WO2021142148A1 - Compositions antimicrobiennes à l'état solide et leurs procédés de production et d'utilisation - Google Patents

Compositions antimicrobiennes à l'état solide et leurs procédés de production et d'utilisation Download PDF

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Publication number
WO2021142148A1
WO2021142148A1 PCT/US2021/012536 US2021012536W WO2021142148A1 WO 2021142148 A1 WO2021142148 A1 WO 2021142148A1 US 2021012536 W US2021012536 W US 2021012536W WO 2021142148 A1 WO2021142148 A1 WO 2021142148A1
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composition
salt
acid
wound
magnesium
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PCT/US2021/012536
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English (en)
Inventor
Scott NOBLITT
Edwin NEAS
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Armis Biopharma, Inc.
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Priority claimed from US16/736,546 external-priority patent/US20200276149A1/en
Application filed by Armis Biopharma, Inc. filed Critical Armis Biopharma, Inc.
Priority to US17/758,452 priority Critical patent/US20230030675A1/en
Priority to EP21738304.1A priority patent/EP4087557A4/fr
Priority to JP2022541784A priority patent/JP2023509515A/ja
Publication of WO2021142148A1 publication Critical patent/WO2021142148A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/327—Peroxy compounds, e.g. hydroperoxides, peroxides, peroxyacids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing within the same carbon skeleton a carboxylic group or a thio analogue, or a derivative thereof, and a carbon atom having only two bonds to hetero atoms with at the most one bond to halogen, e.g. keto-carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/336—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having three-membered rings, e.g. oxirane, fumagillin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/357—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like

Definitions

  • the present invention relates to solid state antimicrobial, disinfecting, and wound healing compositions and methods for producing and using the same.
  • the compositions contain a peracid, a hydroperoxide, the parent carboxylic acid of the peroxyacid, and a salt.
  • compositions and methods for reducing and/or eliminating microbial organisms from various surfaces Conventional antimicrobial cleansing products such as hard surface cleaners and surgical disinfectants are typically formulated to provide bacteria removal during washings. Only a few such products have been shown to provide a residual effectiveness against Gram-positive bacteria; however, even such compositions provide only limited residual effectiveness against Gram-negative bacteria.
  • residual effectiveness it is meant that the subject antimicrobial controls microbial growth on a substrate by either preventing growth of microbes or engaging in continuous kill of microbes for some period of time following the washing and/or rinsing process.
  • Peracetic acid has been applied for purposes such as disinfecting medical supplies, preventing biofilm formation in pulp industries, disinfecting during water purification, and plumbing disinfection.
  • Peracetic acid is produced by a reaction between hydrogen peroxide and acetic acid or it can also be produced by oxidation of acethaldehyde.
  • Peracetic acid is a very powerful oxidant; the oxidation potential outranges that of chlorine and chlorine dioxide.
  • Peracetic acid is not known to be involved in any significant cellular metabolism and is typically produced with toxic sulfuric acid catalyst.
  • a drawback of the peroxyacid-based chemical disinfectants is their inherent lack of stability, which poses a challenge for shelf-life when used for long term applications.
  • a peracid-based disinfectant which is an effective broad spectrum antimicrobial, is in an easily removable homogenous antimicrobial coating composition providing both short-term and extended long-term antimicrobial efficacy after application to a surface or a wound.
  • new topical wound sanitizers, healers or both and in particular there is a need to develop peroxyacids that are effective sporocides, bactericids and virucides for wounds which are easy to handle and store.
  • peroxyacids that are easy to handle and store and that have a low corrosive nature. It is therefore desirable to develop a sanitizer that does not decompose rapidly and violently and that can be used as a topical wound sanitizer or as an antimicrobial coating.
  • the present invention relates to novel antimicrobial, disinfecting, and/or wound healing compositions and methods for producing and using the same.
  • the compositions contain a peracid, a hydroperoxide, the parent carboxylic acid of the peroxyacid, and a salt.
  • the present disclosure provides a solid-state antimicrobial composition containing a peroxyacid, a hydroperoxide, the parent carboxylic acid of the peroxyacid, and a salt selected from a lithium salt, a sodium salt, a potassium salt, a rubidium salt, a cesium salt, a zinc salt, a magnesium salt, a calcium salt and a combination thereof.
  • the hydroperoxide is hydrogen peroxide.
  • the salt is a magnesium salt.
  • the magnesium salt is selected from a magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium acetate tetrahydrate, and a combination thereof.
  • the magnesium salt is magnesium acetate tetrahydrate.
  • the peroxyacid is peracetic acid.
  • the peroxyacid is a magnesium salt of the peroxyacid.
  • the composition further contains at least one of a bis(hydroperoxide) or an epoxide.
  • the peroxyacid is peracetic acid and the bis(hydroperoxide) is 3,3-bis(hydroperoxy)butanoic acid.
  • the composition is formulated as a wound healing composition.
  • the wound healing composition is formulated as a gel, a liquid, lotion, skin patch, irrigation gel, a spray, application granules, or a combination thereof.
  • the present disclosure provides a method for treating a wound infection in a subject comprising contacting the infected wound in the subject with a therapeutically effective amount of the composition of the first aspect.
  • the infected wound is a surgical wound, battle wound, accidental wound, thermal burn wound, chemical burn wound, chronic wound, decubitus ulcer, foot ulcer, venous ulcer, laser treatment wound, sunburn, or an abrasion.
  • the infected wound is contacted with the composition once a day.
  • the composition is formulated as a gel, a liquid, lotion, skin patch, irrigation gel, a spray, application granules, or a combination thereof.
  • FIG. 1 is a graphic illustration of phases of wound healing.
  • FIG. 2 is a schematic illustration of inflammatory phases of wound healing.
  • FIG. 3 is a reaction scheme for a reaction comprising pyruvic acid and hydrogen peroxide according to an embodiment of the present invention.
  • FIG. 4 is a reaction scheme for a reaction comprising acetoacetic acid and hydrogen peroxide according to an embodiment of the present invention.
  • FIG. 5 is a reaction scheme for a reaction comprising maleic acid and hydrogen peroxide according to an embodiment of the present invention.
  • FIG. 6 is a reaction scheme for a reaction comprising citraconic acid and hydrogen peroxide according to an embodiment of the present invention.
  • wt % refers to the weight percent relative to the total weight of the solution or dispersion.
  • Microorganism is meant to include any organism comprised of the phylogenetic domains of bacteria and archaea, as well as unicellular (e.g., yeasts) and filamentous (e.g., molds) fungi, unicellular and filamentous algae, unicellular and multicellular parasites, viruses, virinos, and viroids.
  • "Film-forming agent” or “water soluble or water dispersible coating agent,” which may be used interchangeably herein, refer to agents that form a film and are employed to provide protective coating to the surface of interest. These agents are either water soluble or water dispersible. These agents are described in further detail below.
  • Antimicrobial agent refers to a compound or substance having antimicrobial properties
  • Biocide refers to a chemical agent, typically broad spectrum, which inactivates or destroys microorganisms.
  • a chemical agent that exhibits the ability to inactivate or destroy microorganisms is described as having "biocidal" activity.
  • Biofilm refers to a structured community of microorganisms encapsulated within a self-developed polymeric matrix and adherent to a living or inert surface.
  • Drying refers to a process by which the inert solvent or any other liquid present in the formulation is removed by evaporation.
  • Disinfectant as used herein is a chemical that kills 99.9% of the specific test microorganisms in 10 minutes under the conditions of the test. (Germicidal and Detergent Sanitizing Action of Disinfectants, Official Methods of Analysis of the Association of Official Analytical Chemists, paragraph 960.09 and applicable sections, 15th Edition, 1990 (EPA Guideline 91-2)).
  • Licus as used herein, comprises part or all of a target surface suitable to be coated.
  • the present invention relates to antimicrobial, disinfecting, and/or wound healing compositions and methods for producing and using the same.
  • the compositions contain a peroxyacid, a hydroperoxide, the parent carboxylic acid of the peroxyacid, and a salt.
  • Some aspects of the present invention provide methods for treating a wound on a subject by contacting the wound with a therapeutically effective amount of the composition.
  • peroxyacids or peracids are compounds of oxidized form of a base organic acid (generally a carboxylic acid) that exist in equilibrium with an oxidizer (generally hydrogen peroxide) and water.
  • Peracids may be oxidized from other carboxylic acids, e.g. acetic acid, citric acid, succinic acid, short chain fatty acids, etc.
  • peracid As used herein, “peracid,” “peroxyacid,” “percarboxylic,” and “peroxy-carboxylic acid,” and are used interchangeably herein and refer to compounds generally having the formula R(C0 3 H) n , where, for example, R is an alkyl, arylalkyl, cycloalkyl, aromatic, or heterocyclic group, and n is one, two, or three, and named by prefixing the parent acid with “peroxy-.”
  • the R group can be saturated or unsaturated as well as substitut-ed or unsubstituted.
  • Peroxycarboxylic acids can be made by the direct action of an oxidizing agent on a carboxylic acid, by autoxidation of aldehydes, or from acid chlorides, and hydrides, or carboxylic anhydrides with hydrogen or sodium peroxide.
  • Peroxycarboxylic acids useful in the compositions and methods of the present invention include peroxyformic, peroxyacetic, peroxypropionic, peroxybutanoic, peroxy- pentanoic, peroxyhexanoic, peroxyheptanoic, peroxyoctanoic, peroxynonanoic, peroxy-decanoic, peroxyundecanoic, peroxydodecanoic, or the peroxyacids of their branched chain isomers, peroxylactic, peroxymaleic, peroxyascorbic, peroxyhydroxyacetic, peroxyoxalic, peroxymalonic, peroxysuccinic, peroxyglutaric, peroxyadipic, peroxypimelic and peroxy-suberic acid and mixtures thereof.
  • the compositions of the invention utilize a combination of several different peroxycarboxylic acids.
  • the composition includes one or more Cl to C4 peroxycarboxylic acids and one or more C5 to C 11 peroxycarboxylic acids.
  • the peroxycarboxylic acid is peracetic acid (C2), peroxy propionic acid (C3), peroxybutanoic acid (C4), peroxysuccinic and peroxymalonic acid.
  • C2 peracetic acid
  • C3 peroxy propionic acid
  • C4 peroxybutanoic acid
  • peroxysuccinic and peroxymalonic acid peroxysuccinic and peroxymalonic acid.
  • both the peroxy-succinic and peroxymalonic acid may come from the alpha-keto dicarboxylic acids.
  • these acids exist in the Krebs cycle they are metabolically active.
  • compositions also include the parent carboxylic acid of the peroxyacid.
  • the parent carboxylic acid is meant the corresponding carboxylic acid from which the peroxyacid is derived or is degraded into under a typical storage or production conditions.
  • the parent acid is acetic acid
  • the peroxyacid is peroxyacetic acid.
  • Suitable parent carboxylic acids include, for example, formic acid, acetic acid, propionic acid, butanoic acid, pentanoic acid, hexanoic acid, heptanoic acid, octanoic acid, nonanoic acid, decanoic acid, undecanoic acid, dodecanoic acid, or the acids of their branched chain isomers, lactic acid, maleic acid, ascorbic acid, hydroxyacetic acid, oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid and suberic acid and mixtures thereof.
  • the parent carboxylic acid is present in the composition of the invention in an amount of about 120.4 mM or less, typically, about 12.4 mM or less, more typically, about 6.2 mM or less, often about 2.5 mM or less, more often, about 1.2 mM or less, still more often about 0.62 mM or less, yet more often about 0.31 mM or less, and most often about 0.062 mM or less.
  • compositions and methods of the present invention include peroxyacetic acid.
  • Peroxyacetic (or peracetic) acid is a peroxycarboxylic acid having the formula: CH3COOH.
  • peroxyacetic acid is a liquid having an acrid odor at higher concentrations and is freely soluble in water, alcohol, ether, and sulfuric acid.
  • the peroxyacid is a magnesium salt of the peroxyacid.
  • the composition also contains a hydroperoxide, such as for example hydrogen peroxide or an organic peroxide.
  • a hydroperoxide such as for example hydrogen peroxide or an organic peroxide.
  • the hydroperoxide is hydrogen peroxide.
  • the amount of hydrogen peroxide present in the wound healing compositions of the invention is about 715 mM or less, typically about 71.5 mM or less, more typically about 35.8 mM or less, often about 14.3 mM or less, more often about 7.2 mM or less, still more often about 3.6 mM or less, yet more often about 1.8 mM or less, and most often about 0.35 mM or less.
  • the composition further contains one or more optional compounds, such as for example tartaric acid, formic acid, c/.s-epoxysuccinic acid, methyltartaric acid, acetic acid, cv.v-epoxym ethyl succinic acid, maleic acid, citramalic acid, citraconic acid or a combination thereof.
  • the composition also optionally includes an oxidized acetoacetate compound.
  • the composition contains acetoacetic acid.
  • Acetoacetic acid is one of the ketone bodies (along with 3-hydroxybutyric acid and acetone, although acetone is just a byproduct), which are major energy sources for the body, parti cu-larly during starvation.
  • Ketone bodies are involved in pathways related to the Kreb’s cycle, lipogenesis, sterol biosynthesis, glucose metabolism, b-oxidation of fatty acids, mitochondrial electron transport chain, intracellular signal transduction pathways, hormonal signaling, and the microbiome (Cotter, D. G., et al, Am. ./. Physiol, Heart Circ. Physiol ., 2013, 304, H1060-H1076).
  • acetoacetic acid can be converted into acetyl-CoA in vivo, its ability to affect biological processes is extremely high. However, its presence in the solution is unexpected because acetoacetic acid is an unstable compound that reacts intramolecularly and irreversibly, producing acetone and carbon dioxide. Thus, it is expected to be unstable in all solvents and even as a solid compound.
  • acetoacetic acid represents a rather unique case where a compound is stabilized by the addition of hydrogen peroxide, whereas normally the addition of a per-oxide leads to chemical oxidation/degradation.
  • This stabilization is caused by the formation of a range of possible peroxide “adducts” with its ketone functionality and possibly its carboxylic acid. Because both moieties are required for intramolecular “self-destruction”, the formation of these other forms slows down the decomposition of the compound.
  • Peroxide adducts may include 3,3- bis(hydroperoxy)butanoic acid, 3,3-bis(hydroperoxy)butaneperoxoic acid, 3-oxobutane-peroxoic acid, and 5-hydroperoxy-5-methyl-l,2-dioxolan-3-one. This stabilization is shown in the reaction scheme of FIG. 4.
  • the compositions may be further stabiliz-ed by citramalic acid or an acetoacetate ester, such as methyl or ethyl acetoacetate.
  • the composition also contains a bis(hydroperoxide), or an epoxide, or both.
  • the composition further contains a peroxyacid that is peracetic acid and a bis(hydroperoxide) that is 3,3- bis(hydroperoxy)butanoic acid.
  • the compositions may contain peroxycitraconic acid.
  • the peroxycitraconic acid may be either (2Z)-4-hydroperoxy-3 -methyl -4-ox obut-2-enoic acid, (2Z)-4- hydroperoxy-2-methyl-4-oxobut-2-enoic acid, or a mixture thereof.
  • the compositions may comprise diperoxycitraconic acid, i.e., (2Z)-2-methyl-but-2-enediperoxoic acid.
  • the antimicrobial composition further comprises peroxycitramalic acid.
  • the peroxycitramalic acid may be either 4-hydroperoxy-2-hydroxy-2-methyl-4-oxobutanoic acid, 4-hydroperoxy-3-hydroxy-3-methyl-4-oxobutanoic acid, or a mixture thereof.
  • the antimicrobial composition is in the solid-phase. In some embodiments, the composition is in the form of a powder.
  • the solid-phase composition provides certain advantages over liquid-phase antimicrobial treatments. One advantage associated with the present invention is that the solid-phase antimicrobial composition is easier to apply and control than a liquid-based composition. In part, this is because the solid-phase composition does not release its antimicrobial components until it comes into contact with moisture, for example from body tissue or fluid.
  • the solid-phase composition attaches to the surface of the article, substrate, skin or wound better than liquid compositions. Additionally, the solid form of the composition advantageously enables the slow release of the antimicrobial compounds in the composition, once the compsition comes into contact with fluids and/or tissue, such as for example those on or in a subject's body.
  • the solid-phase composition may be configured so that the release of the antimicrobial compounds within the composition (e.g., peroxycarboxylic acid) is sustained over a predetermined time period of continuous or intermittent exposure to fluids such as bodily fluids.
  • the solid-phase antimicrobial composition is more stable than compositions containing the individual compounds reacted to form the solid-phase antimicrobial composition.
  • the solid-phase antimicrobial composition is useful for preventing or diminishing the risk of infection even for subjects who have become resistant to antibiotics.
  • the peroxyxcarboxylic acid in the antimicrobial composition is able to breach the cell walls of microbes and destroy the contents of the cell, rendering the microbes incapable of developing resistance to the composition.
  • the solid-phase form of the composition makes it easier to get the antimicrobial composition directly to or near the site of microbes, where it can destroy them.
  • the composition can be made by any suitable method.
  • the solid phase antimicrobial composition contains a salt.
  • the solid-phase peroxyxcarboxylic acid salt can be made by mixing hydrogen peroxide, a peroxycarboxylic acid, a salt, to form a solid-phase peroxycarboxylic acid salt precipitate.
  • the reaction to form the solid-phase composition can be performed in a solvent, which may be water, or a lower (water-soluble) alcohol, such as, for example, methanol, ethanol, isopropanol and the like.
  • the peroxycarboxylic acid can first be solubilized, for example by pre-dissolving it in an organic solvent.
  • organic co-solvents include, for example, ethyl acetate, t-butyl alcohol, methanol, tetrahydrofuran, tetrahydropyran, and ethanol and mixtures thereof, with ethyl acetate and t-butyl alcohol being most preferred.
  • Some organic solvents are not preferred because they can react with the peroxycarboxylic acids. This group includes dimethyl sulfoxide, carbon disulfide, and solvents which contain multiple bonds.
  • the organic co-solvent selected not solubilize the peroxycarboxylate product to a significant extent. This will facilitate the isolation of the product as a solid precipitate.
  • the precipitate can be separated by any standard technique. For example, filtration, decantation, and/or centrifugation can be used.
  • the precipitate can then be washed, for example, with water, and if used, an organic co-solvent, to remove any unreacted starting materials. Finally, the precipitate is dried to remove excess water. This may be achieved by any standard means of drying. For example, vacuum desiccation, mild heating at ambient pressure, or air drying may be used.
  • the salt is a basic metal salt.
  • the amount of basic metal salt added to the reaction mixture is sufficient to adjust the pH of the reaction solution to, from about 2 to about 8, preferably from about 3.5 to about 7.5, more preferably from about 3.8 to about 7, and most preferably less than 5.
  • Lower pHs are preferred as the peroxycarboxylic acid may rapidly destruct at high pH, which undesirably reduces the amount of retained peroxycarboxylic acid.
  • the pH of the reaction solution is lower than the pKa of the peroxycarboxylic acid.
  • the reaction may take place at a pH of from about 3.8 to about 7.5, when using peroxyacetic acid, which has apKa of 8.2.
  • the molar ratio of peroxycarboxylic acid to metal salt may vary, depending on which salt is being used. The preferred ratio is that which enables essentially all of the metal and peroxycarboxylic acid to interact, and essentially none of each compound to be wasted.
  • the amount of metal from the metal salt, and the amount of peroxycarboxylic acid utilized in the reaction solution or suspension is such that the molar ratio of metal to peroxycarboxylic acid is from about 0.01:1 to about 10:1.
  • the molar ratio of metal to peroxy carboxylic acid is from about 0.5 : 1 to about 8:1. In another embodiment of the invention the molar ratio of basic metal salt to peroxycarboxylic acid is from about 0.01:1 to about 0.5:1. In another embodiment of the invention the molar ratio of basic metal salt to peroxycarboxylic acid is no more than 0.5:1. In another embodiment of the invention the molar ratio of basic metal salt to peroxycarboxylic acid is about 6:1. In yet another embodiment of the invention the molar ratio of metal to peroxycarboxylic acid is about 1.5:1. In still another embodiment of the invention, the molar ratio of metal to peroxycarboxylic acid is about 0.7: 1. In a further embodiment of the invention, the antimicrobial composition contains from about 0.1 wt % to about 85 wt % of the peroxycarboxylic acid.
  • Coatings of the composition according to the present invention have a tendency to quickly lose their antimicrobial activity over time, which is believed to be the result of evaporation of the neat peracid.
  • the salt in the composition forms a salt of the peracid, which testing has shown to retain antimicrobial activity over a lengthy accelerated aging test.
  • the salts in the composition serve to stabilize the antimicrobial composition.
  • peroxycarboxylic acids are highly volatile due to their high vapor pressures. They are also known to readily lose their active oxygen, making them unstable.
  • active oxygen is meant the oxygen contained in a molecule that is easily transferred via a chemical reaction to another compound. Peroxycarboxylic acids tend to be even more unstable when mixed with other compounds.
  • compositions containing peroxycarboxylic acids have poor storage stability.
  • Previous attempts to provide antimicrobial solutions containing hydrogen peroxide and peroxycarboxylic acid were unsuccessful in the absence of the basic metal salt, due in large part, to loss, during the drying process, of most of the peroxycarboxylic acid from the formulation, due to volatilization.
  • the liquid antimicrobial composition suffered comparable losses of hydrogen peroxide, resulting in a final antimicrobial composition that did not have the desired antimicrobial properties.
  • the formation of the solid-phase peroxycarboxylate metal salt overcomes the challenge of maintaining the volatile components of the antimicrobial composition, producing a dry antimicrobial composition having the desired properties.
  • the addition of basic metal salts to the antimicrobial composition is thus useful for achieving a quantifiable amount of peroxycarboxylic acid in the antimicrobial composition, even though the more volatile species are still lost.
  • the peroxycarboxylate moiety of the antimicrobial composition's peroxycarboxylic acid associates with the metal in the basic metal salt in such a way that provides stability to the solid-phase peroxycarboxylic acid metal salt.
  • the active oxygen in the metal peroxycarboxylate is retained during storage to a greater extent than is the active oxygen contained in the corresponding peroxycarboxylic acid.
  • the solid-phase peroxycarboxylic acid metal salts have superior odor, dispersibility and handling properties relative to the corresponding peroxycarboxylic acids.
  • the long-term stability of the solid-phase peroxycarboxylic acid metal salt may be negatively affected by the presence of water. Therefore, during drying of the solid- phase peroxycarboxylic acid metal salt precipitate, it is desirable to eliminate as much of the solution-phase water as possible. In a preferred embodiment, only waters of crystallization are present in the solid-phase peroxycarboxylic acid metal salt. In another preferred embodiment, the solid-phase peroxycarboxylic acid metal salt contains no more than 12 water molecules per metal ion, with the amount of acceptable water molecules depending on the peroxycarboxylic acid being used. Suitable salts include, for example, a lithium, sodium, potassium, rubidium, cesium, zinc salt, magnesium, or calcium salt, or any combination thereof.
  • the salt is a magnesium salt, such as for example a magnesium oxide, magnesium hydroxide, magnesium carbonate, magnesium acetate tetrahydrate, and a combination thereof. In some embodiments, the salt is magnesium acetate tetrahydrate.
  • the reaction solution or suspension can also contain other additives.
  • the reaction solution or suspension can also include a polyethylene glycol (PEG).
  • PEG polyethylene glycol
  • Any type of polyethylene glycol may be used for the invention, whether a low molecular weight PEG, such as for example, PEG 200, PEG 300 or PEG 400, a high molecular weight PEG, such as for example PEG 3350, PEG 4000, PEG 10,000 or PEG 35,000, or a medium molecular weight PEG.
  • the amount of polyethylene glycol will depend on a variety of factors, such as for example, the application or the type of peroxycarboxylic acid.
  • the polyethylene glycol is present in the reaction mixture in an amount of from greater than 0 to 75 weight percent, based on the total weight of the reaction mixture.
  • compositions may also be affected by the humidity under compositions are stored.
  • the compositions are stored under conditions where the relative humidity is less than about 43, preferably less than about 40, more preferably less than about 35.
  • a “stable" composition is one which maintains sufficient physical properties and active oxygen content long enough to be useful, about twelve months.
  • the composition of the present invention have utility in numerous household products.
  • the present invention thus also provides an antimicrobial product containing the compositions of the present invention.
  • the product is a household care product.
  • the house hold care product is selected from hard surface cleaners, deodorizers, fabric care compositions, fabric cleaning compositions, manual dish detergents, automatic dish detergents, floor waxes, kitchen cleaners, bathroom cleaners, and combinations thereof.
  • the antimicrobial product is selected from hard surface cleaners, deodorizers, fabric care compositions, fabric cleaning composi-tions, manual dish detergents, automatic dish detergents, floor waxes, kitchen cleaners, bathroom cleaners, and combinations thereof.
  • Antimicrobial products of the invention can be used in a wide variety of settings including, but not limited to, in health care facilities such as hospitals, rehabilitation, assisted living facilities, etc.
  • the antimicrobial product is a medical device disinfectant. Still in other embodiments, the antimicrobial product is used as a disinfectant for aseptic filling equipment. Yet in other embodiments, the antimicrobial product is used in an aseptic food processing system. In other embodiments, the antimicrobial product is used as a disinfectant for biofilms in water systems. Still in other embodiments, the antimicrobial product is used as a disinfectant for waste water treatment.
  • the composition is a wound healing composition.
  • the wound healing composition is formulated as a gel, a liquid, lotion, skin patch, irrigation gel, a spray, application granules, or a combination thereof for healing wounds.
  • topical antiseptics should be toxic to bacteria but should have no significant toxicity to underlying tissues, and ideally, they should also preserve or enhance host defense against infection.
  • the present invention also provides a method for treating wounds including, but not limited to, surgical wounds, battle wounds, accidental wounds, thermal burn wounds, chemical burn wounds, chronic wounds, decubitus ulcesr, foot ulcers, venous ulcers, laser treatment wounds, sunburns, or abrasions.
  • the infected wound is contacted with the composition daily.
  • Methods of the invention promote wound healing and typically rapidly kill high levels of viruses, vegetative bacteria, fungi, mycobacteria and spores.
  • compositions and methods of the invention eliminate bacteria, enhance body's defense system, and enhance the healing process.
  • compositions disclosed in the present embodiments can kill high levels of bacteria and spores in biofilms and in high protein environments without being corrosive and having virtually no cellular toxicity issues.
  • compositions capable of forming shelf-stable coatings containing the magnesium salt of peroxyacetic acid were prepared by drying solutions containing a magnesium salt, acetic acid, hydrogen peroxide, peracetic acid, and poly(ethylene glycol) (PEG).
  • the starting magnesium salt was magnesium hydroxide, magnesium carbonate, or magnesium acetate tetrahydrate (an anhydrous magnesium acetate salt would also be effective since it is being dissolved in a water- containing mixture).
  • the acetic acid/hydrogen peroxide/peracid source was an aqueous solution (called “PAA Source” in this document) usually containing 8-12 wt% peracid (peracetic acid), 15- 22 wt% hydrogen peroxide, and 14-20 wt% acetic acid. Coatings were also be made in the presence of silica particles (up to 2.8%). Finally, the remainder of the solution typically consisted of water, but the short-chain alcohols methanol, ethanol, and isopropanol were also successfully used, with the shortest chains being the most successful.
  • a typical coating-solution mixture consisted of the following, which was used immediately after mixing:

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Abstract

La présente invention concerne des compositions antimicrobiennes, désinfectantes et cicatrisantes et leurs procédés de production et d'utilisation. Les compositions peuvent contenir un peroxyacide, un hydroperoxyde, de l'acide carboxylique parent du peroxyacide et un sel.
PCT/US2021/012536 2017-07-07 2021-01-07 Compositions antimicrobiennes à l'état solide et leurs procédés de production et d'utilisation WO2021142148A1 (fr)

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US17/758,452 US20230030675A1 (en) 2017-07-07 2021-01-07 Solid state antimicrobial compositions and methods for producing and using same
EP21738304.1A EP4087557A4 (fr) 2017-07-07 2021-01-07 Compositions antimicrobiennes à l'état solide et leurs procédés de production et d'utilisation
JP2022541784A JP2023509515A (ja) 2017-07-07 2021-01-07 固体抗菌組成物、並びにその製造方法及び使用方法

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US11839213B2 (en) 2008-11-20 2023-12-12 Armis Biopharma, Inc. Antimicrobial, disinfecting, and wound healing compositions and methods for producing and using the same
US11969399B2 (en) 2017-07-07 2024-04-30 Armis Biopharma, Inc. Compositions and methods for remediating chemical warfare agent exposed skin

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US20100108942A1 (en) * 2008-10-31 2010-05-06 Ecolab Inc. Enhanced stability peracid compositions
US20130330397A1 (en) * 2011-02-17 2013-12-12 Chd Bioscience, Inc. Wound Care Products with Peracid Compositions
US20150093425A1 (en) * 2013-09-30 2015-04-02 Chemlink Laboratories, Llc Environmentally preferred antimicrobial compositions
WO2019010465A1 (fr) * 2017-07-07 2019-01-10 Armis Biopharma, Inc. Compositions antimicrobiennes, désinfectantes et cicatrisantes et leurs procédés de production et d'utilisation
US20200246511A1 (en) * 2019-02-04 2020-08-06 Armis Biopharma, Inc. Methods and devices to reduce the risk of infection

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US20100108942A1 (en) * 2008-10-31 2010-05-06 Ecolab Inc. Enhanced stability peracid compositions
US20130330397A1 (en) * 2011-02-17 2013-12-12 Chd Bioscience, Inc. Wound Care Products with Peracid Compositions
US20150093425A1 (en) * 2013-09-30 2015-04-02 Chemlink Laboratories, Llc Environmentally preferred antimicrobial compositions
WO2019010465A1 (fr) * 2017-07-07 2019-01-10 Armis Biopharma, Inc. Compositions antimicrobiennes, désinfectantes et cicatrisantes et leurs procédés de production et d'utilisation
US20200246511A1 (en) * 2019-02-04 2020-08-06 Armis Biopharma, Inc. Methods and devices to reduce the risk of infection

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11839213B2 (en) 2008-11-20 2023-12-12 Armis Biopharma, Inc. Antimicrobial, disinfecting, and wound healing compositions and methods for producing and using the same
US11969399B2 (en) 2017-07-07 2024-04-30 Armis Biopharma, Inc. Compositions and methods for remediating chemical warfare agent exposed skin

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