0092] Prepare a 0.01M glutathione solution in water. Prepare a 0.1M NaNO2 solution in water. Combine 5mL of each solution and the resulting solution will turn bright red. Pour the solution into a sneaker with a foul odor and test it after 12 hours. No odor remains in the shoe after 12 hours.

[0093] It should be understood that the appended claims are not limited to the explicit and specific compounds, compositions or methods described in the detailed description, which may vary between specific embodiments falling within the scope of the appended claims. With respect to any Markush group relied upon for specific features or specific aspects of the various embodiments described herein, different, special and / or unexpected results may be obtained from each member of the corresponding Markush group independent of all other Markush members. Each member of the Markush group may be relied upon individually and / or in combination and provides adequate support for specific embodiments within the scope of the appended claims.

[0094] In addition, any ranges and sub-ranges relied upon in describing various embodiments of the present invention fall within the scope of the appended claims independently and collectively, and are understood to describe and contemplate all ranges including integer values ​​and / or fractional values ​​therein, even if these values ​​are not explicitly written herein. One of skill in the art will readily recognize that the enumerated ranges and sub-ranges fully describe and enable various embodiments of the present invention, and that these ranges and sub-ranges may be further described as being associated half, one-third, one-quarter, one-fifth, etc. As just one example, the range of "0.1 to 0.9" may also be described as 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, which are individually and collectively within the scope of the appended claims, and may be individually and / or collectively relied upon, and provide sufficient support for specific embodiments within the scope of the appended claims. In addition, with respect to language defining or modifying a range, such as "at least", "greater than", "less than", "no more than", etc., it should be understood that such language includes sub-ranges and / or upper or lower limits. As another example, a range of "at least 10" inherently includes a subrange of at least 10 to 35, a subrange of at least 10 to 25, a subrange of 25 to 35, etc., and each subrange can be relied upon individually and / or collectively and provides sufficient support for specific embodiments within the scope of the appended claims. Finally, single numbers within the disclosed ranges can be relied upon and provide sufficient support for specific embodiments within the scope of the appended claims. For example, a range of "1 to 9" includes various single integers, such as 3, and single numbers that include decimal points (or fractions), such as 4.1, which can be relied upon and provide sufficient support for specific embodiments within the scope of the appended claims.

[0095] The present invention has been described herein in an illustrative manner, and it should be understood that the terms that have been used are intended to be descriptive, not restrictive. In light of the above teachings, many modifications and variations of the present invention are possible. The present invention may be implemented in a manner other than that specifically described within the scope of the appended claims. The subject matter of all combinations of independent claims and dependent claims, including single and multiple dependent claims, is expressly contemplated herein.

Claims

1. A method for sterilizing or disinfecting an article using 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 reacts with the nitrosating compound in situ on or near the article to form a nitrosothiol compound; wherein when said article is contacted with said reaction mixture, said nitrosothiol decomposes to form nitric oxide; and Wherein the nitric oxide is formed in an amount to sterilize or disinfect the item.

2. The method of claim 1, wherein the nitrosothiol compound comprises a primary nitrosothiol.

3. The method of claim 1, wherein the nitrosothiol compound decomposes into nitric oxide within 1 hour after forming the nitric oxide precursor.

4. The method of claim 1, wherein the thiol-containing compound comprises cysteine ​​or a derivative thereof, a polymer or filler derived from thiol, or a combination thereof.

5. The method of claim 1, wherein the thiol-containing compound comprises cysteine ​​or a derivative thereof.

6. The method of claim 5, wherein the cysteine ​​or a derivative thereof comprises cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-N-acetylpenicillamine, bucillamine, or a combination thereof.

7. The method of claim 1, wherein the nitrosating compound comprises nitrite / nitrite ester.

8. The method of claim 7, wherein the nitrite / nitrite ester comprises sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, tert-butyl nitrite, isoamyl nitrite, amyl nitrite, nitrite, ion-pair nitrite, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrite compounds, or combinations thereof.

9. The method of claim 1, wherein the nitrosothiol compound is formed in the presence of an acid.

10. The method of claim 9, wherein the acid comprises hydrochloric acid, citric acid, methanesulfonic acid, ethanesulfonic acid, propanesulfonic acid, butanesulfonic acid, acetic acid, glycolic acid, propionic acid, hydroxypropionic acid, α-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, iminoacetic acid, or a combination thereof.

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

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

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

14. The method of claim 1, wherein the reaction mixture is formulated as a cleaning composition or a desiccant composition, wherein the solvent is provided by air humidity.

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; wherein the first component and the second component are separated from each other; wherein at least one of the first component and the second component further comprises a solvent; and The composition of the thiol-containing compound and the nitrosated compound is such that the thiol-containing compound and the nitrosated compound react in the presence of a solvent to form a nitric oxide precursor, and the nitric oxide precursor decomposes to form nitric oxide.

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

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

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

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

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

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

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

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

24. The multi-component composition of claim 23, wherein the cysteine ​​or derivative thereof comprises cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-N-acetylpenicillamine, bucillamine, or a combination thereof.

25. The multi-component composition of claim 15, wherein the nitrosating compound comprises a nitrite / nitrite ester.

26. The multi-component composition of claim 25, wherein the nitrite / nitrite ester comprises sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, tert-butyl nitrite, isoamyl nitrite, amyl nitrite, nitrite, ion-pair nitrite, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrite compounds, or combinations thereof.

27. The multi-component composition of claim 15 further comprising an acid.

28. The multi-component composition of claim 27, wherein the acid comprises hydrochloric acid, citric acid, methane sulfonic acid, ethane sulfonic acid, propane sulfonic acid, butane sulfonic acid, acetic acid, glycolic acid, propionic acid, hydroxypropionic acid, alpha-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, alpha-hydroxy acid, ethylenediaminetetraacetic acid (EDTA), phosphonic acid, octylphosphonic acid, acrylic acid, polyacrylic acid, aspartic acid, polyaspartic acid, p-hydroxybenzoic acid, iminoacetic acid, or a combination thereof.

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

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

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

32. A multi-component composition for providing nitric oxide, the multi-component composition comprising: A first component comprising a thiol-containing compound having a particle size of about 1 nm to about 10 mm; A second component comprising a nitrosated compound having a particle size of about 1 nm to about 10 mm; and in, The composition of the thiol-containing compound and the nitrosating compound is such that the thiol-containing compound and the nitrosating compound react in the presence of a solvent to form a nitric oxide precursor, which decomposes to form nitric oxide.

33. The multi-component composition of claim 32, wherein the first component and the second component are substantially uniformly dispersed.

34. The multi-component composition of claim 32, wherein at least one of the first component and the second component further comprises a carrier.

35. The multi-component composition of claim 34, wherein the carrier comprises silica gel, sodium polyacrylate, or a combination thereof.

36. The multi-component composition of claim 32, wherein at least one of the first component and the second component further comprises a cleaning agent.

37. The multi-component composition of claim 36, wherein the cleaning agent comprises a detergent, an enzyme, or a combination thereof.

38. The multi-component composition of claim 32, wherein the nitric oxide precursor comprises a primary nitrosothiol.

39. The multi-component composition of claim 32, wherein the nitric oxide precursor decomposes to form nitric oxide within 1 hour after the nitric oxide precursor is formed.

40. The multi-component composition of claim 32, wherein the thiol-containing compound comprises cysteine ​​or a derivative thereof, a thiol-derived polymer or filler, or a combination thereof.

41. The multi-component composition of claim 40, wherein the thiol-containing compound comprises cysteine ​​or a derivative thereof.

42. The multi-component composition of claim 41, wherein the cysteine ​​or derivative thereof comprises cysteine, glutathione, acetylcysteine, penicillamine, acetylpenicillamine, S-nitroso-N-acetylpenicillamine, bucillamine, or a combination thereof.

43. The multi-component composition of claim 32, wherein the nitrosating compound comprises a nitrite / nitrite ester.

44. The multi-component composition of claim 43, wherein the nitrite / nitrite ester comprises sodium nitrite, calcium nitrite, potassium nitrite, tetrabutylammonium nitrite, dicyclohexylammonium nitrite, butyl nitrite, isobutyl nitrite, tert-butyl nitrite, isoamyl nitrite, amyl nitrite, nitrite, ion-pair nitrite, silver nitrite, zinc nitrite, iron nitrite, copper nitrite, transition metal-nitrite compounds, or combinations thereof.

45. The multi-component composition of claim 32 further comprising an acid.

46. ​​The multi-component composition of claim 45, wherein the acid comprises hydrochloric acid, citric acid, methane sulfonic acid, ethane sulfonic acid, propane sulfonic acid, butane sulfonic acid, acetic acid, glycolic acid, propionic acid, hydroxypropionic acid, alpha-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, alpha-hydroxy acid, ethylenediaminetetraacetic acid (EDTA), phosphonic acid, octylphosphonic acid, acrylic acid, polyacrylic acid, aspartic acid, polyaspartic acid, p-hydroxybenzoic acid, iminoacetic acid, or a combination thereof.

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

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

49. The multi-component composition of 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 nitrosated compound; and a mixing chamber in fluid communication with the first compartment and the second compartment for combining the first compartment and the second compartment; The composition of the thiol-containing compound and the nitrosated compound is such that the thiol-containing compound and the nitrosated compound react in the presence of a solvent to form a nitric oxide precursor, and the nitric oxide precursor decomposes to form nitric oxide.

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

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

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