Source: http://www.google.com/patents/US6379685?dq=7,134,016
Timestamp: 2014-12-27 09:47:22
Document Index: 76346753

Matched Legal Cases: ['art.\n13', 'art.\n16', 'art.\n29', 'art.\n31', 'art.\n32', 'art 2', 'art 1', 'art 2', 'art 2', 'art 1', 'art 2', 'art 2', 'art 1', 'art 2']

Patent US6379685 - Acidic aqueous chlorite teat dip with improved emollient providing shelf ... - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inAdvanced Patent SearchPatentsThe mastitis control teat dip composition of the invention provides a softening, soothing, smoothing, relaxing property, a rapid initial kill, a useful highly pseudoplastic rheology, a barrier/film-forming capacity, a unique antimicrobial composition that is stable over an extended period of time, and...http://www.google.com/patents/US6379685?utm_source=gb-gplus-sharePatent US6379685 - Acidic aqueous chlorite teat dip with improved emollient providing shelf life, sanitizing capacity and tissue protectionAdvanced Patent SearchPublication numberUS6379685 B1Publication typeGrantApplication numberUS 09/159,729Publication dateApr 30, 2002Filing dateSep 24, 1998Priority dateSep 26, 1997Fee statusPaidAlso published asCA2304947A1, CA2304947C, DE69808578D1, DE69808578T2, EP0906724A1, EP0906724B1, US6436444, US6699510, US20030206971, USRE41279, WO1999016418A1Publication number09159729, 159729, US 6379685 B1, US 6379685B1, US-B1-6379685, US6379685 B1, US6379685B1InventorsFrancis L. Richter, Cathy M. Paquette, Richard K. Staub, Donald R. VegoeOriginal AssigneeEcolab Inc.Export CitationBiBTeX, EndNote, RefManPatent Citations (36), Non-Patent Citations (11), Referenced by (18), Classifications (16), Legal Events (5) External Links: USPTO, USPTO Assignment, EspacenetAcidic aqueous chlorite teat dip with improved emollient providing shelf life, sanitizing capacity and tissue protectionUS 6379685 B1Abstract The mastitis control teat dip composition of the invention provides a softening, soothing, smoothing, relaxing property, a rapid initial kill, a useful highly pseudoplastic rheology, a barrier/film-forming capacity, a unique antimicrobial composition that is stable over an extended period of time, and unexpected long term microbial control when compared to the prior art materials disclosed in patents and used in the marketplace. The compositions of the invention are made by combining an aqueous thickened liquid composition containing the organic components which can be combined with a simple aqueous solution of a salt of chlorous acid, preferably an alkali metal chlorite. The materials can be combined, blended into a smooth viscous material containing an emollient package and can be immediately contacted with the target animals. The compositions of the invention provide rapid initial kill, consistent long term kill and chemical and rheological stability.
We claim: 1. A physically and chemically stable mastitis treating composition in an acidulant part and a chlorite part, that can effectively reduce microbial populations, on contact with a teat surface and for an extended period, said composition comprising:
(a) an aqueous acidulant part comprising: (i) about 0.1 to 15 weight percent of an anti-microbial weak acid or salt thereof or mixtures thereof; (ii) about 0.1 to 15 weight percent of a weak organic or inorganic acid, or salts thereof, or mixtures thereof, the acid selected from the group consisting of a phosphoric acid, lactic acid, glycolic acid; (iii) a rheology modifier comprising about 0.01 to 10 weight percent of a pseudoplastic thickener; (iv) about 0.1 to 10 weight percent of lanolin or a lanolin derivative; and (v) about 0.1 to 15 weight percent of a polyhydroxy emollient; (vi) a major proportion of water; and (b) a chlorite part, substantially free of an organic component, consisting essentially of an alkali metal chlorite salt; wherein the composition exhibits rheology that promotes cling to immobilize the composition on the teat surface and provides a barrier to environmental contamination and wherein the composition exhibits effective antimicrobial action lasting at least one week without dermal irritation to the teat surface after application.
2. The composition of claim 1 wherein the alkali metal chlorite comprises sodium chlorite and the organic acid comprises lactic acid.
3. The composition of claim 1 additionally comprising about 0.01 to 8 weight percent of a polymeric film forming agent selected from polyvinyl alcohol, polyvinyl acetate and mixtures thereof.
4. The composition of claim 1 wherein the emollient comprises glycerin, propylene glycol or mixtures thereof.
5. The composition of claim 1 wherein the weak acid comprises a hydrocarbon sulfonic acid and the inorganic acid comprises phosphoric acid.
7. The composition of claim 1 wherein the antimicrobial weak acid comprises a mixture of a C7-11 carboxylic acid and an alkane sulfonic acid wherein the alkane comprises 6 to 12 carbon atoms.
9. The composition of claim 1 further comprising about 0.05 to 2 weight percent of a xanthan thickener and about 0.1 to 5 weight percent of a film-forming agent selected from the group consisting of a polyvinyl alcohol, a polyvinyl acetate and mixtures thereof.
10. The composition of claim 1 wherein the pH of the composition is about 2.5 and 4.5.
11. The composition of claim 1 wherein the pH of the composition is about 2.5 to 3.5.
12. The composition of claim 1 wherein the chlorite part is a solid inorganic part.
13. The composition of claim 12 wherein the chlorite part is a solid tablet comprising equal proportions of sodium carbonate and sodium chlorite.
14. The composition of claim 1 further comprising a humectant selected from sorbitol, mannitol, a glucose derivative and mixtures thereof.
15. The composition of claim 1 wherein the chlorite part is an aqueous inorganic part.
16. The composition of claim 9 wherein the polyvinyl alcohol has a molecular weight Mn of about 15 to 100�103, and a degree of hydrolysis of about 92 to 97%.
17. A physically aid chemically stable mastitis treating concentrate composition comprising an acidulant part and a chlorite part, that can effectively reduce microbial populations, on contact with a teat surface and for an extended period, said composition comprising:
(a) an aqueous acidulant part comprising: (i) about 1 to 35 weight percent of an anti-microbial weak acid or salt thereof or mixtures thereof, (ii) about 1 to 35 weight percent of a weak organic or inorganic acid, or salts thereof, or mixtures thereof, the acid selected from the group consisting of a phosphoric acid, lactic acid, glycolic acid; (iii) a rheology modifier comprising about 0.01 to 20 weight percent of a pseudoplastic thickener; (iv) a film forming agent comprising about 0.01 to 10 weight percent of a polymer; (v) about 0.1 to 10 weight percent of lanolin or a lanolin derivative; and (vi) about 0.1 to 15 weight percent of a polyhydroxy emollient; (vii) a major proportion of water; and (b) a chlorite part, substantially free of an organic component, consisting essentially of an alkali metal chlorite salt; wherein the concentrate is adapted to be diluted with water at a ratio of about 0.1 to 1 part each of each of the acid and chlorite parts per each 1 to 100 parts of water and the resulting composition exhibits rheology that promotes cling to immobilize the composition on the teat surface and provides a barrier to environmental contamination and wherein the composition exhibits effective antimicrobial action lasting at least one week without dermal irritation to the teat surface after application. 18. The composition of claim 17 wherein the alkali metal chlorite comprises sodium chlorite and the organic acid comprises lactic acid.
19. The composition of claim 17 additionally comprising about 0.01 to 8 weight percent of a polymeric film forming agent selected from polyvinyl acetate and mixtures thereof.
20. The composition of claim 17 wherein the emollient comprises glycerin, propylene glycol or mixtures thereof.
21. The composition of claim 17 wherein the weak acid comprising a hydrocarbon sulfonic acid and the inorganic acid comprises phosphoric acid.
22. The composition of claim 21 wherein the hydrocarbon sulfonic acid comprises an alkane sulfonic acid wherein the alkane group has 6 to 18 carbon atoms.
23. The composition of claim 17 wherein the antimicrobial weak acid comprises a mixture of a C7-11 carboxylic acid and an alkane sulfonic acid wherein the alkane comprises 6 to 12 carbon atoms.
24. The composition of claim 21 wherein the hydrocarbon sulfonic acid comprises alkylbenzene sulfonic acid wherein the alkyl group has 9 to 18 carbon atoms.
25. The composition of claim 17 wherein the composition further comprises about 0.05 to 2 weight percent of a xanthan thickener and about 0.1 to 5 weight percent of a film-forming agent selected from the group consisting of a polyvinyl alcohol, a polyvinyl acetate and mixtures thereof.
26. The composition of claim 17 wherein the pH of the composition is about 2.5 to 4.5.
27. The composition of claim 17 wherein the pH of the composition is about 2.5 to 3.5.
28. The composition of claim 17 wherein the chlorite part is a solid inorganic part.
29. The composition of claim 28 wherein the chlorite part is a solid tablet comprising equal proportions of sodium carbonate and sodium chlorite.
30. The composition of claim 28 wherein the chlorite part is a powdered inorganic part.
31. The composition of claim 17 wherein the chlorite part is an aqueous inorganic part.
32. The composition of claim 25 wherein he polyvinyl alcohol has a molecular weight Mn of about 15 to 100�103, and a degree of hydrolysis of about 92 to 97%.
33. The composition of claim 17 further comprising a humectant selected form the group consisting of sorbitol, manitol, a glucose derivative and mixtures thereof.
34. The composition of claim 1 additional comprising 0.01 to 10 weight percent of aloe vera, hydantoin or mixtures thereof.
35. The composition of claim 17 additionally comprising about 0.5 to 15 weight percent of aloe vera, hydantoin of mixtures thereof.
This application is a cip of Ser. No. 08,938,653 filed Sep. 26, 1997.
FIELD OF THE INVENTION The invention relates to a bovine teat dip composition that can be mixed using two parts, a simple chlorite solution and an acid or acidulant formulation, to form a stable, effective composition that can be used in routine dairy procedures.
BACKGROUND OF THE INVENTION Bovine mastitis is the most common and most costly disease affecting dairy herds. Some estimates suggested at least half of the dairy animal population have some degree or form of mastitis. This condition results in lowered milk yield and reduced quality. Economic loss to mastitis in the U.S. is estimated at about $1.8 billion or approximately 10% of total milk sales with about two-thirds of this loss due to reduced milk production from infected cows. Mastitis is an inflammation of the mammary gland. Similarly, inflammation is one response of a tissue or organ to insult or injury. An injury caused by physical, chemical or thermal trauma can produce an inflammatory response. In the dairy cow, mastitis typically results from microorganisms, usually bacteria, that invade the udder, multiply in the delicate milk producing tissues, and synthesize toxins, a by-product of bacterial metabolism. The characteristic features of inflammation are swelling, heat, redness, pain and disturbed function.
While the animal immune system can fight intramammary infections, many chronic infections remain sub-clinical (asymptomatic) and undetected unless diagnosed by laboratory testing. Sub-clinical mastitis can result in a reservoir of micro-organisms that leads to the infection of other animals within the herd. More than 80 species of microorganisms have been identified as causal agents, although approximately 95% of mastitis is caused by four pathogens; Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysagalactiae, and Streptococcus uberis. Mastitis causing pathogens fall into two categories namely contagious and environmental. Contagious bacteria, such as Streptococcus agalactiae and Staphylococcus aureus, primarily colonize host tissue sites such as mammary glands, teat canals, teat skin lesions etc. and are spread from one infected cow to another during the milking process. Environmental bacteria, often streptococci, enterococci and coliform organisms, are commonly present within the cow's surroundings from sources such as cow feces, soil, plant material, bedding or water, and infect by casual opportunistic contact with an animal during the inter-milking period. This distinction, although not exclusive, is of practical importance because different dairy herd maintenance measures are needed for the different groups of microorganisms. In all bovine mastitis cases, whatever the causal microorganism, the route of transmission of the invading pathogen into the inner gland of the udder is through the teat orifice and teat canal.
Management of dairy herds focuses attention on treatment of both established mastitis and on prevention of new intramammary infections. Therapy and hygiene are the two fundamental components of an effective mastitis control protocol. Each is applied in concert, and each operates independently. The primary effect of therapy is to increase the rate of eliminating established infections; whereas, hygiene reduces the frequency of infection by interrupting transmission vectors. We cannot present all ancillary factors that may be employed for the elimination and prevention of mastitis, however, the most effective therapy and hygiene practices are, respectively, antibiotic infusion treatment of the udder's four quarters at the end of lactation; and, post-milking teat antisepsis or �teat dipping� during lactation.
Researchers agree, and an abundance of published evidence supports the concept, that dipping teats into an effective antimicrobial solution immediately after each milking is the single most effective procedure for decreasing new intramammary infections in lactating cows. Between 1955 to 1970, Dodd and co-workers (F. K. Neave, F. H. Dodd, and R. G. Kingwell, 1966, �A Method of Controlling Udder Disease�, Vet. Rec. 78:521; F. K. Neave, F. H. Dodd, R. G. Kingwell and D. R. Westgarth, 1969, �Control of Mastitis in the Dairy Herd by Hygiene and Management�, J. Dairy Sci. 52:696; F. H. Dodd, D. R. Westgarth, F. K. Neave and R. G. Kingwill, 1969, �Mastitis�The Strategy of Control�, J. Dairy Sci. 52:689; and F. H. Dodd, and F. K. Neave, 1970, �Mastitis Control�, Proceedings, Nat'l. Inst. Res. Dairying, pp. 21-60) conducted extensive epidemiologic investigations in commercial dairy herds. From this work, they developed the conceptual basis for modem mastitis control methods of which teat dipping is an integral component. The efficacy and value of teat dipping has since been confirmed in dozens of field trials, and it is now accepted that an effective teat dip can reduce the incidence of new intramammary infections at least 50% and often up to 90%.
To reduce mastitis, commercial teat dips have been developed containing a variety of antimicrobial agents including iodophors, quaternary ammonium compounds, chlorhexidine salts, chlorine release compounds (e.g. alkali hypochlorites), oxidizing compounds (e.g. hydrogen peroxide, peracids), protonated carboxylic acids (e.g. heptanoic, octanoic, nonanoic, decanoic, undecanoic acids), acid anionics (e.g. alkylaryl sulfonic acids), and chlorine dioxide (from chlorite). These agents, which have varying degrees of effectiveness, limit the transmission of mastitis by reducing pathogen populations on the teat. Teat dips, can also be divided into two broad classifications. The Class I type are antimicrobial and are applied to kill microorganisms already present in the teat canal or on the surface of the teat skin. By design, their microbiological effect is immediate and their targets primarily the contagious organisms that are vectored between animals during the pre-milking, milking and post milking process. The Class II type teat dip, often referred to as a �teat sealer,� is a film-forming or coating composition which may or may not be antimicrobial; and, functions by developing a residual protective barrier on the teat thus providing prophylaxis by sealing the teat off from its environment. The film which forms on the surface of the teat serves as a physical barrier through which mastitis causing pathogens cannot penetrate during the intermilking period.
General disclosures of teat dip technology are shown in: �Current Concepts of Bovine Mastitis.� 1996, Fourth Ed. National Mastitis Council, Madison Wis.; P. A. Murdough and J. W. Pankey, 1993. �Evaluation of 57 Teat Sanitizers Using Excised Cow Teats�, J. Dairy Sci. 76:2033-2038; J. W. Pankey et al., 1984, �Uptake on Post-milking Teat Antiseptics�, J. Dairy Sci. 67:1336-1353; R. J. Farnsworth, 1980, �Role of Teat Dips in Mastitis Control�, J. Am. Vet. Med. Assoc. 76:1116-1118; W. N. Philpot, 1979, �Control of Mastitis by Hygiene and Therapy�, J. Dairy Sci. 62:168-176; W. N. Philpot and J. W. Pankey, 1978, �Hygiene in the Prevention of Udder Infections V. Efficacy of Teat Dips Under Experimental Exposure to Mastitis Pathogens�, J. Dairy Sci. 61:956-963; R. P. Natzke, 1977, �Role of Teat Dips and Hygiene is Mastitis Control�, J. Amer. Vet. Med. Assoc. 170:1196-1198; W. N. Philpot and J. W. Pankey, 1975, �Hygiene in the Prevention of Udder Infections. III. Effectiveness of 59 Teat Dips for Reducing Bacterial Populations on Teat Skin�, J. Dairy Sci. 58:209-216; R. J. Eberhart and J. M. Buckalew, 1972, �Evaluation of a Hygiene and Dry Period Therapy Program for Mastitis Control�, J. Dairy Sci. 55:1683-1691; W. D. Schultze and J. W. Smith, 1972, �Effectiveness of Postmilking Teat Dips�, J. Dairy Sci. 55:426-431; D. P. Wesen and L. H. Schultz, 1970, �Effectiveness of a Post-Milking Teat Dip in Preventing New Udder Infections�, J. Dairy Sci. 53:1391-1403; and British Pat. No. 1,144,637 (Kelco Chemicals Ltd.), published March 5, 1969. U.S. Pat. No. 4,199,602 (Lentsch) issued Apr. 22, 1980, U.S. Pat. No. 4,258,056 (Lentsch) issued Mar. 24, 1981; and U.S. Pat. No. 4,376,787 (Lentsch) issued Mar. 15, 1983 disclose nitroalkanol, amino carboxylate/sulfonate, and sulfonate based compositions. U.S. Pat. No. 4,446,153 (Yang) issued May 1, 1984 discloses a benzyl alcohol/phenyl ethanol based composition.
Typical disclosures of intermilking or protective (barrier-type) film-forming teat dips or teat �sealers� can be found in Akers et. al., U.S. Pat. No. 3.066.071, issued Nov. 27, 1962; Kraus, U.S. Pat. No. 3,222,252, issued Dec. 7, 1965 (but, see Philpot et. al., J. Dairy Science 58:205-216); Coughman and Brown, U.S. Pat. No. 3,993,777, issued Nov. 23, 1976; Pugliese, U.S. Pat. No. 4,049,830, issued Sep. 20, 1977; and Andrews et al., U.S. Pat. No. 4,113,854, issued Sep. 12, 1978. A teat sealer similar or identical to the Andrews et. al. film-forming composition is in commercial use and has been discussed in the dairy science literature. See, for example, R. J. Farnsworth et. al., 1980, �Use of a Teat Sealer for Prevention of Intramammary Infections in Lactating Cows�, J. Am. Vet. Med. Assoc. 177:441-444; and R. J. Farnsworth et. al., 1981, �The Effect of a Teat Sealer on Coliform Mastitis�, The Bovine Practitioner, No. 16, pp. 28-29. Still further examples of barrier-type film-formers for bovine teats can be found in Silver et al., U.S. Pat. No. 4,199,564, issued Apr. 22, 1980; Dybas et al., U.S. Pat. No. 4,311,709, issued Jan. 19, 1982; Marhavka, U.S. Pat. No. 5,017,369, issued May 21, 1991; and Schmidt et al., U.S. Pat. No. 5,503,838, issued Apr. 2, 1996.
U.S. Pat. No. 3,993,777, referenced above, discloses an aqueous thickened quat based formulation of high viscosity containing emollients such as lanolin and glycerin. a The material forms a protective film and bacteriostatic barrier about the teat which is easily removed by washing; thus, transitioning from water insoluble protective films which in practice are peeled from the teat to water washable films. However, the shortfall of this teaching is the use of hydroxyethylcellulose employed as a thickener (its most typical function) in the preferred formulation which, by chance, has the characteristic of forming pliable non-brittle films upon drying. In herd practice, such cellulosic thickeners seldom perform the dual-function role of providing a tenacious barrier, being too readily removed because of its water-sensitivity, wherein the performance of the antimicrobial barrier is lost. U.S. Pat. No. 4,311,709 also discloses a film-forming methycellulose having similar disadvantage as a teat dip barrier. U.S. Pat. No. 4,049,830 discloses a bovine teat dip composition which delivers an oil-in-water emulsion to the teat and, upon drying, forms an antimicrobial lipid solids barrier which remains soft and tacky for prolonged periods and is water washable. Herd experience has shown that soft barriers are too easily abraded or otherwise sloughed off during the intermilking period with subsequent reduction or loss of biocidal function. U.S. Pat. No. 5,017,369 discloses antimicrobial mastitis treatment compositions which utilize a water resistant film-forming agent, polyvinyl alcohol. This art teaches away from incorporation and use of thickener admixtures, suggesting that adequate viscosity can be obtained simply by adjusting the amount of polyvinyl alcohol in the composition. Such compositions are, in application, at commercial disadvantage because polyvinyl alcohol by itself does not provide effective teat cling nor does it decrease the mobility of the dipping liquid which is manifested by excessive drain-off and loss of product; and, therefore significant reduction of barrier function and microbial performance. U.S. Pat. No. 5,503,838 overcomes this disadvantage in disclosing antimicrobial teat dip compositions containing polyvinyl alcohol in cooperation with thickening agents such as a xanthan gum. Unfortunately, neither U.S. Pat. No. 5,017,369 which typically embodies chlorhexidene gluconate or quaternary ammonium compounds as the antimicrobial; nor, U.S. Pat. No. 5,503,838 which uses iodine as the preferred biocidal agent, address the issue of teat dermal irritation caused by residual barrier films containing resident, chemically aggressive, often toxic, antimicrobial agents which remain on skin contact for extended periods of time.
Alliger, U.S. Pat. No. Re. 31,779, reissued Dec. 25, 1984; Alliger, U.S. Pat. No. 4,330,531 (Alliger) issued May 18, 1982; Kross et al., U.S. Pat. No. 4,891,216, issued Jan. 2, 1990; Davidson et al., U.S. Pat. No. 4,986,990, issued Jan. 22, 1991; Davidson et al., U.S. Pat. No. 5,185,161, issued Feb. 9, 1993; and Kross, U.S. Pat. No. 5,597,561 disclose technology embodied in a commercial composition sold as an antimicrobial barrier teat dip under the name UDDER-GOLD PLUS (Alcide Corp., Redmond, Wash.). The patents disclose two aqueous solutions, described as gels, adapted to be mixed in a 50/50 proportion wherein (according to patent and product literature) chlorous acid/chlorine dioxide are generated by chemical reaction of α-hydroxy-benzene-acetic acid (mandelic acid) and sodium chlorite present in first and second gels respectively. The second gel can contain a thickener. Later patents disclose a homopolymer of 2-acrylamido-2-methylpropane sulfonic acid (polysulfonic acid) which forms a protective film over the teat. Although this composition has proven effective, it is not without problem. The herdsman is advised to mix and use the admixture for only one herd milking, discarding any extra. This attribute is likely a consequence of chlorine dioxide loss (hence, loss of antimicrobial efficacy) either from chemical incompatibility and/or off-gassing. The polysulfonic acid �gelling agent� does not immobilize the treatment on the teat and significant drippage/waste occurs. U.S. Pat. No. 5,597,561 teaches that polysulfonic acid has proven problematic because of its strong affinity to the dermal tissue and tendency to form a solid matrix which is difficult to remove by washing.
BRIEF DESCRIPTION OF THE INVENTION We have discovered a mastitis control treatment having important functional properties which are uniquely combined into one composition. The compositions of the invention provide a soothing softening emollient character, rapid initial kill, long lasting antimicrobial activity, a stable chemistry and rheology. The blend of lanolin composition and polyhydroxy emollients provide enhanced softening, smoothing, soothing character to treated skin. The compositions of the invention possess favorable rheology that promotes cling and immobilizes the mastitis treatment on the teat. The composition develops a barrier giving prophylactic protection and containing at least one resident agent for continuous biocidal protection. The composition does not cause dermal irritation and, is removable by a simple water-washing technique. The barrier has sufficient adherence to withstand premature loss of integrity due to abrasion of environmental conditions. Compositions of this invention are mastitis control and prevention treatments often described as �teat dips,� though of course methods of topical aseptic application other than immersion or �flooding� might be used by the herdsman; for example, spraying, brushing, swabbing or foaming onto the teats. When employed as a teat dip, which is a particularly effective practice of application, the teats of the animal are dipped into a reservoir or receptacle containing a composition of the present invention; whereupon, the source is removed, and, preferably one-half to three-fourths of the distal teat has been coated with treatment. After application (by whatever method), the resident treatment adheres onto the teat until drying occurs and development of a protective film results which provides an antimicrobial barrier and prophylactic shield thus protecting the teat from pathogens and adverse environmental factors.
A pseudoplastic aqueous rheology is effected in the composition of the invention by admixtures of polymeric materials such as a xanthan gum and polyvinyl alcohol compositions. When shear stress is applied to the composition (i.e., dipping), product viscosity is reduced allowing easy and rapid application to the teat; and, upon the release of shear (i.e., removal of source), total viscosity recovery occurs almost instantaneously immobilizing the coating, providing cling and assuring little waste by drippage. Further, said compositions have little or no viscoelastic character which thus allows the treatment to flow and to coat the teat smoothly, forming a continuous efficacious layer over the skin of the teat without formation of muscilage streamers as the applicator is withdrawn. The compositions flow slightly down the teat following application to form a thicker layer or �plug� across the orifice of the teat canal; and, thus cause a more effective prophylactic barrier against bacteria entering the teat canal.
A unique preferred antimicrobial composition is accomplished that can contain one fugitive biocidal agent, chlorine dioxide, and one or more non-fugitive acid biocidal agents such as a C6-12 carboxylic acid, including heptanoic acid, pelargonic acid (nonanoic acid), etc.; an anionic sulfonate, including dodecylbenzenesulfonic acid, and other acidic antimicrobials and mixtures thereof. Such admixtures provide superior cooperative antimicrobial effect. The combined agents provide an immediate, additive biocidal action to contagious mastitis causing pathogens present on the teat when the composition is first applied. A continuous, longer term antimicrobial action is afforded by the non-volatile agents which become enveloped into the barrier film upon drying. Chlorine dioxide, formed in-situ by reacting ingredients within the composition, is present only during the initial application of treatment onto the teat and can off-gas during treatment dry-down. This effect is advantageous because the superior antimicrobial properties of chlorine diodide are utilized to destroy the pathogens of greatest concern to the herdsman, i.e., the contagious mastitis causing organisms already on the teat and in the distal teat canal orifice; but, once applied, chlorine dioxide dissipates and thus removes the potential for severe teat skin irritation which otherwise might result from this very reactive chemical; and, for any incidental residuals in the producers milk. Heptanoic acid or nonanoic (pelargonic) acid, which are preferred antimicrobial agents within compositions of the present invention, and/or dodecylbenzenesulfonic acid, all being of non-volatile character, augment the biocidal performance of chlorine dioxide upon initial application; and, as treatment drying occurs with subsequent barrier formation, become resident within the prophylactic coating wherein the agents provide continuous and efficacious antimicrobial protection from mastitis causing environmental organisms. After the chlorine dioxide component, made in situ by the combination of the aqueous acidulant part with the aqueous chlorite part, becomes volatilized and is thus removed from the composition, the composition maintains extended antimicrobial activity and the composition maintains an effective barrier, including a milk duct plug, to environmental pathogens and soils.
Surprising and unexpected long term chlorine dioxide residence and chemical stability results in practice which is in distinct contrast to commercial embodiments of prior art, specifically and particularly the commercial antimicrobial teat dip sold under the name UDDER-GOLD PLUS (Alcide Corp. Redmond, Wash.), having affixed use instructions which advise the user to blend, in equal proportions, only sufficient admixture of cooperative parts (UDDER-GOLD PLUS BASE and UDDER-GOLD PLUS ACTIVATOR) for one herd milking�discarding any remainder.
We have discovered that preferred mastitis treatment compositions of this invention, once having formed chlorine dioxide in-situ from chemical reactants blended together by the herdsman in preassigned proportion, retain this antimicrobial agent and associated antimicrobial property within the admixed teat treatment for extended periods of time. A typical useful application life span of such product being approximately one month following preparatory blending. We believe this unusual chlorine dioxide stability is an additional consequence of the Theological properties of the preferred compositions whereby the chlorine dioxide gas is entrapped and held homogeneously dispersed throughout the product. Such attribute has many practical advantages for the herdsman including convenience of preblending large mixtures of teat treatment and eliminating need for repeatedly preparing the exact quantity applied at each milking, reducing wasteful and costly disposal of unused, but unstable product which cannot be saved for next milking; and, enhanced safety for the user who would otherwise be exposed to off-gassing chlorine dioxide fumes during the milking process.
The compositions of the invention comprise an admixture comprised of two cooperative parts: The first part, of major or equal proportion, having, in aqueous liquid mixture, an acid component and the plurality of components used in the mastitis control compositions of this invention and including all ingredients of organic structure including rheology modifiers and thickeners; emollients, humectants, conditioners and medicaments; surfactants and hydrotropes; antimicrobial agents and preservatives; buffers, acidulants; chromophores and the like: The second part, of equal or minor proportion, being a chlorous acid or salt thereof, more specifically, an alkali metal chlorite; being of aqueous liquid, particulate-powder, or compressed or cast molten solid form; and, generally in practice, added to the first part of the admixture. Further, the aforementioned second part must, if liquid, be readily miscible or, if solid, be easily soluble within the first part to effect rapid homogeneous blending which is of particular importance when large quantities of this admixture are prepared on site by the herdsman. Experience has taught that favorable admixture blending is best accomplished by liquids of the second part having no ordered structure, i.e. no thickened or gelled character; and, by solids of the second part having large surface area. In practice, this means liquids having fluid characteristics similar to water, and solids having particulate form.
The primary function of the second part is to carry the chlorine dioxide release agent into the admixture of this mastitis control treatment; however, lesser adjuvants may be included within, e.g., alkali metal carbonate salts added to commercial chlorite solutions to improve stability. Such lesser adjuvants must not alter, to any appreciable degree, rheology properties of the second part other than characteristic of the aqueous carrier itself. Once joined, the alkaline chlorine (III)/chlorite composition of the second part is blended into the acidic solution of the first part with resulting admixture having a buffered pH of approximately 3.0; whereupon, and by chemical reaction well known in the scientific art and literature, the disproportionation of chlorine (III)/chlorite occurs with a measured rate of formation of chlorine dioxide. Because this reaction begins immediately and because only very small quantities of chlorine dioxide are required for pronounced microbiocidal effect, the thus prepared mastitis control treatment is ready for application as soon as needed.
Commercial compositions of the invention are held within a user friendly dual or �duet� packaging combination designed to contain and transport parts A and B of these compositions together in predetermined and premeasured proportions and to be cooperative in the blending process wherein the user pours or otherwise causes the entire contents of package B, an equal or minor proportion, to be discharged into package A, an equal or major proportion, which then becomes the container and holding device for the admixture or final mastitis control treatment.
BRIEF DESCRIPTION OF THE DRAWINGS FIGS. 1A , 1B, 1C, 1D, 2A and 2B are graphical representations of the test data and comparisons shown in the tables of data in the application.
FIG. 1A is a four week biocidal efficacy analysis of Example II using the food contact sanitizing protocol.
FIG. 1B is a four week biocidal efficacy analysis of Example II using the food contact sanitizing protocol with a 10% milk challenge.
FIGS. 1C and 1D detail four week biocidal biocidal efficacy analyses of the UDDER GOLD PLUS formulation obtained under similar conditions as the data in FIGS. 1A and 1B respectively.
FIG. 2A is a graph showing the four week efficacy analysis of the UDDER GOLD PLUS formulation using the porcein skin test protocol.
FIG. 2B is a four week efficacy analysis of Example II using the procein skin test protocol.
DETAILED DESCRIPTION OF THE INVENTION Components Used in the Mastitis Control Compositions of this Invention
Acidulants are necessary ingredients within the mastitis control treatments of the invention to maintain the appropriate pH for dissociation of the chlorite/chlorine dioxide release agent and to prevent dissociation of heptanoic, octanoic, nonanoic, decanoic and undecanoic carboxylic acids employed as non-fugitive antimicrobial agents. Carboxylic acids become increasingly biocidal as the pH falls below their pKa value; consequently, for the carboxylic acids mentioned above, a pH ranging from about 2.5 to 5.5, preferably from about 2.5 to 4.5 and most preferably from about 2.5 to 3.5 is desirable. The acidic component used to prepare the acidic teat dip compositions of the invention will comprise a weak inorganic acid or a weak organic acid which can be dissolved in the aqueous system of the invention to produce an acidic pH. A pH substantially less than about 1 can result in substantial irritation, while a pH greater than about 5 can unacceptably reduce the efficiency of the composition. The term �weak� as used in reference to an acidic component is intended to refer to an acid in which the first dissociation step does not proceed essentially to completion when the acid is dissolved in water at ambient temperatures at a concentration within a range useful to form the present compositions. Such inorganic and organic acids are also referred to as weak electrolytes as the term is used in Textbook of Quantitative Inorganic Analysis, I. M. Kolthoff et al., eds., The Macmillan Co. (3d ed., 1952) at pages 34-37, the disclosure of which is incorporated by reference herein.
Most common commercially-available weak inorganic and organic acids can be used in the invention. Preferred weak inorganic acids include phosphoric acid and sulfamic acid. Useful weak organic acids include acetic acid, hydroxyacetic acid, citric acid, tartaric acid and the like. Acidulants found useful include organic and inorganic acids such as citric acid, lactic acid, acetic acid, glycolic acid, adipic acid, tartaric acid, succinic acid, propionic acid, malic acid, alkane sulfonic acids, cycloalkane sulfonic acids, as well as phosphoric acid and the like or mixtures thereof Preferred acidulants are those commonly referred to as C2-6 alpha-hydroxycarboxylic acids, that group of acids which contain a hydroxy function in the alpha position directly adjacent to the carbon atom bearing the carboxyl function, examples of alpha-hydroxymonocarboxylic acids being glycolic, lactic and hydroxybutanoic acid; and, examples of hydroxydicarboxylic acids being malic and tartaric acids. We have found a surprising interaction between the acidulant material and a second antimicrobial acid composition. Preferably, the acidulant material comprises the C2-6 alpha-hydroxy carboxylic acid in combination with a secondary antimicrobial acid composition. The second antimicrobial acid composition can comprise a C7-11 carboxylic acid or a hydrocarbon sulfonic acid composition. These materials work together to provide a cooperative antimicrobial action which effects initial kill from chlorine dioxide contributed by the acidulated chlorite and a long lasting kill in the barrier layer from the carboxylic acid/sulfonic acid material. This cooperation of ingredients is an important aspect of the invention.
Used in personal care products, alpha-hydroxycarboxylic acids absorb moisture from the atmosphere and therefore, when applied topically, increase moisture content and plasticity of the stratum corneum. They have had significant impact on skin treatment due to their ability to reduce corneocyte adhesion and accelerate cell proliferation within the basal layers. Though mechanism of action is not yet fully understood, alpha-hydroxycarboxylic also are thought to stimulate synthesis of collagen and mucopolysaccharides in the dermis. At use levels under 10%, skin care benefits are derived through a continued pattern of product usage. Continued use of products with alpha-hydroxycarboxylic acids levels below 10% has been shown to result in gradual reduction of fine lines and an improvement in skin texture through accelerated desquamation. Although conjecture at present, it is believed that some, if not all of these advantages may also be transferred upon the bovine teat skin. By incorporating an alpha-hydroxycarboxylic acid, healing may be accelerated; and, by �smoothing� the dermal surface, cleaning and asepsis may be improved. The most preferred alpha-hydroxycarboxylic acid for compositions of this invention is lactic acid.
Numerous inorganic and organic antimicrobial agents may be utilized in teat dip compositions including (but not limited to) chlorine and bromine release compounds (e.g. alkali and alkaline earth hypochlorites and hypobromites, isocyanurates, chlorinated derivatives of hydantoin, sulfamide, amine, etc.), iodine release complexes of surfactants or polymers such as polyvinylpyrrolidone (termed iodophors), quaternary ammonium compounds, chlorhexidine salts, peroxide and peroxyacid compounds, protonated short chain carboxylic acids, acidified anionic surfactants and chlorine dioxide. Of these typically applied antimicrobial agents which have been investigated for control of bovine mastitis, protonated short chain (C7-11)carboxylic acids, acidified alkylaryl sulfonates and chlorine dioxide are proven efficacious against mastitis causing microorganisms; and, are preferred in compositions of the present invention. More specifically, dodecylbenzene sulfonic acid, protonated C7-11 carboxylic acids and chlorine dioxide are especially preferred antimicrobial agents.
Inorganic thickeners are generally compounds such as colloidal magnesium aluminum silicate (VEEGUM�), colloidal clays (Bentonites), or silicas (CAB-O-SILS�) which have been fumed or precipitated to create particles with large surface to size ratios. Natural hydrogel thickeners of use are primarily vegetable derived exudates. For example, tragacanth, karaya, and acacia gums; and extractives such as caragheenan, locust bean gum, guar gum and pectin; or, pure culture fermentation products such as xanthan gum are all potentially useful in the invention. Chemically, all of these materials are salts of complex anionic polysaccharides. Synthetic natural-based thickeners having application are cellulosic derivatives wherein the free hydroxyl groups on the linear anhydro-glucose polymers have been etherified or esterified to give a family of substances which dissolve in water and give viscous solutions. This group of materials includes the alkyl and hydroxyllalkycelluloses, specifically methylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethycellulose, hydroxyethylcellulose, ethylhydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose. Synthetic petroleum-based water soluble polymers are prepared by direct polymerization of suitable monomers of which polyvinylpyrrolidone, polyvinylmethylether, polyacrylic acid and polymethacrylic acid, polyacrylamide, polyethylene oxide, and polyethyleneimine are representative.
All thickeners do not work with equal effectiveness in this invention. Preferred aqueous thickening agents which are more useful in this invention are those which are extremely pseudoplastic (non-Newtonian, rapid relaxation), tend not to develop a rigid three-dimensional structure from interpolymer interactions, have a low or negligible viscoelastic character and possess a high gel strength. Such Theological properties are manifested in a teat dip composition which has a smooth flowing appearance, is easy to pour and apply onto the teat, coats uniformly without forming muscilage streamers as the applicator is withdrawn and remains firmly in place without significant sag. Examples of preferred rheology modifiers are xanthan gum and the hydroxylalkylcelluloses. Generally, the concentration of thickener used in the present invention will be dictated by the final composition any by the method of teat application. Spraying or misting requires a lower composition viscosity for easy and effective application of treatment than dipping. Film-forming barrier dips typically require high apparent viscosity necessary to form thick coatings on teats which insures improved prophylactic effect.
For compositions of this invention designed to provide a barrier for prophylactic protection, additional film-forming agents are included which typically work in conjunction with thickeners. In fact, many of the aforementioned rheology modifiers are themselves film formers of greater or lesser effectiveness; however, a preferred grade of polyvinyl alcohol when used with preferred thickeners such as xanthan gum or hydroxyalkylcelluloses affords particularly useful properties to compositions of this teaching, most notably the development of �balanced� films on treated teats which are sufficiently water-sensitive to be stripped off with conventional udder washing, but capably adherent to the teat skin to withstand premature loss of integrity between milkings and intrinsically resistant to environmental exposure; and, in addition, are of such structure as to successfully occlude antimicrobial agents within the film matrix for continuing biocidal effect against mastitis causing organisms. The success of the barriers thus formed by compositions of this invention are, in part, a consequence of a hydrophobic-hydrophilic balance, caused when non-volatile ingredients, especially fatty acids, surfactants and hydrotropes, become resident throughout the film and whose individual properties become additive with those characteristics of the thickeners and film formers. Such inclusions also plasticize the film and render it pliable.
Polyvinyl alcohol compositions can be used as a film former. Variation of film flexibility, water sensitivity, ease of salvation, viscosity, film strength and adhesion can be varied by adjusting molecular weight and degree of hydrolysis. The preferred polyvinyl alcohol for use in compositions herein has a degree of hydrolysis greater than 92%, preferably greater than 98%, most preferably greater than 98.5%; and, has a molecular weight (Mn) that falls in the range of between about 15,000 and 100,000, but preferably between 40,000 and 70,000 corresponding to a solution viscosity (4% wt aqueous solution measured in centipoise (cP) at 20� C. by Hoeppler falling ball method) of 12-55 cP and 12-25 cP respectively.
In general, the pH of bovine mastitis control treatments can vary from a low of about pH 2.0 to a maximum of approximately 11.0 depending primarily upon the choice of antimicrobial agent being incorporated in the composition because optimal efficacy normally occurs with a specific, narrow, pH range. Therefore the buffering agent or system is chosen accordingly. The preferred pH range of compositions of this invention is typically from 2.5 to 5.5 most preferably, about 2.5 to 3.5�the lower value being a limit to prevent excessive irritation on the teat surface; and, the upper limit set to enhance chlorine dioxide formation and maintain antimicrobial effect of the protonated carboxylic acid(s) and/or acidified anionic surfactant. A typical and preferred buffer system would be citric acid and its alkali metal salt. However, any acidulant and corresponding conjugate weak base could be used.
Teat dip compositions of the present invention generally also comprise an emollient and/or humectant to lubricate, condition, soothe, smooth, soften, and generally reduce and promote the healing of irritation on the teat surface. Such irritation may result either from the antimicrobial agent, from the mechanical action of the milking machine or from environmental conditions such as wind chill, dehydration, abrasion and sunburn. Any water soluble or dispersible skin conditioning agent may be used in this present invention. Compositions such as polyhydric alcohols are useful in the invention including glycerin, sorbitol, mannitol, and propylene glycol and its homopolymers; fatty acid esters of simple monohydril alcohols including isopropyl palmitate or isopropyl myristate and similar esters; polyol esters of fatty acids; and, ethoxylated lanolins, vegetable oils, and similar natural sourced derivatives such as aloe. Preferred emollients to be used in the invention include glycerin, sorbitol, and propylene glycol. A preferred emollient system for use in the invention comprises a combination of lanolin and a polyhydroxy emollient composition. The preferred emollient composition comprises lanolin, a lanolin derivative combined with a polyhydroxy compound selected from the group consisting of glycerin, sorbitol, glucitol, propylene glycol and mixtures thereof. Lanolin, a commodity material, also known as wool fat, oespios, agnin, alaporin, is a waxy fatty secretion of sheep. In sheep, sebaceous glands secrete a �fat-like� waxy secretion which is deposited onto the woll fiber. Chemically a wax, the material is a complex mixture of esters and polyesters of 33 high-molecular-weight alcohols and 33 fatty acids. The alcohols are of three types: aliphatic alcohols, steroidal alcohols and triterpenoid alcohols; the acids are of three types: saturated non-hydroxylated acids, unsaturated non-hydroxylated acids and hydroxylated acids. Liquid lanolin is rich in low molecular weight branched aliphatic acids and alcohols while waxy lanolin is rich in high molecular weight straight chain acids and alcohols. Reviews regarding compositions, derivatives, modifications and uses are found in Barnet, Drug and Cosmet. Ind., Ad, 744 (1957); 83, 292 (1958); Leideritz, Chem. Ikerztg., 83, 707 (1959); F. Fawaz et al., Ann. Pharm. Franc., 33, 217, 226 (1973). Rheological properties of lanolin are discussed in F. Poisieux, Pharm. Acta. Helv., 51, 289 (1976). Please also the monograph: E. V. Truter, Wool Wax, Chemistry and Technology, (Interscience, 1956). The typical lanolin product contains about 20-25 wt % water and is yellowish white in color having a slight odor. The material is, for all practical purposes, insoluble in water but is soluble in chloroform or ether with the inherent separation of water from the wax lipid mass. Anhydrous lanolin is yellowish, tenacious, semisolid fatty appearing material, with a slight odor. Anhydrous lanolin melts at 38-42� C., is insoluble in water, but sparingly soluble in alcohol while freely soluble in benzene, chloroform, ether, carbon disulfide, acetone or petroleum ether. Lanolin is a natural product material produced in the manufacture of wool yarn. A preferred emollient composition contains a lanolin derivative in combination with a polyhydroxy compound. A variety of relatively neutral emollient lanolin species are known including a lanolin glycerol ester or ether, acetylated lanolin alcohol, lanolinamide DEA isopropyl lanolate, oleyl lanolate, hydrogenated lanolin, hydroxylated lanolin, lanolin lanoleate, isobutylated lanolin oil, lanolin ricinoleate, lanolin wax and a polyethylene glycol derivative of lanolin (PEG-lanolin). The PEG-lanolin derivative (CAS number 61790-81-6) can contain from about 5 to about 100 moles of ethylene glycol per mole of the PEG lanolin derivative. Preferred derivatives comprise about 40 to 85 moles of ethylene oxide per mole derivative. These materials are sold under the tradenames LANETO-50; SOLAN-50; ETHOXYLAN-50; SOLULAN-75 from a variety of commercial sources. A preferred humectant for use in these materials comprises combining, in a fully formulated teat dip material, about 0.01 to about 100 parts by weight of the PEG lanolin derivative for each one part by weight of a polyhydroxy compound selected from the group consisting of glycerine, sorbitol, glucitol and mixtures thereof. The preferred teat dip compositions contain about 0.1 to about 15 wt % of the polyhydroxy humectant combination, preferably about 0.2 to 5 wt % and about 0.1 to 10 wt. %, preferably 0.5 to 5 wt. % of the lanolin composition. The combination of the lanolin derivative and the polyhydroxy emollient compound provides surprisingly enhanced soothing protection for animals exposed to repeated milking and harsh conditions.
The surfactant or surfactant admixture of the present invention can be selected from compatible water soluble or water dispersible nonionic, or anionic surface-active agents; or mixtures of each or both types. Nonionic and anionic surfactants offer diverse and comprehensive commercial selection, low price; and, most important, excellent detersive effect�meaning surface wetting. Surface-active or �wetting agents� function to increase the penetrant activity of the invention into the tissue surface at risk from mastitis causing pathogens. Nonionic surfactants useful in the invention are generally characterized by the presence of an organic hydrophobic group and an organic hydrophilic group and are typically produced by the condensation of an organic aliphatic, alkyl aromatic or polyoxyalkylene hydrophobic compound with a hydrophilic alkaline oxide moiety which in common practice is ethylene oxide or a polyhydration product thereof, polyethylene glycol. Practically any hydrophobic compound having a hydroxyl, carboxyl, amino, or amido group with a reactive hydrogen atom can be condensed with ethylene oxide, or its polydration adducts, or its mixtures with alkoxylenes such as propylene oxide to form a nonionic surface-active agent. The length of the hydrophilic polyoxyalkylene moiety which is condensed with any particular hydrophobic compound can be readily adjusted to yield a water dispersible or water soluble compound having the desired degree of balance between hydrophilic and hydrophobic properties.
Useful nonionic surfactants in the present invention include: Block polyoxypropylene-polyoxyethylene polymeric compounds based upon propylene glycol, ethylene glycol, glycerol, trimethylolpropane, and ethylenediamine as the initiator reactive hydrogen compound. Examples of polymeric compounds made from a sequential propoxylation and ethoxylation of initiator are commercially available under the trade name PLURONIC� manufactured by BASF Corp. PLURONIC� compounds are difunctional (two reactive hydrogens) compounds formed by condensing ethylene oxide with a hydrophobic base formed by the addition of propylene oxide to two hydroxyl groups of propylene glycol. This hydrophobic portion of the molecule weighs from about 1,000 to about 4,000. Ethylene oxide is then added to sandwich this hydrophobe between hydrophilic groups, controlled by length to constitute from about 10% by weight to about 80% by weight of the final molecule. TETRONIC� compounds are tetra-functional block copolymers derived from the sequential additional of propylene oxide and ethylene oxide to ethylenediamine. The molecular weight of the propylene oxide hydrotype ranges from about 500 to about 7,000; and, the hydrophile, ethylene oxide, is added to constitute from about 10% by weight to about 80% by weight of the molecule.
Other useful surfactants are nonionics made by adding ethylene oxide to ethylene glycol to provide a hydrophile of designated molecular weight; and, then adding propylene oxide to obtain hydrophobic blocks on the outside (ends) of the molecule. The hydrophobic portion of the molecule weighs from about 1,000 to about 3,100 with the central hydrophile comprising 10% by weight to about 80% by weight of the final molecule. These �reverse� PLURONIC�'s are manufactured by the BASF Corporation under the trade name PLURONIC� surfactants. Likewise, the TETRONIC� surfactants are produced by the BASF Corporation by the sequential addition of ethylene oxide and propylene oxide to ethylenediamine. The hydrophobic portion of the molecule weighs from about 2,100 to about 6,700 with the central hydrophile comprising 10% by weight to 80% by weight of the final molecule.
Tertiary amine oxides corresponding to the general formula: can be used wherein the→bond is a conventional representation of a semi-polar bond; and R1, R2, and R3 may be aliphatic, aromatic, heterocyclic, alicyclic groups or a combination of such groups thereof. Generally, for amine oxides of detergent interest, R1 is an alkyl radical of from about 8 to about 24 carbon atoms; R2 and R3 are selected from the group consisting of alkyl or hydroxyalkyl of 1�3 carbon atoms and mixtures thereof; R4 is an alkylene or a hydroxyalkylene group containing 2 to 3 carbon atoms; and n ranges from 0 to about 20. Useful water soluble amine oxide surfactants are selected from the coconut or tallow dimethyl amine oxides.
Alternatively, the compositions of the invention may be comprised of any number of optional ingredients, i.e. adjuvants. Depending upon the benefits provided, adjuvants may partially or wholly displace the carrier in the composition. Generally, in accordance with the invention, there may be included within this composition formulary adjuvants which assist in the application of the invention with respect to physical and chemical stability, barrier film formation, teat health maintenance, performance, physical form and manufacturing process anesthetics. Of course, these functions may be accomplished exclusively by composition ingredients already described or admixtures thereof; however, formulary or application or performance situations may occur requiring additional effect which may be accomplished by introducing an additional inorganic or organic agent or agents and mixtures thereof into the composition.
Table �Bovine Mastitis Treatment Admixture Compositions�, below, provides guidelines for consistent concentrations in accordance with this invention.
0.1-30 The following examples and data are provided to illustrate preferred embodiments of the invention and contain a best mode.
EXAMPLE I Example I is a representative embodiment of this invention which illustrates a bovine mastitis treatment having barrier film properties. Antimicrobial effect is provided by generation of chlorine dioxide caused by disproportionation of chlorite ion upon admixture of composition base with activator and by the resident biocidal activity of protonated nonanoic acid.
A 16 liter batch of the following experimental base formula part and 1 kilogram of the ClO2 −1 part was prepared by blending the ingredients as shown.
(KELTROL � K5C151)
**ELVANOL � Premix,
*KELTROL � K5C151 is a grade of xanthan gum manufactured by Kelco. **ELVANOL � Premix: 10% aqueous solution of ELVANOL � 90-50. ELVANOL � 90-50 is a grade of polyvinyl alcohol manufactured by E. I. duPont. Activator ClO2 −1 Formula (Part II) (pH=12.3)
About 3376 grams of the base formula part were blended with about 92.89 grams of the CLO2 −1 part (the ClO2 − is 0.32% of total composition). The viscosity (Brookfield Model DV-II Viscometer, spindle No. 1, 20 rpms at 25� C.) was about 304 cps.
EXAMPLE II Example II is a further example of this invention which differs from Example I in that the resident biocidal activity is contributed by dodecylbenzene sulfonic acid. The hydrotropic agent, octane sulfonate, is not required in this formula for physical stability.
*KELTROL � K5C151
*KELTROL � K5C151 is a grade of xanthan gum manufactured by Kelco. **ELVANOL � *Premix: 10% aqueous solution of ELVANOL � 90-50. ELVANOL � 90-50 is a grade of polyvinyl alcohol manufactured by E. I. duPont. Activator ClO2 −1 Formula (Part II) (pH=12.3)
(#1, 20 rpm
@ 25� C.)
EXAMPLE III Example III is a representative composition of the invention illustrating a bovine mastitis treatment without a barrier film property and having no thickening nor film-forming agents. A surfactant, NEODOL� 25-9, is included for teat cleansing and surface wetting.
A two hundred grain batch of the following experimental base formula and a 1 kilogram batch of the ClO2 −1 activator part was made.
Dye -F, D & C
*Pigment: PYLAKLOR � Yellow LX-10192 and Permanent Green S-722 (50:50 blend) manufactured by Pylam Products Co. Inc. Ingredients
EXAMPLE IV Example IV is a further modification of Example III using sorbitol as an emollient in place of glycerin. A two hundred gram batch of the following experimental base formula and a 1 kilogram batch of the ClO2 − activator part was made.
ethoxylate NEODOL �
*Pigment: PYLAKLOR � Yellow LX-10192 and Permanent Green S-722 (50:50 blend) manufactured by Pylam Products Co. Inc. Activator ClO2 −1 Formula (Part II) (pH=12.3)
EXAMPLE V Example V is a further composition of the invention illustrating a bovine mastitis treatment without a barrier film property, again having no thickening nor film-forming agents and using phosphoric acid as the acidulant. A surfactant, NEODOL� 25-9, is included for teat cleansing and surface wetting. A two hundred gram batch of the following experimental base formula and a 1 kilogram batch of the ClO2 −1 activator part was made.
EXAMPLE VI Examples VI, VII and VIII are compositional variations of Example I which contain the homologous carboxylic acids octanoic, decanoic and a mixture thereof respectively.
KELTROL � K5C151
*ELVANOL � Premix: See p. 27 Activator ClO2 −1 Formula (Part 2) (pH=12.3)
The mixed product made with 100 grams of Part 1 formula and 2.75 grams of Part 2 is buffered to pH 2.9.
EXAMPLE VII A 200 gram batch of the following experimental base formula and a 1 kilogram batch of the ClO2 − activator part was prepared.
*ELVANOL � Premix,
*ELVANOL � Premix: See p. 27 Activator ClO2 −1 Formula (Part 2)(pH=12.3)
The mixed product made with 100 grams of the Base Part 1 Formula combined with 2.75 grams of the activator Part 2 ClO2 −1 formula. The material is buffered to pH 2.9.
EXAMPLE VIII A 200 gram batch of the following experimental base formula and a 1 kilogram batch of the ClO2 − activator part was prepared.
*KORTACID � - C8:C10
*KORTACID �: 3:1 Octanoic/deanoic blend manufactured by Akzo Chemical. *ELVANOL � Premix: See p. 27 Activator ClO2 −1 Formula (Part 2) (pH=12.3)
The mixed product made using 100 grams of Part 1 and 2.75 grams of Part 2 is buffered to pH 2.9.
EXAMPLE IX Example IX is an additional variation of Example I containing heptanoic acid and n-propanol in place of nonanoic and isopropanol respectively.
1000 gram batch of this experimental base formula was prepared; and, 1000 grams of the ClO2 − part was prepared by blending the ingredients as shown. Two typical admixtures of parts I and II were then prepared or illustrated.
93 (6.28% active) → 0.16% NaClO2 EXAMPLE X A 500 gram batch of the following experimental base formula was prepared for preliminary testing. This example is similar to Example I with n-propanol and half of the NaClO2 amount.
**Pigment
*ELVANOL � Premix: See p. 27 **Pigment: See p. 29 Activator Formula (Part II) (pH=12.0)
93 (6.28% active) → 0.16% NaClO2 EXAMPLE XI A 1000 gram batch of the following experimental base formula was prepared for testing. This composition is similar to Example III with NAS and thickener.
**Pigment 5.0%
1000.00→
pH =�
*Pigment: See p. 29 Ingredients
EXAMPLE XII A 1000 gram batch of the following experimental base formula was prepared for testing. This composition is similar to Example IV with an octane sulfonate.
Base Formula (Part I) (H=2.7)
pH = �
Activator Formula (Part II) (pH=12.3)
EXAMPLE XII A 1500 gram batch of the following experimental base formula was prepared for testing. Similar to Example III with NAS, thickener and heptanoic acid.
1.377 (6.25% active)
2.754 (6.25% active)
12.39 (6.25% active)
EXAMPLE XIV A 1500 gram batch of the following experimental base formula was prepared for testing. Similar to Example IV with NAS and heptanoic acid.
**Dye/Pigment 5.0%
**Pigment: See p. 29 Activator Formula (Part II) (pH=12.0)
Germicidal and Detergent Sanitizing Action of Disinfectants Testing Created From AOAC Method 960.09
2. Nutrient Agar B (French Slants):
1. Tryptone Glucose Extract Agar (TGE):
1. Neutralizer Stock:
a. A mixture of 49.5 mL Chambers solution and 49.5 mL of 1% aqueous Na2S2O3 2. Neutralizer Blanks:
a. Aseptically dispense 9 ml of neutralizer into sterile 25�150 mm test tubes for use in the test.
3. Phosphate Buffer Stock (0.25M)
4. Phosphate Buffer Dilution Water
250 ml Erlenmeyer flasks, 100 ml volumetric flasks, pipettes, glass beads, 20�150 and 25�150 mm test tubes. Sterilize for 20 minutes at 121� C. or in a dry air oven at 180� C. for 180 minutes.
2. Petri Dishes
Sterile disposable petri dishes, 15�100 mm.
3. French Bottles (milk dilution bottles)
175 ml flint glass bottles
4. Water Bath
Constant temperature water bath that can maintain a test temperature �2� C. of required test temperature. Monitor temperature throughout the test.
5. Transfer Loops
Suitable metal or plastic disposal transfer loops
Maintain on Nutrient Agar A slants at 4� C. with transfers to new stock slants once per month (reference SOP MS031 for culture maintenance). From the stock culture slant, make >3 and <30 consecutive transfers on nutrient agar slants with incubation at 37� C.�2� C. for 20-24 hours. If only one daily transfer has been missed, no special procedures are required; if 2 or more daily transfers are missed, repeat with 3 daily transfers.
Inoculate french slants by washing the growth from the Nutrient Agar A slant into 99 ml of phosphate buffer as follows: Use 5 ml of buffer on the slant and rinse this into the balance of the 99 ml of buffer. Mix this suspension well and add 2 ml of suspension to each french slant. Tilt the slant back and forth to cover the surface. Remove the excess suspension Aseptically. Incubate the slants at 37� C.�2� C. for 18-24 hours.
Standardize the culture suspension by dilution using sterile phosphate buffered water to yield 10�109 organisms per milliliter. 10�109 organisms/ml corresponds roughly to % transmittance readings of 0.1% to 1.0%T at 580 nm. It is recommended that each individual operator determine what %T readings they need to achieve a 10�109 organisms/ml culture suspension prior to performing this test since validity of the test is based on having the proper inoculum.
Dispense 99 ml of test substance into a sterile 250 ml Erlenmeyer flask. Prepare triplicate flasks for each test substance to be tested. Place flasks containing test substance into a 25� C. temperature water and let rest ≧20 minutes or until reaches test temperature.
Dispense 90 ml of test substance and 10 mL of milk challange into a sterile 250 ml Erlenmeyer flask, mix and remove 1.0 mL. Prepare duplicate flasks for each test substance to be tested. Place flasks containing test substance into a 25� C. temperature water and let rest ≧20 minutes or until reaches test temperature
→ 100 → 10−2 → 10−4 → 106 ture
From the 10−6 dilution, plate 1 ml (106) and 0.1 ml (10−7) in quadruplicate. Use pour plate technique with TGE medium. Invert and incubate at 37� C.�2� C. for 48 hours.
For regulatory documentation testing, plate 1 ml (10−1) and 0.1 ml (10−2) from the neutralizer blank tube in quadruplicate. For non-regulatory testing, serial dilutions may be performed in sterile phosphate buffer to yield dilutions of 10−1, 10−3, and 10−5. These dilutions are usually single platings. Use pour plate technique with neutralized (appropriate for test substance inactivation) TGE medium. Invert and incubate at 37� C. �2� C. for 48 hours.
Determine the resistance of the test system to phenol according to standard procedures. The test system must meet the resistance specified in that SOP.
Test A=Add 1 ml of test substance use-solution to 9 ml of the neutralizer and mix. Add 0.1 ml of �10−3 cfu/ml test system suspension, mix.
Test B=Add 1 ml of test substance diluent to 9 ml of the neutralizer and mix. Add 0.1 ml of �10−3 cfu/ml test system suspension, mix.
Test C=Add 0.1 ml of �10−3 cfu/ml test system suspension to 9 ml of phosphate buffered dilution water and mix.
The data obtained will show the neutralizer to be effective if a≡c. The neutralizer will be observed not be detrimental to the cells if b≡c.
Plate 1 ml of diluent used in the test. Incubate at 37� C.�2� C. for 48 hours.
When freshly prepared both the composition of Example II and UDDER GOLD PLUS achieved a greater than 5 log reduction after 15 seconds with and without a 10% milk challenge against both Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229.
After one week, Example II achieved a >5 log reduction after 15 seconds with and without a 10% milk challenge against both Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229. UDDER GOLD PLUS achieved a 1.42 log reduction against Escherichia coli ATCC 11229 in 15 seconds without milk, while achieving a 0.61 log reduction with the 10% milk challenge. Against Staphylococcus aureus ATCC 6538 UDDER GOLD PLUS achieved a log reduction of 1.42 without milk, and 0.59 with a 10% milk challenge.
After three weeks, Example II achieved a >5 log reduction after 15 seconds with and without a 10% milk challenge against Staphylococcus aureus ATCC 6538. Against Escherichia coli ATCC 11229 a reduction of3.91 was seen with the 10% milk challenge while a 5.67 log reduction was seen without the challenge. UDDER GOLD PLUS achieved a 1.86 log reduction against Escherichia coli ATCC 11229 in 15 seconds without milk, while achieving a 0.26 log reduction with the 10% milk challenge. Against Staphylococcus aureus ATCC 6538 UDDER GOLD PLUS achieved a log reduction of 1.78 without milk, and 0.36 with a 10% milk challenge.
Escherichia coli ATCC II1229
1. One inch squares of sterile lyophilized porcine skin (Corethium�2, Johnson & Johnson UK) were rehydrated in sterile distilled water for 1 hour.
3. The squares were then place din a sterile petri dish and inoculated with 10 microliters of a 24 hour broth culture for the organism to be tested. After inoculation, samples were allowed a contact time of 5 minutes.
6. Plates were incubated at 37� C. for 48 hours.
7. A neutralization test was also performed.
ExposureTime to
ClO2 Example II Formula 5
The teat dip compositions of the invention using nonanoic acid and a sulfonate material in a formulation with 1-propanol, were tested for their properties in coating and forming a useful antimicrobial layer that maintains a sufficient quantity of material on the animal. A simulated test was conducted involving a test tube. In the method a Kimax� brand glass test tube (20 mm�150 mm) is weighted, and dipped approximately 2 inches into the teat dip being tested. The test tube is then removed from the dip and placed on hanging rack for 10 minutes above a beaker that was previously weighted. At the end of 10 minutes the beaker and the test tube are each weighed again and the data is entered into the table. The dry weight is obtained by allowing the resulting teat dip film to dry for 24 hrs.
Simulated Teat Dipping Test UDDER GOLD PLUS Wet Wt.
Test. Tube @
Comments: Wet Wt. = 10 minutes Dry Wt. = 24 hours Simulated Teat Dipping Test Composition of Example I Wet Wt.
Comments: Wet St. = 10 minutes Formula Example I =2.5% 1-Propanol Dry Wt. = 24 hours 1.5% C9 17.0% NAS A brief examination of the tabulated data show that the rheology of the material of Example I maintains a larger quantity of material on the simulated animal when compared to the rheology of the commercial teat dip formulation. These data suggest that the composition of Example I would be somewhat more effective in mastitis treatment because the formulations of the invention would maintain a larger quantity of treating composition in a longer lasting film than the commercial materials. In other testing we have found that the identity of the antibacterial material, carboxylic acid, fatty acid, phosphoric acid or sulfonic acid, does not significantly change the rheology of the material and a fully formulated material having rapid initial kill and long term kill can be formulated in a long lasting film-forming composition. The following Examples show a preffered emolient/humectant foemulation technology.
Ex XV Chlorine Dioxide Teat Dip Item
Kelzan T
0.301 5
Sorbitol, 70% (Glucitol)
LAS, 97%
2.002 8
Elvanol Premix, 10%
10 Pylaklor Yellow
LLXI-10192, 5.0%
11 Sunsperse Blue GS
0.103 TOTAL
1stir at least 1 hr./check clarity 2stir 10 minutes 3pH =→ should be �2.70 Mixing Instructions
1. Add item 1 to mix tank. Turn on agitator. Slowly add item 2.
2. Add item 3 and mix until dissolved.
3. Charge item 4 with water through an eductor funnel, Hercules mixing tee or manually continue agitation at a slow addition rate. Lumping may result if added too quickly. Mix for 1 hour or until item 4 is completely solubilized.
Have QC check for clarity
Note: Complete solubilization is crucial before additional items are added.
4. Add items 5 and 6. Mixing well between each addition.
5. Slowly add item 7 to avoid high concentrations of localized acidity. Mix-10 minutes.
6. Slowly add item 8 and mix well. Add item 9 and mix well.
7. Add items 10 and 11. Final mix is 30 mintues.
8. Transfer and filter batch with 80 ({fraction (3/16)} inch) mesh strainer. Sample for QC.
Activator Sodium Chlorite Solution�6.25% Aqueous Item
1. Add item 1 to the mix tank.
2. Slowly add item 2 (mix ratio 3376 gs. Acidualnt with 93 gs. Of the Activator) and mix well.
Ex XVI: Chlorine Dioxide Teat Dip; Pre DipFormula Purpose
Prepare a 1000 g batch of the following experimental predip formula for physical stability testing.
0.1001 5
2.0002 8
Sunsperse Blue GS
0.0103 TOTAL
1stir at least 1 hr./check clarity 2stir 10 minutes 3pH =� 2.70 Mixing Instructions
1. Add item to mix tank. Turn on agitator. Add item 2 and mix until dissolved.
2. Slowly add item 3.
3. Charge item 4 with water through an eductor funnel, Hercules mixing tee or manually continue agitation at a slow addition rate. Lumping may result if added too quickly.
Mix for 1 hour or until item 4 is completely solubilized.Have QC check for clarity
5. Slowly add item 7 to avoid high concentrations of localized acidity. Mix 10 minutes.
6. Slowly add item 8 and mix well.
7. Add item 9. Final mix is 30 minutes.
Activator-Sodium Chlorite Solution�6.25% Item
2. Slowly add item 2 (mix ratio 3376 gs. Predip Formula with 93 gs. Of the Activator)and mix well.
Ex. XVII Chlorine Dioxide Teat Dip; Pre/Post Dip Formula Purpose
Prepare a 5 gallon batch of the following experimental pre/post dip
Pre/Post Formula Item
0.101 5
2.062 9
10 Pylaklor Yellow LX-10192, 5.0%
0.053 TOTAL
3. Charge item 4 with water through an eductor funnel, Hercules mixing tee or manually continue agitation at a slow addition rate. Lumping may result if added too quickly. Mix for 1 hour or until item 4 is completely solubilized.Have QC check for clarity
4. Add items 5, 6 and 7. Mixing well between each addition.
5. Slowly add item 8 to avoid high concentrations of localized acidity. Mix until dispersed�approximately 10 minutes.
6. Slowly add item 9 and mix well.
7. Add items 10 and 11. Final mix is 30 minutes.
Activator Formula-Sodium Chlorite Solution�6.25% Item
2. Slowly add item 2 and mix well.
Ex. XVIII Conc. Chlorine Dioxide Teat Dip; Udder Wash & Teat Dip Formula Purpose
Prepare a 100 g batch of the following experimental udder wash & teat dip formula for stability testing at 122� F. temperature condition.
Sortitol, 70%
10 Lactic Acid, 88%
100.001 1product looked good - no particulates Activator Formula: 3.125% Sodium Chlorite Item
Sodium Chlorite, 25% aqueous
After 24 hrs. at 122� F., the above product IS stable.
After 4 days at 122� F., the above product IS stable.
After 1 week at 122� F., the above product IS stable
Example XIX Conc. Chlorine Dioxide Teat Dip Item
Sunsperse Blue GS Dye
Neodol 25-9 nonionic
LAS, 97% anionic sulf.
Laneto 50 (EO)75 - lanolin
Activator Formula: 3.125% Sodium Chlorite Item
1 part Acid Formula: 1 part Activator Formula
CLO2 titr. RTU=885 ppm
DETAILED DISCUSSION OF THE DRAWINGS FIG. 1A and FIG. 1B are a graphical representations of the data shown in the tables from page 46 to 50 showing the results of a four week biocidal efficacy analysis of Example II using the food contact sanitizing protocol shown at pages 41 to 45 preceding the data in the specification. Clearly, from zero time through four weeks the composition of Example II had a kill substantially greater than a 5 log reduction in microbial populations of both model microorganisms. This data was taken without a milk challenge. However, FIG. 1B shows, within experimental error, similar properties using the same food contact sanitizing protocol with a 10% milk soil challenge. The week 2 and week 3 kill of E. coli is not easily explained in view of the 5.5 log reduction obtained in week 4 for that model microorganism. However, overall the results are strikingly successful in reducing microorganism populations on food contact surfaces.
FIG. 1C and FIG. 1D are graphical representations of data showing the results of the four week biocidal efficacy analysis of a commercial teat dip composition sold under the tradename UDDER GOLD PLUS.
FIG. 2A, a graphical representation of the data shown in the tables from page 52 to 56 is a four week efficacy analysis of the UDDER GOLD PLUS chlorine dioxide teat dip formulation measured using the procein skin protocol at pages 51 to 52 in the specification. In all test periods the material failed to achieve greater than a 2 log reduction.
FIG. 2B, prepared from the corresponding data given in the forementioned tables, shows a four week efficacy analysis of Example II using the porcein skin protocol. Clearly, under these more difficult conditions using the porcein skin substrate as a test vehicle, the log reductions in kill are not as great as those for food contact surfaces, however, the biocidal efficacy of Example II exceeded that of the well regarded UDDER GOLD PLUS chlorine dioxide formulations.
FIG. 3, shows a graph of the change in viscosity measured in centipoise plotted against shera rpm for UDDER GOLD PLUS and Example II and Example IX of the invention. The examples of the invention should show classic non-neutonian or nonlinear viscosity with respect to shear. At low shear, i.e., low rpm, the viscosity is high. As shear increases, viscosity drops. In sharp contrast, viscosity of the UDDER GOLD PLUS formulation shows much less pseudoplastic behavior. The viscosity is substantially constant as shear or rpm increases. This viscosity information is consistent with the data of the previous table and demonstrates that the viscoelastic behavior of the compositions of the invention are likely to coat and adhere to teat tissue more efficiently fan than UDDER GOLD PLUS. Since the materials are sheared somewhat upon application, the materials will flow on to the teat surface. However, when shear is removed, the teat dips obtain high viscosity and tend to adhere more tenaciously than a composition such as UDDER GOLD PLUS having linear viscosity. The substantial difference in viscosity at low shear (low rpm) demonstrates that the materials should coat the teat with substantially more material and after drying have a more effective environmental barrier.
The procedure is as follows. Place �500 mls of the experimental teat dip in 600 ml beaker. Record viscosity measurements at various rpms. Apparatus: Brookfield RVT Viscometer, spindle #1 and 2, various rpm (see chart below). Start Temperature:
73.6� F.�Stop Temperature: 73.8� F.
U. Gold Plus
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CorporationSystem and method for cleaning teats of a milk-producing animalWO2005037327A2 *Oct 6, 2004Apr 28, 2005Water Technologies LtdChlorine dioxide gel and associated methodsWO2007089473A2 *Jan 23, 2007Aug 9, 2007Basf Catalysts LlcThickened fluid composition comprising chlorine dioxide* Cited by examiner, � Cited by third partyClassifications U.S. Classification424/405, 424/407International ClassificationA61P31/04, A61K33/00, A61K9/20, A61K31/19, A61K31/20, A01N59/00, A61P43/00, A61K31/185Cooperative ClassificationY10S514/944, Y10S514/964, Y10S514/887, Y10S514/97, A01N59/00European ClassificationA01N59/00Legal EventsDateCodeEventDescriptionOct 2, 2013FPAYFee paymentYear of fee payment: 12Sep 22, 2009FPAYFee paymentYear of fee payment: 8Sep 27, 2005FPAYFee paymentYear of fee payment: 4Nov 12, 2002CCCertificate of correctionNov 12, 1998ASAssignmentOwner name: ECOLAB INC., MINNESOTAFree format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:RICHTER, FRANCIS L.;PAQUETTE, CATHY M.;STAUB, RICHARD K.;AND OTHERS;REEL/FRAME:009578/0101;SIGNING DATES FROM 19981029 TO 19981030RotateOriginal ImageGoogle Home - Sitemap - USPTO Bulk Downloads - Privacy Policy - Terms of Service - About Google Patents - Send FeedbackData provided by IFI CLAIMS Patent Services©2012 Google