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MXPA00002962A - Acidic aqueous chlorite teat dip providing shelf life, sanitizing capacity and tissue protection - Google Patents

Acidic aqueous chlorite teat dip providing shelf life, sanitizing capacity and tissue protection

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Publication number
MXPA00002962A
MXPA00002962A MXPA/A/2000/002962A MXPA00002962A MXPA00002962A MX PA00002962 A MXPA00002962 A MX PA00002962A MX PA00002962 A MXPA00002962 A MX PA00002962A MX PA00002962 A MXPA00002962 A MX PA00002962A
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MX
Mexico
Prior art keywords
composition
acid
chlorite
organic
parts
Prior art date
Application number
MXPA/A/2000/002962A
Other languages
Spanish (es)
Inventor
Francis L Richter
Cathy M Paquette
Richard K Staub
Original Assignee
Ecolab Inc
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Publication date
Application filed by Ecolab Inc filed Critical Ecolab Inc
Publication of MXPA00002962A publication Critical patent/MXPA00002962A/en

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Abstract

The mastitis control teat dip composition of the invention provides 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 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.

Description

SEALANT OF ACID AQUEOUS CHLORITE TETAS THAT PROVIDES SHELF LIFE, SANITATION CAPACITY AND TISSUE PROTECTION FIELD OF THE INVENTION This invention relates to a bovine sealant composition for bovine cattle that can be mixed using two parts, a simple chlorite solution and an acidic or acidulant formulation, to form a stable, effective composition, which can be used in routine dairy procedures.
BACKGROUND OF THE INVENTION Bovine mastitis is the most common and most expensive disease affecting dairy cattle. Some estimates suggest that at least half of the animal population of the dairy industry has some degree or form of mastitis. This condition results in decreased milk yield and reduced quality. Economic loss from mastitis in the United States is estimated at approximately $ 1.8 billion (billions) of United States dollars, or approximately 10 percent of total milk sales with approximately two-thirds of this loss due to the production of reduced milk of infected cows. Mastitis is an inflammation of the mammary gland. Similarly, inflammation is a response of a tissue or organ to an assault or injury. An injury caused by physical, chemical or thermal trauma can produce an inflammatory response. In the dairy cow, mastitis is typically the result of miero-organisms, usually bacteria, which invade the udder, multiply in the delicate tissues that produce milk, and synthesize toxins, a byproduct of bacterial metabolism. The characteristic aspects of inflammation are swelling, heat, redness, pain and disturbed function. Although the animal's immune system can fight against intramammary infections, many chronic infections remain subclinical (asymptomatic) and are not detected unless they are diagnosed by laboratory tests. Subclinical mastitis can result in a container of micro-organisms that leads to the infection of other animals in the herd. More than 80 species of microorganisms have been identified as causative agents, although approximately 95 percent of mastitis is caused by four pathogens: Staphylococcus aureus, Streptococcus agalactiae, Streptococcus dysacralactiae, and Streptococcus uberis. The pathogens that cause mastitis 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, lactophore ducts, teat skin lesions, etc., and 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 in sources such as manure, soil, plant material, resting area, or water, and are infected by casual contact. opportunistic with an animal during the period between milkings. This distinction, although not exclusive, is of practical importance because different dairy cattle maintenance measures are needed for different groups of micro-organisms. In all cases of bovine mastitis, whatever the causative micro-organism, the route of transmission of the invading pathogen in the internal gland of the udder is through the orifice of the teat and the lactophore duct. The administration of dairy cattle focuses attention on both the treatment of established mastitis and the prevention of new intramammary infections. Therapy and hygiene are two fundamental components of an effective mastitis control protocol. Each one is applied in concert, and each one operates independently. The main effect of the therapy is to increase the elimination rate of established infections; while, hygiene reduces the frequency of the infection by interrupting the transmission vectors. We can not present all the auxiliary factors that can be used for the elimination and prevention of mastitis, however, the therapy and the most effective hygienic practices, respectively, are the treatment of antibiotic infusion of the four quarters of the udder at the end of lactation; and antisepsis of tits after milking or "tits bath" during breastfeeding. Researchers agree, and abundant published evidence supports the concept, that immersing tits in an effective antimicrobial solution immediately after each milking is the single most effective procedure to decrease new intramammary infections in lactating cows. Between 1955 to 1970, Dodd et al., (FK Neave, FH Dood, and RG Kingwell, 1966, "A Method of Controlling Udder Disease." Vet. Rec. 78: 521; FK Neave, FH Dodd, RG King. Westgarth, 1969, "Control of Mastitis in the Dairy Herd by Hygiene and Management", J. Dairy Sci. 52: 696, FH Dodd, DR Westgarth, FK Neave and RG Kingwill, 1969, "Mastitis - The Strategy of Control", J. Dairy Sci. 52: 689; and FH Dodd, and FK Neave, 1970, "Mastitis Control," Proceedings, Nat '1. Inst. Res. Dairying, pp. 21-60) conducted extensive epidemiological investigations in commercial dairy cattle. . From this work, the conceptual basis for the modern methods of control of mastitis was developed, of which the immersion of tits is an integral component. The effectiveness and value of tits immersion has since been confirmed in dozens of field trials, and it is now accepted that an effective tits bath can reduce the incidence of new intramammary infections by at least 50 percent and often by 90 percent. To reduce mastitis, commercial teat sealers have been developed which contain a variety of antimicrobial agents including iodophores, quaternary ammonium compounds, chlorhexidine salts, chlorine releasing compounds (eg, alkali hypochlorites), oxidizing compounds (eg peroxide) of hydrogen, peracids), protonated carboxylic acids (for example, heptanoic, octanoic, nonanoic, decanoic, undecanoic acids), anionic acids (for example alkylarylsulfonic acids), and chlorine dioxide (from chlorite). These agents, which have several degrees of effectiveness, limit the transmission of mastitis by reducing the pathogenic populations in the teat. Tote sealers can also be divided into two broad classifications. The Class I type are antimicrobial and are applied to kill the micro-organisms that are already present in the lactophore duct or on the surface of the skin of the teat. By design, its microbiological effect is immediate and its objectives are mainly contagious organisms that are transmitted between animals during the preordeña, the order and the postordeña process. Class II tits sealer, often referred to as a "tummy sealer," is a film or coating forming composition that may or may not be antimicrobial; and, it works by developing a residual protective barrier on the teat thus providing prophylaxis by sealing the teat of its environment. The film that form on the surface of the teat serves as a physical barrier through which the pathogens that cause mastitis can not penetrate during the period between milkings. The general descriptions of breast sealant technology are shown in: "Current Concepts of Bovine Mastitis." 1996, Fourth Ed. National Mastitis Council, Madison WI.; 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. 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. Buckale, 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 Patent No. 1,144,637 (Kelco Chemicals Ltd.), published March 5, 1969. United States Patent No. 4,199,602 (Lentsch) published April 22, 1980, United States Patent Number 4,258,056 (Lentsch) published on March 24, 1981; and U.S. Patent No. 4,376,787 (Lentsch) published March 15, 1983 disclose compositions based on nitroalkanol, aminocarboxylate / sulfonate, and sulfonate. U.S. Patent No. 4,446,153 (Yang) published May 1, 1984 discloses a composition based on benzyl alcohol / phenyl ethanol. Typical descriptions of immersion baths of tits that form film between milking or protective (barrier type) or "sealants" of teats can be found in Akers et al., United States Patent No. 3,066,071, published November 27, 1962; Kraus, U.S. Patent No. 3,222,252 published December 7, 1965 (but, see Philpot et al., J. Dairy Science 58: 205-216); Coughman and Brown, Patent of the United States of North America number 3,993,777, published on November 23, 1976; Pugliese, United States of America Patent Number 4,049,830, published September 20, 1977; and Andrews et al., U.S. Patent No. 4,113,854, issued September 12, 1978. A tits sealer similar or identical to that of Andrews et al., a film-forming composition is in commercial use and has been discussed in the literature of dairy science. 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 other examples of bovine barrier film formers can be found in Silver et al., United States Patent No. 4,199,564, issued April 22, 1980; Dybas et al., U.S. Patent No. 4,311,709, published January 19, 1982; Marhavka, Patent of the United States of America number 5,017,369, published May 21, 1991; and Schmidt et al., U.S. Patent No. 5,503,838, issued April 2, 1996. Those skilled in the art in the treatment of bovine mastitis know that antimicrobial tightener sealant compositions (Class I type) that do not form protective films with barrier properties have shortened the residual time in the teat and its efficiency is quickly lost due to adsorption, ion pairing, oxidation or simply detachment. In addition, these teats sealants often fail to slow the entry of bacteria into the lactophore duct during the period between milkings and do not provide protection to the teat from irritation caused by wind, sun or contact abrasion. As described in the art, attempts have been made to provide antimicrobial tether sealants with film forming materials designed to form protective barriers on the skin of the tits; and, to present a continuous protection against the pathogens that cause mastitis, both contagious and environmental, and, of the irritation caused by exposure to adverse environmental elements. The first researchers discovered that the incorporation of a protective barrier system that forms film in a tits sealer was fraught with technical problems, be it physical-chemical problems with composition or application / performance problems in practice. The best prophylactic, and most environmentally durable barriers are water-insoluble synthetic organics made of homopolymers or heteropolymers of two or more different monomers. This applies either to compositions based on volatile solvents or to latices of film-forming polymers which are suspensions of water-insoluble polymer. U.S. Patent No. 3,066,071 typifies the first type; and U.S. Patent No. 4,113,854 discloses typical compositions of the latter class. Typically, barrier films formed on the teats when applied from volatile solvent-based blister sealant compositions are not user, animal or environmental friendly. In practice, these materials subject the skin of the teat, to the irritating and dry effects of organic solvents. Compositions containing film-forming polymer latexes suffer from volatile solvent problems since polymer latices are often suspensions of water-insoluble polymer or polymers that are in water; however, commercial latices necessarily include stabilizers, preservatives, suspending agents, etc., which adds complexity; and, as such, are often incompatible with the most preferred and most effective antimicrobial agents. All polymeric films insoluble in water, which generally form a flexible film almost rubber on the skin of the teat, must be removed peeling. In practice, these mastitis control compositions have not received wide acceptance due to the inconvenience, and delayed, and often problematic removal process prior to milking. U.S. Patent No. 3,222,252 discloses a bovine tea sealer consisting of vegetable oils of the drying or semi-drying types and certain fatty acid esters. In concept, this description bridges the gap between synthetic polymer coatings and natural polymer coatings. In practice, oil-based sealants have proven to be ineffective in preventing mastitis, and are difficult to remove from teats. In fact, its use has tended to increase the incidence of mastitis (see Philpot et al., J. Dairy Science 58: 205-216). U.S. Patent No. 3,993,777, mentioned above, discloses a high viscosity aqueous formulation that forms a protective film and bacteriostatic barrier around the teat that is easily removed by washing; thus, making the transition from water-insoluble protective films that in practice are peeled from the teat to washable films with water. However, a disadvantage of this teaching is the use of the hydroxyethylcellulose used as a thickener (its most typical function) in the preferred formulation which, by chance, has the characteristic of forming non-brittle, foldable films after drying. In cattle practice, these cellulosic thickeners rarely perform the dual role of providing a tenacious barrier, being also easily removable due to their sensitivity to water, where the performance of the antimicrobial barrier is lost. U.S. Patent No. 4,311,709 also discloses a methylcellulose forming film having a similar disadvantage as a tipping barrier. The Patent of the United States of North America number 4No. 049,830 discloses a tipping sealant composition which delivers an oil-in-water emulsion to the teat and, after drying, forms a barrier of antimicrobial lipid solids that remains smooth and viscous for extended periods and is washable in water. Experience with cattle has shown that soft barriers are too easily scraped or otherwise detached during the period between milkings with subsequent reduction or loss of biocidal function. U.S. Patent No. 5,017,369 discloses antimicrobial mastitis treatment compositions utilizing a water resistant film forming substance, polyvinyl alcohol. These teachings depart from the incorporation and use of thickener mixtures, suggesting that adequate viscosity can be obtained simply by adjusting the amount of polyvinyl alcohol in the composition. These compositions, in application, are at a commercial disadvantage because the polyvinyl alcohol itself does not provide an adhesion to the effective teat nor does it diminish the mobility of the immersion liquid which is manifested by excessive draining and loss of the product and, therefore by the significant reduction of the barrier function and microbial performance. U.S. Patent No. 5,503,838 overcomes this disadvantage by describing antimicrobial tonic sealant compositions containing polyvinyl alcohol in cooperation with thickening agents such as xanthan gum. Unfortunately, neither US Pat. No. 5,017,369 which typically includes chlorhexidene gluconate or quaternary ammonium compounds as the antimicrobial.; and U.S. Patent No. 5,503,838 which uses iodine as the preferred biocidal agent, attacks the problem of dermal irritation of the teat caused by residual barrier films containing frequently toxic, chemically aggressive, resident antimicrobial agents, which they remain in contact with the skin for long periods of time. Alliger, Patent of the United States of North America number Re. 31,779, republished on December 25, 1984; Alliger, U.S. Patent No. 4,330,531 (Alliger) published May 18, 1982; Kross et al., U.S. Patent No. 4,891,216, published January 2, 1990; Davidson et al., U.S. Patent No. 4,986,990, published January 22, 1991; Davidson et al., U.S. Patent No. 5,185,161, published February 9, 1993; and Kross, U.S. Patent No. 5,597,561 describe technology immersed in a commercial composition sold as tonic sealant with antimicrobial barrier under the name of UDDER GOLD PLUS (Alcide Corp., Redmond, WA). The patents describe two aqueous solutions, described as gels, adapted to be mixed in a 50/50 ratio where (according to the literature of patents and products) chlorous acid / chlorine dioxide is generated by chemical reaction of the alpha-acid. hydroxy-benzene-acetic acid (mandelic acid) and the sodium chlorite present in the first and second gels respectively. The second gel may contain a thickener. The subsequent patents describe a homopolymer of 2-acrylamido-2-methylpropane sulfonic acid (polysulfonic acid) which forms a protective film on the teat. Although this composition has proven to be effective, it is not without problem. The farmer is recommended to mix and use the mixture for only one milking of the cattle, discarding everything extra. This attribute is probably a consequence of the loss of chlorine dioxide (hence loss of antimicrobial efficacy) either from chemical incompatibility and / or from gasification. The "gelling agent" of polysulfonic acid does not immobilize the treatment in the teat and there is significant dripping / waste. U.S. Patent No. 5,597,561 teaches that polysulfonic acid has proved problematic because of its strong affinity to the dermal tissue and tendency to form a solid matrix which is difficult to remove by washing. There remains a substantial need after these attempts for compositions of barrier-type sealants that form a long-lasting protective film or shield that have immediate and long-lasting antimicrobial effect against a broad spectrum of mastitis-causing organisms.
BRIEF DESCRIPTION OF THE INVENTION We have discovered a mastitis control treatment that has important functional properties that are uniquely combined in a composition. The compositions of the invention provide rapid initial elimination, long-lasting antimicrobial activity, stable chemistry and rheology. The compositions of the invention possess favorable rheology that promotes adhesion and immobilizes the treatment of mastitis in the teat. The composition develops a barrier which provides prophylactic protection and which contains at least one resident agent for continuous biocidal protection. The composition does not cause dermal irritation and is removable by a simple technique of washing with water. The barrier has sufficient adhesion to withstand premature loss of integrity due to abrasion of environmental conditions. The compositions of this invention are treatments for the control and prevention of mastitis frequently described as "tummy sealers", although of course the methods of topical aseptic application other than immersion or "flooding" could be used by the farmer, - example, spray, broaching, smearing or foaming on the tits. When used as a teat bath, which is a particularly effective application practice, the tits of animals are immersed in a container or receptacle containing a composition of the present invention; after that the source is removed, and preferably half to three quarters of the distal teat have been coated with the treatment. After application (by any method), the resident treatment adheres to the teat until drying occurs and results in the development of a protective film which provides an antimicrobial barrier and prophylactic shield thus protecting the pathogen's teat and of adverse environmental factors. The mastitis control compositions of the invention comprise components dissolved or suspended in a vehicle or aqueous medium. The components of the composition include a chemical that generates chlorine dioxide such as sodium chlorite, an acidulant which may contain a protic acid component and an active antimicrobial acid component., an agent that forms organic film, rheology modifying materials, a hydrotrope, an emollient, a surfactant, a regulator if necessary, a colorant and other optional materials. A pseudoplastic aqueous rheology is carried out in the composition of the invention by mixtures of polymeric materials such as xanthan gum and polyvinyl alcohol compositions. When shear stress is applied to the composition (ie, immersion), the viscosity of the product is reduced allowing easy and quick application to the teat; and, after the release of the shear stress (ie the removal of the source), the total recovery of the viscosity occurs almost instantaneously immobilizing the coating, providing adhesion and ensuring little waste by dripping. In addition, the compositions have very little or no viscoelastic character which thus allows the treatment to flow and coat the teat uniformly, forming an effective continuous layer on the teat skin without the formation of unidirectional fluids of mucilage according to the Applicator is removed. The compositions flow slightly down the teat after application to form a more viscous or "plug" layer through the hole of the lactophore duct; and, in this way, a more effective prophylactic barrier is caused against bacteria entering the lactophore duct. An attribute of film formation / occlusive polymer barrier is contributed by the inclusion of polyvinyl alcohol intermediate or completely hydrolyzed. The carefully compounded polyvinyl alcohol compositions of this invention provide the mastitis control treatment, after drying, with a balanced barrier layer that remains foldable and maintains integrity in the teat; which can become antimicrobial through the wrapping of biocidal agents, and which does not cause irritation; and, which provides significantly improved and prolonged protection to the teat during the interorder period by structured adherence, and at the same time does not sacrifice the ease of removal prior to milking. A preferred single antimicrobial composition which may contain a fugitive biocidal agent, chlorine dioxide, and one or more non-fugitive acidic biocidal agents such as carboxylic acid with 6 to 12 carbon atoms, including heptanoic acid, pelargonic acid (nonanoic acid) is achieved. ) , etc; an anionic sulfonate, including dodecylbenzenesulfonic acid, and other acidic antimicrobials and mixtures thereof. These mixtures provide a superior cooperative antimicrobial effect. The combined agents provide an additive, immediate biocidal action to the pathogens that cause contagious mastitis present in the teat when the composition is applied for the first time. A long-term, continuous antimicrobial action is presented by the non-volatile agents which are involved in the barrier film during drying. Chlorine dioxide, formed at the site by reacting the ingredients within the composition, is present only during the initial application of the treatment on the teat and can be gasified during the drying of the treatment. This effect is advantageous because the superior antimicrobial properties of chlorine dioxide are used to destroy the pathogens of greatest concern to the farmer, ie the organisms that cause contagious mastitis already in the teat and in the hole of the distal lactophore duct; but, as soon as it is applied, the chlorine dioxide dissipates and thus removes the potential for severe irritation of the skin of the teat, which would otherwise result from this highly reactive chemical; and, of incidental waste in the milk produced. Heptanoic acid or nonanoic acid (pelargonic), which are preferred antimicrobial agents within the compositions of the present invention, and / or dodecylbenzenesulfonic acid, all non-volatile, increase the biocidal performance of chlorine dioxide after the initial application; and, as the drying of the treatment occurs with subsequent barrier formation, they become resident within the prophylactic coating wherein the agents provide continuous and effective antimicrobial protection of the environmental organisms causing mastitis. After the chlorine dioxide component, made at the site by the combination of an aqueous acidulant part with the aqueous chlorite part, is volatilized and thus removed from the composition, the composition maintains extended antimicrobial activity and the composition maintains an effective barrier, which includes a plug of the milk duct, for pathogens and environmental dirt. Surprisingly and unexpectedly, the long-term residence of chlorine dioxide and chemical stability results in practice which is in contrast to the commercial modalities of the prior art, specifically and particularly the commercial antimicrobial tea sealer sold under the name UDDER-GOLD PLUS (Alcide Corp. Redmond, A), which has attached user instructions that warn the user to mix, in equal proportions, just enough mix of the cooperative parts (UDDER-GOLD PLUS BASE and UDDER-GOLD PLUS ACTIVATOR) for a dairy milking -discarding the rest. We have discovered that the compositions of the preferred mastitis treatment of the present invention, as soon as the chlorine dioxide is formed at the site from the chemical reagents mixed together by the farmer in pre-assigned proportion, retain their antimicrobial agent and associated antimicrobial property. within the treatment of mixed tits for longer periods of time. A typical application life of this product is approximately one month after the preparatory mix. We believe that this stability of the unusual chlorine dioxide is an additional consequence of the rheological properties of the preferred compositions whereby the chlorine dioxide gas is trapped and remains homogeneously dispersed throughout the product. This attribute has many practical advantages for the farmer that include the convenience of pre-mixing large blender treatment mixtures and eliminating the need to repeatedly prepare the exact amount applied to each milking, reducing the waste and costly waste of unused but unstable product. Can not save for the next milking; and, increase the safety of the user who would otherwise be exposed to the gasified chlorine dioxide gases during the milking process. The compositions of the invention comprise a mixture composed of two cooperative parts: the first part, the greater or equal proportion, which has, in an aqueous liquid mixture, an acidic 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 medications; surfactants and hydrotropes; antimicrobial and preservative agents; regulators, acidulants; chromophores and the like. The second part, of equal or lesser proportion, is chlorous acid or salt thereof, more specifically, an alkali metal chlorite; being an aqueous liquid, powder in particles, or solid form compressed or cast in mold; and, generally in practice, added to the first part of the mixture. Furthermore, the aforementioned second part must, if liquid, be easily miscible or, if solid, be easily soluble within the first part to effect rapid homogeneous mixing which is of particular importance when the farmer prepares large quantities of this mixture in the place. Experience has shown that the combination of favorable mixing is best carried out by liquids of the second part that do not have an ordered structure, that is, without thickened or gelled character; and, by solids of the second part having large surface area. In practice this means liquids that have the characteristic of fluids similar to water, and solids that have a particulate form. The main function of the second part is to bring the chlorine dioxide release agent into the mixture of this mastitis control treatment; however, lower adjuvants may be included, for example, alkali metal carbonate salts added to commercial chlorite solutions to improve stability. These lower adjuvants must not alter, to any appreciable extent, the rheological properties of the second part other than the characteristics of the same aqueous carrier. Once attached, the alkali (III) / chlorite composition of the second part is combined in the acid solution of the first part with the resulting mixture having a regulated pH of about 3.0; after which, and by chemical reaction well known in the art and scientific literature, the disproportionation of chlorine (III) / Chlorite occurs with a measured rate of chlorine dioxide formation. Because this reaction begins immediately and because only very small amounts of chlorine dioxide are required for the pronounced microbiocidal effect, the mastitis control treatment thus prepared is ready for application as needed. The commercial compositions of the invention are maintained with a dual or "duet" combination of user-friendly packaging designed to contain and transport the A and B parts of these compositions together in predetermined and pre-measured proportions and to be cooperative in the combination process. where the user pours or otherwise causes the entire content of package B, an equal or lesser proportion, to be unloaded into package A, an equal or greater proportion, which then becomes the container and device of maintenance of the final treatment mixture for the control of mastitis.
BRIEF DISCUSSION OF THE DRAWINGS Figures 1A, IB, 1C, ID, 2A and 2B are graphical representations of the test data and comparisons shown in the data tables in the application. Figure 1A is a four week biocidal efficacy test of Example II using the food contact sanitation protocol. Figure IB is a four-week biocidal efficacy test of Example II using the food contact sanitation protocol with a 10 percent milk stimulus. Figures 1C and ID detail the four-week biocidal efficacy analysis of the UDDER GOLD PLUS formulation obtained under similar conditions as the data in Figures 1A and IB respectively. Figure 2A is a graph showing the four week efficacy analysis of the UDDER GOLD PLUS formulation using the porcine skin test protocol. Figure 2B is a four week efficacy analysis of Example II using the porcine skin test protocol. Figure 3 is a graph showing the change in viscosity with changing shear of two exemplary teats sealants, Examples II and IX, of the application compared to the UDDER GOLD PLUS formulation.
DETAILED DESCRIPTION OF THE INVENTION Components used in the compositions for the control of mastitis of this invention The present invention can generally comprise in a composition for the treatment of control and prevention of mastitis a vehicle, an acidulant or mixture, an antimicrobial agent or mixture, a rheology modifier or mixture, a film forming or mixing agent, a regulatory system, a hydrotrope or mixture, an emollient or mixture, a surfactant or mixture of surfactants, a chromophore or dye, and optional adjuvants. Preferred compositions of this invention comprise ingredients that are generally considered safe, and are not themselves or in mixture incompatible with milk or milk products. Likewise, the ingredients can be selected for any given composition that cooperate in their combined effects whether incorporated for antimicrobial efficacy, physical integrity of the formulation or to facilitate the healing and health of the teat. Generally, the composition comprises a vehicle that functions to dilute the active ingredients and facilitates the application of the intended surface. The carrier is generally an aqueous medium such as water, or an organic liquid such as an oil, a surfactant, an alcohol, an ester, an ether, or an organic or aqueous mixture of any of these. Water is preferred as a carrier or diluent in compositions of this invention due to its universal availability and unquestionable economic advantages over other liquid diluents. The acidulants are necessary ingredients within the mastitis control treatments of the invention to maintain the pH suitable for the dissociation of the chlorite / chlorine dioxide release agent and to avoid the dissociation of heptanoic, octanoic, nonanoic, decanoic and undecanoic used as non-fugitive antimicrobial agents. The carboxylic acids become increasingly biocides as the pH falls below its pKa value; accordingly, for the carboxylic acids mentioned above, a pH ranging from 2.5 to 5.5, preferably from 2.5 to 4.5 and more preferably from about 3.5 to 3.5 is desirable. The acid component used to prepare the tonic sealant 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 may result in substantial irritation, while a pH greater than about 5 may unacceptably reduce the efficiency of the composition. The term "weak" as used in reference to the acid component is intended to refer to an acid in which the first dissociation step does not essentially continue to completion when the acid is dissolved in water at ambient temperatures at a concentration within a useful range to form the present compositions. Such inorganic and organic acids are also referred to as weak electrolytes as the term used in Textbook of Quantitative Inorganic Analysis, I.M. Kolthoff et al., Eds. , The Macmillan Co. (Third edition 1952) on pages 34-37, the description of which is incorporated by reference herein. The 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. Useful acidulants 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, alkanesulfonic acids, cycloalkane sulphonic acids, as well as phosphoric acid and similar or mixtures thereof. Preferred acidulants are those commonly referred to as alpha hydroxycarboxylic acids with 2 to 6 carbon atoms, which group together acids that contain a hydroxy function in the alpha position directly adjacent to the carbon atom bearing the carboxyl function, examples of alpha hydroxymonocarboxylic acids are acid glycolic, lactic and hydroxybutanoic acid; and, examples of hydroxydicarboxylic acids are malic and tartaric acids. We have found a surprising interaction between the acidulant material and a second antimicrobial acid composition. Preferably, the acidulating material comprises the alpha-hydroxy carboxylic acid having from 2 to 6 carbon atoms in combination with a secondary antimicrobial acid composition. The second antimicrobial acid composition may comprise carboxylic acid having from 6 to 12 carbon atoms or a hydrocarbon sulphonic acid composition. These materials work together to provide a cooperative antimicrobial action which effects the initial removal from the chlorine dioxide contributed by the acid chlorite and a long term removal in the barrier layer by the carboxylic acid / sulphonic acid material. This cooperation of ingredients is an important aspect of the invention. Used in personal care products, alpha-hydrocarboxylic acids absorb moisture from the atmosphere and therefore, when applied topically, increase the moisture content and plasticity of the stratum corneum. They have had a significant impact on the treatment of the skin due to their ability to reduce corneocyte adhesion and accelerate cell proliferation within the basal layers. Although the mechanism of action is not yet fully understood, alpha-hydroxycarboxylic acid is also thought to stimulate the synthesis of collagen and mucopolysaccharides in the dermis. At usage levels, below 10 percent, the benefits in skin care are derived through a continuous pattern of product use. The continuous use of products with alpha-hydroxycarboxylic acids at levels less than 10 percent have shown that they result in a gradual reduction of fine lines and an improvement in skin texture through accelerated desquamation. Although at the moment it is conjecture, it is believed that some, if not all, of these advantages can also be transferred to the bovine skin. Incorporating an alpha-hydroxycarboxylic acid, healing can be accelerated; and by "smoothing" the dermal surface, cleaning and asepsis can be improved. The most preferred alpha-hydroxycarboxylic acid for the compositions of the invention is lactic acid.
Numerous inorganic and organic antimicrobial agents can be used in blister sealant compositions that include, but are not limited to, chlorine and bromine release compounds (eg hypochlorites and alkaline and alkaline earth hypobromites, isocyanurates, chlorinated hydantoin derivatives, sulfonamide, amine, etc.), iodine release complexes of surfactants or polymers such as polyvinylpyrrolidone (termed iodophores), quaternary ammonium compounds, such as chlorhexidine, peroxy and peroxyacid compounds, short chain carboxylic acid protonates, acidified anionic surfactants and chlorine dioxide. Of these typically applied antimicrobial agents that have been investigated for the control of bovine mastitis, carboxylic acids with short chain carbon atoms of 6 to 12 protonated, acidified alkylaryl sulfonates and chlorine dioxide have been shown to be effective against micro-organisms that cause mastitis; and, they are preferred in the compositions of the present invention. More specifically, dodecylbenzene sulphonic acid, carboxylic acids with 6 to 12 protonated carbon atoms and chlorine dioxide are especially preferred antimicrobial agents. The composition of the invention may also contain one or more rheology modifiers, to increase the viscosity, or thickness and cause the aqueous treatment to adhere to the superficial skin of the teat. Adhesion allows the composition to remain in contact with transient and resident pathogenic bacteria for longer periods of time, promoting microbiological efficacy and resisting waste due to excessive dripping. The rheology modifier can be a film former or act cooperatively with a film forming agent to form a barrier that provides additional protection. Water-soluble or water-dispersible rheology modifiers that are useful can be classified as inorganic or organic. The organic thickeners can also be divided into natural and synthetic polymers, the latter can still be divided into synthetic based on natural and synthetic petroleum-based substances. Inorganic thickeners are generally compounds such as colloidal aluminum-magnesium silicate (VEEGUM®), colloidal clays (bentonites), or silicas (CAB-0-SILS®) that have been smoked or precipitated to create particles with large proportions of surface against size. The natural hydrogel thickeners used are mainly plant-derived exudates. For example, gum tragacanth, karaya, and acacia; and extractives such as caragena, locust bean gum, guar gum and pectin; or pure culture fermentation products such as xanthan gum are potentially useful in the invention.
Chemically, all these materials are salts of complex anionic polysaccharides. Natural synthetic based thickeners having application are cellulose derivatives wherein the free hydroxyl groups in the linear anhydrous glucose polymers have been etherified or esterified to produce a family of substances that dissolve in water and give viscous solutions. This group of materials includes alkyl and hydroxyalkylocelluloses, specifically methylcellulose, hydroxyethylmethylcellulose, hydroxypropylmethylcellulose, hydroxybutylmethylcellulose, hydroxyethylcellulose, ethylhydroxyethylcellulose, hydroxypropylcellulose, and carboxymethylcellulose. The petroleum-based synthetic water-soluble polymers are prepared by the 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 thickeners that are most useful in this invention are those which are extremely pseudoplastic (not Newtonian), of rapid relaxation), do not tend to develop a rigid three-dimensional structure of the interactions of the interpolymers, have a low or negligible viscoelastic character and possess a high gel strength. These rheological properties are manifested in a tipping sealant composition that has a continuous flow appearance, is easy to pour and apply over the teat, coats uniformly without forming unidirectional currents of mucilage as the applicator is removed and remains firmly in place without significant bagging. Examples of the preferred rheology modifiers are xanthan gum and the hydroxyalkyl celluloses. Generally, the concentration of the thickener used in the present invention will be dictated by the final composition and by the application method on the teat. Spraying or fogging requires a lower composition viscosity, for easy and effective treatment application, than immersion. Film forming barrier baths typically require high apparent viscosity necessary to form thick coatings on the teats which ensures an improved prophylactic effect. For compositions of the invention designed to provide a barrier for prophylactic protection, additional film-forming agents are included which typically work in conjunction with the thickeners. In fact, many of the aforementioned rheology modifiers are themselves film-makers of greater or lesser effectiveness; however, a preferred degree of polyvinyl alcohol when used with the preferred thickeners such as xanthan gum or hydroxyalkylcelluloses presents particularly useful properties to the compositions of this teaching, most notably the development of "balanced" films on the treated tits that are sufficiently sensitive to water to be peeled with conventional free washing, but able to adhere to the skin of the teat to withstand the premature loss of integrity between milkings and intrinsically resistant to exposure to the environment; and, in addition, they are of such a structure that they successfully cap antimicrobial agents within the film matrix to continue the biocidal effect against organisms that cause mastitis. The success of the barriers thus formed by the compositions of this invention are, in part, a consequence of the 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 these characteristics of thickeners and film formers. These inclusions also plasticize the film and make it foldable. The polyvinyl alcohol compositions can be used as a film former. The variation of film flexibility, water sensitivity, ease of solvation, viscosity, film strength and addition can be varied by adjusting the molecular weight and degree of hydrolysis. The preferred polyvinyl alcohol for use in compositions herein has a degree of hydrolysis greater than 92 percent, preferably greater than 98 percent, more preferably greater than 98.5 percent; and, it has a molecular weight (Mn) that falls in the range of between 15,000 and 100,000, but preferably between 40,000 and 70,000 corresponding to a solution viscosity (4 weight percent aqueous solution measured in centipoise (cP) at 20 ° C). C by the method of falling ball Hoeppler) of 12-55 centipoises and 12-25 centipoises respectively. The classic definition of a regulated solution is one that contains both a weak acid and its conjugated weak base, whose pH changes only slightly by adding acid or alkali. The weak acid becomes a regulator when alkali is added, and the weak base becomes a regulator when acid is added. The maintenance of the pH of the compositions described in the present invention is necessary to minimize undesirable chemical changes that may inhibit the microbiological efficacy of the antimicrobial agent or cause a toxic or irritant effect on the teat. Any compatible organic or inorganic material or mixture of materials having the desired effect of maintaining the pH of the composition within the ranges described can be used as the regulatory agent or regulatory system in the present invention. The primary concern is the pH changes caused by naturally occurring chemicals that are carried to the composition, after application on the teat by exudations of the skin, milk or environmental dirt; and pH shifts that sometimes accompany the chemical equilibria established within the compositions as the ingredients change or the concentrations vary. In general, the pH of the bovine mastitis control treatments can vary from as low as pH 2.0 to a maximum of about 11.0 depending mainly on the choice of the antimicrobial agent that is being incorporated into the composition because the optimum efficacy is normally presents with a specific, narrow pH range. Therefore the agent or regulatory system is chosen in accordance with the foregoing. The preferred pH range of the compositions of this invention is typically 2.5 to 5.5 more preferably, about 2.5 to 3.5 - the lower value being a limit to avoid excessive irritation on the surface of the teat; and setting the upper limit to prevent the formation of chlorine dioxide and maintain the antimicrobial effect of the acid or the protonated carboxylic acids and / or the acidified anionic surfactant. A typical and preferred regulatory system would be citric acid and its alkali metal salt. However, any acidulant and the corresponding conjugated weak base can be used. Solubilizing agents called hydrotropes or couplers can generally be used in compositions of the present invention to maintain physical single phase integrity and storage stability. To this end, any number of ingredients known to those skilled in the art in the formulation art can be employed, such as monofunctional and polyfunctional alcohols. These preferably contain from about 1 to about 6 carbon atoms and from about 1 to about 6 hydroxy groups. Examples include ethanol, isopropanol, normal propanol, 1,2-propanediol, 1,2-butanediol, 2-methyl-2,4-pentanediol, mannitol and glucose. Also useful are higher glycols, polyglycols, polyoxides, glycol ethers and propylene glycol ethers. Useful additional hydrotropes include the free acids and alkali metal salts of sulfonated alkylaryls such as toluene, xylene, eumeno and sulfonates.of phenol or of phenol ether or diphenol ether; alkyl and dialkyl naphthalene sulfonates and alkoxylated derivatives. The most preferred hydrotrope for most preferred embodiments of this invention is one octane sulfonate or mixtures of 1-octane sulfonate and 1,2-octane disulfonate manufactured and maintained for proprietary use under the name AS by Ecolab Inc. San Paul, MN The blister sealant compositions of the present invention generally also comprise an emollient and / or humectant to lubricate, condition and in general reduce and promote healing of the surface irritation of the application teat that could result from the antimicrobial agent, the mechanical action of the milking machine or environmental conditions such as wind chill, dehydration, abrasion and sunburn. Any water-soluble or water-dispersible skin conditioning agent can be used in the present invention. Compositions such as polyhydric alcohols are useful in the invention including glycerin, sorbitol, mannitol, and propylene glycol and their homopolymers; fatty acid esters of simple monohydric alcohols including isopropyl palmitate or isopropyl myristate and similar esters; esters of fatty acid polyols; and, ethoxylated lanolins, vegetable oils, and derivatives of the same natural sources such as aloe. Preferred emollients for use in the invention include glycerin, sorbitol, and propylene glycol. The surfactant or the surfactant mixture of the present invention can be selected from water-soluble or water-dispersible compatible 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, more importantly, excellent detergent effect - meaning wetting of the surface. The surface active agents or "wetting agents" function to increase the penetrating activity of the invention on the tissue surface at risk of mastitis caused by pathogens. The nonionic surfactants useful in the invention are generally characterized by the presence of organic hydrophobic group and an organic hydrophilic group and are typically produced by the condensation of an organic aliphatic, aromatic alkyl or polyoxyalkylene hydrophobic compound with a hydrophilic alkaline oxide fraction which in common practice it is ethylene oxide or a polyhydration product thereof, polyethylene glycol. Virtually any hydrophobic compound that has a hydroxyl group, carboxyl, amino, or amido with a reactive hydrogen atom can be condensed with ethylene oxide, or its polyducting adducts, or mixtures thereof with alkoxylenes such as propylene oxide to form an active agent on the nonionic surface. The length of the hydrophilic polyoxyalkylene fraction that is condensed with any hydrophobic compound can be easily adjusted to produce a water-dispersible or water-soluble compound having the desired degree of balance between hydrophilic and hydrophobic properties. Useful nonionic surfactants of the present invention include: block polyoxypropylene-polyoxyethylene polymer compounds based on propylene glycol, ethylene glycol, glycerol, trimethylolpropane, and ethylenediamine as the initiating reactive hydrogen compound. Examples of polymeric compounds made from sequential propoxylation and ethoxylation of the initiator are commercially available under the tradename PLURONIC® manufactured by BASF Corp. PLURONIC® compounds are difunctional (two reactive hydrogens) formed by the condensation of 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. The ethylene oxide is then added to sandwich this hydrophobe between hydrophilic groups, controlled by length to constitute from about 10 weight percent to about 80 weight percent of the final molecule. TETRONIC® compounds are tetrafunctional block copolymers derived from the sequential addition 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 hydrophilic ethylene oxide is added to constitute from about 10 weight percent to about 80 weight percent of the molecule. Also useful nonionic surfactants include the condensation products of one mole of alkylphenol wherein the alkyl constituent contains from about 8 to about 18 carbon atoms with from about 3 to about 50 moles of ethylene oxide. The alkyl group can, for example, be represented by diisobutylene, diamyl, polymerized propylene, isoctyl, nonyl, and dinonyl. Examples of commercial compounds of this chemistry are available commercially under the trade name IGEPAL® manufactured by Rhone-Poulenc and TRITON® manufactured by Union Carbide. Also useful nonionic surfactants include products of the condensation of one mole of straight or branched chain alcohol, saturated or unsaturated having from about 6 to about 24 carbon atoms with from about 3 to about 50 moles of ethylene oxide. The alcohol fraction may consist of mixtures of alcohols in the range of carbon outlined above or may consist of an alcohol having a specific number of carbon atoms within this range. Examples of similar commercial surfactants are available under the trade name NEODOL® manufactured by Shell Chemical Co. and ALFONIC® manufactured by Vista Chemical Co. The products of the condensation of one mole of straight or branched chain saturated or unsaturated carboxylic acid having from about 8 to about 18 carbon atoms with from about 6 to about 50 moles of ethylene oxide. The acid fraction may consist of mixtures of acids in the range of carbon atoms previously delineated or may consist of an acid having a specific number of carbon atoms within the range. Examples of commercial compounds of this chemistry are commercially available under the tradename NOPALCOL® manufactured by Henkel Corporation and LIPOPEG® manufactured by Lipo Chemicals Inc. In addition to ethoxylated carboxylic acids, commonly called polyethylene glycol esters, other alkanoic acid esters formed by reaction with glycerides, glycerin, and polyhydric alcohols (saccharide or sorbitan / sorbitol) have application in this invention. All these ester fractions have one or more reactive hydrogen sites in their molecule which can undergo additional acylation or addition of ethylene oxide (alkoxide) to control the hydrophilicity of these substances. Other useful nonionic surfactants made by the addition of ethylene oxide to ethylene glycol to provide a hydrophilic of designated molecular weight; and then add propylene oxide to obtain hydrophobic blocks on the outside (end) of the molecule. The hydrophobic portion of the molecule weighs from about 1,000 to about 3,100 with the central hydrophilic comprising 10 weight percent to about 80 weight percent of the final molecule. These "inverse" PLURONIC® are manufactured by the BASF Corporation under the trade name PLURONIC® surfactants. Likewise, TETRONIC® surfactants are produced by the BASF Corporation through 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 hydrophilic comprising 10 weight percent to 80 weight percent of the final molecule. The tertiary amino oxides corresponding to the general formula: R2 I R '(OR) nN A OR R3 they can be used where the link is a conventional representation of the semipolar link; and R 1, R 9, and R 1 may be aliphatic, aromatic, heterocyclic, alicyclic, or a combination of these groups thereof. Generally, for amino oxides of detergent interest, R is an alkyl radical of from about 8 to about 24 carbon atoms; R and R are selected from the group consisting of alkyl or hydroxyalkyl of 1 to 3 carbon atoms and mixtures thereof; R 4 is an alkylene or a hydroxyalkylene group containing from 2 to 3 carbon atoms; and n ranges from 0 to about 20. Useful water-soluble amine oxide surfactants are selected from coconut or tallow dimethylamine oxides.
Also useful in the present invention are surface active substances that are categorized as anionic because the charge in the hydrophobe is negative; or surfactants in which the hydrophobic section of the molecule carries no charge unless the pH is high for neutrality or above (eg, carboxylic acids). Carboxylate, sulfonate, sulfate and phosphate are the polar (hydrophilic) solubilizing groups found in anionic surfactants. Of the cations (against ions) associated with these polar groups, sodium, lithium and potassium impart solubility in water and are more preferred in compositions of the present invention. Examples of suitable synthetic water-soluble anionic compounds are the alkali metal salts (such as sodium, lithium and potassium) or the mononuclear alkyl aromatic sulphonates such as the alkylbenzene sulfonates containing from about 5 to about 18 carbon atoms in the the alkyl group in a straight or branched chain, for example, the alkylbenzene sulfonate or alkylonaphthalene sulfonate salts, dialkylonaphthalene sulfonate and alkoxylated derivatives. Other anionic detergents are olefin sulfonates, which include long-chain alkene sulfonates, long-chain hydroxyalkene sulfonates or mixtures of alkene sulfonates and hydroxyalkane sulfonates and alkylpoly (ethyleneoxy) ether sulfonates. Also included are alkyl sulfates, alkyl poly (ethyleneoxy) ether sulphates and aromatic sulfates poly (ethyleneoxy) sulfates such as sulfates or condensation products of ethylene nonylphenol dioxide (usually having one to six oxyethylene groups per molecule) . Co-folded iodines offer the advantage of being chromophores, that is, easily visible when applied to the teat. Other antimicrobial agents do not have this characteristic; therefore, compositions of this invention may include a water-soluble or dispersible coloring agent (dye or pigment or blends) which renders the chromophore composition, having high contrast with the skin of the teat and allowing the dairy manager visually discerns that the tits have been treated. Alternatively, the compositions of the invention can be composed of any number of optional ingredients, i.e., adjuvants. Depending on the benefits provided, the adjuvants may partially or totally displace the vehicle in the composition. Generally, according to the invention, forms that assist in the application of the invention with respect to physical and chemical stability, barrier film formation, maintenance of teat health, performance, can be included within this composition. physical and aesthetic form of the manufacturing process. Of course, these functions can be carried out exclusively by the composition ingredients described or mixtures thereof; however, the form or application or performance situations may have to require additional effect which can be carried out by introducing an additional inorganic or organic agent or agents and mixtures thereof into the composition. The compositions of the invention optionally may include medicaments, for example sun screens such as para-amino benzoic acid and curative agents such as allantoin or urea to provide curative action and stimulation of new tissue formation; preservatives such as methylparaben, propylparaben, sorbic and benzoic acid or salts thereof to retard bacterial growth and prolong shelf life; antioxidants such as BHT (butylated hydroxytoluene), BHA (butylated hydroxyanisole), TBHQ (tert-butylhydroquinone), or propyl gallate to retard oxidative or hydrolytic degradation; sequestering agents such as aminopolycetates, polyphosphonates, aminopolyphosphonates, polycarboxylates, and condensed phosphates; dispersing or suspending agents having polyelectrolyte character such as polyacrylate and similar polycarboxylates of homopolymer or copolymer structure; and manufacturing processing agents, for example defoaming additives used to facilitate bonding and mixing.
A wide variety of useful ingredients in the treatment of mastitis control can be included in the compositions herein. This list is not intended to be exhaustive and other optional ingredients, which may not be listed, but which are well known in the art, may also be used in the composition. The examples are not intended to be limited in any way, in certain classes some of the individual adjuvants may overlap other categories. The adjuvants employed are selected so as not to interfere with the antimicrobial action of the composition and to avoid physical or chemical instability of the product. The "Bovine Mastitis Treatment Mix Composition" Table, below, provides a guideline for consistent concentrations according to this invention.
INGREDIENT USEFUL QUANTITY PREFERRED MORE PREFERRED (% WEIGHT) (% WEIGHT) (% WEIGHT) VEHICLE 40.0 - 98.0 50.0 - 98.0 60.0 - 98.0 ACIDULANT MIXTURE 1.0 - 12.0 1.0 - 10.0 1.0 - 8.0 AND / OR ANTIMICROBIAL MODIFIER 0.0 - 10.0 0.01 - 7.5 0.1 - 5.0 REOLOGIA FILM MAKER 0.0 - 12.0 0.01 - 8.0 0.1 - 4.0 REGULATOR 0.0 - 15.0 0.01 - 10.0 0.1 - 5.0 HYDROTHROP 0.0 - 20.0 0.0 - 15.0 0.1 - 10.0 EMOLIENT 0.5 - 60.0 1.0 - 40.0 1.5 - 20.0 TENSION 0.0 - 60.0 0.01 - 40.0 0.1 - 20.0 COLORING 0.0 - 1.0 0.001 - 0.8 0.002 - 0.6 OPTIONAL ADJUVANT 0.0 - 5.0 0.1 - 4.0 0.1 - 3.0 The following examples and data are provided to illustrate preferred embodiments of the invention and contain a better mode. Example 1 Example 1 is a representative embodiment of this invention illustrating a bovine mastitis treatment having barrier film properties. The antimicrobial effect is provided by the generation of chlorine dioxide caused by disproportionation of chlorite ion after mixing the base of the composition with activator and by the resident biocidal activity of the protonated nonanoic acid. A batch of 16 kilograms of the next part I of experimental base formula one kilogram of the C102-1 part was prepared by mixing the ingredients as shown. Base formula (part I) (pH = 2.8): * KELTROL® K5C151 is a grade of xanthan gum manufactured by Kelco ** ELVANOL® pre-mix: 10 percent aqueous solution of ELVANOL® 90-50, ELVANOL® 90-50 is a polyvinyl alcohol grade manufactured by E. I. DuPont.
Activator C102-1 Formula (Part II) (pH = 12.3) Approximately 3376 grams of the base formula part was bound with approximately 92.89 grams of the C102 part (the C102 is 0.32 percent of the total composition).
Viscosity (Brookfield viscometer model DV-II, spindle number 1. 20 rpm at 25 ° C) was approximately 304 cps.
Example II Example II is another example of this invention that differs from Example I in that the resident biocidal activity is contributed by dodecylbenzene sulphonic acid. The hydrotropic agent, octane sulfonate, is not required in this formula for physical stability. A batch of seven kilograms of the next base formula part and a one kilogram batch of the activating part C102 was prepared.
Base formula (Part I) (pH = 2.9) * KELTROL® K5C151 is a grade of xanthan gum manufactured by Kelco ** ELVANOL® Premix: 10 percent aqueous ELVANOL® solution 90-50, ELVANOL® 90-50 is a polyvinyl alcohol grade manufactured by E. I. DuPont. Activator C102_1 Formula (Part II) (pH = 12.3): Approximately 3376 grams of the base formula part was mixed with approximately 92.98 grams of the activating part C102. The stable rheology and pH of the combined formula is shown as follows: Example III Example III is a representative composition of the invention which illustrates a bovine mastitis treatment without a barrier film property and which does not have thickeners or film formers. A surfactant, NEODOL® 25-9, is included for cleaning the teat and moistening the surface. A batch of two hundred grams of the following experimental base formulation and a one kilogram batch of the activating part C10_1 was made.
Base formula (Part I) (pH = 2.7) * Pigment: PYLAKLOR® Yellow LX-10192 and permanent green S-722 (50:50 mix) manufactured by Pylam Products Co. Inc.
Activator C102 -_1J- Formula (Part II) (pH = 12.3) Approximately 200 grams of the base formula mixed with approximately 5.5 grams of the activating part of C102. pH of the final mixture is approximately 2.9.
Example IV Example IV is another modification of Example III using sorbitol as an emollient in place of glycerin. A batch of two hundred grams of the following experimental base formula and a one kilogram batch of the activating part 1 ClOo was made. Base Formula (Part I) (pH = 2.7) * Pigment: PYLAKLOR® Yellow LX-10192 and permanent green S-722 (50:50 mix) manufactured by Pylam Products Co. Inc.
Activator C102_1 Formula (Part II) (pH = 12.3): Approximately 200 grams of the base formula is mixed with approximately 5.5 grams of the activating part of C102. The pH of the final mixture is approximately 2.9.
Example V Example V is another composition of the invention which illustrates a treatment of bovine mastitis without a barrier film property, which again does not have thickeners or film-forming agents and which uses phosphoric acid as an acidulant. A surfactant, NEODOL® 25-9, is included for cleaning the teat and moistening the surface. A batch of two hundred grams of experimental base formula following and a batch of one kilogram of activating part C102 was made.
Base Formula (Part I) (pH = 2.7) igmento: PYLAKLOR® Yellow LX-10192 and permanent green S- (50:50 mix) manufactured by Pylam Productos Co. Inc.
Activator C102_1 Formula (Part II) (pH = 12.3) Approximately 200 grams of the base formula is mixed with 1 about 5.5 grams of the activating part of C102. The pH of the final mixture is approximately 2.9. Example VI Examples VI, VII and VIII are compositional variations of Example I containing the octanoic, decanoic homologic carboxylic acids and a mixture thereof respectively. A batch of two hundred grams of the following experimental base formula and a one kilogram batch of the activating part C102 was prepared. Base formula (Part I) (pH = 2.7): * ELVANOL® premix: 10 percent aqueous solution of ELVANOL® 90-50. ELVANOL® 90-50 is a polyvinyl alcohol grade manufactured by E. I. DuPont. Activator C102-1 Formula (Part II) (pH = 12.3): The mixed product was made with 100 grams of part I formula and 2.75 grams of part II is about pH 2.9.
Example VII A batch of 200 grams of the following experimental base formula and a batch of one kilogram of activating part C102" 1 was prepared. Base formula (Part I) (pH = 2.6! * ELVANOL® Premix: 10 percent aqueous ELVANOL® solution 90-50. ELVANOL® 90-50 is a polyvinyl alcohol grade manufactured by E. I. DuPont. Activator C102_1 Formula (Part II) (pH = 12.3): The mixed product made with 100 grams of the formula of part I base combined with 2.75 grams of the formula C102 part II of activator. The mixture has an approximate pH of 2.9.
Example VIII A batch of 200 grams of the following experimental base formula and a one kilogram batch of the activating part of C102 was prepared.
Base formula (Part I) (pH = 2.7) * KORTACID®: 3: 1 octanoic / decanoic manufactured by Akzo Chemical. ** ELVANOL® pre-mix: 10 percent aqueous solution of ELVANOL® 90-50. ELVANOL® 90-50 is a polyvinyl alcohol grade manufactured by E. I. DuPont.
Activator ClO ^ 1 Formula (Part II) (pH = 12.3): The mixed product was made using 100 grams of part I and 2.75 grams of part II with an approximate pH of 2.9.
Example IX Example IX is a further variation of the Example I containing heptanoic acid and n-propanol instead of nonanoic acid and isopropanol respectively. A batch of 1000 grams of this experimental base formula was prepared; and, 1000 grams of the C102 part was prepared by mixing the ingredients as shown. Two typical mixtures of part I and part II were then prepared as illustrated.
Base formula (Part I) (pH = 2.8) Activating formula (Part II) (pH = 12.0) Typical mixing ratios Example X A batch of 500 grams of the following experimental base formula was prepared for preliminary testing. This example is similar to Example I with n-propanol and half the amount of NaC102. Base formula (part I) (pH = 2.8): * KELTROL® K5C151 is a grade of xanthan gum manufactured by Kelco. ** ELVANOL® premix: 10 percent aqueous solution of ELVANOL® 90-50 ELVANOL® 90-50 is a polyvinyl alcohol grade manufactured by E. I. DuPont. *** Pigment: PYLAKLOR® Yellow LX-10192 and permanent green S-722 (50:50 mix) manufactured by Pylam Products Co. Inc.
Activating formula (Part II) (pH = 12.0) Example XI A 1000 gram batch of the following experimental base formula was prepared for testing. This composition is similar to Example III with ÑAS and thickener.
Base formula (Part I) (pH = 2.7) igmento: PYLAKLOR® Yellow LX-10192 and permanent green S- (50:50 mix) manufactured by Pylam Productos Co. Inc.
Activating formula (Part II) (pH = 12.3) Typical mixing ratios: Example XII A 1000 gram batch of the following experimental base formula was prepared for testing. This composition is similar to Example IV with ÑAS.
Base Formula (Part I) (pH = 2.7): Pigment: PYLAKLOR® Yellow LX-10192 and permanent green S-722 (50:50 mix) manufactured by Pylam Products Co. Inc.
Activator Formula (Part II) (pH = 12.3) Example XIII A batch of 1500 grams of the following experimental base formula was prepared for testing. Similar to Example III with ÑAS and heptanoic acid.
Base formula (Part I) (pH = 2.7) * Pigment: PYLAKLOR Yellow LX-10192 and green permanent S-722 (50:50 mix) manufactured by Pylam Products Co. Inc.
Activator Formula (Part II) (pH = 12.0) Typical mixing ratios Example XIV A batch of 1500 grams of the following experimental base formula was prepared for testing. This composition is similar to Example III with ÑAS and heptanoic acid.
Base formula (Part I) (pH = 2.7) * Pigment: PYLAKLOR Yellow LX-10192 and green permanent S-722 (50:50 mix) manufactured by Pylam Products Co. Inc.
Activator Formula (Part II) (pH = 12.0) Typical mixing ratios: Germicidal and decontaminating sanitizing action of disinfectant tests created from the AOAC method 960.09 A test to determine the efficacy of antimicrobial products used to clean up, non-porous food contact surfaces. Culture medium 1. Nutrient agar; 2. Agar B nutrient (French inclinations); Subculture medium 1. Trypton glucose extract (TGE) agar; 2. Agar neutralized glucose extract; The neutralizer used should be appropriate to test the inactivation of the substance.
Reagents 1. Neutralizing controls: a. A mixture of 49.5 milliliters of Chambers solution and 49.5 milliliters of 1 percent aqueous Na2S203. 2. Regulated phosphate broth (0.25M) 3. Regulated phosphate dilution water Apparatus 1. Glassware: 250 milliliter Erlenmeyer flasks, 100 milliliter volumetric flasks, pipettes, glass beads, 20 x 150 test tubes and 25 x 150 mm. Sterilize for 20 minutes at 121 degrees centigrade in a dry air oven at 180 degrees centigrade for 180 minutes. 2. Petri dishes sterile disposable petri dishes, 15 x 100 mm. 3. French bottles (bottles of milk dilution); 175 milliliter stone glass bottles 4. Water Bath Water bath at constant temperature that can be maintained at the desired temperature ± 2 degrees Celsius from the desired temperature required. Monitor the temperature throughout the test. 5. Transfer Cycles Suitable transfer cycles of metal or disposable plastic. 6. Sterile Buchner funnel containing Whatman's # 2 filter paper. Staphylococcus aureus ATCC 6538 Escherichia coli ATCC 11229 Maintain Nutrient Agar in cultures inclined at 4 ° C with transfers to tilted cultures of new broth once a month (reference SOP MS031 for crop maintenance). From the tilt of broth cultivation, make transfers >; 3 and < 30 consecutive in nutrient agar inclinations with incubation of 37 ° C ± 2 ° C for 20-24 hours. If only one daily transfer has been lost, no special procedures are required; if two or more transfers are lost daily, repeat with three daily transfers. Inoculate French slopes by washing the culture of the Agar A Nutrient tilt with 99 milliliters of phosphate buffer as follows: use 5 milliliters of regulator in the tilt and rinse this in the remaining 99 milliliters of regulator. Mix this suspension well and add 2 milliliters of suspension to each French incline. Incubate the tilt back and forth to cover the surface. Remove excess suspension aseptically. Incubate the inclinations at 37 ° C ± 2 ° C for 18-24 hours. Remove the culture from the agar surface using 3 milliliters of phosphate buffer and sterile glass beads rotated forward and backward to remove the culture. Filter the suspension through a sterile Buchner funnel containing Whatman's # 2 filter paper that has been pre-wetted with one milliliter of phosphate buffer. Collect the suspension in a sterile test tube. Standardize the suspension of the culture by dilution using water regulated with sterile phosphate to produce 10 x 107 organisms per milliliter. 10 x 10 organisms per milliliter corresponds approximately to the percentage of transmission reading from 0.1 percent to 1.0 percent T at 580 nm. It is recommended that each individual operator determine which percentage readings of T they need to achieve a culture suspension of 10 x 10 organisms per milliliter to perform this test since the validity of the test is based on having the appropriate inoculation. Technique of Operation Dispense 99 milliliters of test substance into a sterile 250 milliliter Erlenmeyer flask. Prepare flasks in triplicate for each test substance to be tested. Place the flasks containing the test substance in water at 25 degrees Celsius and let stand = 20 minutes or until it reaches the temperature of the test.
Technique of Operation with milk stimulation Dispense 90 milliliters of test substance and 10 milliliters of milk stimulation in an Erlenmeyer flask. 250 milliliters sterile, mix and remove 1.0 milliliter. Prepare flasks in duplicate for each test substance to be tested. Place the flasks containing the test substance in water at a temperature of 25 degrees centigrade and let stand = 20 minutes or until the temperature of the test is reached. List the numbers of inocula in sterile phosphate buffer. The enumeration of inoculum numbers will be done as follows: Prepared Test 1: 100 1: 100 1: 100 1: 100 Cultivation? 10 °? 10"2? 10" 4? 10"6 Of the dilution, the one milliliter plate and 7 ^ 0.1 milliliter (10) in quadruplicate Use plate technique poured with TGE medium Invest and incubate at 37 ° C ± 2 ° C for 48 hours Shake the test flasks and add one milliliter of culture to 99 milliliters of Dilution of test substance halfway between the flask side and the center Avoid touching the sides of the flask with the pipette Transferring one milliliter portions to the appropriate neutralizer (based on the inactivation of the test substance) after 15 seconds Exposure time and mix well Longer exposure times may be used depending on the test substance, pretesting and / or study For regulatory documentation test, the 1 milliliter (10"1) and 0.1 milliliter (10 milliliter) plate ~ 2) of the neutralizer control tube in c uuprupled. For non-regulatory testing, serial dilutions should be performed in sterile phosphate buffer to produce dilutions of 10, 10, and 10.
These dilutions are usually uniquely plated. Use technique of pouring into plate with neutralized TGE medium (suitable for inactivation of the test substance). Invert and incubate at 37 ° C ± 2 ° C for 48 hours. Controls 1. Phenol resistance method Determine the resistance of the test system to phenol according to standard procedures. The test system must satisfy the resistance specified in SOP. 2. Neutralization Method (created from ASTM E 1054-91) Verification of the neutralization method must be carried out in duplicate in each test system. If more than one concentration of use solution is used, try the most concentrated solution. The tests should be carried out as follows: Test A = Add one milliliter of test substance of use solution to 9 milliliters of the neutralizer and mix. Add 0.1 milliliter of approximately 10 cfu / ml of test system suspension, mix. Test B = Add one milliliter of diluent of test substance to 9 milliliters of the neutralizer and mix. Add 0.1 milliliter of approximately 10 cfu / ml of test system suspension, mix. Test C = Add 0.1 milliliter of approximately 10"cfu / ml of test system suspension to 9 milliliters of phosphate buffer dilution water and mix, let the tests stand for 30 minutes, then enumerate them by plating 0.1 and one milliliter using technique of pouring plate and incubating 48 hours at the specific temperature of the system The data obtained will show that the neutralizer is effective if a = c The neutralizer will be observed that it is not harmful to the cells if b = c 3. Diluent control Plaque milliliter of diluent used in the test, incubate at 37 ° C ± 2 ° C for 48 hours.
TABLE 1 Results zero time Escherichia coli ATCC 11229 TABLE 1A Staphylococcus aureus ATCC 6538 Conclusions: When both the composition of Example II and UDDER GOLD PLUS are prepared again, a reduction of more than 5 log after 15 seconds and without stimulation of 10% of milk against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229. Results of a week TABLE IB Escherichia coli ATCC 11229 TABLE 1C Staphylococcus aureus ATCC 6538 After one week, Example II achieved a reduction to >5 log after 15 seconds with and without a 10 percent milk stimulus against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229. UDDER GOLD PLUS achieved a reduction of 1.42 log against Escherichia coli ATCC 11229 in 15 seconds without milk, while that achieved a reduction of 0.61 log with the stimulus of 10 percent in milk. Against Staphylococcus aureus ATCC 6538 UDDER GOLD PLUS achieved a log reduction of 1.42 without milk, and 0.59 with stimulus of 10 percent milk. Results of two weeks.
TABLE ID Escherichia coli ATCC 11229 TABLE 1E Staphylococcus aureus ATCC 6538 After two weeks, Example II achieved a reduction to > 5 log after 15 seconds with and without a 10 percent milk stimulus against Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229 a reduction of 4.00 was seen with stimulus of 10 percent milk while a reduction of 5.74 log was seen without the stimulus. UDDER GOLD PLUS achieved a 2.06 log reduction against Escherichia coli ATCC 11229 in 15 seconds without milk, while achieving a reduction of 0.26 log with the stimulus of 10 percent in milk. Against Staphylococcus aureus ATCC 6538 UDDER GOLD PLUS achieved a log reduction of 2.09 without milk, and 0.32 with stimulus of 10 percent milk. Results of three weeks. TABLE IF Escherichia coli ATCC 11229 TABLE 1G Staphylococcus aureus ATCC 6538 After three weeks, Example II achieved a reduction of > 5 log after 15 seconds with and without a 10 percent milk stimulus against Staphylococcus aureus ATCC 6538. Against Escherichia coli ATCC 11229 a reduction of 3.91 was seen with 10 percent milk stimulation while a reduction of 5.67 log was saw without encouragement. UDDER GOLD PLUS achieved a reduction of 1.86 log against Escherichia coli ATCC 11229 in 15 seconds without milk, while achieving a reduction of 0.26 log with the stimulus of 10 percent milk. Against Staphylococcus aureus ATCC 6538 UDDER GOLD PLUS achieved a log reduction of 1.78 without milk, and 0.36 with milk stimulus of 10 percent. Four week results TABLE 1H Escherichia coli ATCC 11229 TABLE II Staphylococcus aureus ATCC 6538 After four weeks, Example II achieved a reduction of > 5 log after 15 seconds with and without a 10 percent milk stimulus against Staphylococcus aureus ATCC 6538. Against Escherichia coli ATCC 11229. UDDER GOLD PLUS achieved a 1.2 log reduction against Escherichia coli ATCC 11229 in 15 seconds without milk, At the same time, it achieved a 0.6 log reduction with the 10 percent milk stimulus. Against Staphylococcus aureus ATCC 6538 UDDER GOLD PLUS achieved a log reduction of 1.3 without milk, and 0.6 with milk stimulation of 10 percent.
Swine skin test An analysis was done to determine the antimicrobial activity of tits sealers applied to porcine skin inoculated with Staphylococcus aureus ATCC 6538 and Escherichia coli ATCC 11229. Using the following test method: 1. 2.5 cm squares of sterile lyophilized porcine skin (Corethium® 2. Johnson &Johnson UK) were rehydrated in sterile distilled water for one hour. 2. The hydrated skin frames were immersed in each breast sealer formulation for 10 seconds and hung upright to allow the excess to run off. 3. The boxes were placed in a sterile petri dish and inoculated with 10 microliters of a 24-hour broth culture of the organism to be tested. After inoculation, the samples were left in a contact time of 5 minutes. 4. The leather frames were placed in a tube containing 20 milliliters of the appropriate neutralizer. 5. Samples were centrifuged at 10, 10.3, and 10.5 dilutions were plated in order to enumerate the survivors 6. The plates were incubated at 37CC for 48 hours 7. A test was also performed. neutralization.
Parameters of the method Test systems: Staphylococcus aureus ATCC 6538 Escherichia coli ATCC 11229 Test temperature: Ambient temperature Exposure time: 5 minutes Subculture medium: Tryptone glucose extract agar Incubation: 37 ° C for 48 hours Results: TABLE 2A Zero Time Staphylococcus aureus ATCC 653) TABLE 2B Escherichia coli ATCC 11229 Results: One week TABLE 2C Staphylococcus aureus ATCC 6538 TABLE 2D Escherichia coli ATCC 11229 Results: Two weeks TABLE 2E Staphylococcus aureus ATCC 6538 Escherichia coli ATCC 11229 TABLE 2F Results: Three weeks TABLE 2G Staphylococcus aureus ATCC 6538 TABLE 2H Escherichia coli ATCC 11229 Results: Four weeks TABLE 21 Staphylococcus aureus 15CC 6538 TABLE 2J Escherichia coli ATCC 11229 These results show the compositions of the invention are superior in these antimicrobial tests a commercial tits sealer. These data are representative of antimicrobial properties of the exemplary formulations of the invention. The tonic sealant compositions of the invention using nonanoic acid and a sulfonate material in a 2-propanol formulation were tested to see their coating properties and form an antimicrobial layer that maintains a sufficient amount of material in the animal. A simulated test involving a test tube was carried out. In the method a Kimax ® glass test tube (20 millimeters by 150 millimeters) was weighed, and approximately 5 centimeters was dipped in the tits bath that was being tested. The test tube was then removed from the bath and placed in a hanger for 10 minutes on top of a beaker that had previously been weighed. After 10 minutes the beaker and the test tube were weighed again and the data entered into the table. The dry weight was obtained by allowing the resulting teat bath film to dry 24 hours.
UDDER GOLD PLUS simulated tummy seal test Comments: Wet weight = 10 minutes Dry weight = 24 hours Simulated Tits Sealer Test Composition of Example 1 Comments: Wet weight = 10 minutes Dry weight = 24 hours Formula Example I = 2.5% 2-propanol 1.5% C9 18.0% ÑAS A brief examination of the tabulated data shows that the rheology of the material of Example I maintains a greater amount of material in the simulated animal when compared to the rheology of the commercial tether sealant formulation. These data suggest that the composition of Example I would be somewhat more effective in the treatment of mastitis because the formulations of the invention would retain a greater amount of film treating composition of longer duration than commercial materials. In other tests we have found that the identity of the antibacterial material, carboxylic acid, fatty acid, phosphoric acid or sulphonic acid, does not significantly change the rheology of the material and a fully formulated material that has a rapid initial elimination and long-term elimination can be formulated in a long-lasting film-forming composition.
DETAILED DESCRIPTION OF THE DRAWINGS Figure 1A and Figure IB are graphical representations of the data shown in Tables 1-11 showing the result of the four week biocidal efficacy test of Example II using a food contact sanitation protocol. preceding the specification data. Clearly, from time zero to four weeks the composition of Example II has a substantially greater elimination than a five log reduction in the microbial populations of both model micro-organisms. These data are taken without a milk stimulus. However, Figure IB shows, within the experimental error, similar properties using the same sanitation protocol of contact with food with a milk dirt stimulus of 10 percent. Week two and week three the elimination of E. coli is not easily explained in view of the reduction of 5.5 log obtained in week four for that model microorganism. However, the overall results are shockingly successful in reducing the populations of microorganisms on surfaces in contact with food. Figure 1C and Figure ID are graphical representations of data showing the results of the four-week analysis of sanitizing efficacy of surfaces in contact with biocidal feeds of a commercial tea-sealant composition sold under the trade name UDDER GOLD PLUS. The superiority in performance of the composition of Example II compared to UDDER GOLD PLUS is markedly particular in the weeks of one to four. Figure 2A, a graphic representation of the data shown in tables 2A-2J is a four-week efficacy analysis of the UDDER GOLD PLUS chlorine dioxide tonic sealant formulation measured using the porcine skin protocol. In all test periods the material failed to achieve more than a 2 log reduction. Figure 2B, prepared from the corresponding data given in the aforementioned tables, shows a four week efficacy analysis of Example II using the porcine skin protocol. Clearly, under these more difficult conditions using the porcine skin substrate as a test vehicle, the log reductions in elimination are not as great as those of the surfaces in contact with the food, however, the biocidal efficacy of Example II exceeds the of the UDDER GOLD PLUS chlorine dioxide formulations well considered. Figure 3 shows a plot of the change in viscosity measured in centipoises plotted against shear (rpm) for UDDER GOLD PLUS and Example II and Example IX of the invention. The examples of the invention should now show classical non-Newtonian or non-linear viscosity with respect to shear stress. At low shear stress, that is, low rpm, the viscosity is high. As the shear increases, the viscosity goes down. In great contrast, the viscosity of the UDDER GOLD PLUS formulation shows much less pseudoplastic behavior. The viscosity is substantially constant as the shear or rpm increases. This viscosity information is consistent with the data of the above table and demonstrates that the viscoelastic behavior of the compositions of the invention is likely to coat and adhere to the teat tissue more efficiently than UDDER GOLD PLUS. Since the materials have shear stress after application, the materials will flow over the surface of the teat. However, as the shear is removed, the tipping sealants obtain high viscosity and tend to adhere more tenaciously than compositions such as UDDER GOLD PLUS having linear viscosity. The substantial difference in viscosity at low shear stress (low rpm) demonstrates that the materials should cover the teat with substantially more material and after drying have a more effective environmental barrier. The procedure is as follows. Place approximately 500 milliliters of the experimental tits sealer in a 600 milliliter beaker.
Record the viscosity measurements at several rpms. Apparatus: Brookfield RVT Viscometer, spindle number 1 and 2, several rpm (see table below). Initial temperature 73.6 ° F-final temperature 73.8 ° F The above specification, examples and data provide a clear basis for understanding the operation of the compositions and methods of the invention. Although the invention can be incorporated in a variety of specific examples and processes, the invention resides in the claims appended hereto. In the claims, the proportions are expressed in parts by weight per hundred parts of the claimed anti-masturbation composition as a whole.

Claims (37)

1. A composition for treating physically and chemically stable mastitis, in an acidifying part and in a part of chlorite, which can effectively reduce microbial populations in contact and over an extended period, the composition comprising: (a) an acidifying part comprising organic ingredients, the organic ingredients comprising: (i) about 0.1 to 15 parts by weight of a weak antimicrobial acid or salt thereof or mixtures thereof; (ii) about 0.1 to 15 parts by weight of a weak organic or inorganic acid, or salts thereof, or mixtures thereof selected from the group consisting of phosphoric acid or lactic acid; and (iii) a significant proportion of water; and (b) a chlorite portion, substantially free of organic component, consisting essentially of an alkali metal chlorite salt; wherein the composition exhibits rheology that promotes adhesion to immobilize the composition on the surface of the teat and provides a barrier to environmental contamination.
2. The composition of claim 1 wherein the alkali metal chlorite comprises sodium chlorite.
3. The composition of claim 1 wherein the organic acid comprises lactic acid.
4. The composition of claim 1 wherein the inorganic acid comprises phosphoric acid.
The composition of claim 1 wherein the antimicrobial acid comprises a hydrocarbon sulphonic acid.
The composition of claim 5 wherein the hydrocarbon sulfonic acid comprises an alkanesulfonic acid wherein the alkane group has from 6 to 18 carbon atoms.
The composition of claim 1 wherein the weak antimicrobial acid comprises a mixture of carboxylic acid having from 6 to 12 carbon atoms and an alkanesulfonic acid wherein the alkane comprises from 6 to 12 carbon atoms.
The composition of claim 5 wherein the hydrocarbon sulfonic acid comprises alkylbenzene sulfonic acid wherein the alkyl group has from 9 to 18 carbon atoms.
The composition of claim 1 wherein the composition comprises about 0.1 to 20 parts by weight of an organic polymeric thickener, an organic polymeric film forming agent or mixtures thereof.
10. The composition of claim 9, wherein the composition comprises a mixture of about 0.05 to 2 parts by weight of a xanthan thickener and about 0.1 to 5 parts by weight of a film-forming agent selected from the group consisting of an alcohol polyvinyl acetate, a polyvinyl acetate and mixtures thereof.
The composition of claim 9, wherein the organic polymeric thickener comprises a material that imparts pseudoplastic behavior with threshold shear stress for the final composition.
The composition of claim 1 wherein the composition additionally comprises from 1 to 10 parts of an emollient.
The composition of claim 1, wherein the pH of the composition comprising the acidifying part and the chlorite part is from about 2.5 to 4.5.
The composition of claim 1, wherein the Ph of the composition comprising the acidifying part and the chlorite part is about 2 to 3.5.
15. The composition of claim 1, wherein the chlorite part is a solid inorganic part.
The composition of claim 15, wherein the chlorite portion is a solid tablet comprising approximately equal proportions of sodium carbonate and sodium chlorite.
17. The composition of claim 15, wherein the chlorite portion is an inorganic powder.
18. The composition of claim 1, wherein the chlorite part is an aqueous inorganic part.
The composition of claim 10, wherein the polyvinyl alcohol has a molecular weight (Mn) of about 15 to 100 x 103 and a degree of hydrolysis of about 92 to 99 percent.
20. A method to reduce microbial populations in a dairy animal tit with a tits sealer and to introduce an antimicrobial barrier layer into the dairy animal, the method comprising forming a composition for the treatment of mastitis by combining: (a) an acidifying part comprising organic ingredients, the organic ingredients comprising: (i) about 0.1 to 15 parts by weight of an antimicrobial hydrocarbon sulphonic acid or salt thereof or mixtures thereof; (ii) about 0.1 to 15 parts by weight of a weak organic or inorganic acid, or salts thereof, or mixtures thereof selected from the group consisting of phosphoric acid or lactic acid; and (iii) a significant proportion of water; and (b) a chlorite portion, substantially free of an organic component, consisting essentially of an alkali metal chlorite salt; to form a thickened aqueous thickened sealant material containing less than about 3900 parts per million sanitizer component of oxygenated chlorine; wherein the composition exhibits rheology that promotes adhesion to immobilize the composition on the surface of the teat and provides a barrier to environmental contamination; and apply the composition to the animal.
21. The method of claim 20 wherein the alkali metal chlorite comprises sodium chlorite.
22. The method of claim 20 wherein the organic acid comprises lactic acid.
23. The method of claim 20 wherein the inorganic acid comprises phosphoric acid.
The method of claim 20 wherein the hydrocarbon sulfonic acid comprises an alkanesulfonic acid wherein the alkane group has from 6 to 12 carbon atoms.
25. The method of claim 20 wherein the hydrocarbon sulfonic acid comprises alkylbenzene sulphonic acid wherein the alkyl group has from 9 to 18 carbon atoms.
26. The method of claim 20 wherein the composition comprises a polymeric thickener, or a polymer film forming agent or mixtures thereof.
27. The method of claim 26 wherein the composition comprises a mixture of about 0.05 to 2 parts by weight of a xanthan thickener and about 0.1 to 5 parts by weight of a film-forming agent selected from the group consisting of a polyvinyl alcohol , a polyvinyl acetate and mixtures thereof.
The method of claim 26 wherein the organic polymeric thickener comprises a material that imparts pseudoplastic behavior with threshold shear for the final composition.
29. The method of claim 20 wherein the composition additionally comprises from 1 to 10 parts of an emollient.
30. The method of claim 20, wherein the Ph of the combined end material of the acidifying part and the chlorite part has a Ph of about 2.5 to 4.5.
31. The method of claim 20, wherein the Ph of the combined end material of the acidifying part and the chlorite part has a Ph of about 2.5 to 3.5.
32. The method of claim 20, wherein the chlorite part is an aqueous inorganic part.
33. The method of claim 20, wherein the chlorite part is a solid inorganic part.
34. The method of claim 33, wherein the chlorite portion is a solid tablet comprising approximately equal proportions of sodium carbonate and sodium chlorite.
35. The method of claim 33, wherein the chlorite part is an inorganic powder.
36. The method of claim 21, wherein the polyvinyl alcohol has a molecular weight (Mn) of about 15 x 103 to 100 x 103, and a degree of hydrolysis of about 92 to 99 percent.
37. A composition for treating physically and chemically stable mastitis, in an acidifying part and in a part of chlorite, which can effectively reduce microbial populations in contact and over an extended period, the composition comprising: (a) an acidifying part comprising ingredients organic, the organic ingredients comprising: (i) about 0.1 to 15 parts by weight of a weak antimicrobial acid or salt thereof or mixtures thereof; (ii) about 0.1 to 15 parts by weight of a weak organic or inorganic acid, or salts thereof, or mixtures thereof selected from the group consisting of phosphoric acid or lactic acid; and (iii) a significant proportion of water; and (b) a chlorite portion, substantially free of organic component, consisting essentially of an alkali metal chlorite salt.
MXPA/A/2000/002962A 1997-09-26 2000-03-24 Acidic aqueous chlorite teat dip providing shelf life, sanitizing capacity and tissue protection MXPA00002962A (en)

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