SYNERGISTIC MIXTURES OF AROMATIC ALCOHOLS AND DERIVATIVES THEREOF AND TROPOLONE (DERIVATIVES)

• US 20070054967A1
• Filed: 08/01/2006
• Published: 03/08/2007
• Est. Priority Date: 06/17/2005
• Status: Active Grant

• Current Assignee: Symrise AG
• Original Assignee: Symrise Gmbh & Co. Kg (Symrise AG)
• Inventors: Pillai, Ravikumar, Johncock, William, Schmaus, Gerhard, Roeding, Joachim
• Granted Patent: US 10,022,310 B2
• Time in Patent Office: Days
• US Class Current: 514/717
• CPC Class Codes: A01N 2300/00 Combinations or mixtures of active ingredients covered by classes A01N27/00 - A01N65/48 with other active or formulation relevant ingredients, e.g. specific carrier materials or surfactants, covered by classes A01N25/00 - A01N65/48
• CPC Class Codes: A01N 31/04 Oxygen or sulfur attached to an aliphatic side-chain of a carbocyclic ring system
• CPC Class Codes: A01N 35/06 containing keto or thioketo groups as part of a ring, e.g. cyclohexanone, quinone; Derivatives thereof, e.g. ketals
• CPC Class Codes: A01N 39/00 Biocides, pest repellants or attractants, or plant growth regulators containing aryloxy- or arylthio-aliphatic or cycloaliphatic compounds, containing the group or , e.g. phenoxyethylamine, phenylthio-acetonitrile, phenoxyacetone
• CPC Class Codes: A01N 43/90 having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 2800/52 Stabilizers
• CPC Class Codes: A61K 2800/524 Preservatives
• CPC Class Codes: A61K 2800/59 Mixtures
• CPC Class Codes: A61K 31/045 Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
• CPC Class Codes: A61K 31/047 having two or more hydroxy groups, e.g. sorbitol
• CPC Class Codes: A61K 31/05 Phenols cannabinoids A61K31/658
• CPC Class Codes: A61K 31/075 Ethers or acetals
• CPC Class Codes: A61K 31/122 having the oxygen directly attached to a ring, e.g. quinones, vitamin K1, anthralin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 8/34 Alcohols
• CPC Class Codes: A61K 8/347 Phenols
• CPC Class Codes: A61K 8/35 Ketones, e.g. benzophenone
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61Q 15/00 Anti-perspirants or body deodorants deodorisation of air A61L9/00
• CPC Class Codes: A61Q 17/00 : Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
• CPC Class Codes: A61Q 17/005 : Antimicrobial preparations
• CPC Class Codes: A61Q 17/04 : Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: A61Q 19/005 : Preparations for sensitive skin
• CPC Class Codes: A61Q 19/007 : Preparations for dry skin
• CPC Class Codes: A61Q 19/08 : Anti-ageing preparations
• CPC Class Codes: A61Q 5/02 : Preparations for cleaning the hair
• CPC Class Codes: A61Q 5/12 : Preparations containing hair conditioners
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

An antimicrobial mixture comprising or consisting of:
one or more compounds of the formula (I) their salts or solvates,

• • wherein R¹ and R² in each case independently of one another are chosen from the group consisting of: H, OH, F, Cl, Br and I, and wherein X in each case denotes:
    (CH₂)_m where m=1, 2 or 3 or
    OCH_2n where n=1, 2 or 3 or
    O—CH₂—CH(R³)
  • where R³═CH₃ or CH₂OH or
    (CH₂—O_pCH₂ where p=1 or 2, wherein in the compound(s) of the formula I
  • a primary alcohol function CH₂OH is optionally replaced by a radical which is chosen from the group consisting of CH₂OR⁴, COOH and COOR⁴ and/or
  • a secondary alcohol function CHOH is optionally replaced by the radical CHOR⁴,
  • wherein each R⁴ denotes an aliphatic or aromatic radical, independently of the meaning of further radicals, and
    one, two or more compounds chosen from the group consisting of the tropolones of the formula (II)
  • wherein the substituents R⁵, R⁶, R⁷, R⁸, R⁹ independently of one another have the following meaning: H; linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms; OH;
  • OR¹⁰, wherein R¹⁰ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms; COOH;
  • COOR¹¹, wherein R¹¹ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;
  • NO₂,
  • NH₂, F, Cl, Br, I.

Claims

1-11. -11. (canceled)

12. An antimicrobial mixture comprising:

(a) one or more compounds of the formula (I)

their salts or solvates,

wherein R¹ and R² in each case independently of one another are chosen from the group consisting of;

H, OH, F, Cl, Br and I,

and wherein X in each case denotes;

(CH₂)_m

where m=1, 2 or 3

or

OCH_2n

where n=1, 2 or 3

or

O—

CH₂—

CH(R³)

where R³═

CH₃ or CH₂OH

or

(CH₂—

O_pCH₂

where p=1 or 2,

wherein in the compound(s) of the formula I

a primary alcohol function CH₂OH is optionally replaced by a radical which is chosen from the group consisting of CH₂OR⁴, COOH and COOR⁴

and/or

a secondary alcohol function CHOH is optionally replaced by the radical CHOR⁴,

wherein each R⁴ denotes an aliphatic or aromatic radical, independently of the meaning of further radicals,

and

(b) one, two or more compounds chosen from the group consisting of the tropolones of the formula (II)

wherein the substituents R⁵, R⁶, R⁷, R⁸, R⁹ independently of one another have the following meaning;

H;

linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

OH;

OR¹⁰, wherein R¹⁰ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

COOH;

COOR¹¹, wherein R¹¹ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

NO₂, NH₂,

F, Cl, Br, I.

13. An antimicrobial mixture according to claim 12,

wherein constituent (a) comprises one or more compounds which are chosen from the group consisting of:

benzyl alcohol, 2-phenylethyl alcohol, 2-phenoxyethanol, 3-phenoxypropanol, 1-phenoxy-propan-2-ol, 3-phenoxy-propane-1,2-diol and the derivatives of these alcohols in which a primary alcohol function CH₂OH is replaced by a radical which is chosen from the group consisting of;

CH₂OR⁴, COOH and COOR⁴, where R⁴=aliphatic or aromatic radical and/or a secondary alcohol function CHOH is replaced by the radical CHOR⁴, where R⁴=aliphatic or aromatic radical

benzyloxymethanol and (benzyloxymethoxy)-methanol.

14. An antimicrobial mixture according to claim 12, wherein constituent (a) comprises 2-phenoxyethanol.

15. An antimicrobial mixture according to claim 12, wherein constituent (b) comprises or consists of:

tropolone (formula (II);

R⁵, R⁶, R⁷, R⁸, R⁹═

H),

alpha-thujaplicin (formula (II);

R⁵=iso-propyl, R⁶, R⁷, R⁸, R⁹═

H),

beta-thujaplicin (formula (II);

R⁶=iso-propyl, R⁵, R⁷, R⁸, R⁹═

H)

gamma-thujaplicin (formula (II);

R⁷=iso-propyl, R⁵, R⁶, R⁸, R⁹═

H)

or a mixture of these compounds.

16. An antimicrobial mixture according to claim 12, comprising an amount of constituent (b) in the range of 0.001-10 wt. %, based on the amount of constituent (a).

17. An antimicrobial mixture according to claim 12, comprising one or more additional constituents (c) selected from the group consisting of

(c) 2,4-hexadienoic acid (sorbic acid) and its salts, formaldehyde and paraformaldehyde, 2-hydroxybiphenyl ether and its salts, 2-zinc-sulfidopyridine N-oxide, inorganic sulfites and bisulfites, sodium iodate, chlorobutanolum, 4-ethylmercury-(II)5-amino-1,3-bis(2-hydroxybenzoic acid), its salts and esters, dehydracetic acid, formic acid, 1,6-bis(4-amidino-2-bromophenoxy)-n-hexane and its salts, the sodium salt of ethylmercury-(II)-thiosalicylic acid, phenylmercury and its salts, 10-undecylenic acid and its salts, 5-amino-1,3-bis(2-ethylhexyl)-5-methyl-hexahydropyrimidine, 5-bromo-5-nitro-1,3-dioxane, 2-bromo-2-nitro-1,3-propanediol, N-(4-chlorophenyl)-N′

-(3,4-dichlorophenyl)-urea, 4-chloro-m-cresol, 2,4,4′

-trichloro-2′

-hydroxy-diphenyl ether, 4-chloro-3,5-dimethylphenol, 1,1′

-methylenebis(3-(1-hydroxymethyl-2,4-dioximidazolidin-5-yl)urea), poly-(hexamethylenediguanide) hydrochloride, hexamethylenetetramine, 1-(3-chloroallyl)-3,5,7-triaza-1-azonia-adamantane chloride, 1-(4-chlorophenoxy)-1-(1H-imidazol-1-yl)-3,3-dimethyl-2-butanone, 1,3-bis(hydroxymethyl)-5,5-dimethyl-2,4-imidazolidinedione, 1,2-dibromo-2,4-dicyanobutane, benzethonium chloride, 2,2′

-methylene-bis(6-bromo-4-chlorophenol), bromochlorophene, mixture of 5-chloro-2-methyl-3(2H)-isothiazolinone and 2-methyl-3(2H)-isothiazolinone with magnesium chloride and magnesium nitrate, 2-benzyl-4-chlorophenol, 3-(4-Chlorphenoxy)-1,2-propanediol (Chlorphenesin), 2-chloroacetamide, chlorhexidine, chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, N-alkyl(C₁₂-C₂₂)trimethyl-ammonium bromide and chloride, 4,4-dimethyl-1,3-oxazolidine, N-hydroxymethyl-N-(1,3-di(hydroxymethyl)-2,5-dioxoimidazolidin-4-yl)-N′

-hydroxy-methylurea, 1,6-bis(4-amidino-phenoxy)-n-hexane and its salts, glutaraldehyde, 5-ethyl-1-aza-3,7-dioxabicyclo(3.3.0)octane, 3-(4-chlorophenoxy)-1,2-propanediol, hyamines, alkyl(C₈-C₁₈)-dimethyl-benzyl-ammonium chloride, alkyl-(C₈-C₁₈)-dimethyl-benzylammonium bromide, alkyl-(C₈-C₁₈)-dimethyl-benzyl-ammonium saccharinate, benzyl hemiformal, 3-iodo-2-propynyl butylcarbamate, sodium hydroxymethyl-aminoacetate and sodium hydroxymethyl-aminoacetate, imidazolidinylurea, diazolidinylurea, sodium hydroxymethylglycinate, chlorphenesin, DMDM hydantoin, methylchloroisothiazolinone, methylisothiazolinones, branched or unbranched 1,2-alkanediols having 6 to 12 carbon atoms, triclosan, climbazole, octoxyglycerol (ethylhexyl glycerol), Octopirox (1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone, 2-aminoethanol), chitosan, totarol, farnesol, geranylacetol, glycerol monolaurate, arylalkyl alcohols (preferably 4-methyl-4-phenyl-2-pentanols, 2,2-dimethyl-3-phenylpropanol), essential oils with antimicrobial properties and isolates from essential oils with antimicrobial properties like e.g. thymol, eugenol, perfume oils or single aroma chemicals with antimicrobial activity, and polyglycerol esters, preferably polyglyceryl 3-caprylates.

18. An antimicrobial mixture according to claim 12, wherein the amount of constituent (a) and/or the amount of constituent (b) in each case considered in itself is not antimicrobially active, but the total amount of constituents (a) and (b) is antimicrobially active.

19. A cosmetic or pharmaceutical formulation or foodstuff comprising

an antimicrobial mixture comprising

(a) one or more compounds of the formula (I)

their salts or solvates,

wherein R¹ and R² in each case independently of one another are chosen from the group consisting of:

H, OH, F, Cl, Br and I,

and wherein X in each case denotes;

(CH₂)_m

where m=1, 2 or 3

or

OCH_2n

where n=1, 2 or 3

or

O—

CH₂—

CH(R³)

where R³═

CH₃ or CH₂OH

or

(CH₂—

O_pCH₂

where p=1 or 2,

wherein in the compound(s) of the formula I

a primary alcohol function CH₂OH is optionally replaced by a radical which is chosen from the group consisting of CH₂OR⁴, COOH and COOR⁴

and/or

a secondary alcohol function CHOH is optionally replaced by the radical CHOR⁴,

wherein each R⁴ denotes an aliphatic or aromatic radical, independently of the meaning of further radicals,

and

(b) one, two or more compounds chosen from the group consisting of the tropolones of the formula (II)

wherein the substituents R⁵, R⁶, R⁷, R⁸, R⁹ independently of one another have the following meaning;

H;

linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

OH;

OR¹⁰, wherein R¹⁰ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

COOH;

COOR¹¹, wherein R¹¹ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

NO₂,

NH₂,

F, Cl, Br, I,

and

(c) further conventional constituents,

the total amount of constituents (a) and (b) being in the range of from 0.01 to 10 wt. %, based on the total weight of the formulation or of the foodstuff.

21. A method preserving or antimicrobially treating of a perishable product, with the following step:

bringing of the perishable product into contact with an antimicrobially active amount of a mixture comprising;

(a) one or more compounds of the formula (I)

their salts or solvates,

wherein R¹ and R² in each case independently of one another are chosen from the group consisting of;

H, OH, F, Cl, Br and I,

and wherein X in each case denotes;

(CH₂)_m

where m=1, 2 or 3

or

OCH_2n

where n=1, 2 or 3

or

O—

CH₂—

CH(R³)

where R³═

CH₃ or CH₂OH

or

(CH₂—

O_pCH₂

where p=1 or 2,

wherein in the compound(s) of the formula I

a primary alcohol function CH₂OH is optionally replaced by a radical which is chosen from the group consisting of CH₂OR⁴, COOH and COOR⁴

and/or

a secondary alcohol function CHOH is optionally replaced by the radical CHOR⁴,

wherein each R⁴ denotes an aliphatic or aromatic radical, independently of the meaning of further radicals,

and

(b) one, two or more compounds chosen from the group consisting of the tropolones of the formula (II)

wherein the substituents R⁵, R⁶, R⁷, R⁸, R⁹ independently of one another have the following meaning;

H;

linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

OH;

OR¹⁰, wherein R¹⁰ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

COOH;

COOR¹¹, wherein R¹¹ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

NO₂,

NH₂,

F, Cl, Br, I.

22. A method preserving or antimicrobially treating as in claim 21, wherein said antimicrobial activity is against Aspergillus niger.

23. A method for the cosmetic and/or therapeutic treatment of at least one of

(i) microorganisms which cause body odour,

(ii) microorganisms which cause acne and,

(iii) microorganisms which cause mycoses,

comprising topical application of an antimicrobially active amount of a mixture comprising

(a) one or more compounds of the formula (I)

their salts or solvates,

wherein R¹ and R² in each case independently of one another are chosen from the group consisting of:

H, OH, F, Cl, Br and I,

and wherein X in each case denotes;

(CH₂)_m

where m=1, 2 or 3

or

OCH_2n

where n=1, 2 or 3

or

O—

CH₂—

CH(R³)

where R³═

CH₃ or CH₂OH

or

(CH₂—

O_pCH₂

where p=1 or 2,

wherein in the compound(s) of the formula I

a primary alcohol function CH₂OH is optionally replaced by a radical which is chosen from the group consisting of CH₂OR⁴, COOH and COOR⁴

and/or

a secondary alcohol function CHOH is optionally replaced by the radical CHOR⁴,

wherein each R⁴ denotes an aliphatic or aromatic radical, independently of the meaning of further radicals,

and

(b) one, two or more compounds chosen from the group consisting of the tropolones of the formula (II)

wherein the substituents R⁵, R⁶, R⁷, R⁸, R⁹ independently of one another have the following meaning;

H;

linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

OH;

OR¹⁰, wherein R¹⁰ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

COOH;

COOR¹¹, wherein R¹¹ is a linear or branched, saturated or unsaturated, aliphatic hydrocarbon radical having up to 30 C atoms;

NO₂,

NH₂,

F, Cl, Br, I.