EP1109452A2 - Freeze-resistant topical germicides and methods related thereto - Google Patents

Freeze-resistant topical germicides and methods related thereto

Info

Publication number
EP1109452A2
EP1109452A2 EP99968601A EP99968601A EP1109452A2 EP 1109452 A2 EP1109452 A2 EP 1109452A2 EP 99968601 A EP99968601 A EP 99968601A EP 99968601 A EP99968601 A EP 99968601A EP 1109452 A2 EP1109452 A2 EP 1109452A2
Authority
EP
European Patent Office
Prior art keywords
antifreeze
composition
esterifying
och
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP99968601A
Other languages
German (de)
English (en)
French (fr)
Inventor
Robert D. Kross
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Alcide Corp
Original Assignee
Alcide Corp
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Alcide Corp filed Critical Alcide Corp
Publication of EP1109452A2 publication Critical patent/EP1109452A2/en
Withdrawn legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/14Ethers
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/10Aromatic or araliphatic carboxylic acids, or thio analogues thereof; Derivatives thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N1/00Preservation of bodies of humans or animals, or parts thereof
    • A01N1/02Preservation of living parts
    • A01N1/0205Chemical aspects
    • A01N1/021Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
    • A01N1/0221Freeze-process protecting agents, i.e. substances protecting cells from effects of the physical process, e.g. cryoprotectants, osmolarity regulators like oncotic agents
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/02Saturated carboxylic acids or thio analogues thereof; Derivatives thereof
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a singly bound oxygen or sulfur atom attached to the same carbon skeleton, this oxygen or sulfur atom not being a member of a carboxylic group or of a thio analogue, or of a derivative thereof, e.g. hydroxy-carboxylic acids
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/06Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions

Definitions

  • the present invention is generally directed to freeze-resistant topical germicides for application to skin, particularly the teat of a dairy cow, wherein the germicide is a one-part disinfecting composition containing an organic acid germicide and an non-esterifying antifreeze, or a two-part system comprising a first part and a second part adapted to be mixed to yield a disinfecting composition.
  • the germicide is a one-part disinfecting composition containing an organic acid germicide and an non-esterifying antifreeze, or a two-part system comprising a first part and a second part adapted to be mixed to yield a disinfecting composition.
  • dairymen Since bacterial transfer and proliferation tend to be lower in colder environments, dairymen must balance the potential problems associated with freezing and chapping with the potential for elevated somatic cell counts and clinical mastitis, often choosing to forgo the use of post-milking dips in freezing weather conditions. Other dairymen elect to switch to dips with higher levels of skin softeners and emollients as the temperatures drop, while still others elect dry powder dips, which are basically moisture absorbers with little antimicrobial effectiveness. In an attempt to avoid the above problems, freeze-resistant teat dips have been proposed. For example, a teat-dip composition which freezes below -20°C is disclosed in Japanese Patent No. 8175989.
  • the base composition of the dip as provided in one example of that document, comprises about 30% each of propylene glycol and lactic acid, and 7% sorbitan.
  • a freeze-resistant teat dip containing chlorhexidine disinfectant, and at least 80 wt% of a volatile alcohol, is disclosed in U.S. Patent No. 4,434,181.
  • a non-freezing teat dip which contains, as its base, over 60 wt% of propylene glycol.
  • the active germicide in the product is a combination of C8 and CIO alkanoic acids.
  • the shelf-life of this product is limited, however, due to tendency of the acid to react with the glycol to form esters, which continuously reduces the amount of available acid in the formulation and thus the product's effectiveness. For example, periodic analysis of such a teat dip indicates a loss of 20% of the acid in only a six-month period at ambient conditions, and over a 10% loss of the acid in just one-month at 100°F.
  • a similar problem is encountered if one were to introduce glycol-types of antifreeze into other acid-containing germicidal teat dips.
  • the present invention is directed to freeze-resistant topical germicides for application to, for example, the teat of a dairy cow.
  • Such compositions resist freezing in ambient winter conditions, and do not react with organic acidic germicides and/or buffering agents. Further, the compositions of this invention maintain compatibility between the freeze-resistant and antimicrobial agents.
  • the topical germicides of this invention may generally be classified as one-part or two-part formulations.
  • the one-part formulation comprises an organic acid germicide and an non-esterifying antifreeze, while the two-part formulation (hereinafter referred to as a "system") comprises a first part and a second part adapted to be mixed to yield the topical germicide.
  • the first part comprises a metal chlorite and a chlorite-stable antifreeze
  • the second part comprises (a) an organic acid germicide and a non-esterifying antifreeze, or (b) an inorganic acid and either an alcohol or a non-esterifying antifreeze.
  • a one-part freeze- resistant aqueous disinfecting composition containing an organic acid germicide and an non-esterifying antifreeze, wherein the non-esterifying antifreeze contains from 4 to 16 carbon atoms and has no primary carbon atom bearing a hydroxyl group.
  • Non-esterifying antifreezes my be an ether having at least one ether linkage between two carbon atoms, an ether-alcohol having at least one ether linkage between two carbon atoms and with at least one secondary carbon atom bearing a hydroxyl group, or an ester having at least one ester linkage between two carbon atoms.
  • the non-esterifying antifreeze has the structure R'-O-CH 2 -CH(OR 2 )-R 3 , wherein R 1 is C,. 8 alkyl, and R 2 and R 3 are the same or different and independently selected from hydrogen or C,. g alkyl, and each secondary carbon atom of the C,. 8 alkyl moiety is optionally substituted with a hydroxyl group.
  • Representative antifreezes include those compounds wherein R 1 is C,. 8 alkyl moiety, R 2 is hydrogen, and R 3 is C,. 8 alkyl moiety; wherein R 1 is C, .8 alkyl moiety, R 2 is hydrogen and R 3 is methyl; and wherein R 1 , R 2 and R 3 are C, .g alkyl.
  • the non-esterifying antifreeze has the structure R 4 -CH(OR 5 )-CH 2 -O-CH 2 -CH(OR 2 )-R 3 , wherein R 2 , R 3 , R 4 and R 5 are the same or different and independently selected from hydrogen and C,. 8 alkyl, and each secondary carbon atom of the C,. 8 alkyl moiety is optionally substituted with a hydroxyl group.
  • Representative antifreezes include those compounds wherein R 4 is C,. 8 alkyl and R 5 is hydrogen; and wherein R 4 is C,. 8 alkyl and R 5 is C,. 8 alkyl.
  • Non-esterifying antifreezes also include compounds of the above structures wherein at least one oxygen atom is bound to -CO(C j . 8 alkyl) to form an ester.
  • Typical non-esterifying antifreezes of this invention include propylene glycol monomethyl ether having the structure CH 3 OCH 2 CH(OH)CH 3 , propylene glycol monoethyl ether having the structure CH 3 CH 2 OCH 2 CH(OH)CH 3 , propylene glycol monopropyl ether having the structure CH 3 CH 2 CH 2 OCH 2 CH(OH)CH 3 , propylene glycol monoisopropyl ether having the structure CH 3 CH(CH 3 )OCH 2 CH(OH)CH 3 , dipropylene glycol having the structure CH 3 CH(OH)CH 2 OCH 2 CH(OH)CH 3 , dipropylene glycol methyl ether having the structure
  • the non-esterifying antifreeze may be present at a concentration ranging from about 10% to about 75% by weight of the composition, and typically from 15% to 50% by weight of the composition.
  • the organic acid germicide may be an alpha-hydroxy carboxylic acid having a pKa between about 2.8 and about 4.2, such as glycolic acid, lactic acid, malic acid, mandelic acid, citric acid, tartaric acid, and mixtures thereof.
  • Other organic acid germicides include formic acid, acetic acid, propionic acid, benzoic acid, caprylic acid, capric acid, hydroxybenzoic acid, and mixtures thereof.
  • the organic acid germicide is present at a concentration between about 0.25% and about 7.5% by weight of the disinfecting composition, and typically from 2% and 5% by weight of the disinfecting composition.
  • the disinfecting composition may be formulated as solution, cream or gel, and may include one or more optional components such as a textural modifier, a surfactant, an odorant, a colorant, and mixtures thereof.
  • a two-part freeze-resistant disinfecting system comprising a first part and a second part adapted to be mixed to yield an aqueous disinfecting composition.
  • the first part prior to mixing, comprises a metal chlorite and a chlorite-stable antifreeze.
  • the second part prior to mixing, comprises (a) an organic acid germicide and a non-esterifying antifreeze, or (b) an inorganic acid and either an alcohol or a non-esterifying antifreeze.
  • the chlorite- stable and non-esterifying antifreezes contain from 4 to 16 carbon atoms and have no primary carbon atom bearing a hydroxyl group.
  • the metal chlorite of the first part is an alkali or alkaline earth chlorite, such as sodium chlorite or potassium chlorite, and is typically sodium chlorite.
  • the metal chlorite is present in the first part at a concentration such that, when combined with the second part, it is present within the disinfecting composition at a concentration ranging from about 0.005% to about 1% by weight, generally from 0.05% to 0.5% by weight, and typically from 0.1 % to 0.4% by weight.
  • the chlorite-stable antifreeze is as disclosed above with regard to the non-esterifying antifreeze of the freeze-resistant aqueous disinfecting composition.
  • the chlorite-stable antifreeze is present within the first part at a concentration ranging from about 10%» to about 75% by weight, and typically from 15% to 50% by weight of the first part.
  • the second part comprises an organic acid and a non-esterifying antifreeze.
  • the organic acid and the non-esterifying antifreeze of the second part is as disclosed above with regard to the organic acid and the non-esterifying acid of the freeze-resistant aqueous disinfecting composition.
  • the one-part disinfecting composition may be employed as the second part of the two-part system.
  • the second part comprises an inorganic acid and either an alcohol or a non-esterifying antifreeze.
  • Representative inorganic acids include phosphoric acid, monosodium acid phosphate, sulfuric acid, hydrochloric acid, or sodium bisulfate.
  • the inorganic acid is present in the second part at a concentration such that, when combined with the first part and before reacting therewith, it is present within the disinfecting composition at an initial concentration ranging from 0.001% to 2% by weight, and typically from 0.01% to 1.0% by weight.
  • Representative alcohols include polyols, such as glycerine, sorbitol and propylene glycol, while the non-esterifying antifreeze is as disclosed above with regard to the non-esterifying antifreeze of the freeze-resistant aqueous disinfecting composition.
  • the alcohol or the non-esterifying antifreeze is present within the second part at a concentration ranging from about 10% to about 75% by weight, and typically from 15% to 50%) by weight of the second part.
  • the first and second parts of the two-part freeze resistant system of this invention may be independently formulated as solutions, creams or gels, and may further include one or more optional components such as a textural modifier, a surfactant, an odorant, a colorant, and mixtures thereof.
  • methods are disclosed for disinfecting a substrate by contacting the substrate with an effective amount of the one-part freeze- resistant aqueous disinfecting composition of this invention, or the disinfectant composition resulting from the combination of the first and second parts of the two-part freeze-resistant disinfecting system of this invention.
  • Suitable substrates in this regard include skin and, more specifically, the teat of a dairy cow.
  • Freeze resistance has traditionally been imparted to aqueous systems, such as radiator coolants, by incorporation therein of such water-soluble alcohols as methanol (a mono-hydroxy compound) or glycols (which contain two alcoholic functions) such as ethylene glycol.
  • methanol a mono-hydroxy compound
  • glycols glycols which contain two alcoholic functions
  • ethylene glycol ethylene glycol.
  • Molecules which contain a greater number of hydroxyl groups referred to as "polyols”
  • polyols such as glycerin and sugars
  • a freeze-resistant teat dip formulation particularly one which incorporates organic acids as either active ingredients or buffers
  • the above alcohols are not suitable. This is due to esterification of the hydroxyl moiety by reaction with the carboxylic acid of the organic acid.
  • a material such as propylene glycol to reduce the freezing temperature of a teat dip, in which organic acids are either the germicide or the source of buffering, is counterindicated by the tendency for the acid to esterify and lose germicidal functionality.
  • the lower levels of acid which result give rise to higher pH formulations, so that the remaining acid will tend to exist to a greater degree in the non- functioning anionic form.
  • esterification of secondary hydroxyl groups such as the hydroxyl at the 2-position of propylene glycol
  • esterification of primary alcohols such as the hydroxyl at the 1 -position of propylene-glycol
  • a non-esterifying antifreeze is employed in combination with one or more organic acids.
  • Such non-esterifying antifreeze agents generally contain from 4 to 16 carbon atoms, and contain one or more ether, secondary alcohol and/or ester moieties.
  • Such non-esterifying antifreezes do not, however, contain any primary carbon bearing a hydoxyl group.
  • a freeze-resistant aqueous disinfecting composition containing an organic acid germicide and an non-esterifying antifreeze, wherein the non-esterifying antifreeze contains from 4 to 16 carbon atoms and has no primary carbon atom bearing a hydroxyl group.
  • Suitable non-esterifying antifreezes may be generally characterized as an ether having at least one ether linkage between two carbon atoms, an ether-alcohol having at least one ether linkage between two carbon atoms and with at least one secondary carbon atom bearing a hydroxyl group, or an ester having at least one ester linkage between two carbon atoms.
  • Representative non-esterifying antifreezes have the structure R'-O-CH 2 -
  • R 1 is C,. 8 alkyl
  • R 2 and R 3 are the same or different and independently selected from hydrogen or C,. 8 alkyl, and each secondary carbon atom of the C,. 8 alkyl moiety is optionally substituted with a hydroxyl group.
  • Suitable compounds are those wherein R 1 is C,. 8 alkyl moiety, R 2 is hydrogen and R 3 is C,. 8 alkyl moiety; wherein R 1 is C, .8 alkyl moiety, R 2 is hydrogen and R 3 is methyl; and wherein R 1 , R 2 and R 3 are C,. 8 alkyl.
  • representative non-esterifying antifreezes have the structure R 4 -CH(OR 5 )-CH 2 -O-CH 2 -CH(OR 2 )-R 3 , wherein R 2 , R 3 , R 4 and R 5 are the same or different and independently selected from hydrogen and C,. 8 alkyl, and each secondary carbon atom of the C,. 8 alkyl moiety is optionally substituted with a hydroxyl group.
  • Suitable compounds are those wherein R 4 is C,. 8 alkyl and R 5 is hydrogen; and wherein R 4 is C,. 8 alkyl and R 5 is C,. 8 alkyl.
  • Non-esterifying antifreezes also include compounds of the above structures wherein at least one oxygen atom is bound to -CO(C,. 8 alkyl) to form an ester.
  • More specific representative non-esterifying antifreezes of this invention include (but are not limited to) propylene glycol monomethyl ether (CH 3 - OCH 2 CH(OH)CH 3 ) propylene glycol monoethyl ether (CH 3 CH 2 -OCH 2 CH(OH)CH 3 ), propylene glycol monopropyl ether (CH 3 CH 2 CH 2 -OCH 2 CH(OH)CH 3 ), propylene glycol monoisopropyl ether (CH 3 CH(CH 3 )-OCH 2 CH(OH)CH 3 ), dipropylene glycol (CH 3 CH(OH)CH 2 OCH 2 CH(OH)CH 3 ), dipropylene glycol methyl ether (CH 3 CH(OCH 3 )CH 2 OCH 2 CH(OH)CH 3 ), dipropylene glycol ethyl ether (CH 3 CH(OCH 2 CH 3 )CH 2 OCH 2 CH(OH)CH 3 ), and dipropylene glycol acetate (CH 3 CH
  • Preferred non-esterifying antifreezes are those that are soluble in water at ambient winter temperatures to at least 1 part by weight of compound per 4 parts of water. Their concentration should be from about 10% to about 75% by weight, and typically from 15% to 50%) by weight of the disinfecting composition.
  • the freezing point of the disinfecting composition should be at or below 14°F (-10°C), generally below about 7°F (-14°C), and typically below about 0°F (-18°C).
  • the organic acid germicide may be an alpha-hydroxy carboxylic acid having a pKa between about 2.8 and about 4.2, such as glycolic acid, lactic acid, malic acid, mandelic acid, citric acid, tartaric acid, and mixtures thereof.
  • Other organic acid germicides include formic acid, acetic acid, propionic acid, benzoic acid, caprylic acid, capric acid, hydroxybenzoic acid, and mixtures thereof.
  • the organic acid germicide is present at a concentration between about 0.25% and about 7.5% by weight of the disinfecting composition, and typically from 2% and 5% by weight of the disinfecting composition.
  • the pH of the mixed disinfecting composition should lie in the range of about 2 to about 5, and typically from about 2.4 to about 4.5.
  • organic acids such as citric
  • their level of use is generally in the range of about 0.1 % to about 1.0%, where the amount utilized depends to a significant degree on the chemical characteristics of the specific formulation.
  • a two-part freeze-resistant disinfecting system comprising a first part and a second part adapted to be mixed to yield an aqueous disinfecting composition.
  • the first part prior to mixing, comprises a metal chlorite and a chlorite-stable antifreeze.
  • the second part prior to mixing, comprises (a) an organic acid germicide and a non-esterifying antifreeze, or (b) an inorganic acid and either an alcohol or a non-esterifying antifreeze.
  • the chlorite- stable and non-esterifying antifreezes contain from 4 to 16 carbon atoms and have no primary carbon atom bearing a hydroxyl group.
  • the metal chlorite of the first part is an alkali or alkaline earth chlorite, such as sodium chlorite or potassium chlorite, and is typically sodium chlorite.
  • the metal chlorite is present in the first part at a concentration such that, when combined with the second part, it is present within the disinfecting composition at a concentration ranging from about 0.005% to about 1% by weight, generally from 0.05% to 0.5% by weight, and typically from 0.1% to 0.4% by weight of the disinfecting composition.
  • the chlorite-stable and non-esterifying antifreezes of the first and second parts, respectively, may be the same or different. Such antifreezes contain from 4 to 16 carbon atoms and have no primary carbon atom bearing a hydroxyl group. In the case of the chlorite-stable antifreeze, a primary alcohol will oxidize upon contact with chlorite, and is thus to be avoided.
  • the chlorite-stable and non-esterifying antifreezes may be an ether having at least one ether linkage between two carbon atoms, an ether- alcohol having at least one ether linkage between two carbon atoms and with at least one secondary carbon atom bearing a hydroxyl group, or an ester having at least one ester linkage between two carbon atoms.
  • Representative chlorite-stable and non-esterifying antifreezes have the structure R 1 -O-CH 2 -CH(OR 2 )-R 3 , wherein R 1 is C,. 8 alkyl, and R 2 and R 3 are the same or different and independently selected from hydrogen or C,. 8 alkyl, and each secondary carbon atom of the C,. 8 alkyl moiety is optionally substituted with a hydroxyl group.
  • Suitable compounds are those wherein R 1 is C,. 8 alkyl moiety, R 2 is hydrogen and R 3 is C, .8 alkyl moiety; wherein R 1 is C,. 8 alkyl moiety, R 2 is hydrogen and R 3 is methyl; and wherein R 1 , R 2 and R 3 are C,.
  • representative chlorite- stable and non-esterifying antifreezes have the structure R 4 -CH(OR 5 )-CH 2 -O-CH 2 - CH(OR 2 )-R 3 , wherein R 2 , R 3 , R 4 and R 5 are the same or different and independently selected from hydrogen and C,. g alkyl, and each secondary carbon atom of the C,. 8 alkyl moiety is optionally substituted with a hydroxyl group.
  • Suitable compounds are those wherein R 4 is C ] . 8 alkyl and R 5 is hydrogen; and wherein R 4 is C,. 8 alkyl and R 5 is C,. 8 alkyl.
  • Chlorite-stable and non-esterifying antifreezes also include compounds of the above structures wherein at least one oxygen atom is bound to -CO(C,. 8 alkyl) to form an ester.
  • More specific representative chlorite-stable and non-esterifying antifreezes of this invention include (but are not limited to) propylene glycol monomethyl ether (CH 3 -OCH 2 CH(OH)CH 3 ) propylene glycol monoethyl ether (CH 3 CH 2 -OCH 2 CH(OH)CH 3 ), propylene glycol monopropyl ether (CH 3 CH 2 CH 2 - OCH 2 CH(OH)CH 3 ), propylene glycol monoisopropyl ether (CH 3 CH(CH 3 )- OCH 2 CH(OH)CH 3 ), dipropylene glycol (CH 3 CH(OH)CH 2 OCH 2 CH(OH)CH 3 ), dipropylene glycol methyl ether (CH 3 CH(OCH 3 )CH 2 OCH 2 CH(OH)CH 3 ), dipropylene glycol ethyl ether (CH 3 CH(OCH 2 CH 3 )CH 2 OCH 2 CH(OH)CH 3 ), and dipropylene glycol
  • Preferred chlorite-stable and non-esterifying antifreezes are those that are soluble in water at ambient winter temperatures to at least 1 part by weight of compound per 4 parts of water. Their concentration should be from about 10% to about 75% by weight, and typically from 15% to 50% by weight of the disinfecting composition.
  • the freezing point of the disinfecting composition should be at or below 14°F (-10°C), generally below about 7°F (-14°C), and typically below about 0°F (- 18°C).
  • the second part comprises an organic acid and a non-esterifying antifreeze.
  • the second part may be the freeze-resistant aqueous disinfecting composition as disclosed above, containing an organic acid and a non-esterifying antifreeze.
  • the organic acid germicide may be an alpha-hydroxy carboxylic acid having a pKa between about 2.8 and about 4.2, such as glycolic acid, lactic acid, malic acid, mandelic acid, citric acid, tartaric acid, and mixtures thereof.
  • Other organic acid germicides include formic acid, acetic acid, propionic acid, benzoic acid, caprylic acid, capric acid, hydroxybenzoic acid, and mixtures thereof.
  • the organic acid germicide is present in the second part such that, following mixture with the first part, it has a concentration between about 0.25% and about 7.5%) by weight of the disinfecting composition, and typically from 2% and 5% by weight of the disinfecting composition.
  • the non- esterifying antifreeze of the second part in this embodiment is as disclosed above, and is present at a concentration such that, following mixture with the first part, it is present at a concentration from about 10% to about 75% by weight, and typically from 15% to 50%) of the disinfecting composition.
  • the second part comprises an inorganic acid in combination with either an alcohol or a non-esterifying antifreeze.
  • the non-esterifying antifreeze of this embodiment is as disclosed above, while representative alcohols include polyols, such as glycerine, sorbitol and propylene glycol.
  • Representative inorganic acids include phosphoric acid, monosodium acid phosphate, sulfuric acid, hydrochloric acid, sodium bisulfate, and mixtures thereof.
  • the inorganic acid is present in the second part at a concentration such that, when combined with the first part and before reacting therewith, it is present within the disinfecting composition at an initial concentration ranging from 0.001% to 2% by weight, and typically from 0.01% to 1.0% by weight.
  • the alcohol or non-esterifying antifreeze is present within the second part at a concentration such that, when combined with the first part, it is present in the disinfecting composition at a concentration from about 10% to about 75% by weight of the disinfecting composition, and typically from 15% to 50% by weight of the disinfecting composition.
  • ingredients may be included in the one-part freeze resistant aqueous disinfecting composition, as well as the first part, second part, or both first and second parts of the two-part system.
  • Such ingredients include (but are not limited to) wetting agents, textural modifiers, film-forming polymers, colorants and mixtures thereof.
  • the wetting agents facilitate contact of the disinfecting composition with the skin, and can be selected from those materials recognized to provide this effect, in both identity and amount.
  • Textural modifiers are those materials which primarily affect the body of the mixed disinfecting composition in terms of retention, flow and lubricity.
  • thickening agents such as alkyl celluloses, alkoxy celluloses, xanthan gum, guar gum, and polyacrylamide derivatives, of which the polymer of 2- acrylamido-2-methylpropane sulfonic acid is a preferred example.
  • Other textural modifiers include lanolin derivatives, acyl lactylates, polyethylene glycol, glyceryl esters, and mixtures thereof.
  • Film-forming polymers include the above-referenced polyacrylamides, as well as the class of poly(vinyl alcohols/vinyl acetates) and polyvinyl pyrollidone. Colorants are generally selected from the group found acceptable for use in skin-contacting formulations, and are known to those skilled in the art.
  • a method for disinfecting a substrate comprises contacting the substrate with an effective amount of the one-part freeze-resistant disinfecting composition of this invention, or contacting the substrate with an effective amount of the disinfecting composition formed by mixing the two-part disinfecting system of this invention.
  • Suitable substrates include the skin or tissue of a warm-blooded animal and, in a preferred embodiment, the teat of a dairy cow.
  • this invention is directed to a method for making a disinfecting composition
  • a method for making a disinfecting composition comprising mixing the first part and the second part of the two-part disinfecting system, as well as mixing the respective compounds to form the first and second parts of the two-part system, and to form the one-part disinfectant composition.
  • both the first and second parts are aqueous solutions, creams or gels.
  • at least one of the first or second parts is in a concentrated form, and the concentrated form (either solid or liquid) is mixed with the other part and then diluted with water, or diluted with water and then mixed with the other part.
  • This Example illustrates the preparation of a freeze-resistant germicidal formulation that remains free-flowing to below about 10°F (-12°C). It suppresses the chapping and cracking of skin to which it is applied, which might otherwise occur in sub-freezing temperatures.
  • the gold-colored formulation which has a citrus odor, can kill approximately 10 4 logarithms of the microbial pathogen Staphylococcus aureus deposited onto a simulated cow teat after 1 minute of contact.
  • the residual germicide on the teat surface can also destroy at least 10 2 logarithms of the environmental pathogen Streptococcus uberis 12 hours after deposition onto the teat following a 30 minute contact.
  • Example 1 The above Example 1 is repeated, using 35 gms of propylene glycol monomethyl ether, 0.1 gms of methyl salicylate in place of the citral, and 0.00065 gms of methylene blue in place of the yellow and red colorants.
  • the blue formulation thus prepared has a wintergreen odor, remains liquid to below about 0°F (-18°C), and has a viscosity of 305 cps.
  • This example illustrates the use of the present invention in a two part chlorous acid-forming germicidal barrier teat dip, in which both parts, as well as the mixed formulation, remain fluid to a temperature below 0°F.
  • a first thickened liquid is prepared by mixing the following ingredients: Coamedia brand poly (sulfonic acid), 16% solid 16.00% Sodium hydroxide, IN 16.00%
  • a second thickened liquid is prepared by mixing the following ingredients:
  • Poloxamer 188 0.40%
  • the two thickened liquids are blended, preferably within two hours before application.
  • the resulting liquid remains fluid on the cow's teats throughout the intermilking period, preventing chapping and cracking, while providing continuous antimicrobial activity to suppress mastitis formation.
  • EXAMPLE 4 This example illustrates the use of the present invention in a freeze- resistant topical germicide which contains a film-forming agent and which remains fluid to below 0°F.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Environmental Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Dentistry (AREA)
  • Engineering & Computer Science (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP99968601A 1998-09-03 1999-08-31 Freeze-resistant topical germicides and methods related thereto Withdrawn EP1109452A2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US14694798A 1998-09-03 1998-09-03
US146947 1998-09-03
PCT/US1999/019987 WO2000013506A2 (en) 1998-09-03 1999-08-31 Freeze-resistant topical germicides and methods related thereto

Publications (1)

Publication Number Publication Date
EP1109452A2 true EP1109452A2 (en) 2001-06-27

Family

ID=22519703

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99968601A Withdrawn EP1109452A2 (en) 1998-09-03 1999-08-31 Freeze-resistant topical germicides and methods related thereto

Country Status (8)

Country Link
EP (1) EP1109452A2 (ko)
JP (1) JP2002524397A (ko)
KR (1) KR20010079726A (ko)
AU (1) AU6023999A (ko)
BR (1) BR9913432A (ko)
CA (1) CA2342844A1 (ko)
MX (1) MXPA01002282A (ko)
WO (1) WO2000013506A2 (ko)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6902747B1 (en) 2000-05-03 2005-06-07 Westfaliasurge, Inc. Iodine-propylene glycol teat dip
US6582734B1 (en) * 2000-07-20 2003-06-24 Ecolab Inc. Antimicrobial composition useful for the treatment of bovine mastitis
US7109241B1 (en) 2000-10-02 2006-09-19 Ecolab, Inc. Antimicrobial compositions formulated for use in cold temperature conditions and methods of use thereof
MY129350A (en) * 2001-04-25 2007-03-30 Bristol Myers Squibb Co Aripiprazole oral solution
US20070042094A1 (en) 2005-08-22 2007-02-22 Alcide Corporation Oxidation method and compositions therefor
CN104884044B (zh) 2012-12-21 2018-05-18 利拉伐控股有限公司 含羧酸混合物的杀菌组合物以及作为局部消毒剂的应用
CA3072651A1 (en) * 2017-08-25 2019-02-28 Unilever Plc An antimicrobial composition
MX2020001923A (es) 2017-08-25 2020-03-24 Unilever Ip Holdings B V Una composicion antimicrobiana.
KR102610200B1 (ko) * 2018-02-12 2023-12-06 고려대학교 산학협력단 벤조일 유도체군과 중쇄지방산을 포함하는 살균용 조성물
KR102077726B1 (ko) * 2019-05-23 2020-02-17 주식회사 엘브스바이오켐 내동성 살균제 조성물 및 그 제조방법

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5185161A (en) * 1984-03-21 1993-02-09 Alcide Corporation Disinfection method and composition therefor
US4945110A (en) * 1987-06-15 1990-07-31 Quali Tech, Inc. Membrame-forming veterinary antibacterial teat dip
US5534266A (en) * 1994-06-20 1996-07-09 Devtech Corporation Bovine teat dip
DE69511244T2 (de) * 1994-12-14 2000-03-02 Alcide Corp Haftende desinfizierende zusammensetzungen und verfahren und entsprechendes verfahren
JPH08175989A (ja) * 1994-12-26 1996-07-09 Nissan Gosei Kogyo Kk ***炎の予防のための組成物
US5772985A (en) * 1995-09-08 1998-06-30 Alcide Corporation Method for treating bovine hairy heel warts
US6221823B1 (en) * 1995-10-25 2001-04-24 Reckitt Benckiser Inc. Germicidal, acidic hard surface cleaning compositions

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO0013506A2 *

Also Published As

Publication number Publication date
WO2000013506A3 (en) 2000-11-16
MXPA01002282A (es) 2002-08-20
CA2342844A1 (en) 2000-03-16
JP2002524397A (ja) 2002-08-06
BR9913432A (pt) 2001-10-09
WO2000013506A2 (en) 2000-03-16
KR20010079726A (ko) 2001-08-22
AU6023999A (en) 2000-03-27

Similar Documents

Publication Publication Date Title
US6123966A (en) Stabilized two-part disinfecting system and compositions and methods related thereto
AU676897B2 (en) Iodine barrier teat dip
US4891216A (en) Disinfecting compositions and methods therefor
US5651977A (en) Adherent disinfecting compositions and methods relating thereto
US4049830A (en) Bovine teat dip
CN104884044B (zh) 含羧酸混合物的杀菌组合物以及作为局部消毒剂的应用
JP3249780B2 (ja) 改良された被膜形成性動物皮膚予防保護剤組成物
EP1109452A2 (en) Freeze-resistant topical germicides and methods related thereto
CA3150040A1 (en) Liquid dressing compositions and their veterinary uses
AU769364B2 (en) Iodine containing antimicrobial compositions for mastitis control
US5618841A (en) Composition of iodophor teat dip for the prevention of mastitis and a process for using the same
PL196077B1 (pl) Kompozycja dezynfekująca
US5741553A (en) Pet repellants
US20040091553A1 (en) Composition and method for mammary disinfection during winter conditions
CN109673637B (zh) 用于防腐的液体浓缩物
KR20200041494A (ko) 축사용 부동 세정 및 살균소독제
US20020119949A1 (en) Prophylactic teat treatment
CN113163754B (zh) 稳定的含碘抗微生物***浸液组合物
WO2004057966A1 (en) Compositions and methods for control of bovine mastitis
US20230414653A1 (en) Topical chlorine dioxide treatment for mammalian teats
WO1998044794A1 (en) Compositions and methods for skin disinfection employing mandelic acid
Hemling et al. Evaluation of bovine teat condition in commercial dairy herds: 6. Teat condition-prevention and cure through teat dips
GB2200845A (en) Teat-treating composition

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20010403

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

AX Request for extension of the european patent

Free format text: AL;LT;LV;MK;RO;SI

17Q First examination report despatched

Effective date: 20020718

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20021128