WO2005048709A1 - Use of panthenol in teat dip/spray preparations - Google Patents

Use of panthenol in teat dip/spray preparations Download PDF

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Publication number
WO2005048709A1
WO2005048709A1 PCT/EP2004/012024 EP2004012024W WO2005048709A1 WO 2005048709 A1 WO2005048709 A1 WO 2005048709A1 EP 2004012024 W EP2004012024 W EP 2004012024W WO 2005048709 A1 WO2005048709 A1 WO 2005048709A1
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Prior art keywords
teat
panthenol
iodine
skin
teats
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PCT/EP2004/012024
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French (fr)
Inventor
Robert Elliott
Irmgard Immig
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Dsm Ip Assets B.V.
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Publication of WO2005048709A1 publication Critical patent/WO2005048709A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
    • A01N37/36—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/18—Iodine; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0041—Mammary glands, e.g. breasts, udder; Intramammary administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7015—Drug-containing film-forming compositions, e.g. spray-on

Definitions

  • the present invention deals with the use of panthenol in teat dip and spray preparations to improve teat skin conditions and with corresponding novel and improved preparations useful in the treatment of teats.
  • the maintenance of a healthy teat skin in cows is a prerequisite for udder health and milk of high quality. Every milking incorporates a threat to teat conditions and this threat is increasing with higher milking frequency (up to 3 times a day).
  • teat skin abrasion In countries, which rely on grazing systems to produce milk, teat sunburn and abrasions caused by grasses are additional significant problems for dairy farmers. Rough and chapped teat skin provides a place for bacteria to attach and survive.
  • teat chapping The severity of teat chapping is positively correlated with increased colonization by Staphylococcus aureus (Fox et al., Am. J. Vet. Res. 52, 799-802 [1991]). They can invade the udder through the teat orifice, which increases the probability of new intramammary infections (Neave et al., J. Dairy Sci., 52, 696-706 [1969] ). Healthy teat skin is a natural defence against skin opportunistic bacteria. It is well known that reducing chafing and the extent of cuts and abrasions on cow teats helps reduce the number of skin opportunistic organisms.
  • Postmilking teat dipping is widely considered to be perhaps the most effective management component to prevent and spread mastitis in a milking herd (Burmeister et al, J. Dairy Sci. 81, 1904-1909 [1998]).
  • Many dips or sprays are known which contain oxidative germicides like iodine, peroxide, chlorine or non oxidative germicides like nisin and lauricidin or alcohols. Besides their desired bactericidal effects they can be, however, also irritating to the teat skin due to a pH as low as 2-3.
  • skin conditioners are added.
  • Emollients used in teat sprays or dips are among others glycerine, propylene glycol and glycol esters.
  • panthenol and panthenol derivatives have excellent wound healing and skin conditioning properties in humans. They have, e.g., special application in the treatment of breasts of breast feeding women with an ointment containing 5% panthenol which treatment reduces the risk of nipple fissures by half or two thirds and promotes healing of lesions despite the continuation of breast feeding
  • panthenol can be used as additive in teat dips and sprays thereby improving their properties.
  • the present invention deals with novel aqueous antimicrobial compositions useful in the treatment of animal teats which are characterized by an effective amount of panthenol.
  • the invention deals especially with a method of improving . aqueous antimicrobially active teat dips or sprays by adding to them an effective amount of panthenol.
  • the invention deals with the use of panthenol for the preparation and the improvement of aqueous compositions useful in the treatment of animal teats.
  • panthenol refers to 2.4-dihydroxy-N-(3-hydroxypropyl)-3.3- dimethylbutanamide in form of the racemate as well as the D(+)-form which is the carrier of the vitamin activity.
  • panthenol e.g., esters, N-substituted compounds or addition salts, which turn out to have the same advantageous properties can also be used in and are part of the present invention.
  • aqueous antimicrobial compositions useful in the treatment of animal teats refers to formulations which are described in the prior art and are commercially available as solutions for use as post milking dips and sprays.
  • the solutions may be in the form of concentrates such as described, e.g., in USP 5.885.620 (which is incorporated herein by reference), which can be stored up to several months before they are diluted in water (1:2-80 parts) for use.
  • the antimicrobial agents which in the prior art are also designated germicidal agents, belong to two main types according to their mode of action, viz. oxidizing and non-oxidizing agents of which the latter are a preferred embodiment of the present invention.
  • non-oxidizing germicides useful in teat dips are chlorhexidine, DDBSA (dodecyl benzene sulfonic acid), lauricidin and nisin while examples of oxidizing germicides are iodine, chlorine, chlorine dioxide or hydrogen peroxide. From the latter group iodine is the most preferred active germicidal/antimicrobial agent with over 100 iodine teat dips available in the USA and probably more than 500 globally. Iodine levels in these products as well as the number and concentration of other components in the teat dips or sprays can vary widely.
  • animal in the context of the present invention relates to those animals which are relevant for the supply of humans with milk such as cattle, goats or sheep.
  • panthenol in accordance with the present invention, new teat dips and teat sprays are provided which are characterized by containing panthenol and by improved qualities.
  • the content of panthenol or its derivative within the dips/ sprays, viz. the effective amount, can vary within a broad range of concentration, and is normally in the range of from about 0.1 to about 8% (w/w), preferably from about 0.5 to about 5% (w/w).
  • compositions are particularly useful to provide post-milking teat sanitizing solutions that leave a residual barrier film on the teat surface between milkings.
  • the compositions of the invention are applied to the teats after each milking, by dipping the teat into the liquid composition.
  • the compositions dry to provide a continuous protective film.
  • the compositions of the invention are typically "teat dips", however, as known in the art, other methods of topical applications besides teat-dipping that provide barrier films can be used such as spraying the teats with a corresponding spray, i.e. a liquid under pressure in a suitable container.
  • the films prepared using the teat-dip compositions of the invention have the ability to persist between milkings, but can be readily removed by typical pre-milking udder preparation such as washing with water or an aqueous sanitizer, or by dipping the teat in a predip and wiping with a cloth or paper towel.
  • typical pre-milking udder preparation such as washing with water or an aqueous sanitizer, or by dipping the teat in a predip and wiping with a cloth or paper towel.
  • the aqueous solutions can contain 0.01-1.4% (w/w) of available (titrable) iodine (USP 5.643.608, incorporated into the present application by reference), preferably 0.1-0.75%, most preferably (1500 ppm).
  • iodine is soluble in water only to the extent of 300 ppm at room temperature it is advantageous to complex the iodine with non-ionic surfactants, described, e.g., in USP 3.285.816, 3.728.449 and 5.368.868, which include ethylene oxide-propylene oxide copolymers, nonylphenol ethoxylated glucosides, e hoxylated sorbitol esters, alcohol alkoxylates or combinations of the various nonionic surfactants.
  • PVP Polyvinylpyrrolidone
  • a polymeric material compatible with teat skin is seldom used as iodine solubilizer because of its costs.
  • the preferred nonionic surfactants are the ethylene oxide-propylene oxide copolymers (poloxamers) and the nonylphenolethoxylates.
  • Poloxamer surfactants include those described in USP 5.368.868 as well as other commercially available poloxamers.
  • Useful poloxamers include Pluronic ® surfactants (BASF Corporation).
  • the iodine complexing agents may be included in the compositions of the invention in a weight ratio of complexing agent to iodine of about 2:1 to 20:1, and preferably of about 2:1 to 12:1.
  • the free iodine content of the solution may be from about 5-125 ppm and may preferably be from about 5-8 or 20-50 ppm over an ambient temperature storage period of at least 3 months as described, e.g., in USP 5.643.608.
  • the dip contains a film-forming agent as described, e.g., in USP 5.776.479.
  • film-forming agents are selected from the group consisting of hydroxyethylcellulose, methyl hydroxypropylcellulose, and ethylhydroxyethylcellulose.
  • film-forming agents are the following non-toxic, food grade, commercially available, film-forming agents: Natrosol ® (nonionic water-soluble hydroxyethylcellulose from Aqualon, Wilmington, Del.); Methocel ® (methyl hydroxypropylcellulose made from cellulose and propylene oxide and available from Dow Chemical); Bermocoll E® (non-ionic, water soluble ethyl hydroxyethylcellulose from Akzo Nobel).
  • Natrosol ® nonionic water-soluble hydroxyethylcellulose from Aqualon, Wilmington, Del.
  • Methocel ® methyl hydroxypropylcellulose made from cellulose and propylene oxide and available from Dow Chemical
  • Bermocoll E® non-ionic, water soluble ethyl hydroxyethylcellulose from Akzo Nobel.
  • Preferred film forming agents are Methocel ® E50LV, Methocel ® K100, Methocel ® F50, Natrosol® 250KR, Bermocoll E®351 FQ, Bermocoll E ® 411 FQ, and Bermocoll E ® 320 FQ.
  • the film-forming agents mentioned above are compatible with other composition ingredients and may provide viscosity to the formulation.
  • the film-forming agent as supplied by the manufacturer is used at a concentration of about 0.25 to 10% and preferably about 0.25 to 6.0% (w/w) of the composition.
  • the aqueous component (water) is provided in the compositions of the invention to achieve the desired ratio of the ingredients and to achieve the desired viscosity.
  • Buffering agents are included in the compositions as necessary to provide a pH in the range of 3 to 9 preferably > 4 but ⁇ 7.5 (pH 4 to 7 for complexed iodine), to thereby maximize the stability of the composition and to minimize potential irritation to the animal's teats.
  • Buffers suitable for the aqueous compositions of the invention are those as known in the art, for example, citrate, phosphate, lactate, acetate, and carbonate buffers.
  • ingredients which are optionally used in teat dips/sprays comprise, skin conditioning or skin moisturing agents (emollients), wetting agents, thickeners and - in case of iodine based dips - iodate.
  • Skin conditioning agents are generally classified as moisturizers or moisture barriers. Moisturizers are additives that attract moisture to the outer layers of the skin to keep it soft and supple. The moisture is pulled from the air or from the deeper layers of skin. Common moisturizers include glycerin, polyethylene glycol, propylene glycol, sorbitol, and aloe. Glycerin propylene glycol, glycol ethers and sorbitol are used alone or in combinations in concentrations typically ranging from 2 to 10%. At equal concentrations, glycerin has a 1.35x moisture-binding capacity compared to propylene glycols and a 4x binding capacity compared with sorbitol.
  • Sorbitol shows a higher dynamic hygroscopicity.
  • propylene glycol is often used in concentrated products where glycerin is more difficult to formulate.
  • Moisture barriers function by creating a barrier to prevent evaporation of moisture already present in the skin. The functional properties are determined by measuring the trans-epidermal water loss (TEWL).
  • TEWL trans-epidermal water loss
  • Typical moisture barriers are lanolin or lanolin derivatives, e.g., ethoxylated lanolin, which are more water soluble.
  • wetting agents for example sodium dioctylsulfosuccinate, viscosity modifiers (thickeners), for example xanthan gum, and dyes.
  • iodine containing compositions may also incorporate iodate.
  • Iodate if optionally included, is typically used at a concentration of about 0.005 to 0.5%(w/w) and preferably about 0.01 to 0.4% (w/w).
  • concentration of about 0.005 to 0.5%(w/w) and preferably about 0.01 to 0.4% (w/w).
  • Table shows the weight ranges of ingredients useful for iodine-based compositions of the invention.
  • Germicidal Agent 0.05-1.25% 0.1-0.75%
  • Iodine Iodide 1:0.1-1:0.8 1:0.15-1:0.6
  • Emollient (optional) 0-12% 2-10% Dye (optional) 0-0.2% 0.05-0.1%
  • compositions are:
  • compositions of the present invention can be prepared by methods known to the person skilled in the art, e.g., by mixing commercially available ingredients in the desired weight ratios or by adding an effective amount of panthenol to a commercially available teat dip and, if desired, packing the mixture obtained into spraying cans.
  • the preparations of the present invention represent an improvement in the post- milking teat treatment of, e.g., cattle, when compared with the effects of prior art products. This could be shown in double blind tests with dairy cows using an aqueous iodine-based germicidal teat dip (ProactiveTM) + 5% (w/w) panthenol..
  • ProactiveTM aqueous iodine-based germicidal teat dip
  • panthenol. panthenol.
  • the teats of the right hand side of the udder were used as control while the left hand side teats were used for the treatment, thus every cow being her own control.
  • the evaluations were based on a subjective scoring system developed and described by the University of Wisconsin (Department of Dairy Science Milk Quality Resources) for teat end and teat skin classifications (G.A.
  • Each teat was sprayed with 2-3 ml of the product for 2-3 seconds to ensure maximum coverage of each teat with the desinfectant.
  • the first 4 weeks of the trial were used to obtain the baseline teat condition measurements using only the control teat spray.
  • Teat skin was evaluated on all teats. The evaluations were based on a subjective scoring system developed and described by the University of Wisconsin for teat skin classifications. A veterinarian did the scoring twice per month immediately after the milk clusters were removed.
  • Each teat was palpated. The scoring was done by gently rolling the teat between the fingers. The classification system was going from a scale of 0 to 3 The lower the score the better was the teat condition.
  • panthenol slightly improved teat skin. It makes the skin softer and improves teat hardness significantly (p ⁇ 0.05): Tables J. and 2 below. Thus, panthenol increases elasticity of the teat skin and makes it less vulnerable against abrasions.
  • Control 0 0.09 0.41 0.417 0.25 0.28 0.356 0.266 Treatment 0 0.101 0.263 0.33 0.316 0.26 0.22 0.233

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Abstract

Aqueous antimicrobial compositions useful in the treatment of animal teats, characterized by an effective amount of panthenol, normally 0.1-8% (w/w), and the use of panthenol for the preparation of such compositions.

Description

Use of Panthenol in Teat Dip/Spray Preparations
The present invention deals with the use of panthenol in teat dip and spray preparations to improve teat skin conditions and with corresponding novel and improved preparations useful in the treatment of teats. The maintenance of a healthy teat skin in cows is a prerequisite for udder health and milk of high quality. Every milking incorporates a threat to teat conditions and this threat is increasing with higher milking frequency (up to 3 times a day). One of the main problems that occur with milking is teat skin abrasion. In countries, which rely on grazing systems to produce milk, teat sunburn and abrasions caused by grasses are additional significant problems for dairy farmers. Rough and chapped teat skin provides a place for bacteria to attach and survive. The severity of teat chapping is positively correlated with increased colonization by Staphylococcus aureus (Fox et al., Am. J. Vet. Res. 52, 799-802 [1991]). They can invade the udder through the teat orifice, which increases the probability of new intramammary infections (Neave et al., J. Dairy Sci., 52, 696-706 [1969] ). Healthy teat skin is a natural defence against skin opportunistic bacteria. It is well known that reducing chafing and the extent of cuts and abrasions on cow teats helps reduce the number of skin opportunistic organisms. Postmilking teat dipping is widely considered to be perhaps the most effective management component to prevent and spread mastitis in a milking herd (Burmeister et al, J. Dairy Sci. 81, 1904-1909 [1998]). Many dips or sprays are known which contain oxidative germicides like iodine, peroxide, chlorine or non oxidative germicides like nisin and lauricidin or alcohols. Besides their desired bactericidal effects they can be, however, also irritating to the teat skin due to a pH as low as 2-3. To prevent skin irritation skin conditioners are added. Emollients used in teat sprays or dips are among others glycerine, propylene glycol and glycol esters. They improve skin conditions by acting also as moisturizers. Lanolin or lanolin derivatives are used as moisture barriers. On the other hand it is known since long that panthenol and panthenol derivatives have excellent wound healing and skin conditioning properties in humans. They have, e.g., special application in the treatment of breasts of breast feeding women with an ointment containing 5% panthenol which treatment reduces the risk of nipple fissures by half or two thirds and promotes healing of lesions despite the continuation of breast feeding
(Grύnberger, Wiener Med. Wochenzeitschrift, No. 13/14, 150-151 [j.948]; Dubecq and Detchart, Med. Prat.: special edition, May 1977).
Surprisingly, nothing appears to be known so far about the beneficial effects of panthenol on teats of animals, especially animals which are relevant for the supply of humans with milk, and their use in teat dips/sprays.
It has now been found that such effects do exist and that panthenol can be used as additive in teat dips and sprays thereby improving their properties.
Therefore, the present invention deals with novel aqueous antimicrobial compositions useful in the treatment of animal teats which are characterized by an effective amount of panthenol. The invention deals especially with a method of improving . aqueous antimicrobially active teat dips or sprays by adding to them an effective amount of panthenol. In another embodiment the invention deals with the use of panthenol for the preparation and the improvement of aqueous compositions useful in the treatment of animal teats. The term "panthenol" refers to 2.4-dihydroxy-N-(3-hydroxypropyl)-3.3- dimethylbutanamide in form of the racemate as well as the D(+)-form which is the carrier of the vitamin activity. Both forms are commercially available in highly pure quality or can be prepared and obtained according to methods well-known in the art. Derivatives of panthenol, e.g., esters, N-substituted compounds or addition salts, which turn out to have the same advantageous properties can also be used in and are part of the present invention.
The term "aqueous antimicrobial compositions useful in the treatment of animal teats" refers to formulations which are described in the prior art and are commercially available as solutions for use as post milking dips and sprays. The solutions may be in the form of concentrates such as described, e.g., in USP 5.885.620 (which is incorporated herein by reference), which can be stored up to several months before they are diluted in water (1:2-80 parts) for use. The antimicrobial agents, which in the prior art are also designated germicidal agents, belong to two main types according to their mode of action, viz. oxidizing and non-oxidizing agents of which the latter are a preferred embodiment of the present invention. Examples of non-oxidizing germicides useful in teat dips are chlorhexidine, DDBSA (dodecyl benzene sulfonic acid), lauricidin and nisin while examples of oxidizing germicides are iodine, chlorine, chlorine dioxide or hydrogen peroxide. From the latter group iodine is the most preferred active germicidal/antimicrobial agent with over 100 iodine teat dips available in the USA and probably more than 500 globally. Iodine levels in these products as well as the number and concentration of other components in the teat dips or sprays can vary widely.
The term "animal" in the context of the present invention relates to those animals which are relevant for the supply of humans with milk such as cattle, goats or sheep.
In accordance with the present invention new teat dips and teat sprays are provided which are characterized by containing panthenol and by improved qualities. The content of panthenol or its derivative within the dips/ sprays, viz. the effective amount, can vary within a broad range of concentration, and is normally in the range of from about 0.1 to about 8% (w/w), preferably from about 0.5 to about 5% (w/w).
The compositions are particularly useful to provide post-milking teat sanitizing solutions that leave a residual barrier film on the teat surface between milkings. Preferably the compositions of the invention are applied to the teats after each milking, by dipping the teat into the liquid composition. The compositions dry to provide a continuous protective film. While the compositions of the invention are typically "teat dips", however, as known in the art, other methods of topical applications besides teat-dipping that provide barrier films can be used such as spraying the teats with a corresponding spray, i.e. a liquid under pressure in a suitable container. The films prepared using the teat-dip compositions of the invention have the ability to persist between milkings, but can be readily removed by typical pre-milking udder preparation such as washing with water or an aqueous sanitizer, or by dipping the teat in a predip and wiping with a cloth or paper towel. In case of iodine-based teat dips the aqueous solutions can contain 0.01-1.4% (w/w) of available (titrable) iodine (USP 5.643.608, incorporated into the present application by reference), preferably 0.1-0.75%, most preferably (1500 ppm). Since iodine is soluble in water only to the extent of 300 ppm at room temperature it is advantageous to complex the iodine with non-ionic surfactants, described, e.g., in USP 3.285.816, 3.728.449 and 5.368.868, which include ethylene oxide-propylene oxide copolymers, nonylphenol ethoxylated glucosides, e hoxylated sorbitol esters, alcohol alkoxylates or combinations of the various nonionic surfactants. Polyvinylpyrrolidone (PVP), a polymeric material compatible with teat skin, is seldom used as iodine solubilizer because of its costs. The preferred nonionic surfactants are the ethylene oxide-propylene oxide copolymers (poloxamers) and the nonylphenolethoxylates. Poloxamer surfactants include those described in USP 5.368.868 as well as other commercially available poloxamers. Useful poloxamers include Pluronic® surfactants (BASF Corporation). The iodine complexing agents may be included in the compositions of the invention in a weight ratio of complexing agent to iodine of about 2:1 to 20:1, and preferably of about 2:1 to 12:1. The free iodine content of the solution may be from about 5-125 ppm and may preferably be from about 5-8 or 20-50 ppm over an ambient temperature storage period of at least 3 months as described, e.g., in USP 5.643.608.
In order to obtain teat dips with high adhesion characteristics it is advantageous that the dip contains a film-forming agent as described, e.g., in USP 5.776.479. Such film- forming agents are selected from the group consisting of hydroxyethylcellulose, methyl hydroxypropylcellulose, and ethylhydroxyethylcellulose. Exemplary of these film-forming agents are the following non-toxic, food grade, commercially available, film-forming agents: Natrosol® (nonionic water-soluble hydroxyethylcellulose from Aqualon, Wilmington, Del.); Methocel® (methyl hydroxypropylcellulose made from cellulose and propylene oxide and available from Dow Chemical); Bermocoll E® (non-ionic, water soluble ethyl hydroxyethylcellulose from Akzo Nobel). Preferred film forming agents are Methocel® E50LV, Methocel® K100, Methocel® F50, Natrosol® 250KR, Bermocoll E®351 FQ, Bermocoll E®411 FQ, and Bermocoll E®320 FQ.
The film-forming agents mentioned above are compatible with other composition ingredients and may provide viscosity to the formulation. A viscosity of about 50-1000cP, preferably of 200-800 cP, is desirable. The film-forming agent as supplied by the manufacturer is used at a concentration of about 0.25 to 10% and preferably about 0.25 to 6.0% (w/w) of the composition.
The aqueous component (water) is provided in the compositions of the invention to achieve the desired ratio of the ingredients and to achieve the desired viscosity.
Buffering agents are included in the compositions as necessary to provide a pH in the range of 3 to 9 preferably > 4 but < 7.5 (pH 4 to 7 for complexed iodine), to thereby maximize the stability of the composition and to minimize potential irritation to the animal's teats. Buffers suitable for the aqueous compositions of the invention are those as known in the art, for example, citrate, phosphate, lactate, acetate, and carbonate buffers.
Other ingredients which are optionally used in teat dips/sprays comprise, skin conditioning or skin moisturing agents (emollients), wetting agents, thickeners and - in case of iodine based dips - iodate.
Skin conditioning agents are generally classified as moisturizers or moisture barriers. Moisturizers are additives that attract moisture to the outer layers of the skin to keep it soft and supple. The moisture is pulled from the air or from the deeper layers of skin. Common moisturizers include glycerin, polyethylene glycol, propylene glycol, sorbitol, and aloe. Glycerin propylene glycol, glycol ethers and sorbitol are used alone or in combinations in concentrations typically ranging from 2 to 10%. At equal concentrations, glycerin has a 1.35x moisture-binding capacity compared to propylene glycols and a 4x binding capacity compared with sorbitol. Sorbitol, however, shows a higher dynamic hygroscopicity. For iodine teat dips, propylene glycol is often used in concentrated products where glycerin is more difficult to formulate. Moisture barriers function by creating a barrier to prevent evaporation of moisture already present in the skin. The functional properties are determined by measuring the trans-epidermal water loss (TEWL). Typical moisture barriers are lanolin or lanolin derivatives, e.g., ethoxylated lanolin, which are more water soluble.
Other optional ingredients include wetting agents, for example sodium dioctylsulfosuccinate, viscosity modifiers (thickeners), for example xanthan gum, and dyes.
Finally, to improve iodine stability, iodine containing compositions may also incorporate iodate. Iodate, if optionally included, is typically used at a concentration of about 0.005 to 0.5%(w/w) and preferably about 0.01 to 0.4% (w/w). The following table shows the weight ranges of ingredients useful for iodine-based compositions of the invention.
INGREDIENT BROAD RANGE PREFERRED RANGE
Germicidal Agent (Iodine) 0.05-1.25% 0.1-0.75%
Complexing Agent: Iodine 2:1-20:1 2:1-12:1
Iodine : Iodide 1:0.1-1:0.8 1:0.15-1:0.6
Iodate (optional) 0-0.5 0.01-0.4
Panthenol 0.1-8% 0.5-5%
Film-forming Agent (optional) 0-10% 0.25-6%
Emollient (optional) 0-12% 2-10% Dye (optional) 0-0.2% 0.05-0.1%
Wetting Agent (optional) 0-2.0% 0.01-0.5%
Thickener (optional) 0-0.5 0.01-0.3%
Buffer To provide pH 4-7 To provide pH 4.5-6.5
Water q.s. ad 100% q.s. ad 100%
Viscosity 50-1000 cP 100-800 cP
Representative formulations are:
INGREDIENT PERCENT (W/W)
Panthenol 5.0
Natrosol ® 250 KR 0.625
Pluronic ® PI 05 3.0
Caustic Soda - 50% 0.14
Citric Acid, Anhydrous 0.3
Glycerin, 100% 6.0
Xanthan gum 0.2
Sodium Dioctylsulfosuccinate - 75% 0.1
Sodium Iodate 0.02
Hydriodic Acid 0.18
Iodine 0.5
Propylene Glycol 0.18
Water q.s. ad 100 2. Panthenol 5.0
Proactive ™ (DeLaval) 95.0
The compositions of the present invention can be prepared by methods known to the person skilled in the art, e.g., by mixing commercially available ingredients in the desired weight ratios or by adding an effective amount of panthenol to a commercially available teat dip and, if desired, packing the mixture obtained into spraying cans.
The preparations of the present invention represent an improvement in the post- milking teat treatment of, e.g., cattle, when compared with the effects of prior art products. This could be shown in double blind tests with dairy cows using an aqueous iodine-based germicidal teat dip (Proactive™) + 5% (w/w) panthenol.. The teats of the right hand side of the udder were used as control while the left hand side teats were used for the treatment, thus every cow being her own control. The evaluations were based on a subjective scoring system developed and described by the University of Wisconsin (Department of Dairy Science Milk Quality Resources) for teat end and teat skin classifications (G.A. Mein et al, Evaluation of bovine teat conditions in commercial dairy herds: 1. Non-infectious factors. http://www.uwex.edu/milkquality/Udder_Health/index.htm). Teat skin condition was slightly and teat hardness was significantly improved in the panthenol treated teats. Thus it could be concluded that panthenol makes the animal skin softer, more elastic and less vulnerable against skin abrasions.
Experimental design showing that use of panthenol in teat dip/spray preparations improve teat skin conditions:
The effect of the addition of 5% D-panthenol 75 L (DSM Nutritional Products) in a germicide teat dip (DeLaval Proactive®) on teat conditions was evaluated over a period of approximate 200 days from January to August 2003 in a double blirid test with 61 Holstein Frisian dairy cows. The animals were milked twice in a tandem milking parlour (model 2x5). The parlour was equipped with two spraying guns for the teat dip application. The teats of the right hand side of the udder were used as control (blue spraying device) while the left hand side of the teats where used for the treatment (black spraying device). Thus every cow was her own control. Each teat was sprayed with 2-3 ml of the product for 2-3 seconds to ensure maximum coverage of each teat with the desinfectant. The first 4 weeks of the trial were used to obtain the baseline teat condition measurements using only the control teat spray. Teat skin was evaluated on all teats. The evaluations were based on a subjective scoring system developed and described by the University of Wisconsin for teat skin classifications. A veterinarian did the scoring twice per month immediately after the milk clusters were removed. Each teat was palpated. The scoring was done by gently rolling the teat between the fingers. The classification system was going from a scale of 0 to 3 The lower the score the better was the teat condition.
Data analyses
Data was analysed by the SAS statistical package using the means procedure.
Differences between the treatments were proven by the Wilcoxon procedure (Wilcoxon, F. and R.A. Wilcox, 1964: Some rapid approximate statistical procedures. Revised pamphlet.
Pearl River, N.Y., Lederle Laboratories of the American Cynamid Company). The minimum level of significance was 95%.
Results and Conclusion
The primary objective of the trial was to observe whether a postdip germicide- emollient-panthenol 5% combination significantly affects teat skin condition. The results can be summarized as follows: Panthenol slightly improved teat skin. It makes the skin softer and improves teat hardness significantly (p<0.05): Tables J. and 2 below. Thus, panthenol increases elasticity of the teat skin and makes it less vulnerable against abrasions.
Table 1: Effect of panthenol on teat skin
Date 14.01 12.02 26.02 11.03 26.03 08.04 25.04 07.05
Control 0 0.09 0.41 0.417 0.25 0.28 0.356 0.266 Treatment 0 0.101 0.263 0.33 0.316 0.26 0.22 0.233
Date 21.05 04.06 25.06 08.07 23.07 06.08
Control 0.316 0.28 0.228 0.37 0.332 0.283 Treatment 0.233 0.246 0.298 0.259 0.274 0.208
Table 2: Effect of panthenol on teat hardness
Date 14.01 12.02 26.02 11.03 26.03 08.04 25.04 07.05
Control 0.46 1.06' 1.62 0.94 1.13 1.21 1.475 »' 1.16 Treatment 0.39 0.69b 1.56 0.94 0.85 1.0 1.03 0.84
Date 21.05 04.06 25.06 08.07 23.07 06.08
Control 1.25' 1.07' 1.19' 1.39' 1.08' 1.06' Treatment 0.88b 0.74b 0.89b 0.94b 0.55b 0.58b
Means in columns with unlike superscripts differ significantly (p<0.05)

Claims

Claims
1. An aqueous antimicrobial composition useful in the treatment of animal teats characterized by an effective amount of panthenol.
2. A composition as claimed in claim 1 wherein the antimicrobial agent is of oxidative type. .
3. A composition as claimed in claim 1 or 2 wherein the antimicrobial agent is iodine.
4. A composition as claimed in claim 3 wherein the iodine is in complexed form
5. A composition as claimed in any one of claims 1 to 4 comprising panthenol in an amount of 0.1 to 8% (w/w).
6. A composition as claimed in any one of claims 1 to 5 for the treatment of bovine teats.
7. The use of panthenol for the preparation of compositions as claimed in any one of claims 1-6.
8. The invention as hereinbefore described, especially with reference to the examples.
PCT/EP2004/012024 2003-11-05 2004-10-25 Use of panthenol in teat dip/spray preparations WO2005048709A1 (en)

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