• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
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    • 专利摘要:
    this invention relates to antimicrobial compositions comprising: an amino acid, a derivative of an amino acid, a salt of an amino acid, a salt of a derivative of an amino acid or mixtures thereof; an antimicrobial component comprising two or more antimicrobial quaternary ammonium compounds, or at least one antimicrobial quaternary ammonium compound and chlorhexidine or a salt thereof; and a polar solvent, and formulations that include antimicrobial compositions. in particular, the invention relates to antimicrobial compositions that can be used on the skin.
    公开号:BR112017021002B1
    申请号:R112017021002-9
    申请日:2016-04-01
    公开日:2020-05-26
    发明作者:Christopher Plummer；Rhiannon Sian Hurd
    申请人:Byotrol Plc；
    IPC主号:
    专利说明:

    ANTIMICROBIAL COMPOSITION, USE OF A COMPOSITION, METHOD TO SUBSTANTIALLY REDUCE OR CONTROL THE FORMATION OF MICROBIAL COLONIES ON OR IN A SURFACE, HAND SANITIZERS, PRODUCT FOR THE INJURY CARE, PRODUCT FOR CARE AND ANIMALS, HYDROPETIC AND HYDROPODS , ANTIMICROBIAL SCARF
    [001] This invention relates to antimicrobial compositions and formulations that include antimicrobial compositions. In particular, the invention relates to antimicrobial compositions that can be used on the skin.
    [002] Microorganisms, such as bacteria and viruses, for example, norovirus, polio virus and adenovirus, are well known to present health hazards due to infection or contamination. Along with fungi, yeasts and other micro-organisms, they can also cause deterioration of items, such as food, clothing and produce unpleasant odors. When microorganisms are present on the surface of a substrate, such as skin, they can reproduce quickly to form colonies.
    [003] Many antimicrobial agents can destroy microorganisms that are present in a wide range of environments. For example, antimicrobial agents that can be used in medical, industrial, commercial, domestic and marine environments are known. Many of the known antimicrobial agents have previously been included in compositions for use in these environments for various applications.
    [004] The known antimicrobial agents and the compositions containing these antimicrobial agents act through several different mechanisms.
    [005] For example, many antimicrobial agents are poisonous to microorganisms and therefore destroy microorganisms with which
    Petition 870190136609, of 12/19/2019, p. 11/48 / 37 get in touch. Examples of this type of antimicrobial agent include hypochlorites (bleaching agents), phenol and compounds thereof, and copper, tin and arsenic salts.
    [006] However, although many of these antimicrobial agents are effective against microorganisms and appropriate for certain environments, their mechanisms can make them unsuitable or disadvantageous for topical application to human skin due to their harmful effects on human health or in skin condition . For example, the hypochlorite bleaching agent is very effective in killing microorganisms on solid surfaces, but unsuitable for application to the skin due to its corrosive properties. In addition, these materials tend to be effective in a humid environment for sterilization and cleaning, but they stop working right after drying.
    [007] Many skin sanitizers are alcohol based. They are typically an alcohol-containing preparation designed for application to the hands to reduce the amount of viable microorganisms in the hands. Such preparations typically contain 60% to 95% ethanol or isopropanol. However, although isopropyl alcohol has established antibacterial properties, it has the disadvantage that, when used regularly, it can cause dryness and skin irritation. As a result, some people may be reluctant to use such creams, soaps and other compositions that comprise significant levels of isopropanol.
    [008] Some antimicrobial agents are highly toxic to humans and animals and are dangerous to handle. Therefore, handling, treatment and specialized equipment are required in order to handle them safely. The manufacture and disposal of compositions that comprise this type of antimicrobial agent can therefore be problematic. There may also be problems associated with the use of compositions that contain this type of antimicrobial agent, particularly
    Petition 870190136609, of 12/19/2019, p. 12/48 / 37 on consumables where it is difficult to guarantee that they are used for the designated purposes.
    [009] In this document, unless the context otherwise indicates, "toxicity" is intended to refer to toxicity for complex organisms, such as mammals. References to “toxic” must be interpreted accordingly.
    [0010] The increased inspection of the environmental credentials of chemical products also restricts the use of antimicrobial agents not only for topical application on the skin, but for general use. For example, some antimicrobial agents, once they enter the environment, can harm other organisms. They can also be very stable and persist in the environment for long periods, which causes concerns about accumulation and residual levels.
    [0011] Due to these factors, the list of effective and available antimicrobial agents, particularly for use on the skin, has become more restricted and the burden of new antimicrobial registrations more prohibitive. At the same time, the public is increasingly concerned about sanitizing both people and property after outbreaks, such as MRSA, in hospitals.
    [0012] There is a need to provide compositions for a variety of applications and uses, such as compositions for use on the skin, for example, hand sanitizing agents, which have antimicrobial properties and address one or more of the problems set out above. However, doing so is not a direct matter. There are regulations, such as the Biocidal Products Regulations (Directive 98/8 / EC), which regulate the use of antimicrobial agents in terms of both the nature and the amount of a given antimicrobial agent that can be used. Additionally, the potential reactivity of an antimicrobial agent, since in a composition, it is important, since some agents
    Petition 870190136609, of 12/19/2019, p. 13/48 / 37 antimicrobials become inactive by chemical reaction. Even when an antimicrobial agent is not deactivated by chemical reaction, it can have its activity suppressed by other components of the composition.
    [0013] The present inventors have surprisingly found that the above deficiencies can be overcome by certain combinations of components. It has also been found that compositions containing these combinations of components can have some surprising and unexpected properties.
    [0014] The listing or discussion of a document published in an apparently earlier manner in this specification should not necessarily be regarded as an acknowledgment that the document is part of the state of the art or is common knowledge.
    [0015] The present invention provides an antimicrobial composition which comprises:
    (i) an amino acid, a derivative of an amino acid, a salt of an amino acid, or a salt of a derivative of an amino acid or a mixture thereof;
    (ii) an antimicrobial component comprising two or more antimicrobial quaternary ammonium compounds or at least one antimicrobial quaternary ammonium compound and chlorhexidine, or a chlorhexidine salt; and (iii) a polar solvent.
    [0016] Amino acids are well-known organic compounds that are essential for life. They are characterized by having an amine functional group (NH2) attached to carbon adjacent to a carboxylic acid (CO2H) functional group, along with a side chain that is specific for the amino acid. An amino acid has the general formula shown below.
    Petition 870190136609, of 12/19/2019, p. 14/48
    5/37
    Laleral chain - Q - Q —Q H
    NHj
    [0017] Since amino acids have both an amine group and a carboxylic acid group, they can act as both a base and an acid. At low pH, the predominant form will have a neutral carboxylic acid group and a positive ammonium ion (net charge +1). At high pH, it will have a negative carboxylate group and a neutral amino group (net charge -1). At an intermediate pH, the amino acid will normally contain both a negative carboxylate group and a positive ammonium group, in order to have zero net charge.
    [0018] Arginine is one of the most common amino acids and is shown below.
    [0019] Some additional examples of common amino acids are glycine, lysine, glutamate, glutamine, aspartate, asparagine, histidine, proline, methionine, cysteine, serine, threonine, isoleucine, phenylalanine, tyrosine, tryptophan, valine and leucine. The structures of these amino acids are well documented.
    [0020] The term "amino acid" includes chains of amino acids, such as peptides and polypeptides. Peptides are formed when individual amino acids are linked together through peptide bonds (amide) formed by the reaction of the amino group of one amino acid with the carboxyl group of another. The shortest peptides are dipeptides that consist of two amino acids joined by a single peptide bond, followed by tripeptides, tetrapeptides, and so on. A polypeptide is a long, continuous, unbranched peptide chain.
    [0021] The term "derived from an amino acid" means a
    Petition 870190136609, of 12/19/2019, p. 15/48 / 37 amino acid in which the alpha-amino and / or carboxyl functional groups are replaced by an alternative organic group, or an amino acid in which the functional groups in the side chain of an amino acid are replaced by an alternative organic group or an amino acid in which the alpha-amino and / or carboxyl functional groups are replaced by an alternative organic group and / or the functional groups in its side chain are also replaced by an alternative organic group. Alternative organic groups include, but are not limited to, alkenyl, phenyl, amide, ester, alcohol and ether groups or combinations thereof. An example of an amino acid derivative is N-lauroyl-L-arginine ethyl ester whose structure is shown below.
    ° 0
    H
    Η 2 ΝγΝ n'h 2
    The term “salt of an amino acid” means the form
    N ^ (CH 2 ) f 0 CH3
    Π
    [0022] cationic or anionic amino acid combined with a counterion, which is an ion of opposite charge. The cationic form of the amino acid is formed by the transfer of a positively charged hydrogen ion from an acid to an amino group on the amino acid. The counterion is derived from the acid from which the hydrogen ion is transferred. The anionic form of the amino acid is formed by the loss of a positively charged hydrogen ion from the carboxylic acid group on the amino acid. In this case, the counterion is derived from the base to which the hydrogen ion is transferred. An example of an amino acid salt is arginine lactate which is commercially available in AH Care L65. AH Care L65 is composed of a lactic acid; mixture of arginine. The structure of arginine lactate is shown below.
    NH h 2 nn
    H h o I II C-IL
    NH 2
    [0023]
    By the term “salt of an amino acid derivative” is meant the
    Petition 870190136609, of 12/19/2019, p. 16/48 / 37 ° W
    N A '(CH 2 ) Í CH3
    Π cr cationic or anionic form of the amino acid derivative, as defined above, combined with a counterion, which is an ion of opposite charge. The cationic form of the amino acid is formed by the transfer of a positively charged hydrogen ion from an acid to an amino group in the amino acid derivative. The counterion is derived from the acid from which the hydrogen ion is transferred. The anionic form of the amino acid derivative is formed by the loss of a positively charged hydrogen ion from the carboxylic acid group in the amino acid derivative. In this case, the counterion is derived from the base to which the hydrogen ion is transferred. An example of a salt of an amino acid derivative is N-lauroyl-L-arginine ethyl ester monohydrochloride which is commercially available from Aminat G whose structure is shown below.
    ^ 0.
    H nh 2
    [0024] Amino acid salts or amino acid derivatives used in the present invention include, without limitation, hydrochloride, tartrate, malonate, succinate, succinamate, malate, glutamate, pyroglutamate and aspartate. In one aspect, the amino acid salt or amino acid derivative is not a phosphonate salt or a phosphorus containing salt, such as monoalkyl phosphate ion, monoalkenyl phosphate ion, monoalkyl phosphonate ion or phosphonate ion of monoalkenyl, such as those having a straight or branched alkyl or alkenyl group having 8 to 20 carbon atoms.
    [0025] Component (i) can comprise a hydrophilic amino acid, or a salt or a derivative of such an amino acid or a salt of such a derivative. Hydrophilic amino acids can have a hydrophilic side chain or can be positively or negatively charged that has a hydrophilic side chain.
    Petition 870190136609, of 12/19/2019, p. 17/48 / 37
    [0026] Component (i) may, for example, comprise a positively charged amino acid, or a salt or a derivative of such an amino acid or a salt of such a derivative.
    [0027] A derivative of an amino acid can be hydrophilic as a result of the modification made to the amino acid. For example, an amino acid can be modified so that it is positively or negatively charged.
    [0028] Hydrophilic amino acids, as defined above, are typically water-soluble.
    [0029] By water-soluble is meant that the amino acid, or a salt or a derivative of such an amino acid or a salt of such a derivative, typically has a solubility in water at 25 ° C of at least about 0.5 g per kg of water. For example, at least about 1 g per kg of water, such as at least about 10 g per kg of water or at least about 50 g per kg of water.
    [0030] Salts and derivatives of amino acids and salts of such derivative suitable for use in the present invention are typically water-soluble.
    [0031] Amino acids that are suitable for use in the present invention can also be classified by their hydropathic index. This index is described, for example, in Kyte, J. and Doolittle, R., 1982, “A simple method for displaying the hydropathic character of a protein”, J mol. Biol. 157: 105 to 132. As the reader versed in the technique will understand, the more positive the value in the Hydropathy Index, the more hydrophobic an amino acid is. Amino acids suitable for use in the present invention include amino acids that have a Hydropathy Index value of 0 (zero) or less, such as -2 or less. Salts and derivatives of such amino acids and salts of such derivative are suitable for use in the present invention. Arginine and its salts and derivatives and salts of such a derivative are suitable for use in the present invention. Arginine has a Hydropathy Index value of -4.5.
    [0032] Alternatively or additionally, the appropriate amino acids for
    Petition 870190136609, of 12/19/2019, p. 18/48 / 37 use in the present invention can be classified by their isoelectric point (pI); which is the pH at which the net charge on the amino acid is zero. At a pH below its isoelectric point, an amino acid will be positively charged. In certain compositions of the invention, it is preferred that the amino acid is positively charged. In that respect, an amino acid that has a pI that is higher than the pH of the composition is used.
    [0033] Amino acids that are suitable for use in the present invention include those with a pI 5 or greater, such as 6 or 6.25 or greater, or 8 or 10 or greater. Salts and derivatives of such amino acids and salts of such derivative are suitable for use in the present invention. Arginine and its salts and derivatives and salts of such a derivative are suitable for use in the present invention. Arginine has a pI of 10.76.
    [0034] Amino acids that are particularly suitable for use in the present invention include those that have a hydropathy index of 0 (zero) or less, such as -2 or less and a pI of 6 or more, 6.25 or more, or 8 or higher or 10 or higher. Salts and derivatives of these amino acids and salts of such derivative are also particularly suitable for use in the present invention.
    [0035] The compositions of the invention comprise chlorhexidine or a chlorhexidine salt. Examples of suitable chlorhexidine salts include acetates, formats, gluconates, hydrochlorides, isoethionates, lactates and succinamates of chlorhexidine. For example, suitable salts include, but are not limited to, chlorhexidine diphosphanylate, chlorhexidine digluconate, chlorhexidine diacetate, chlorhexidine dichloride, chlorhexidine dichloride, chlorhexidine dihydrochloride, chlorhexidine sulfate, dichlorohydrate, chlorhexidine dichloride chlorhexidine thiosulfate, chlorhexidine di-acid phosphate, chlorhexidine difluorophosphate, chlorhexidine diformate, chlorhexidine dipropionate, chlorhexidine diiodobutyrate, chlorhexidine di-n-valerate, malhexidine pro-chloride oxide
    Petition 870190136609, of 12/19/2019, p. 19/48 / 37 chlorhexidine, chlorhexidine succinate, chlorhexidine succinate, chlorhexidine malate, chlorhexidine tartrate, chlorhexidine dimonoglycolate, chlorhexidine monodiglycolate, chlorhexidine dihydrobutyldate, hydroxydexylate. chlorhexidine, chlorhexidine diisothionate, chlorhexidine dibenzoate, chlorhexidine dichlorate, chlorhexidine dimandelate, chlorhexidine diisophthalate, chlorhexidine isoethionate, chlorhexidine di-2-hydroxy-naphthate and embonate.
    [0036] A specific example of a chlorhexidine salt that can be used in the compositions of the invention is chlorhexidine di-gluconate.
    [0037] The quaternary ammonium antimicrobial agent (or agents) used in the present invention is typically soluble in water at ambient temperature and pressure.
    [0038] Suitable antimicrobial quaternary ammonium compounds include the compounds of formula (A) shown below.
    R ^ CH 3
    R CH3 (A) where R 1 and R 2 are each, independently, an unsubstituted and uninterrupted straight chain C8-12 alkyl group. In one respect, the groups R 1 and R 2 contain the same amount of carbon atoms, but this is not essential, and compounds in which R 1 and R 2 contain different amounts of carbon atoms can be used. X - is a halide anion, such as chloride, bromide, fluoride, iodide or sulfonate, saccharin, carbonate or bicarbonate.
    [0039] In one aspect, X - is not a phosphonate salt or a phosphorus containing salt, such as a monoalkyl phosphate ion, a monoalkenyl phosphate ion, a monoalkyl phosphonate ion or a monoalkenyl phosphonate ion , such as those having a straight or branched alkyl or alkenyl group with 8 to 20 carbon atoms.
    [0040] Suitable antimicrobial quaternary ammonium compounds
    Petition 870190136609, of 12/19/2019, p. 20/48 / 37 include benzalkonium compounds that have the formula (B) shown below.
    ch 3 x l + 3
    NC m H 2m + 1
    CH3 (B) where m is 8 to 18, and X - is a halide anion, such as chloride, bromide, fluoride, iodide, sulfonate, saccharin, carbonate or bicarbonate. The compounds of formula (B) are generally called benzalkonium compounds. Benzalkonium chloride is supplied and / or used as a mixture of C8-18 alkyl groups, particularly a mixture of unsubstituted and straight chain alkyl groups n-C8H17 to nC 18 H 37 , mainly nC 12 H 25 (dodecyl) , nC 14 H 29 (tetradecyl) and nC 16 H 33 (hexadecyl). Preferably, m is 8, 10, 12, 14 and / or 16. More preferably, m is 8 to 12, for example, 8, 10 and / or 12, or from 12 to 16, for example, 12, 14 and / or 16.
    [0041] In the compounds of formula (A), each R 1 and R 2 group is independently an unsubstituted, straight-chain C8-12 alkyl group, for example, an alkyl group containing 8, 9, 10, 11 or 12 carbon atoms. R 1 and R 2 can be the same, for example, R 1 and R 2 can both be alkyl groups containing 8, 9, 10, 11 or 12 carbon atoms.
    [0042] Benzalkonium compounds also include derivatives of benzalkonium compounds by which the alkyl group CmH2m + 1 shown below can be replaced by another organic group. Such organic groups include, but are not limited to, alkenyl, phenyl, amide, ester, alcohol and ether groups or combinations thereof.
    [0043] An example of such a derivative of a benzalkonium compound is diisobutylphenoxyethoxyethyl-dimethylbenzyl ammonium chloride, whose name INCI is benzethonium chloride (typically abbreviated to BENZ). The structure of benzethonium chloride is shown below.
    Petition 870190136609, of 12/19/2019, p. 21/48 / 37
    [0044] The anion of each quaternary ammonium compound in the compositions of the invention can be the same or different. For example, the anion of a compound of formula (A) can be the same or different from the anion of a compound of formula (B). In one aspect, the anion for each compound is chloride.
    [0045] In one aspect of the invention, wherein the composition comprises two or more antimicrobial quaternary ammonium compounds, a compound of formula (A) and a compound of formula (B) may be present, or the composition may comprise more than one compound of formula (A) or more than one compound of formula (B).
    [0046] Examples of quaternary ammonium compounds of formula (A) include di-n-decyldimethyl ammonium chloride, octyl decyl dimethyl ammonium chloride and dioctyl dimethyl ammonium chloride.
    [0047] Examples of commercially available compounds of formula (A) include Acticide DDQ 40 from Thor, Bardac 2240 from Lonza, Bardac 2280 from Lonza and Maquat 4480E from Mason Chemical Company, USA.
    [0048] Examples of quaternary ammonium compounds of formula (B) include N, N-benzyldimethyloctylammonium chloride, N, Nbenzyldimethyldecylammonium chloride, N-dodecyl-N-benzyl-N, N-dimethylammonium chloride, N-tetradecyl chloride -N-benzyl-N, N-dimethylammonium, N-hexadecylN chloride, N-dimethyl-N-benzylammonium, N, N-dimethyl N-benzyl-Noctadecylammonium chloride and mixtures thereof.
    [0049] It will be understood that a single CAS number often refers to more than one blend or mixture. A CAS classification for a commercial preparation typically encompasses blends that comprise specified compounds in quantities within defined ranges. At
    Petition 870190136609, of 12/19/2019, p. 22/48 / 37 compositions that have the CAS numbers cited above are just examples of compositions that have a given CAS number that can be used in the present invention.
    [0050] In the compositions of the present invention, the antimicrobial quaternary ammonium compound is typically not polymerized.
    [0051] Examples of commercially available compounds of formula (B) include Acticide BAC 50M from Thor, Barquat MB50 / 80 from Lonza, Benzethonium Chloride Lonzagard USP from Lonza.
    [0052] Typically, the antimicrobial quaternary ammonium compound or the compounds used in the composition of the invention are selected from the group consisting of di-n-decyldimethyl ammonium chloride (DDAC (CAS number 7173-51-5)), chloride benzalkonium chloride (BAC), such as the benzalkonium chloride of formula (B) above, where m is 8. This benzalkonium chloride has CAS number 68424-85-1, and benzethonium chloride (BENZ).
    [0053] The amount of component (i) and antimicrobial component (ii) present in the compositions of the present invention will vary depending on numerous factors, such as the intended use of the composition and the particular compound (or compounds) used.
    [0054] For example, as will be understood by the person skilled in the art, higher concentrations of (i) and / or (ii) may be required in order to provide sterilization compared to providing sanitization or disinfection.
    [0055] The antimicrobial component (ii) can essentially consist of at least one antimicrobial quaternary ammonium compound and chlorhexidine or a chlorhexidine salt.
    [0056] The antimicrobial component (ii) can consist of at least one antimicrobial quaternary ammonium compound and chlorhexidine or a chlorhexidine salt.
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    [0057] Alternatively, the antimicrobial component (ii) can consist essentially of two or more antimicrobial quaternary ammonium compounds without chlorhexidine.
    [0058] The compositions of the invention may contain two or more antimicrobial quaternary ammonium compounds or at least one antimicrobial quaternary ammonium compound and chlorhexidine, or a chlorhexidine salt as the only antimicrobial compounds in the composition. Alternatively, the compositions of the invention may comprise another suitable antimicrobial agent (or agents) (b), such as those described in the EPA Listing (United States Environmental Protection Agency) and Appendix I and Appendix 3 to the EC Biocide Directive .
    [0059] Typically, the compounds included in the antimicrobial component (ii) are those that are suitable for application to the skin. For example, compounds that meet the regulatory approval required for human hygiene, such as those approved by the European Commission, when used in Type 1 products Product as listed in Annex II of the delegated regulation of the European Commission (US) No. 1062/2014 of August 4, 2014 and / or those approved by the FDA (Food and Drug Administration).
    [0060] Suitable antimicrobial agents (b) that can be included in the antimicrobial component (ii) include antimicrobial agents that are not quaternary ammonium compounds. Preferably, this additional antimicrobial agent (or agents) is soluble in water at room temperature and pressure.
    [0061] Examples of suitable additional antimicrobial agents include, but are not limited to, polymeric biguanidines (eg polyhexamethylene biguanidine (PHMB)), lactic acid, silver, silver salts, eg silver chloride, carbonate silver, silver citrate, silver hydrogen citrate, octenidine HCl, amphoteric compounds, iodophores,
    Petition 870190136609, of 12/19/2019, p. 24/48 / 37 phenolic compounds, amine antimicrobial agents and nitrogen-based heterocyclic compounds, phenyl ortho phenyl (OPP) and nitro bromopropanes (eg, bronopol (INN), 2-bromo-2-nitropropane-1,3diol) , naturally derived biocidal compounds (eg honey and honey extracts, such as those comprising methyl glyoxal), flavenoid antimicrobials and essential oils.
    [0062] In one aspect, the compositions of the invention are free of inorganic antimicrobial agents, such as those comprising silver. In that respect, any additional antimicrobial agent is an organic antimicrobial agent.
    [0063] In one aspect, the compositions of the invention do not comprise PHMB or can be free of polymeric biguanides. For example, they do not contain a biguanide other than chlorhexidine.
    [0064] In one aspect of the invention, the antimicrobial composition does not comprise any isothiazalones and / or any nitrobromopropanes, such as bronopol and / or any hypochlorites.
    [0065] In one aspect of the invention, the antimicrobial composition does not contain antimicrobial compounds that are poorly soluble in water, such as phenolic compounds.
    [0066] Typically, when formulated as a ready-to-use composition, the amount of component (i) can be from about 0.0005 to 10% by weight of the composition, for example, from about 0.005 to about 5% in weight of the composition, such as from about 0.01 to about 1% by weight of the composition. Such compositions may contain about 0.5% by weight of the composition or less than component (i), such as from 0.02 to 0.3% by weight of the composition, such as about 0.2% by weight or 0 , 1% by weight.
    [0067] Typically, when formulated as a ready-to-use composition, the total amount of antimicrobial component (ii) and component (b), if present (i.e., the combined amount of ammonium compound
    Petition 870190136609, of 12/19/2019, p. 25/48 / 37 antimicrobial quaternary and chlorhexidine or a salt thereof and any additional antimicrobial component (b)), can be from about 0.001 to about 10% by weight of the composition, for example, from about 0.005 to about 5% by weight of the composition, such as from about 0.01 to about 1% by weight of the composition.
    [0068] When the composition of the invention is formulated for use as a hand sanitizer, the amount of antimicrobial component (ii) can be from about 0.05 to about 0.5% by weight.
    [0069] The antimicrobial component (ii) can comprise equal amounts of quaternary ammonium compound and chlorhexidine, or salt thereof. For example, if the total amount of antimicrobial component is about 0.2% by weight of the composition, the amount of quaternary ammonium compound would be about 0.1% and the amount of chlorhexidine, or salt thereof, would be about 0.1%.
    [0070] Alternatively, the antimicrobial component can comprise different amounts of quaternary ammonium compound and chlorhexidine.
    [0071] Typically, in the compositions of the invention, the ratio between component (i) and antimicrobial component (ii) ranges from 10: 1 to 1:10.
    [0072] The compositions of the invention comprise a polar solvent (iii). Suitable polar solvents include, but are not limited to, water, alcohols, glycol ethers and mixtures thereof.
    [0073] Suitable alcohols include, but are not limited to, straight or branched chain C1 to C5 alcohols, such as methanol, ethanol, n-propanol, iso-propanol, mixtures of propanol, n-butanol, sec-butanol, tert-butanol, iso-butanol, mixtures of butanol isomers, 2-methyl-1-butanol, npentanol, mixtures of pentanol and amyl alcohol isomers (mixture of isomers), and mixtures thereof.
    [0074] Preferred polar solvents for use in the compositions of
    Petition 870190136609, of 12/19/2019, p. 26/48 / 37 inventions include, without limitation, water, ethanol, isopentidiol, monopropylene glycol, hexylene glycol, 3-Methoxy-3-methyl-1-butanol (MMB), npropanol, isopropanol, ethylene glycol ethers, propylene glycol ethers, butyl diglycol (BDG) and mixtures thereof. In one aspect, the composition comprises water or a mixture of water and one or more alcohols selected from the alcohols described above. In such mixtures, water is preferably the main component. The polar solvent can consist essentially of water or consists of water.
    [0075] If the compositions of the invention comprise an alcohol, the alcohol is typically present in an amount less than the amount necessary for the alcohol to provide an antimicrobial effect, but at a level believed to improve the drying of the composition on the skin. For example, compositions of the invention may comprise up to about 30% by weight of alcohol, such as between 20 and 30% by weight of alcohol or less than about 20% by weight of alcohol, such as from about 15 to about 20% by weight of alcohol.
    [0076] It will be understood that the percentage of alcohol may depend on the use of the composition. For example, when used in a scarf, the composition of the invention can comprise up to 20% alcohol.
    [0077] In one aspect, the compositions of the invention are substantially alcohol-free. For example, the compositions can contain 1% or less by weight of alcohol. For example, the compositions can contain less than 1%, or less than 0.5% by weight or 0.1% by weight or less than an alcohol, such as isopropanol. As an example, the compositions of the invention may not comprise isopropanol or may not comprise alcohol.
    In another aspect, the compositions of the invention can comprise an alcohol up to a level of 70% by weight, for example, up to about 50% by weight.
    Petition 870190136609, of 12/19/2019, p. 27/48 / 37
    [0079] The composition may comprise water or a mixture of water and one or more alcohols selected from the alcohols described above. In such mixtures, water is preferably the main component.
    [0080] For example, the polar solvent can consist or essentially consists of water. As another example, the polar solvent can be water and from about 0 to about 20% by weight, such as from about 15 to about 20% by weight of an alcohol, for example, ethanol or isopropanol.
    [0081] The compositions of the invention can be supplied in concentrated form, for dilution before use, or in ready-to-use form. It is preferred that the compositions of the invention are provided in a ready-to-use form and, unless otherwise specified, information on quantities (such as% by weight or ppm) provided in this document refer to ready-to-use compositions.
    [0082] A concentrate is typically supplied so that, when diluted, the concentrate is 5 to 30% by weight, for example, 10 or 20% by weight of the resulting diluted product.
    [0083] Typically, but not essentially, the compositions of the invention have a concentration of amino acid component (i) from about 0.0005% by weight to about 10% by weight, such as from about 0.005% by weight at about 5 wt% or 0.01 wt% to 1.0 wt%, and a concentration of antimicrobial component (ii) from about 0.001 wt% to about 10 wt%, such as about 0.005% by weight to about 5.0% by weight or 0.01% by weight to 1% by weight. Such compositions may contain about 0.5% by weight of the composition or less than component (i), such as from 0.02 to 0.3% by weight of the composition, such as about 0.2% by weight or 0 , 1% by weight.
    [0084] The pH of the compositions and formulations used can vary within wide limits, for example, from about pH 2 to about pH 12, more preferably, from about pH 3 to about pH 10 or about pH 4.5 to 8. The
    Petition 870190136609, of 12/19/2019, p. 28/48 / 37 pH of a formulation used in the invention may be similar to that of known formulations which are intended to be used for the same or a similar purpose. For example, a formulation that is intended to come into contact with the skin, such as personal care or first aid formulations, will typically have a pH that will not irritate the skin, for example, from about pH 3 to about pH 8 , such as from about pH 4.5 to about pH 7.5 or from about pH 5 to about pH 6.
    [0085] When used as a hand sanitizer, the pH of the compositions of the invention is typically about 5 to about 6.
    [0086] It will be understood that the compositions of the invention may comprise other ingredients commonly used in the art. The nature of any other ingredients used will depend on the nature and the intended purpose of the composition. The person of ordinary skill in the art will know which additional ingredients are suitable for use in the compositions for different applications.
    [0087] The compositions of the present invention may comprise additional materials, such as surfactants, complexing agents, buffering agents, thickening agents, skin conditioning compounds, polar solvents and fragrances.
    [0088] The selection of surfactants will depend on the nature and intended purpose of the composition. Surfactants suitable for use in formulations intended for different purposes will be within the knowledge of the individual of ordinary skill in the art. Similarly, the selection of adequate amounts of surfactant will be within the knowledge of the individual of ordinary skill in the art. Suitable surfactants can be selected from non-ionic, cationic or amphoteric surfactants and mixtures thereof.
    [0089] Some compositions of the invention may comprise a nonionic surfactant. Suitable non-ionic surfactants include, however,
    Petition 870190136609, of 12/19/2019, p. 29/48 / 37 without limitation, amide oxides, alkyl polyglycosides, 1 ° and 2 ° linear and branched alcohol ethoxylates, and ethoxylated / propoxylated block polymers (EOPO).
    [0090] In one aspect, the composition is substantially free or free of anionic surfactant. In another aspect, the compositions of the invention do not comprise an amphoteric surfactant.
    [0091] Some compositions of the invention may comprise an amphoteric surfactant. Suitable amphoteric surfactants include, without limitation, C6-C20 alkylaminoacetates or amphodiacetates (such as cocoanfoacetates), C10-C18 alkyldimethyl betaines, C10-C18 alkyl amidopropyl dimethyl betaines. Examples include, but are not limited to, cocoamidopropyl betaine (CAPB) amphoteric coconut surfactant (Surfac B4, CAS number 61789-40-9), betaim cocoimidazoline, oleoamidopropyl betaine and pine oil imidazoline.
    [0092] Some compositions of the invention may comprise a cationic surfactant. Suitable cationic surfactants include, but are not limited to, undecylenamidopropyltrimony methosulfate and cetrimonium chloride
    [0093] Typically, the amount of surfactant present in the compositions of the invention is in an amount of about 0.01 to 20% by weight. The amount of surfactant depends on numerous factors, such as the pH of the composition and the intended use of the composition.
    [0094] The compositions of the invention can comprise complexing agents. The terms sequestering agents or chelates are sometimes used interchangeably with the term complexing agents. For the purpose of describing this invention, the term complexing agents includes both sequestering and chelating agents. Complexing agents can be used to assist in providing a clear composition even when the compositions of the invention are used with hard water. Examples of
    Petition 870190136609, of 12/19/2019, p. 30/48 / 37 Suitable complexing agents include, but are not limited to, EDTA (ethylenediaminetetraacetic acid), Gluconate, GLDA (Glutamic acid diacetic acid) - Trade name Dissolvine GL, EDDS (ethylenediamine-N, N'-dissuccinic acid ), citrates and gluconates or salts of glutaric, adipic and succinic acids and mixtures thereof. If the complexing agent contains a counterion, that counterion is preferably metallic. Suitable metal counterions include, but are not limited to Na, Ca, Fe, K, Zn, Mg and Mn.
    [0095] Preferred complexing agents are GLDA (Dissolvine) and EDTA.
    [0096] Complexing agents are typically present in an amount of about 100 to 10,000 ppm, preferably about 400 to 3,000 ppm, for example, about 500 to 2,000 ppm.
    [0097] Buffering agents can be included to adjust the pH of the composition to the required value and keep it close to that pH value during storage and use.
    [0098] Suitable pH modifiers include, without limitation, acids, such as citric, sulfamic, hydrochloric, phosphoric, nitric, lactic, formic, acetic, glycolic or gluconic acids or other mineral or organic acids or bases, such as hydroxide sodium or potassium, triethanolamines and carbonates and mixtures thereof.
    [0099] Thickening agents can be included to adjust the viscosity of the composition to the value required for that purpose in order to make the composition more stable; facilitate the application of the composition; or for aesthetic benefits. Examples of thickeners include, but are not limited to, stearoxy hydroxypropyl methylcellulose ether, commercially supplied by Daido chemical corporation under the trade name Sangelose 90, and a polyquaternium 37, supplied by Rheo Lab under the trade name Kleasol 200ST.
    Petition 870190136609, of 12/19/2019, p. 31/48 / 37
    [00100] The compositions of the invention may contain skin conditioning compounds. Suitable skin-conditioning compounds include, without limitation, panthenol, tocopheryl acetate, glycerin, polyquaternium compounds, glyceryl PEG-7-cocoate, and silicones and mixtures thereof. Typically, the compositions of the invention do not comprise mucopolysaccharides.
    [00101] The compositions of the invention may, alternatively or additionally, contain salts, such as alkali metal halides or alkaline earth metals, such as NaCl or KCl. In some situations, the use of salts can facilitate the formation of a stable composition.
    [00102] The compositions of the invention may also contain other ingredients that are standard in the art, such as colorants, fragrances, emollients, antioxidants and mixtures thereof.
    [00103] The compositions of the invention can be free of anionic materials. In the sense of anionic materials, counterions that may be present in any of the ingredients used in the invention, such as counterions associated with a quaternary ammonium compound, are not included. The compositions of the invention can, for example, be free of anionic polyelectrolytes, such as anionic mucomimetic polymers, polystyrene and sulfonic acid polymers and high molecular weight cation exchange resins.
    [00104] It has been found that, in use, the compositions of the invention have advantageous antimicrobial effects, and particularly when applied to the skin surface. For example, such compositions have an antimicrobial effect when initially applied to a surface (called “wet extermination”) and they can also have a residual antimicrobial effect in that they control, reduce or prevent the formation of new microbial colonies on the surface (called “dry extermination”), which can otherwise result in the formation of
    Petition 870190136609, of 12/19/2019, p. 32/48 / 37 more persistent biofilms.
    [00105] The compositions of the invention are also resistant to washing with water and rubbing. This means that the compositions of the invention provide a residual antimicrobial effect even when the surface that has been treated is subsequently rubbed and / or washed or rinsed with water.
    [00106] The compositions of the invention are particularly suitable for use as sanitizers for the skin or hands or on other surfaces. Some compositions are suitable for use on other surfaces. Compositions of the invention typically provide a residual antimicrobial effect.
    [00107] Such compositions can be used in a wide variety of formats and applications for the purpose of skin sanitization. For example, the compositions of the invention are particularly suitable for formulation in mousses, gels, creams, lotions, liquids, sprays and wipes for use in sanitizing the body or skin, such as hand sanitizers.
    [00108] When used in a scarf format, the substrates used to prepare the tissues can be produced from any suitable woven or non-woven material. Suitable tissue materials include, but are not limited to, non-woven fibrous sheet materials and those produced from fibers from natural sources, such as wood pulp, and viscose or other cellulose-based materials, silk fibers and fibers of keratin. The materials comprise from 1 to 100% by weight of a cellulosic material. For example, 100% cellulosic materials, such as viscose or wood pulp, can be used. Other preferred materials include blends of blends of cellulosic and non-cellulosic materials, such as blending viscose with synthetic substrates, such as polyester and polypropylene. The mixed materials can comprise from 1 to 99.9% in
    Petition 870190136609, of 12/19/2019, p. 33/48 / 37 weight of a cellulosic material, such as viscose, for example, from 20 to 80% by weight or from 30 to 70% by weight of a cellulosic material, such as viscose.
    [00109] The compositions of the invention can be used in humans and animals for both therapeutic and non-therapeutic purposes. Examples of products for non-therapeutic uses include products for personal care and personal hygiene. Examples of products for therapeutic purposes include first aid and skin care products.
    [00110] The compositions of the invention can also be in the form of a liquid and packaged in suitable dispensers to provide a foam, mousse or spray in use. The compositions of the invention can be used for foot care products, including those for direct use on the feet and those for treating / deodorizing shoes, particularly sports shoes. The compositions of the invention can also be used in other personal care products that are used for direct application to the skin or hair, for example, soap, bath and shower products, hair care products, including anti-dandruff shampoos and shampoos, conditioners hair products, hair styling products such as hair mousses, gels and sprays, skin care products such as shaving products, cosmetics and hair removal products, deodorants and antiperspirants, baby products, including products for cleaning and purifying babies, such as baby baths, soaps, wipes, moisturizers, anti-greasing cream, products for cleaning surfaces that have regular or high contact with children and babies.
    [00111] The compositions of the invention can be used as hygienic cleaning agents in pet products for direct application to the surface of the animal's skin or its leather or coat for the
    Petition 870190136609, of 12/19/2019, p. 34/48 / 37 purpose of eradicating or inhibiting microorganisms that may otherwise have a detrimental effect on the health, welfare or cleanliness of the animal. Such compositions can also be applied to materials, such as surfaces that come into contact with animals and to which microorganisms can be transferred from the animal. The benefit of such applications is again to eradicate or inhibit such microorganisms that can otherwise be transferred to another animal or human being and also to control or eliminate the by-products that such organisms can produce, such as bad odor. Such applications for pets can include, but are not limited to, sprays for removing stain or odor, disinfectant sprays and wipes, external rabbit hutch cleaners, cage cleaners, sprays and antibacterial wipes for cat excrement trays, shampoos and sprinklers for dogs and cleaning wipes for dogs ears.
    [00112] The compositions of the invention can be used for topical First Aid applications to the skin to sanitize abrasions or wounds on the skin surface to prevent or stop the infection, or to prevent minor infections, such as foot prevention / treatment products. athlete, warts, caruncle, mole / acne. Thus, the invention provides products for such uses, such as wound care or first aid products that comprise a composition of the invention.
    [00113] The compositions of the invention can also be used for medical applications, such as sterilization of catheters, dialysis equipment or other medical equipment; inhibit or eradicate viruses, such as norovirus, polio virus or adenovirus; and prevent or eradicate persistent biofilms.
    [00114] The compositions of the invention can also be used on surfaces other than skin. Examples of applications of the invention to surfaces other than skin include, but are not limited to: surface cleaners, such as those intended for use in bathrooms, kitchens, areas
    Petition 870190136609, of 12/19/2019, p. 35/48 / 37 habitable; hard soil cleaners; carpet cleaners; furniture cleaners; glass / mirror cleaners; sanitary care products, including solid toilet cleaners, such as rim devices and those designed to be placed in the cistern; liquid sanitary cleaners, excluding those comprising hypochlorite bleaching agents; dishwashing products, such as washing liquids, and dishwasher preparations, such as solids (in powder or tablet form) and washing liquids;
    [00115] Laundry products, such as solid detergents (in powder or tablet format); liquid detergents; fabric conditioners and “2 in 1” products that include detergent and fabric conditioner; cleaning products intended for external use, such as those for cleaning wood, stones, concrete or plastics, for example, patio cleaners, garden furniture cleaners / treatment, BBQ cleaners, wall and fence cleaners / treatments; sprays for plants, such as those intended to remove insects, such as plant aphids; sprays for food, such as those suitable for use in food preservation.
    [00116] For the avoidance of doubt, in this specification, when the term "which comprises" or "comprises" is used, it means that the composition or formulation or component that is described must contain the listed ingredient (or ingredients), but can optionally contain additional ingredients. When the term “consisting essentially of” or “consisting essentially of” is used, it means that the composition or formulation or component that is described must contain the listed ingredient (or ingredients) and may also contain some (for example , up to 5% by weight, or up to 1% or 0.1% by weight) of other ingredients provided that any additional ingredients do not affect the essential properties of the composition, formulation or component. When the
    Petition 870190136609, of 12/19/2019, p. 36/48 / 37 term “consisting of”, this means that the composition or formulation or component that is described must contain only the listed ingredient (or ingredients). These terms can be applied in a similar way to processes, methods and uses.
    [00117] By "substantially free" is meant that the composition or formulation or component which is described contains less than 3% by weight, preferably less than 1%, more preferably 0.1% or less in weight of the mentioned ingredient. For example, compositions of the invention that are substantially alcohol-free contain less than 3% by weight of alcohol, preferably less than 1% by weight of alcohol, more preferably 0.1% or less of alcohol.
    [00118] By the term "antimicrobial" is meant a compound or composition that exterminates and / or inhibits the development of microbes (microorganisms). The term “microbicide” is used to refer to compounds or compositions that kill microbes. The compositions of the invention are antimicrobial and / or microbicidal.
    [00119] The term "sanitization" or "sanitizer" means the reduction in the total amount of microbes on a surface.
    [00120] The term "sterilization" means the elimination of microbiological organisms to achieve asepsis (a sterile microbial environment).
    [00121] A microorganism or microbe is an organism that is microscopic (too small to be seen by the human eye). Examples of microorganisms include bacteria, fungi, yeasts, molds, mycobacteria, algae spores, archaea and protists. Microorganisms are generally single cell or unicellular organisms. However, as used in this document, the term "microorganisms" also includes viruses.
    [00122] The compositions of the invention can be antibacterial,
    Petition 870190136609, of 12/19/2019, p. 37/48 / 37 antifungal, anti-algae, antispore, antiviral, anti-yeast and / or anti-mold. [00123] The compositions of the invention are particularly suitable for use against bacteria, such as E.coIí.
    [00124] As used herein, the terms antibacterial, antifungal, anti-algae, antiviral, anti-yeast and anti-mold agents are intended to refer to agents that inhibit the development of the respective microorganisms, but do not necessarily exterminate the microorganisms, and to agents that exterminate the respective microorganisms. Thus, for example, the term antibacterial includes agents that inhibit the development of bacteria, but do not necessarily kill bacteria, and bactericidal agents that kill bacteria.
    [00125] Examples of antibacterial agents include mycobactericides and tuberculocides. Preferably, the compositions of the invention comprise at least one agent selected from antibacterial, antifungal, anti-algae, antispore, antiviral, anti-yeast and anti-mold agents and mixtures thereof. More preferably, the compositions of the invention comprise at least one antibacterial, antiviral, antifungal and / or anti-mold agent.
    [00126] The compositions of the invention can be effective against a wide range of organisms, including Gram negative and Gram positive bacteria, fungi, yeasts, viruses and some spore-forming bacteria. [00127] An advantage of the invention is that it is possible to prevent a wide range of microorganisms from adhering and attaching to the surface and therefore forming a biofilm. Large colonies are also substantially prevented from forming. Thus, the colony's ability to develop is substantially reduced or even impeded. The invention is, therefore, general in its control of microorganisms.
    [00128] In one aspect of the invention, the compositions can be used to reduce or control the formation of a biofilm.
    Petition 870190136609, of 12/19/2019, p. 38/48 / 37
    [00129] As described above, the compositions of the invention advantageously provide a residual antimicrobial effect through which the antimicrobial action continues for a significant period after the initial application of the composition.
    [00130] Typically, the compositions of the invention need not contain materials that are highly toxic to mammals. Antimicrobial agents used in antimicrobial compositions are typically well known and widely understood and tested antimicrobial agents. The effectiveness of known antimicrobial agents is amplified in the formulations of the invention. Therefore, antimicrobial agents that have a low toxicity can be used in antimicrobial compositions. In contrast, many "new" antimicrobial agents for known sanitation techniques use "stronger", more toxic and / or poorly tested materials.
    [00131] The antimicrobial compositions of the invention do not contain materials that produce highly persistent residues or rinses and products that contain heavy metals and their salts. Thus, there is a very low risk of long-term danger.
    [00132] The antimicrobial compositions of the invention do not interfere with the biochemical reproductive pathways of the microorganisms they control. The risk of intensified resistance and the development of resistant strains is therefore low.
    [00133] The antimicrobial compositions of the invention can have a double effect in that they not only provide an antimicrobial effect in use, but can also have a preservative effect in the composition. This means that it is not typically necessary to include additional preservatives in the formulations of the invention.
    [00134] The compositions of the invention typically do not provide the surfaces to which a greasy sensation is applied.
    Petition 870190136609, of 12/19/2019, p. 39/48 / 37
    [00135] In accordance with a further aspect of the invention, the use of the composition of the invention to control, reduce or prevent the formation of colonies of microorganisms on a surface on which it is provided is provided.
    [00136] The present invention provides a method for providing a residual antimicrobial benefit to a surface, such as a hard surface or skin, the method of which comprises applying a composition, as defined herein, to that surface or skin. The composition can, for example, be applied to the surface or skin by spraying the composition on the surface or rubbing the composition on the surface or skin. In a method of the invention, it is not necessary for the method to include any steps other than simply applying the composition to the surface. Thus, a method that essentially consists or consists of applying the composition to the surface or skin is provided.
    [00137] In one aspect of the invention, the surface to which the composition of the invention is applied is a body surface, such as the skin.
    [00138] The antimicrobial compositions of the invention can typically degrade when submerged in water, to provide a low toxicity rinse / leachate that has a short residence time in the environment.
    [00139] In accordance with a further aspect of the invention, the use of an antimicrobial composition of the invention is provided to reduce or prevent the formation of colonies of microorganisms on a surface on which it is provided, such as skin.
    [00140] The antimicrobial compositions of the invention are typically produced using a process as described below.
    [00141] A process for preparing an antimicrobial composition as described in this document which comprises:
    (i) combining component (iii) and component (ii) with
    Petition 870190136609, of 12/19/2019, p. 40/48 / 37 agitation; and (ii) add component (i) to components (iii) and (ii).
    [00142] In some respects, the pH of the solution obtained after step (ii) may require adjustment. Therefore, the present invention also describes a process in which (iii) the pH of the solution is adjusted after step (ii).
    [00143] Preferences and options for a given aspect, feature or parameter of the invention should, unless the context indicates otherwise, be considered to have been revealed in combination with any and all preferences and options for all others aspects, features and parameters of the invention.
    [00144] The invention will now be illustrated by the following non-limiting Examples.
    EXAMPLE 1 - PREPARATION OF TEST SAMPLES AND CONTROLS
    [00145] The compositions as described in Table 1 were prepared using the method of Example 1. The commercially available compounds used in the compositions are listed below.
    [00146] Aminat G is a 20% solution of N-lauroyl-L-arginine ethyl ester monohydrochloride in glycerin, supplied by Seppic. Its main component is a salt of a derivative of the amino acid L-arginine.
    [00147] AH Care L65 is an amphoteric hydroxy complex, which contains an amino acid, arginine and lactic acid. The same is provided by BASF. Both Aminat G and AH Care L65 are commercial examples that contain component (i) of the invention.
    [00148] Acticide DDQ 40, supplied by Thor, contains 40% di-ndecyldimethyl ammonium chloride (DDAC). This is an example of component (ii) of the invention, which is of Formula Type A.
    Acticide BAC 50M, supplied by Thor, which contains 50% benzalkonium chloride (BAC), is also an example of component (ii) of the invention, which is
    Petition 870190136609, of 12/19/2019, p. 41/48 / 37 of Formula B Type.
    [00150] Chlorhexidine di-gluconate (CHDG), supplied by Evonik, as a 20% solution is a further example of component (ii) of the invention.
    [00151] Benzethonium chloride USP, supplied by Lonza, is a benzalkonium derivative and contains diisobutylphenoxyethoxyethyldimethylbenzyl ammonium chloride (BENZ) 100% otherwise known as Benzethonium chloride. It is a further example of component (ii) of the invention.
    [00152] The polar solvent (component (iii)) was placed in a suitably sized vessel (typically 1 liter capacity). A small amount of the polar solvent was retained to allow final weight adjustment. The required amount of the biocide (or biocides) (component (ii)) was then added to the vessel, the vessel being agitated for 5 minutes after the addition of each biocide before the next biocide was added. The required amount of the amino acid, derivative or salt (component (i)) was then added and the vessel was stirred for an additional 5 minutes. The pH was checked and adjusted using lactic acid or sodium hydroxide solution, if required. The solution was then made up to 100% by weight by adding the retained polar solvent and stirred for 10 final minutes.
    [00153] The Control Samples were prepared using the same method, but leaving out one or more of the components (i), (ii) or (iii) of the invention.
    [00154] In Table 1, the% by weight of the compositional components (i) of the invention, Aminat G and AH Care L65, refer to the quantity of the commercially available material and the% by weight of the component (ii) of the invention refer to the amount of the active chemical component, namely DDAC-di-n-decyldimethyl ammonium chloride; CHDG-chlorhexidine digluconate; BENZ-Benzethonium Chloride; or BAC-Benzalkonium Chloride.
    Petition 870190136609, of 12/19/2019, p. 42/48 / 37
    TABLE 1
    Composition Compositional component (i) of the invention Compositional component (ii) of the invention Compositional component (iii) of the invention Components % by weight Components % by weight Components % by weight Formulation 1 Aminat G 0.25 DDACCHDG 0.100.10 Water 99.55 Formulation 2 Aminat G 0.25 DDACBAC 0.100.10 Water 99.55 Formulation 3 AH Care L65 0.50 DDACCHDG 0.100.10 Water 99.30 Control 1 - - DDAC 0.20 Water 99.80 Control 2 Aminat G 0.25 - - Water 99.75 Control 3 - - DDACCHDG 0.100.10 Water 99.80 Control 4 - - DDACBAC 0.100.10 Water 99.80 Control 5 AH Care L65 0.5 - - Water 99.50 Control 6 Aminat G 0.25 DDAC 0.20 Water 99.55 Control 7 Aminat G 0.25 BAC 0.20 Water 99.55 Control 8 - - CHDG 0.20 Water 99.80 Control 9 Aminat G 0.25 CHDG 0.20 Water 99.55 Control 10 AH Care L65 0.5 DDAC 0.20 Water 99.30 Control 11 AH Care L65 0.5 CHDG 0.20 Water 99.30 Control 12 - - DDACCHDG 0.100.10 Water 99.80
    EXAMPLE 2 - EVALUATION OF ANTIMICROBIAL EFFECTIVENESS
    RESIDUAL TEST SAMPLES
    [00155] 25 microliters (0.025 ml) of test sample were applied to a 2cm x 2cm section of Vitro-Skin (as provided by IMS, Inc.) in duplicate on a petri dish. The test sample was spread on the vitro-skin® surface with a sterile inoculation loop that ensured that a perimeter of approximately 0.5 cm was not treated at the edge. The test sample was allowed to dry in vitro-skin® * 2 at 20 ° C in an oven with the Petri dish uncapped for one hour. The Petri dish was then removed from the oven and a strip of polypropylene tissue saturated with a tryptone / sterile saline solution placed inside. The lid was closed and then
    Petition 870190136609, of 12/19/2019, p. 43/48 / 37 placed back in the oven for 4 hours at 20 ° C. After that time, the Petri dish was removed from the oven and 10 ul of a suspension of 1-1.5 x 10 Λ 8 cfu / ml of E. coli K12 * i prepared in tryptone / saline solution were added to the surface of the vitro-skin® containing the test sample and spread with a sterile inoculation loop that ensures that the suspension remains within the treated area of the vitroskin. The bacterial suspension was left in contact with vitroskin for 5 minutes. After that time, the vitro-skin® was removed from the petri dish and placed in a test tube that contained 10ml of neutralization solution. It was gently shaken and left for another 5 minutes after which the tube was vortexed for 1 minute to recover the bacteria from the surface of the vitroskin. A 1 ml sample of this suspension was then transferred to a plate with tryptone soy agar and incubated for 48 hours at 37 ° C. After that time, the log reduction in E. coli K12 was calculated by comparison with the water-treated control.
    [00156] * 1 suspension of NB. E. coli K12 prepared from a '2a' culture grown on tryptone soy agar for 24 hours at 37 ° C, as described in the BS EN microbiology standards, for example, EN1.276: 2009.
    [00157] * 2 vitro-skin® is a test substrate that mimics the surface properties of human skin. It is a non-biological synthetic product that has been formulated to have topography, pH, critical surface tension and ionic strength that are similar to those of human skin. It is a well-known substrate and used by those trained in the art to evaluate the benefits of topological applications of skin care products to the skin, which includes the assessment of biocidal effectiveness of active ingredients applied to the skin. Examples of published works by peers with vitro-skin include the document No. US 20090202463 A1 describes a method for evaluating compositions that provide antimicrobial and antiviral immediate and antibacterial efficacy
    Petition 870190136609, of 12/19/2019, p. 44/48 / 37 residual intensified on the skin surface; evaluation of the effectiveness of organic acids in Hand Cleansers for the prevention of rhinovirus infections as described in the Journal of Antimicrobial Agents and Chemotherapy; 48 (7); July 2004; 2595 to 2598; the document No. US 20120141396 A1 describes disinfectant compositions which provide prolonged antimicrobial property to a variety of surfaces, including skin, as assessed using in vitro-skin.
    RESULTS OF EXAMPLE 2
    FORMULATION 1
    [00158] Formulation 1 and Control Samples 1, 2, 3, 6, 8 and 9 were produced for the compositions described in Table 1 using the method described in Example 1. Samples of Formulation 1 and Control Samples were then tested for antimicrobial efficacy using the method described in Example 2. The results of these tests are shown in Table 2 below.
    TABLE 2
    Composition Log R E.coIí K12 Standard error Formulation 1 4.58 0.26 Control 1 2.98 0.06 Control 2 Tntc * - Control 3 2.64 0.04 Control 6 3.54 0.00 Control 8 Tntc * - Control 9 Tntc *
    * Tntc = too numerous to count
    [00159] The results in Table 2 show that the composition of the invention, namely DDAC combined with CHDG and Aminat G, has superior antimicrobial performance compared to Control 3 which has no Aminat G (component (i) of the invention).
    [00160] Formulation 1 also has superior antimicrobial performance compared to Controls 6 and 9 which are DDAC and CHDG used individually with Aminat G. respectively, and Controls 1 and 8 which are
    Petition 870190136609, of 12/19/2019, p. 45/48 / 37
    DDAC and CHDG used individually without Aminat G, respectively. [00161] Control 2 shows that Aminat G has no antimicrobial activity.
    FORMULATION 2
    [00162] Formulation 2 and Control Samples 1, 2, 4, 6 and 7 were produced for the compositions described in Table 1 using the method described in Example 1. Samples of Formulation 2 and Control Samples were then , tested for antimicrobial efficacy using the method described in Example 2. The results of these tests are shown in Table 3 below.
    TABLE 3
    Composition Log R E.coIí K12 Standard error Formulation 2 3.88 0.04 Control 1 2.98 0.06 Control 2 Tntc * - Control 4 1.88 0.02 Control 6 3.54 0.00 Control 7 2.42 0.12
    * Tntc = too numerous to count
    [00163] The results in Table 3 show that the composition of the invention, namely DDAC combined with BAC and Aminat G, has superior antimicrobial performance compared to Control 4 which does not have Aminat G (component (i) of the invention).
    [00164] Formulation 2 also has superior antimicrobial performance compared to Controls 6 and 7 which are DDAC and BAC used individually with Aminat G, respectively, and Control 1 which is DDAC used alone without Aminat G.
    [00165] Control 2 shows that Aminat G has no antimicrobial activity.
    FORMULATION 3
    Formulation 3 and Control Samples 5, 10, 11 and 12 were produced for the compositions described in Table 1 using the method described in
    Petition 870190136609, of 12/19/2019, p. 46/48 / 37
    Example 1. The Formulation 3 samples and the Control Samples were then tested for antimicrobial efficacy using the method described in
    Example 2. The results of these tests are shown in Table 4 below.
    TABLE 4
    Composition Log R E.coIí K12 Standard error Formulation 3 5.22 0.00 Control 12 2.48 0.03 Control 5 Tntc * - Control 10 2.75 0.25 Control 11 Tntc * -
    * Tntc = too numerous to count
    [00166] The results in Table 4 show that the composition of the invention, namely DDAC combined with CHDG and AH Care L65, has superior antimicrobial performance compared to Control 12 which has no AH Care L65 (component (i) of the invention).
    [00167] Formulation 3 also has superior antimicrobial performance compared to Controls 10 and 11 which are DDAC and CHDG used individually with AH Care L65, respectively.
    [00168] Control 5 shows that AH Care L65 has no antimicrobial activity.
    权利要求:
    Claims (33)
    [1]
    1. Antimicrobial composition, characterized by the fact that it comprises:
    (i) an amino acid that is arginine, N-Lauroyl-L-arginine ethyl ester, arginine lactate, N-Lauroyl-L-arginine ethyl ester monohydrochloride or a mixture thereof;
    (ii) an antimicrobial component consisting of at least one antimicrobial quaternary ammonium compound and chlorhexidine or an additional chlorhexidine salt and optionally an additional antimicrobial component (b) selected from polymeric biguanidines, silver, octenidine HCL, amphoteric compounds, iodophores, isothiazolones, nitrobromines , nitrogen-based heterocyclic compounds; alkyl betaines, alkyl amine oxides; anionic surfactants based on amino acids, and amine antimicrobial agents and mixtures thereof; and (iii) a polar solvent:
    wherein the quaternary ammonia compound is at least one compound of formula (A)
    JN. 3
    R ch 3 in which R1 and R2 are independently a straight chain, an uninterrupted C8-12 alkyl group and X - is a halide anion such as chloride, bromide, fluoride, iodide or sulfonate, saccharin, carbonate or bicarbonate and / or hair minus a benzalkonium compound of formula (B)

    [2]
    2/6 bromide, fluoride, iodide or sulfonate, saccharin, carbonate or bicarbonate; and / or benzethonium chloride.
    2. Composition according to claim 1, characterized by the fact that chlorhexidine is chlorhexidine di-gluconate.
    [3]
    Composition according to either of Claims 1 or 2, characterized in that the benzalkonium compound of formula (B) is benzildimethyl-n-tetradecyl-ammonium chloride, benzildimethyl-n-dodecyl-ammonium chloride, chloride benzyl-C12-C16dimethyl-ammonium chloride, diisobutylphenoxyethoxyethyl-dimethylbenzyl ammonium chloride (otherwise known as Benzethonium chloride) or benzylcocoalkyl-dimethyl-ammonium chloride and / or the compound of formula (A) is di-n-dihyldimethyl chloride ammonium, octyl decyl dimethyl ammonium chloride or dioctyl dimethyl ammonium chloride.
    [4]
    Composition according to any one of Claims 1 to 3, characterized in that the antimicrobial quaternary ammonium compound is selected from the group consisting of di-n-decyldimethyl ammonium chloride (DDAC), benzalkonium chloride ( BAC) and benzethonium chloride (BENZ).
    [5]
    Composition according to any one of claims 1 to 4, characterized in that the antimicrobial component (ii) comprises (a) chlorhexidine or a chlorhexidine salt and (b) di-n-decildimethyl ammonium chloride and / or a benzalkonium chloride of formula (B).
    [6]
    Composition according to claim 5, characterized in that it comprises benzalkonium chloride of formula (B) in which m is 8, 10 or 12.
    [7]
    Composition according to any one of claims 1 to 6, characterized in that it comprises a quaternary ammonium compound CAS number 7173-51-5 and / or 68424-85-1.
    Petition 870190015127, of 02/14/2019, p. 11/16
    3/6
    [8]
    Composition according to any one of claims 1 to 7, characterized in that the amount of component (i) is from 0.0005 to 10% by weight of the composition.
    [9]
    Composition according to claim 8, characterized in that the amount of component (i) is from 0.005 to 5% by weight of the composition.
    [10]
    Composition according to claim 9, characterized in that the amount of component (i) is from 0.01 to 1% by weight of the composition.
    [11]
    Composition according to any one of claims 1 to 10, characterized in that the total amount of component (ii) and component (b), if present, is 0.001 to 10% by weight of the composition.
    [12]
    Composition according to claim 11, characterized in that the total amount of component (ii) and component (b), if present, is 0.005 to 5% by weight of the composition.
    [13]
    Composition according to claim 12, characterized in that the total amount of component (ii) and component (b), if present, is 0.01 to 1% by weight of the composition.
    [14]
    Composition according to any one of Claims 1 to 13, characterized by the fact that the pH of the composition is
    4.5 to 8.
    [15]
    Composition according to any one of claims 1 to 14, the composition being characterized by the fact that it also comprises a complexing agent.
    [16]
    16. Composition according to claim 15, characterized by the fact that the complexing agent is selected from EDTA (ethylene diaminetetraacetic acid), Gluconate, GLDA (diacetic glutamic acid), EDDS (ethylenediamine-N, N '
    Petition 870190015127, of 02/14/2019, p. 12/16
    4/6 disuccinic), DPTA (diethylene triamine pentaacetic acid), HEDTA (hydroxyethyl ethylenediamine triacetic acid), MGDA (methyl glycine diacetic acid), PDTA (1,3-propylene diamine tetra-acetic acid) and EDG (ethanoldiglycinic acid) and mixtures thereof.
    [17]
    17. Composition according to any one of claims 1 to 16, characterized in that the polar solvent is selected from water, ethanol, n-propanol, isopropanol, ethylene glycol ethers, propylene glycol ethers, butyl diglycol (BDG) and dipropylene glycol methyl ether (Trade name Dowanol DPM) and mixtures thereof.
    [18]
    18. Composition according to claim 16 or 17, the composition being characterized by the fact that it is alcohol free.
    [19]
    19. Composition according to any one of claims 1 to 18, characterized in that the amino acid or amino acid derivative salt is not a phosphate salt or a salt containing phosphorus.
    [20]
    20. Composition according to any one of claims 1 to 19, characterized in that it is for use in reducing or controlling the formation of microbial colonies on or on a surface.
    [21]
    21. Use of a composition according to any one of claims 1 to 20, characterized by the fact that it is for the manufacture of a pharmaceutical composition for use in reducing or controlling the formation of microbial colonies on the skin or in a wound.
    [22]
    22. Use of a composition according to any one of claims 1 to 20, characterized in that it is for the manufacture of a pharmaceutical composition for use in reducing or controlling the formation of biofilms on the skin or in a wound.
    [23]
    23. Use of a composition according to any one of claims 1 to 20, characterized by the fact that it is for the manufacture of
    Petition 870190015127, of 02/14/2019, p. 13/16
    5/6 a pharmaceutical composition for use to break, prevent or reduce adhesion and / or attachment of microorganisms to the skin or a wound.
    [24]
    24. Personal care or hygiene product, characterized by the fact that it comprises an antimicrobial composition as defined in any one of claims 1 to 20.
    [25]
    25. Hand sanitizers, characterized by the fact that it comprises an antimicrobial composition as defined in any one of claims 1 to 20.
    [26]
    26. Product for wound care, characterized by the fact that it comprises an antimicrobial composition as defined in any one of claims 1 to 20.
    [27]
    27. Antimicrobial handkerchief, characterized by the fact that it comprises a substrate and an antimicrobial composition as defined in any one of claims 1 to 20.
    [28]
    28. Product for domestic animals, characterized in that it comprises an antimicrobial composition as defined in any one of claims 1 to 20.
    [29]
    29. Use of a composition as defined in any one of claims 1 to 20, characterized in that it is to substantially reduce or control the formation of microbial colonies on or on a rigid surface.
    [30]
    30. Use according to claim 29, characterized by the fact that it is to reduce or control the formation of biofilms.
    [31]
    31. Method for reducing or controlling the formation of microbial colonies on or on a rigid surface, the method being characterized by the fact that it comprises applying a composition, as defined in any one of claims 1 to 20, to that surface.
    [32]
    32. Method according to claim 31, characterized by the fact that it is to reduce or control the formation of biofilms.
    [33]
    33. Method for interrupting, preventing or reducing adherence and / or
    Petition 870190015127, of 02/14/2019, p. 14/16
    6/6 attachment of microorganisms to a rigid surface, the method being characterized by the fact that it comprises applying a composition, as defined in any one of claims 1 to 20, to that surface.
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    同族专利:
    公开号 | 公开日
    TW201709819A|2017-03-16|
    GB201505701D0|2015-05-20|
    WO2016156869A3|2016-11-10|
    WO2016156869A2|2016-10-06|
    HK1246088A1|2018-09-07|
    JP6785789B2|2020-11-18|
    GB2533527A|2016-06-22|
    BR112017021002B8|2020-06-16|
    MY178425A|2020-10-13|
    EP3277086A2|2018-02-07|
    TWI626006B|2018-06-11|
    BR112017021002A2|2018-07-03|
    GB2533527B|2018-10-17|
    JP2018511607A|2018-04-26|
    SG11201707755QA|2017-10-30|
    CN107466207A|2017-12-12|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    GB1283892A|1970-06-08|1972-08-02|Irwin Irville Lubowe|Improvements in and relating to medicinal compositions for application to the skin and/or hair|
    FR2258869B2|1974-01-24|1980-01-04|Phytoderm Lab|
    US4224319A|1979-07-31|1980-09-23|Ernest Marcadet|Antiseptic composition for topical application to the skin|
    JP2541299B2|1988-10-13|1996-10-09|ライオン株式会社|Hair treatment composition for animals|
    US5374418A|1992-02-13|1994-12-20|Kao Corporation|Composition for use in oral cavity|
    US6503952B2|1995-11-13|2003-01-07|The Trustees Of Columbia University In The City Of New York|Triple antimicrobial composition|
    JPH11255629A|1998-01-08|1999-09-21|Sunstar Inc|Composition for oral cavity|
    AU5087199A|1998-06-30|2000-01-17|American Medical Research, Inc.|Method of treating topical ailments|
    US6444710B1|1998-10-27|2002-09-03|Alcon Manufacturing, Ltd.|Use of certain fatty acid/amino acid soaps to enhance antimicrobial effectiveness of topically administrable pharmaceutical compositions|
    JP3636611B2|1999-03-19|2005-04-06|日華化学株式会社|Disinfectant composition|
    AT433663T|2001-08-09|2009-07-15|Miret Lab|NEW CONSERVATION SYSTEMS AND THEIR USE IN COSMETIC MEANS|
    US6656919B1|2002-01-11|2003-12-02|Clarence L. Baugh|Method and a product for the rapid decontamination and sterilization of bacterial endospores|
    US7192601B2|2002-01-18|2007-03-20|Walker Edward B|Antimicrobial and sporicidal composition|
    US20070014740A1|2005-07-15|2007-01-18|Colgate-Palmolive Company|Oral compositions having cationic active ingredients|
    MX2010014528A|2008-07-02|2011-03-03|Miret Lab|Use of cationic surfactants as sporicidal agents.|
    JP5469829B2|2008-08-07|2014-04-16|株式会社カナエテクノス|Disinfectant and disinfectant|
    GB0818869D0|2008-10-15|2008-11-19|Byotrol Plc|Anti-microbial composition|
    JP2010126525A|2008-12-01|2010-06-10|Kao Corp|Method for sterilizing microorganism in biofilm|
    US20110275714A1|2009-01-22|2011-11-10|Laboratorios Miret, S. A.|Use Of Cationic Surfactants As Acaricidal Agents|
    JP5735990B2|2010-02-16|2015-06-17|インサイト ヘルス リミテッド|Composition comprising germination inducer and antibacterial agent|
    GB2501341B|2011-12-29|2014-10-22|Byotrol Plc|Anti-microbial composition|
    WO2013032961A1|2011-08-26|2013-03-07|Ohio University|Compositions and methods for treating biofilms|
    GB201118673D0|2011-10-28|2011-12-14|Byotrol Plc|Anti-microbial composition|
    CN104399082A|2014-12-09|2015-03-11|南阳市汇博生物技术有限公司|Nutrient gel for sterilizing and healing wound surface and preparation method of nutrient gel|GB201614087D0|2016-08-17|2016-09-28|Byotrol Plc|Anti-microbial composition|
    WO2018044840A1|2016-08-31|2018-03-08|Cryovac, Inc.|Synergistic cationic surfactants resulting in microbial inhibition on food surfaces and hard surfaces|
    MX2019003774A|2016-10-07|2019-07-01|Unilever Nv|Personal wash disinfectant liquid.|
    KR101913718B1|2016-10-28|2018-11-01|주식회사 에이치피앤씨|Compositions for sterilization and disinfection comprising octenidine and benzalconium chloride|
    KR20190093203A|2016-12-16|2019-08-08|버텔러스 홀딩스 엘엘씨|Quaternary amine formulations and uses thereof|
    EP3654768A1|2017-08-18|2020-05-27|Lonza LLC|Premoistened wipes with virucidal properties against non-enveloped viruses|
    RU2696259C2|2017-10-23|2019-08-01|Общество С Ограниченной Ответственностью "Сан Системз"|Solubilization of the chlorhexidine base, antiseptic and disinfectant compositions|
    WO2019104213A1|2017-11-22|2019-05-31|Board Of Regents, The University Of Texas System|Antibiofilm formulations and use thereof|
    EP3543396B1|2018-03-19|2021-12-15|Livinguard AG|Organic antimicrobial textile|
    CN112105265A|2018-04-09|2020-12-18|罗地亚经营管理公司|Compositions and methods for durable disinfection|
    CA3097111A1|2018-04-19|2019-10-24|Ucar Health Gmbh|Surface, air, textile, paint, plastic, silicone and wood, polyethylene; metal and derivatives antimicrobial properties|
    CN110317684B|2018-06-22|2021-05-25|华东师范大学|Natural environment-friendly nontoxic kitchen oil stain cleaning agent|
    TWI711469B|2018-09-10|2020-12-01|寶齡富錦生技股份有限公司|Antimicrobial composition and preparation method thereof|
    CN109169653B|2018-10-24|2020-09-29|湖北荷普药业股份有限公司|Cation composite disinfectant and application thereof|
    CN111616148A|2020-05-28|2020-09-04|江苏雪豹日化有限公司|High-efficiency disinfectant|
    GB202012191D0|2020-08-05|2020-09-16|Byotrol Plc|Anti-microbial composition|
    CN112294789A|2020-10-15|2021-02-02|郑涛|Compound preparation for preventing and treating respiratory tract infection and application thereof|
    法律状态:
    2020-03-24| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
    2020-05-26| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 01/04/2016, OBSERVADAS AS CONDICOES LEGAIS. |
    2020-06-16| B16C| Correction of notification of the grant [chapter 16.3 patent gazette]|Free format text: REF. RPI 2577 DE 26/05/2020 QUANO AO TITULO. |
    2022-01-25| B21F| Lapse acc. art. 78, item iv - on non-payment of the annual fees in time|Free format text: REFERENTE A 6A ANUIDADE. |
    优先权:
    申请号 | 申请日 | 专利标题
    GB1505701.1|2015-04-02|
    GBGB1505701.1A|GB201505701D0|2015-04-02|2015-04-02|Anti-microbial composition|
    PCT/GB2016/050932|WO2016156869A2|2015-04-02|2016-04-01|Anti-microbial composition|
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