FR2548023A1 - VETERINARY MEDICINE AND FOOT BATH SOLUTION FOR THE TREATMENT OF OVINE PIETIN - Google Patents

Abstract

VETERINARY MEDICINAL PRODUCT FOR THE TREATMENT OF SHEEP PIETIN; IT COMPRISES AN EFFECTIVE QUANTITY OF: A ZINC SALT SUCH AS ZINC SULFATE, AND B A THIO-ACID FAT OR ONE OF ITS DERIVATIVES, SUCH AS A LAURYLSULFATE TYPE SALT, AS WELL AS AN ADJUVANT AND, IF IT IS SOLID, A SOLUBILIZING AGENT; THE MEDICINAL PRODUCT CAN BE ADMINISTERED LOCALLY BY SUBMITTING ANIMALS TO THE ACTION OF A FOOT BATH CONTAINING THE MEDICINAL PRODUCT, FOR EXAMPLE IN AQUEOUS SOLUTION.

Description

Veterinary medication and foot bath solution

  for the treatment of sheep trampling.

  The present invention relates to a veterinary medicament suitable for the treatment of sheep tramplants. The invention also relates to a solution

  Foot bath for the treatment of foot rot using this medication.

  Sheep trampling is a disease of great economic importance in many parts of Australia and New Zealand.

  in most other sheep-farming countries.

  The disease has been known for about 300 years since it has been discovered that the disease is caused by a specific organism, Bacteroides nodosus, many attempts to produce a therapeutic agent.

  for the treatment of the disease have been performed.

  However, to date, in order to treat the foot by direct application of therapeutic agents, it is necessary to bare the foot before attempting any local treatment. It is therefore necessary to expose all the infected areas by eliminating In addition, this procedure has not proved to be totally effective, especially when large herds of sheep or other animals have to be treated. This is partly that Bacteroides nodosus can survive for extended periods of time by slowly growing in pockets

isolated under the horn.

  One of the aims of the invention is therefore to eliminate or at least reduce some of the difficulties

associated with the prior art.

  The invention provides a veterinary medicament

  for the treatment of trampling, by local application 10 not requiring a bare foot.

  The invention provides a veterinary medicament containing an effective amount of (a) a zinc salt, and (b) a fatty thio-acid or a derivative thereof. The veterinary drug can furthermore understand

(c) an adjuvant agent.

  Surprisingly, the combination of a zinc salt and a fatty thio-acid or a derivative thereof has been found to provide a veterinary drug which can be applied locally to hoofs.

  sheep without having to bare the foot.

  The veterinary medicament may be in the form of a solution. Alternatively, the veterinary medicament may be in the form of a solid. For use, the solid may be dissolved in a suitable solvent. Preferred solvents include water, alcohols and their salts. Ethanol is one of the most preferred alcohols. A mixture of water and ethanol can be used with proportions of ethanol which can be

reach about 20% v / v.

  Zinc salts which are soluble in a solution, in particular an aqueous or alcoholic solution, are therefore preferred. The zinc salts may be chosen from zinc salts formed with an acid and their derivatives. The zinc salts may be chosen from the following: Zinc Halides and Derivatives Zinc salts formed with a preferred acid include the zinc salts of a thio-acid. The zinc salts of a thio-acid may consist of one or more of the group consisting of zinc sulfite, zinc sulphate, zinc sulphonate, zinc hydrosulfite, hydrosulphate of zinc and their derivatives Zinc salts derived from an acid can be used in a hydrated form. The zinc halides may be selected from zinc chloride, zinc bromide, zinc oxide and oxyhalides, for example

zinc perchlorate.

  Other zinc salts that can be used include one or more of the salts selected from the group consisting of zinc acetate, zinc nitrate, zinc ammonium chloride, zinc carbonate, and the like. zinc borate, zinc ethyl sulphate, zinc phenolsulfonate, zinc salicylate

and zinc hydroxyhydrosulphate.

  The zinc salts may be present at any suitable effective concentration. The zinc salt may be present at concentrations of from about 2% w / v to about 100% w / v. Below these concentrations, the veterinary medicinal It may not be completely effective Over these concentra30 tions, the physical nature of the composition may pose difficulties For solid compositions, the zinc salt may be present at concentrations of about 80% w / w relative to the ingredients about 98% w / w active ingredients. A concentration of about 90% w / w over

  Active ingredients can be used.

  The thio-fatty acid or its derivative may be selected from any suitable compound potentiating the absorption of zinc ions in the hoof horn of sheep. Particularly preferred thio-fatty acids are lauric steel derivatives or

  The lauryl sulphate derivatives have proved particularly suitable.

  The lauryl sulphate salts can be used.

  The lauryl sulphate salts may be chosen from the alkali metal, alkaline earth metal, ammonium and amine salts. The alkali metal or alkaline earth metal lauryl sulphates may be chosen from lauryl sulphate.

  of sodium, potassium lauryl sulphate or magnesium lauryl sulphate.

  The ammonium or amine lauryl sulphates may be chosen from ammonium lauryl sulphate, mono-, di or triethanolamine lauryl sulphate, triethanolamine lauryl sulphate and ammonium sulphate.

  monoisopropylamine lauryl sulphate or any of their mixtures.

  Instead of the lauryl sulphate salts mentioned above or in combination with any of them, an alkali metal, alkaline earth metal lauryl ether sulphate can be used.

  corresponding ammonium or amine.

  Thio-fatty acids or their derivatives may be present in any suitable effective concentration. Concentrations may range from about 0.4% w / v to about 10% w / v. A concentration of about 2% w / w may be used. For solid compositions, thio-fatty acids may be present in concentrations of about 2% w / w relative to the active ingredients at about 20% w / w relative to the active ingredients. A concentration of about 10% p / p in relation to the ingredients

assets can be used.

  The veterinary medicaments according to the invention may be in the form of solutions, preferably aqueous or alcoholic solutions. In these embodiments, the zinc salts may be used in a hydrated form. Zinc sulphate, and in particular zinc monohydrate or

  zinc sulphate heptahydrate, can be used.

  Veterinary drugs, as indicated

  above, may be present in a solid form.

  The solid form can then be dissolved when it is desired to treat the foot rot. However, dissolution in the solvents, especially aqueous solvents, may be difficult in some embodiments. The solid composition can be dissolved in

  However, this may be difficult. In addition, undesirable foaming may occur.

  Therefore, the veterinary medicament according to the invention may further comprise an effective amount of a solubilizing agent. Any suitable solubilizing agent acceptable in veterinary medicine may be used. Sulphate salts, especially salts of the type, may be used. Bisulfate A preferred solubilizing agent is sodium hydrogen sulfate. The solubilizing agent may be present in an amount of about 1% w / w based on 2% w / w active ingredients relative to

active ingredients.

  When zinc sulphate monohydrate is used as the zinc salt, about 1.9% w / w of sodium hydrogen sulphate can be added to the active ingredients consisting of zinc salts. In the case of zinc sulphate heptahydrate, about 1.2% w / w can be added to the active ingredients. The veterinary medicament according to the invention may further comprise an adjuvant agent. An azide compound may be present in the composition of the invention. A metal azide may be used.

  alkali Sodium azide is preferred.

  Alternatively, the adjuvant may be selected from alcohols, preferably ethanol, or ammonium nickel hydroxide. These compounds have been shown to enhance the penetration of zinc ions into the

hard horn of the hoof.

  It should be noted that in the treatment of foot rot, the veterinary medicament can be used as a foot bath composition. A suitable composition is 200 g / l zinc sulfate heptahydrate, Zn SO 4 7H 20, and 20 g / l

  sodium lauryl sulphate (sodium dodecyl sulphate), CH 3 (CH 2) 10 CH 3 SO 3 Na, C 12 H 25 Na 4 O 4 S, in the form of an aqueous solution.

  The mixture can be prepared at a concentration about twice that indicated above, with the recommendation of diluting it before use with an equal volume of a solvent, for example water.

  According to another of its aspects, the invention provides a method for the treatment of foot

  sheep which comprises the local administration of a veterinary medicament as described above to animals requiring such treatment.

  The method of the invention may include subjecting the animals to be treated to a footbath containing a veterinary medicament as described above. Treatment may be continued for a period of time sufficient to kill substantially all living B. nodosus. Experiments have shown that at an average concentration of about 500 ppm (μg Zn 2 + / g dry weight of hoof horn), B nodosus

  does not develop and can not be recovered as a living organism from canned cultures.

  It is therefore desirable to continue the process of the invention until a zinc ion concentration of 400 ppm or more is achieved. For example, if the feet are treated with a zinc sulfite / lauryl sulfate solution. for one hour, experiments have shown that zinc salt concentrations greater than 400 ppm can

to be obtained.

  The method of the invention may further comprise repeating the treatment after a predetermined period of time.

proved appropriate.

  The invention will be better understood when reading

  examples which are only illustrative in character and do not limit the scope of the invention.

  Example 1 In Vitro Testing An apparatus for in vitro testing is illustrated by the accompanying drawings in which: Figure 1 illustrates an apparatus used for penetration testing of compounds through the claw tissue, and Figure 2 illustrates an apparatus used to determine the binding of compounds by the claw tissues. The apparatus of FIG. 1 consists of a disposable plastic laboratory apparatus 10 defining a test solution chamber 12 and a sampling chamber 14 A common wall 16 separates the chambers 12 and 14 A sample of hoof 18 to study is subjected in the chamber 12 to the opening 20 of the wall 16 by means of a product

sealing 22.

  Samples 18 for the tests were obtained from recently slaughtered sheep. Soft tissue segments of the sole and bulbar sole (hind part) and harder tissue of the proximal abaxial area of the hoof were used. In all experiments, each segment comprised the entire thickness of the horn varying from 1.3 to 2.4 mm. The segments were fixed in the absorption and penetration apparatus so that the outer surface segments are in contact with the studied solution A silicone adhesive (Dow Corning) has been used as a sealant 22 to hermetically

  segments of claws in the penetration apparatus.

  The sealant itself has been studied for

  check that the agents studied did not enter it.

  After allowing the sealant to proceed, the chamber 12 was filled with the test solution 24 while a saline solution 26 was added to the chamber 14. The apparatus was leak tested. by adding a neutral dye in the test chamber 12 and applying a pressure and measuring the electrical resistance between the two chambers For each solution studied, in a penetration or absorption experiment, a total of eight hoof segments, four

  tender and four hard, was used.

  In the penetration experiments, samples were collected in the sampling chamber 14 at 15 minute intervals during the first hour and then 30 minutes thereafter and were analyzed for the test compound. The penetration rate used is the time elapsed before the compound was first detected in the sampling chamber. For the absorption tests, the apparatus of FIG. 2 was used. The apparatus consisted of a column. An open ended cylinder 30 in which a tightly fitting horn segment 32 was pressed to rest against soft paraffin 34 The inner surface of the segment 32 was pressed into the paraffin 34 so as to prevent the absorption in 10 This surface A rubber stopper 36 has been placed at the base of the column 30 to retain the paraffin. Hoof horn segments for absorption studies were cut into feet with a 1.32 cm leather punch. These segments fit closely to the column With the deep surface of a segment 32 pressed in paraffin 34 (petrolatum), 2.5 ml of solution studied 38

  were applied to the apparent surface.

  In all the uptake studies, the claw segments were contacted for one hour with the test compound and then rinsed and subjected to digestion and analysis of the compound. The samples were digested either by treatment with sodium sulphide at 10% w / v for 48 hours at room temperature either by

  heating with a concentrated mixture of nitric, sulfuric and perchloric acid (1/1/1).

  The following compounds were subjected to penetration and detection by direct spectrophotometric analysis: aminoacridine hydrochloride, chloramphenicol, homidium bromide, squalene, trishydroxymethylnitromethane, α-terpineol and tetrahydrofurfuryl alcohol Colorimetric methods have been used to detect sodium azide, sodium borate, sodium bisulfite and metabisulfite, chromium and potassium sulphate, copper sulphate, formaldehyde, nickel citrate, salicylic acid Zinc sulphate and benzoic acid The analysis of copper, chromium and zinc was also carried out

  by atomic absorption spectrophotometry.

  Results The penetration rates of iso10 compounds in a single solvent are summarized in Table 1. Considerable variability was observed between the individual horn segments Zinc and copper were the metal cations with the fastest penetration and azide the anion with the fastest penetration Penetration of the lipophilic compounds was poor Formaldehyde did not penetrate into the hoof segments, even

  after five days of exposure; its penetration rate was therefore less than 0.02 mm / h.

  The effects of the other compounds on the rate of penetration of the azide are shown in Table 2. Net increases were also observed for treatments with sodium lauryl sulphate and nickel and ammonium hydroxide. The keratolytic agents which are sodium sulphide and sodium thioglycolate, have increased the rate of penetration of the azide, but have also had a corrosive effect on the hoof Neither dimethylsulfoxide (DMSO) nor urea improved penetration The Penetration was generally better through the soft horn of the hoof than through the hard horn of the hoof, except when ethanol or nickel-ammonium hydroxide was used in the treatment. Table 3 groups the effects of other agents on zinc penetration Treatment with sodium lauryl sulphate significantly increased zinc penetration and penetration was further improved by ethanol incorporation With the exception of the bisulfite / urea mixture keratolytic treatments did not significantly increase zinc penetration As with azide, penetration of zinc through the hard horn was faster than through the soft horn in treatments using

  ethanol or nickel and ammonium hydroxide.

TABLE 1

  Rates of Penetration of Compounds Isolated Through the Keratin of Sheep Claws Mean Penetration Rate Compounds Concentrations Solvent mm / h Keratin Hard Keratin Hard Sodium Acid 5% w / v H 20 0, 16 0.10 Cupric Sulphate 20% p / v H 20 0.17 0.13 Zinc acetate 15% w / v H 20 0.18 Zinc sulphate 20% w / v H 20 0.31 0.27 F-N n Co,

C>. M O O

MLEAU 2

  penetration of sodium azide Effect of other compounds on mean penetration rate ConcenComposition Soft keratin Hard keratin Urea 8 M Negligible Negligible Sodium bisulfite 10% w / v Negligible Negligible Sodium bisulfite 4% w / v 0, Negligible and urea 8 M Sodium sulphide 5% w / v 0.54 0.43 Thioglycolate, p H 10.5 2 M 0.44 0.42 Sodium sulphite 30% w / v 0.15 Negligible Ethanol 20% v / v 0.20 0.36 Cuprammo hydroxide 5% w / v 0.32 Negligible nium, p H 9.5 Nickel hydroxide and 1.0% w / v 0.34 Negligible ammonium, p H 9 Nickel hydroxide and 1.0% w / v 0.61 0.74 ammonium, p H 6.4 Sodium lauryl sulphate 5% w / v 1.02 0.74 Dodecyl benzene sulpho 5% w / v Negligible Negligible Sodium succinate Dimethylsulfoxide (DMSO 50% v / v Negligible Negligible to NW Ore NW>

TABLE 3

  Effect of other compounds on zinc penetration (as Zn SO 4 7H 20, 10% w / v) Mean Compound Penetration Rate Concentration mm / h Soft Keratin Hard Keratin Laurylsulfate 2% w / v 1.90 1 Sodium Lauryl Sulphate 2% w / v Sodium 2.31 3.91 and Ethanol 20% w / v Dodecylbenzenesulfon 5% w / v 0.66 0.42 Sodium succinate Sodium azide 5% w / v 0.56 0.48 Laurylsulfate 2% w / v sodium 1.37 1.31 and sodium azide 1% w / v Sodium bisulfite 0.3 M 0.98 0.81 and urea 8 M Thioglycolic acid, 2 M 0, 33 Negligible p H 3,5 Sulfite / tetrathionate, 0.2 M 0.34 Negligible p H 2.5 Nickel hydroxide and 1% w / v 0.46 0.54 ammonium, p H 6.4 n Ul 4 co o, N> rj

TABLE 4

  Zinc fixation in ovine hoof tissue

15 20 25 30

  Zinc ion (mg / g Treatment of hoof horn) Tough hard zinc sulphate 10% w / v Zinc sulphate 20% w / v Zinc hydroxide paste Zinc sulphate 10% w / v in 50% DMSO % Zinc sulphate 10% w / v in% v / v formalin Zinc sulphate 10% w / v in thioglycolic acid 2 M sodium azide 1% w / v Sodium lauryl sulphate 4% w / v

  0.55 0.3-0.67 0.59 0.44-0.74 0.41 0.30-0.57 0.54 0.43-0.69 0.06 0.01-0.10

0.64

  0.36 0.16-0.62 0.48 0.45-0.51 0.22 0.16-0.27 0.29 0.12-0.33 0.04 0.01-0.07 0.26 0.15-0.38 0.31 0.22-0.41

  0.40-0.20-0.53 0.40 0.24-0.67 0.52 0.41-0.59

0.51-0.70 0.53

0.49 to 0.57

0.66

0.54-0.70 0.72

0.62-0.85 0.88

0.68 to 0.99

  1% w / v sodium azide and 2% w / v sodium lauryl sulphate 1% w / v sodium azide and 2% w / v sodium lauryl sulphate and 20% v / v ethanol TABLE 4 (continued 1) 15 Ions zinc (mg / g Treatment of hoof horn) Treatment Tough Dodecylsulfosuccinate 0.62 0.30 sodium 2% w / v 0.61-0.62 0.26-0.35 Cetyltrimethylammonium bromide 0.43 0 , 34 (Cetavlon) 1% w / v 0.35-0.55 0.27-0.39 Nickel ammonium hydroxide 0.61 0.68 p H 6.40 to 5% w / v 0, 42-0.96 0.21-1.56 Studies of zinc uptake by sheep hoof horn are summarized in Table 4. Mean tissue concentrations of 500 μg zinc ions / g and 360 μg of zinc / g ions respectively in the soft and hard horn were observed after exposure of samples to the action of a 10% w / v solution of Zn SO 4 7H 20 for one hour. the exception of formaldehyde, the presence of the other compounds did not have a significant effect on zinc fixation The presence of 10% v / v of formalin reduced absorption to negligible levels After 24 hours of continuous washing of the treated claw segments in running water, 85 to 95% of the sorbed zinc ab30 was retained in the soft horn and 50 to

% in the hard horn.

  Sodium lauryl sulphate has increased zinc penetration suggesting that this C 12 alkyl surfactant can increase the rate of penetration of hydrophilic ions such as Zn and N 3 in sheep hoof horn. This effect was not solely due to the surfactant properties of sodium lauryl sulphate, since neutral or cationic detergents and other anionic detergents have not increased the penetration of these ions to the same extent. rather be due to an increase in the rate of hydrolysis of the side chains of the type

internal amide of keratin.

  In contrast to all other treatments studied, incorporation of nickel and ammonium hydroxide or ethanol resulted in faster penetration of zinc and azide ions through the horn.

  hard hoof only through the soft horn of hoof.

  This effect of ethanol may result from the destabilization of the high glycine and tyrosine proteins of the hard keratins it causes. The nickel and ammonium hydroxide may act by rupture.

  hydrogen bonds inside the keratin.

  However, another hydrogen bonding agent, 8 M urea, did not increase penetration of the azide into the hoof horn. Treatment of sheep footprints with a dry, hardened foot can be improved by the addition of agents increasing penetration through the hard horn of the hoof This work is supported by the Australian Wool

Research Trust Fund.

  Example 2 In Vivo Tests Extensive penetration and chemical uptake tests in sheep hoof revealed a few chemicals (Example 2) that could be used for the treatment of trampling. toxicity of these chemicals vis-à-vis B nodosus were carried out taking into account 35 factors such as ease of use in the field, cost, toxicity and adverse effects on wool, the most A combination of zinc sulphate and sodium lauryl sulphate was investigated. This treatment was studied in sheep with severe trampling in park and exercise trials. The sheep were treated for The best results were obtained when the treatment was applied for one hour on two separate occasions by five days. was evaluated on herds of 500 to

1000 sheep.

  Several trials of this treatment carried out in

  have been completed and trials on herds of 500 to 1000 sheep per property are in progress.

  Results The results of the penetration and fixation tests showed that a combination of

  zinc and sodium lauryl sulphate was the most suitable for penetration treatment.

  Bacteroides nodosus has been shown to be very sensitive to zinc ions. Zinc levels as low as ppm in a culture medium inhibit the development of this organism. However, in the hoof, much higher concentrations are required to kill this organism. were performed with recently slaughtered sheep's feet which were treated with zinc solution for different periods of time to achieve a range of zinc tissues in the hoof. These feet were used to prepare agar plates. Hoof A sufficient amount of zinc to kill B nodosus can in fact accumulate in the claw at concentrations greater than 400 ppm (Vg Zn ++ / g wet hoof horn weight) B nodosus does not develop and can not be recovered as a viable organism from these canned cultures Zn ++ concentrations greater than 400 ppm may be ob held when the feet are treated for an hour with a

  zinc sulphate / sodium lauryl sulphate solution.

  The stability and activity of the treatment solution was also studied in the presence of organic contamination. A treatment solution containing 20% w / v of sheep faeces left at room temperature for 4 weeks did not show any symptoms. significant decrease in zinc concentrations or bactericidal activity with respect to

of B nodosus.

Efficacy and safety

Efficiency Tests in the park.

  Fifteen merino weaning lambs were challenged by light skin scratching

  interdigitally with a needle to dissociate and maintain the group in an enclosure with two infested sheep on damp cellular rubber mats.

  Serological examination of B nodosus isolates from these sheep showed that they were serogroup A. The trampling was allowed to progress until at least three feet of each animal had severe lesions (Notes 3 and 4). The sheep were randomly divided into three groups of five and these groups received the following treatments: (a) Experimental treatment group: This group was treated by foot baths in the composition for one hour on two occasions separated by five days

foot was performed.

  (b) Formalin treatment group: This group was treated by foot baths in 10% v / v formalin for 10 minutes on two occasions at five-day intervals None

  Exposure of the foot was not performed.

  (c) Control group: This group received no treatment None

  Exposure of the foot was not performed.

  Sheep groups (a) and (b) were placed in clean enclosures on wet cellular rubber mats after the first footbath and returned to the same pens after the second foot bath. Sheep in the control group were placed in a clean enclosure on a moist cellular rubber mat together with groups (a) and (b). The high ambient temperature (11 C-28 C) combined with the humid environment, created ideal conditions for dissemination and progression of trampling after treatment The results of this trial are summarized in the table

following.

  After treatment Number of feet reached After treatment (total foot count) Days elapsed _ _ _ _ _ between treatment Number of treatment Treatment of momtons Day O Day 7 Day 14 Day 21 Day 28 and failure * sheep No failure (a) ) Composition 5 17 (57) OOO No failure up to 42 days (b) Formalin 5 19 (68) O 13 (36) 15 (45) 17 (58)> 14 days (c) Control 5 17 (64) ) 18 (68) 19 (59) 17 (59) 18 (67) * By definition failure is a recurrent active injury with

  identification of nodosus B from this lesion.

  Each foot of each sheep was carefully examined weekly for a total of seven weeks. Formalin foot baths lasted only 10 minutes as prolonged exposure would cause considerable lesions. (Littlejohn 1972, Pryor 1959) Foot lesions were assessed according to the Egerton grading system

and Roberts (1971).

  In the treatment of sheep with severe trampling by foot baths without prior bare foot, the new composition was found to be much superior to formalin Sheep treated with the composition were completely cured of foot and all lameness had disappeared seven days after treatment Formalin-treated sheep continued to limp and active trampling was evident 14 days after treatment Sheep treated with the new composition did not appear to be uncomfortable during the stay in the bath. feet. The sheep whose feet soaked in the formalin bath gave clear signs of discomfort and repeatedly removed their feet from the formalin bath. It should be noted, however, that the condition of the feet prior to treatment did not correspond exactly to the conditions. Sheep used in park trials had wet feet permanently for 4 weeks prior to treatment. This softened the foot and may increase the penetration of the foot.

  zinc (compositions) and formalin in the foot.

  Conclusion Complete cure of severe trampling was achieved by two one-hour foot bath treatments administered five days apart with the new composition. The lameness was cured in

  less than seven days Formalin has neither cured nor reduced lameness due to foot rot.

  Field Trials Treatment trials of three flocks of sheep from Property A at Glenaladale, Bairnsdale Shire, Victoria involving approximately 3,000 sheep were performed. Treatment consisted of two one-hour footbaths with the five-part composition. Interval days After the first footbath, the treated animals were placed in a clean exercise area (no other sheep for at least seven days). The sheep were brought back to this exercise area or another clean exercise area after the second treatment The control sheep were kept in a similar exercise area during the 12 weeks of field trials, but this exercise area did not necessarily contain of sheep in the previous seven days In all field trials, 20 stocking densities and rearing practices

  standards were respected as much as possible.

  Six thousand sheep, most of them accompanied

  of lambs, have been treated in this property.

  The foot was diagnosed according to conventional laboratory techniques. The disease was of recent appearance (some notes 3 or 4 of the feet) but was in rapid propagation during the treatment. The climatic conditions during the test were very dry and a considerable degree. B nodosus isolates from this property belonged to serotype A. The sheep were treated on July 20, 1982 and July 27, 1982 with the composition. No bare footing was made. 80 ewes were randomly selected and their feet examined individually. Fifty-nine% of the ewes were found to have foot rot and 23% of the affected sheep had lesion scores of 3 or 4%. these ewes were placed in a separate exercise area during the rest of the trial. These sheep served as a control. The remaining sheep were treated. with the rest of the flock but, after treatment, were placed in a separate exercise area for the remainder of the trial. These sheep constituted a subsample of the treated flock and were examined. Careful at 6 to 12 week intervals after treatment The rest of the flock was examined seven weeks after treatment when mowing. Results for treated and control groups

are shown in the table below.

  No cases of trampling could be observed in treated sheep remaining seven weeks after treatment. Similarly, 10 months after treatment, no 20 cases of foot rot were identified in this property despite good rainfall during last three months Some problems have arisen in the treatment of ewes with young lambs As a result of prolonged treatment in the footbath, some lambs have tried to suckle their mother and have been totally immersed in the composition. These lambs had redness of the membranes surrounding the eyes, however there was no death and the examination two weeks later did not show corneal opacity nor inflammation around

eyes.

  In this trial, the composition was able to completely cure sheep with a recent outbreak of trampling, but in most of this trial the climatic conditions were not favorable for the spread of trampling. The severity of the disease was low. Very few sheep showed the abnormal and excessive hoof growth observed in sheep with the disease for more than one season. An important observation is that the lameness of sheep disappeared in the

week after treatment.

  Number Number Number of Feet Percentage Number of Sheep's Feet Sheep Time Group of sheep with affected sheep's feet affected with healed note (%) <M> 3 or 4 (%) Before pretreatment 40 22 (55) 37 (23) 14 (38) June 1982 control 40 (63) 45 (28) 4 (9) 6 weeks treated 40,000 100% after control treatment 40 (65) 50 (31) 2 ( 4) O% 12 weeks treated 40,000 100% after control treatment 40 11 (28) 18 (116) O 60% w O 0% tn co or> Dl In a property B in Goon Nure, Bairnsdale Shire, Victoria, approximately 2100 ewes of different ages and merino weanlings were treated for several days from November 18, 1982 The B nodosus isolates of the property belonged to serogroup A. This property had an ancient history of foot rot which, in combination with very dry conditions, caused in many sheep excrescences, malformation The large number of sheep in this trial made it impossible to grade the feet or to identify each sheep, so that a subgroup of 50 was taken at this time. randomly in the main group labeled by ear and scoring the feet to assess severity and frequency in the flock. These sheep then served as untreated controls for the remainder of the trial. Two weeks after treatment, the treated sheep began to be examined until all were within 12 weeks

the treatment.

  The treatment protocol was identical to

  that of the tests in the park and the test in the property A The results are grouped below.

  There was a very clear remission of the trampling in the control group during the 12 weeks of the test, certainly due to the very hot and dry conditions. It was therefore difficult to evaluate the effectiveness of the treatment, however two facts stand out Data: treatment greatly reduced tramline frequency but did not heal all sheep. Sheep that remained ill all had significant malformation and growth of the feet and in all cases the lesion was in the the clip As it was observed in 2-8

  Property A, the treated sheep stopped limping within a week, while the diseased sheep continued to limp during the trial.

  Number Number Number of Feet Percentage Number of Feet Sheep Percentage Time Group of Sufferers Achieved Is (%) (q with footnote 3 or 4 (%) Before t Before Witness 50 28 (56) 48 (24) 14 (29) treatment 12 weeks control 50 8 (16) 8 (4) 2 (25) 83 after treatment Treaty 2000 15 (0.75) 15 (0.2) 15 (100) 99.2 * * Relative to frequency before treatment

in the control group.

  % ro) n co o N This trial in Western Victoria involved 243 ewes and adult rams Romney Marsh on property C at Scotts Creek, Camperdown District The sheep on this property were infected with B nodosus serogroup F All the sheep were individually identified and foot-tagged before treatment This property was not suffering from drought and the animals could feed on their eggs Good rains fell during the last 8 weeks of the season. test by creating appropriate conditions for

  dissemination and the evolution of foot

  The treatment protocol was identical to those described in the previous examples except that 11 sheep were removed during the examination.

  initial These sheep had a chronic foot rot with significant deformities and growths of the feet. The results of this test are summarized in the following table.

  Despite the wet conditions during most of the test, there was a significant degree of remission in the control sheep, however, the cure rate of the treated sheep was much higher. remained infected with malformations and growths of the feet and the lesion

  active was invariably in the region of the forceps.

  The lameness of the treated sheep disappeared in a week. Number Number Number Number feet of feet Percentage Time Group of sheep affected with healed mutton affected with MM footnote 3 or 4 (%) Before Witness 46 26 (57) 38 (21) 20 (53 Treatment Treated 193 109 (56) 159 (21) 84 (53) 6 weeks Control 42 (48) 28 (17) 18 (64) 22 after treatment Treated 190 * 6 (3) 6 (0.08) 6 (100) 96 12 weeks Control 42 15 (36) 16 (9.5) 14 (88) 56 after treatment Treaty 181 3 (1.7) 3 (0.4) 3 (100) 94 * These sheep were removed from the treated group

  during the inspection at six weeks.

  Conclusion The above tests, carried out in the wild and in the parks, indicate that the new composition is very effective for the treatment of trampling by foot bath. The treatment ensures a cure rate. greater than 90% of sheep with severe disease without having to be exposed to the foot In sheep in the case of a recent outbreak of foot rot, in the absence of outgrowth and deformation of the hooves, we can

  expect an even higher cure rate.

  However, it can not be expected that the treatment will in any case lead to the eradication of foot rot, since some sheep, particularly those whose

  feet have malformations and growths, are not cured by a single treatment.

  In all tests, the composition rapidly removed lameness due to trampling. The vast majority of affected sheep moved perfectly three to seven days after completion.

treatment.

  Safety (a) For the normal recipient animal that is the sheep: During the free and park trials,

  approximately 3,000 sheep and lambs were treated and the only adverse reaction observed was inflammation around the eyes of the lambs which were fully immersed in the footbath. This inflammation disappeared in two weeks without treatment.

  An attempt was made to observe any adverse reaction in sheep treated with a

concentrated composition in duplicate.

  Experimental Animals Twenty merino sheep were used for this test. These animals were aged from 14 months to 6 years, and presented a body condition ranging from weight loss to a good general state, the growth of wool being between less than 1 cm and 6 5 cm Eleven of these sheep had an acute footprint

or chronic.

  Treatment All the sheep were kept in a composition twice as concentrated as it was reordered for one hour, on two occasions at five

days apart.

  Findings (a) No adverse reactions were observed immediately after treatment One week after treatment, 10 sheep were sacrificed and autopsied by a veterinarian pathologist Special attention was given to those parts of the anatomy exposed to the action of the composition No abnormal findings were made Inborn terpigal skin had a normal macroscopic and histological appearance. No corneal opacity could be detected although the eyes of some animals were accidentally splashed by the composition during treatment. sheep died 4 days after first footbath A complete autopsy revealed that death was due to weight loss and was unrelated to treatment Zinc tissue levels of this animal were not elevated Another sheep died 11 weeks after the completion of the treatment The autopsy revealed that the death was due to a severe parasitic immunity unrelated to treatment Tissue levels of zinc

  this animal were also normal.

  The flock from which the sheep used in this trial were suffering from malnutrition due to drought Several other sheep from this flock (but not those participating in the trial) died in the property during the test.

  this herd was used despite their thinning, since they were then the only sheep infected with foot rot.

  The remaining 8 sheep were sacrificed 14

  days after the completion of the treatment and autopsies.

  In this case also no abnormalities were observed and the macroscopic and histological appearance of the skin

interdigital was normal.

  Another test was conducted to determine if sheep deprived of water are likely to drink

the composition.

  Four sheep were used for this experiment Two sheep were housed in a park

  with dry feed and a drinking trough containing a known volume of composition at the use concentration (group 1) The other two sheep only had access to the dry food (group 2).

  Group 2 served as a control for adverse reactions due to water deprivation and the supply of dry food. After 64 hours, group 1 had not drunk the water. group 1 who started drinking it within minutes As soon as the sheep started to drink, the water was removed and replaced by the composition in an identical container The sheep approached the trough but did not During the next 4 hours we can conclude that the composition is particularly unpalatable to

the sheeps.

  (B) Other domestic animals: A bat dog was kept in a footbath containing the composition (depth 10 cm) so that its legs were immersed for two periods of one minute. Careful examination of the dog's legs revealed no adverse reactions due to

this exhibition.

  (C) As pointed out in the toxicology section of this study, zinc is everywhere in nature and has low toxicity for a wide range of animals studied. The composition is only intended to be used in footbaths which are generally located within the sheep pens; Therefore, it is very unlikely that animals (including birds) having access to the composition will drink it because it has been found to have an unpleasant taste for sheep. The composition also has little risk of causing poisoning because sheep and lambs that have been immersed have had only minor transient effects. Elevated levels of zinc are toxic to aquatic living beings, yet that the composition can be reused (and thus poses little problem of rejection)

  and it is unlikely to be used in the immediate vicinity of streams, this risk is low.

  Of course, the invention is in no way limited to the examples described and shown, it is capable of numerous variants accessible to those skilled in the art depending on the applications envisaged and without departing from it for that purpose. spirit of the invention.

Claims (20)

  Veterinary medicinal product for the treatment of sheep tramplin, characterized in that it contains an effective amount of (a) a zinc salt, and   (b) a fatty thio-acid or a corresponding derivative.   Medicament according to claim 1, characterized in that said zinc salt is soluble in the said effective amount in water, an alcohol or a their mixtures.   Medicament according to claim 1 or 2, characterized in that said zinc salt is formed   with an acid, a corresponding derivative or a mixture of at least two of them.   Medicament according to claim 3, characterized in that said zinc salt is a zinc halide selected from zinc oxyhalides, such as zinc perchlorate, zinc chloride,   zinc bromide and zinc iodide, one of their derivatives or a mixture of at least two of them.   Medicinal product according to claim 4, characterized in that said zinc salt is chloride of zinc.   Medicament according to claim 3, characterized in that said zinc salt is a zinc salt a thio-acid.   A medicament according to claim 6, characterized in that said zinc salt is selected from zinc sulfite, zinc hydrosulfite, zinc sulphate, zinc sulphonate, hydrosulphite,   zinc, zinc hydrosulfate, their derivatives or a mixture of at least two of them.   Medicament according to claim 7, characterized in that said zinc salt is zinc sulfate monohydrate or zinc sulfate heptahydrate.   Medicament according to claim 3, characterized in that said zinc salt is selected from zinc acetate, zinc nitrate, zinc ammonium chloride, zinc carbonate, zinc borate zinc ethyl sulphate, zinc phenolsulfonate, zinc salicylate, hydroxyhydrosulphate zinc and their mixtures.   Drug according to any of   Claims 1 to 9, characterized in that it further comprises a solvent, said zinc salt being present   at a concentration of about 2% w / v to about 100% w / v. 11 Medicinal product according to any of the   Claims 1 to 8, characterized in that said composition is a solid in which said salt of   zinc is present at a concentration of about 80% p / w at about 98% w / w.   12 Medicinal product according to any of the   Claims 1 to 11, characterized in that   thio-fatty acid or its derivative has the effect of potentiating the absorption of zinc ions in the horn of the hoof of sheep.   Medicament according to claim 10, characterized in that said fatty thioacid or its derivative is present at a concentration of about 0.4% p / v at about 10% w / v.   A medicament according to claim 11, characterized in that said fatty thioacid or its derivative is present at a concentration of about 2% w / w to about 20% w / w relative to the active ingredients.   Medicinal product according to one of Claims 1 to 9, 11, 12 or 14, characterized in that it is a solid containing an effective amount a solubilizing agent.   Medicament according to claim 15, characterized in that said solubilising agent is a bisulfate type salt such as sodium hydrogen sulphate. A medicament according to claim 16, characterized in that said solubilizing agent is present at a concentration of about 1% w / w to about   2% w / w compared to the active ingredients.   Medicament according to any one of claims 1 to 17, characterized in that said thio-20 fatty acid or its derivative is a lauric acid derivative or a mixture of at least two of them.   Medicament according to claim 18, characterized in that said lauric acid derivative is a lauryl sulphate or lauryl ether sulphate salt or a mixture of at least two of them.   Medicinal product according to Claim 19, characterized in that the said salt of the lauryl sulphate or lauryl ether sulphate type is chosen from the salts of   alkali metals, alkaline earth metals, aminium and amine and mixtures thereof.   Medicinal product according to Claim 20, characterized in that the said lauryl sulphate salt is chosen from sodium lauryl sulphate, potassium lauryl sulphate and magnesium lauryl sulphate.   a corresponding lauryl ether sulfate and mixtures thereof.   Medicinal product according to claim 20, characterized in that said lauryl sulphate is chosen from ammonium lauryl sulphate, mono-, di or triethanolamine lauryl sulphate, triethanolamine ammonium lauryl sulphate and lauryl sulphate.   monoisopropylamine, a corresponding lauryl ether sulfate and mixtures thereof.   23 Drug according to any of the   Claims 1 to 22, further comprising as an adjuvant agent an azide compound.   Medicament according to claim 23, characterized in that said azide compound is   an alkali metal azide, such as sodium azide.   Medicament according to any one of claims 1 to 22, further comprising as adjuvant an alcohol such as ethanol or hydroxide nickel and ammonium.   26 Medication solution according to one of the   Claims 1 to 25, constituting a footbath for the treatment of sheep footprints, characterized   in that its drug concentration is sufficient to obtain an average concentration of not less than 500 μg of zinc ions / g of weight   wet of hoof horn in said animals.