AU658598B2

AU658598B2 - A pour-on formulation for the administration of anthelmintics

Info

Publication number: AU658598B2
Application number: AU10277/92A
Authority: AU
Inventors: Dieter Duwel; Hans Rochling; Karlheinrich Schmid
Original assignee: Hoechst AG
Current assignee: Hoechst AG
Priority date: 1991-01-19
Filing date: 1992-01-17
Publication date: 1995-04-27
Anticipated expiration: 2012-01-17
Also published as: BG95755A; NO920234D0; UY23355A1; AU1027792A; YU2792A; TR27833A; CS14992A3; HU208623B; FI920190A; JPH04312504A; NO920234L; FI920190A0; IE920150A1; BR9200163A; CA2059602A1; MX9200225A; EP0496316A1; HU9200171D0; HUT62453A; PL293227A1

Description

L-J

x 7 P/00/01o 2/S9 Regulation 3.2(2) Patents Act 1990

ORIGINAL

COMPLETE SPECIFICATION STANDARD PATENT Application Number: Lodged: 00 00 0 000 00 0 e 0 0*0 00 0 0 00 0 00 0000 0400 0 0*044 0 0 Invention Title: A POUR-ON FORMULATION FOR THE ADMINISTRATION OF

ANTHELMINTICS

0 00 0 00 040* 0 00 00 0 *04000 o 0 The following statement is a full description of this invcintion, including the best method of performing it known to us t L iUECI-ST AKTIENGESELLSCHAFT HOE 91/F 016 Dr. WS/Le Description A pour-on formulation for the administration of anthelmintics The present invention relates to pour-on formulations, to a process for the preparation thereof and to the use thereof for controlling helminths in livestock.

A number of publications describe the pour-on, also spoton, process for controlling ectoparasites in livestock: Journ. Econ. Entomology, 53, (1960), pp. 814-817, EP-A-045424, DE-A-3208334, EP-A-120286, EP-A-311180. This entails the liquid preparation of an insecticidal/acaricidal agent being administered by pouring on along the dorsal line from the withers to the tailhead of agricultural productive livestock, especially cattle. The nature 15 of the formulations must be such that spreading achieves 0 44 0 0: an action against the pests on the entire animal body.

oo0 Pour-on formulations which are also active against 0oooo endoparasites when administered in the way described must transport systemically acLive agents through the animal skin into the bloodstream. Preparations of this type are known for levamisole (EP-A-137627, DE-A-3212735, oo° DE-A-2614841) and for ivermectin (EP 89302680). Both 0o 0 compounds are readily soluble in water and solvents so that penetration of the animal skin can be achieved o 25 relatively easily.

A very important group of agents for controlling Sco. endoparasitic helminths are suitably substituted benzimidazole and benzothiazole derivatives, as well as the group of so-called probenzimidazoles (compounds which can be metabolized to benzimidazole derivatives with anthelmintic activity), like the compounds of the formulae I to III listed hereinaftert

A

I. -2- R.

N

-R

1

H

Ia) in which

R

1 is methoxycarbonylainino and

R

2 is n-propylmercapto (albendazole), phenylmercapto (fenbendazole), phenylsulfinyl (oxfendazole), ben~oyl (mebendazole-), p-f luorobenzoyl (flubendazole), p-f luorophenylsulfonyloxy (luxabendazole) cyclopropylcarbonyl (cyclobendazole) n-butyl (parbendazole), n-propoxy (oxibendazole) or H (ca3:bendazim) or Ib) in which R' is 4-thiazolyl and R 2 is H (thiabendazole) or is opropoxyc arbonyl amino (cainbendazole).

N

RII

R 4S in which R 3 is methoxycarbonylamino and R 4 is n-propoxy (tioxidazole).

R~ R R R 6 in which -3-

R

5 is -N=C(NHCOOCH 3 2

R

6 is -NHCOCHO2CH 3

R

7 is phenylmercapto and R 8 is H (febantel); or is-NC NHCH2CH2SO3

H

R

5 is

-N=C

NHCOOCH

3

R

6 is NO2, R 7 is H and R 8 is n-propylmercapto (netobimin); or

R

5 and R 6 are each -NHCSNH-COOCz 2 H, R 7 and R 8 are each H (thiophanate).

These agents are sparingly soluble substances so that it has not hitherto been possible to prepare pour-on formulations in suitable solvents. This is why it has hitherto been necessary to carry out a treatment of helminth-infected livestock (for example cattle or sheep) by the so-called drench process or orally with the aid of a bolus.

0 r *415 The use of the pour-on process would be considerably more economic for the treatment of large herds because it is, inter alia, considerably less time-consuming and laborintensive. It is not necessary to immobilize the live- 2. stock, there is less risk to the treating person from defensive movement of the livestock, and there 's less o 1 0 o stress, especially for livestock unused to being handled.

0 It has been found, surprisingly, that fine-particle dispersions (suspensions) of the said benzimidazoles, 05 benzothiazol:. and probenzimidazoles with anthelmintic 25 activity are able, when suitable penetration-promoting oils are used and administration is by the pour-on process, to enter the body by the transdermal route, where they display a good effect against nematodes and their stages parasitizing the digestive tract and tissues. To do this, it is merely necessary, when the dosage is suitable, to apply a strip of the formulation to the back of the livestock.

I

i 4 The invention therefore relates to preparations which have anthelmintic activity and which contain as active ingredient at least one benzimidazole, benzothiazole or probenzimidazole with anthelmintic activity in fineparticle dispersion in a penetration-promoting agent. It is also possible to use mixtures of the said active ingredients.

The particles of active ingredient in these dispersions should have a particle size from 0.05 to about 30 pm, preferably from 0.5 to 10 pm.

Penetration-promoting oils which can be employed are triglycerides of saturated vegetable fatty acids, for example Miglyol 8120 triglycercol diisostearate or esters of long-chain acids, such as, for example, oleyl oleate, isopropyl myristate, isopropyl palmitate, 2-ethylhexyl palmitate, isooctyl stearate, isopropyl stearate, hexyl laurate or di-n-butyl adipate; as well as long-chain 00. alcohols such as, for example, hexylalcohol, octyl alcohol, decyl alcohol, oleyl alcohol, 2-octyldodecanol,

I

2-hexyldecanol or 2-octyldecanol. All the penetrationpromoting agents can be employed alone or mixed with one another. A particularly good penetration-promoting effect is produced by long-chain alcohols and, among these, in °o particular the 2-alkyl-substituted alcohols. The oils are employed in contents of 5-95% by weight, preferably from 30 to 90% by weight. The fine-particle active ingredients can also be dispersed in water in which penetrationpromoting oils are emulsified, in which case the water 0 content of these dispersions can be up to 50% by weight, :30 preferably up to 30% by weight.

The following can be used as emulsifiers and wetting agents: alkylaryl polyglycol ether alcohols, for example "Triton types, ®Sapogenat T, ®Arkopal types; fatty alcohol polyglycol ethers such as, for example, "Emulsogen M, A and L 18- Table II 5 MS12, oGenapol X-080; alkyl diglycol ether sulfate Na salts such as, for example, eGenapol LRO; Na lauryl sulfate, for example eTexapon K12; ethoxylated castor oil types such as, for example, "Emulsogen EL; C 3 to C 20 alcohol propylene oxide block alkoxylates such as, for example, Hoe S 3510 and HOE S 2436, xylenol ethoxylate with 4-5 EO, tristyrylphenol polyglycol ether and tristyrylphenol polyglycol ether phosphates such as, for example, Hoe S 3474 and Hoe S 3775, alkylarylsulfonic acid calcium and sodium salts such as, for example, phenylsulfonate Ca(70), sorbitan fatty acid esters, for example "Span 60 and 80, polyoxyethylene sorbitan fatty acid esters, for example "Tween 60 and 80 and polyoxyethylene stearates, for example "Myrj 45, 49 and 51.

Dispersants which can be employed are, inter alia: ligninsulfonates such as, for example, "Vanisperse CB and polymerized arylalkylsulfonic acids such as, for example, Darvan No. 3, magnesium and aluminum stearates, especially aluminum monostearate. The auxiliaries are employed in contents of 0.5 to 30%, preferably from 1 to by weight.

Silicone antifoam SE2 can be used, inter alia, as antifoam agent r&-ecSly f (n -cr-i- o- 3 60o7 b-y we3Qk, The content of active ingredient in the formulation can be 1 to 60% by weight, preferably 5-20% by weight.

The invention also relates to a process for the preparation of a pour-on formulation, which comprises converting the fine-particle active ingredients into a suitable administration form.

Various processes can be used to prepare the pour-on formulations, as follows: 1. The active ingredient from the class of benzimidazoles, benzothiazoles or probsnzimidazoles is finely '1 ground in water with the addition of wetting agents 6 and using a bead mill; the penetration- promoting oil is mixed with an emulsifier and emulsified in the aqueous dispersion of active ingredient. This results in a suspo-emulsion in which the active ingredient is suspended as fine particles in water and in which the penetration-promoting oil is emulsified.

2. The active ingredient is ground in a penetrationpromoting oil with the addition of wetting agents and dispersants and using a bead mill.

3. When the substance with anthelmintic activity has the particle fineness described, whether by the use of suitable precipitation methods in the preparation or by use of dry milling, for example, it can also be homogenized in water after addition of wetting agents and dispersants without wet milling. The oil is then emulsified in the aqueous dispersion as described under 1. An air jet mill such as, for example, a spiral jet mill can be used for the dry milling of the active ingredients.

4. When the active ingredient has sufficient particle fineness as described under it can also be dispersed in the penetration-promoting oil without wet milling when suitable wetting agents and dispersants, and zuitable mixing and stirring equipment, are used.

The following descriptions of preparations carried out with fenbendazole by way of example are intended to explain processes i. to 4. without restricting the invention thereto.

A PE 075 stirrer mill from Netzsch-Feinmahltechnik GmbH was used for wet milling of the active ingredients.

An Ultra Turrax apparatus from Janke and Kunkel was i I A, 7 employed for the homogenization with a high-speed stirrer.

Example 1 strength fenbendazole pour-on formulation Fenbendazole is milled together with wetting agents and dispersants and with an antifoam in a stirrer mill until of the particles are smaller than 1 pm, milling for about 4 hours being necessary for this. Glass beads with a diameter of 2 mm are used, the amount of them present being twice as high as that of the active ingredient fenbendazole: 1. fenbendazole dispersion 40.00% by weight fenbendazole, 99.8% pure S4.00% by weight "Genapol X-080 7.00% by weight ®Vanisperse CB 2.00% by weight "Darvan No. 3 1.00% by weight silicone antifoam SE2 46.00% by weight water A solution of the emulsifiers in the oils is prepared by stirring and heating gently at 35-40OC: 2. emulsifier solution 9.38% by weight phenylsulfonate 4.37% by weight Hoe S 3510 S6.25% by weight Hoe S 3474-2 S, 25 40.00% by weight 2-octyldodecanol 21.25% by weight eMiglyol 812 18.75% by weight of fenbendazole dispersion are added to the stirred emulsifier solution. The result is a suspo-emulsion which can easily be poured, is stable on storage and can be used as pour-on 8 preparation.

Example 2 strength fenbendazole pour-on formulation The following mixture is ground in a stirrer mill using glass beads (diameter 2 mm) until 80% of the particles are smaller than 1 pm: 1. fenbendazole dispersion 35.00% by weight fenbendazole, techn. 99.8% pure 4.00% by weight "Genapol X-080 7.00% by weight OVanisperse CB 2.00% by weight ®Darvan No. 3 1.00% by weight "Silicone antifoam SE2 51.00% by weight water Then a solution of the emulsifiers in the oils is prepared by stirring and heating at 35-40°C: 2. emulsifier solution 9.38% by weight phenylsulfonate Ca 4.37% by weight Hoe S 3510 6.25% by weight Hoe S 3474-2 30.00% by weight 2-octyldodecanol 21.40% by weight 'Miglyol 812 28.6% by weight of the aqueous fenbendazole disper- I sion is added slowly to this emulsifier solution with stirring. This results in a fenbendazole pour-on formulation which can easily be poured and is stable on storage.

Example 3 strength fenbendazole pour-on formulation

I

A formulation of the following composition is prepared as

_I

S- 9 described in Examples 1 and 2: 10.02% by weight fenbendazole, 99.8% pure 1.00% by weight "Genapol X-080 1.75% by weight "Vanisperse CB 0.50% by weight "Darvan No. 3 0.25% by weight silicone antifoam SE2 11.48% by weight water 9.37% by weight phenylsulfonate Ca 6.25% by weight Hoe S 3474-2 4.38% by weight Hoe S 3510 35.00% by weight 2-octyldodecanol 20.00% by weight *Miglyol 812 The formulation can easily be poured and is stable on S0, ostorage with respect to homogeneity and stability of 15 active ingredient.

0 0 Example 4 0 A fenbendazole dispersion is milled in a bead mill for 00^° 4 hours as described in Examples 1 and 2 until 82% of the particles are smaller than 1 pm: 1. fenbendazole dispersion 0 ~40.00% by weight fenbendazole, techn. 99.8% pure 4.00% by weight OGenapol LRO paste o56.00% by weight water SThen a solution of the emulsifiers in the mixture of 2-octyldodecanol and Miglyol 8120 is prepared by stirring and heating at 35-40°C: 2. emulsifier solution 9.38% by weight phenylsulfonate Ca 4.37% by weight Hoe S 3510 6.25% by weight Hoe S 3474-2 4, 35.00% by weight 2-octyldodecanol 20.00% by weight OMiglyol 812 25.00% by weight of the described fenbendazole dispersion are slowly added to the emulsifier solution with stirring. This results in a fenbendazole pour-on formulation which can be administered satisfactorily.

Example Firstly a 40% strength fenbendazole dispersion in water is prepared. Milling time 4 hours, particle size rGached: 1 Am.

1. fenbendazole dispersion S40.00% by weight fenbendazole, techn. 99.8% pure S4.00% by weight "Genapol LRO paste 56.00% by weight water 25.0% by weight of the fenbendazole dispersion is added to 70.0% by weight of 2-octyldodecanol with stirring; subsequently 5% of water are also added, likewise with stirring.

The result is a 10% strength fenbendazole pour-on Sformulation which has good pourability and has very good storage stability.

Example 6 The preparation method is as described in Example 5 but the fenbendazole dispersion is only homogenized and not milled so that the active ingredient fenbendazole is used in the particle size as produced in the preparation: of the particles 6 pm.

strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure 1,00% by weight ®Texapon K12 r .r if _i 1 11 19.00% by weight water 70.00% by weight 2-octyldodecanol The formulation is stable on storage and can be administered satisfactorily.

Example 7 Preparation method as described for Example 5. Fenbendazole particle fineness 80% 1 pm.

strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure 1.00% by weight ®Texapon K12 24.00% by weight water 0.

U Da 0 C 0.3 o 3, o 400( 0 v00t 0UoAu 15 4, 0 0.0 40 a oo 00 4 04 9 It 25.00% by weight "Miglyol 812 40.00% by weight 2-octyldodecanol The result is a pour-on formulation which is stable on storage and can be administered satisfactorily.

Example 8 Preparation method as described for Example 6. Fenbendazole particle fineness 50% 6 pm.

strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure 1.00% by weight "Texapon K12 24.00% by weight water 25.00% by weight Miglyol 812 40.00% by weight 2-octyldodecanol The formulation has good storage stability and can be poured satisfactorily.

12- Example 9 Preparation method as described in Example 4. Particle fineness 82% 1 pm.

strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure 1.00% by weight ®Genapol LRO 39.00% by weight water 15.00% by weight Emulsogen A 35.00% by weight 2-octyldodecanol The result is a pour-on formulation which has good storage stability and good pourability.

Example Preparation method as described for Example 4, but "Span is dissolved in 2-octyldodecanol at 80-90 0 C. Fenbendazole particle fineness 82% 1 pm.

strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure 0.89% by weight ®Texapon K12 21.33% by weight water 1.00% by weight "Span S66.78% by weight 2-octyldodecanol I The formulation is stable on storage and can be I administered satisfactorily.

Example 11 Firstly, "Span 60 is dissolved in 2-octyldodecanol at 80-90 C with stirring. After cooling to about 50 0

C,

fenbendazole is added; particle size: 50% of particles 6 pm.

strength fenbendazole pour-on formulation S_ t -13- 10.00% by weight fenbendazole, 99.98% pure 10.00% by weight "Span 80.00% by weight 2-octyldodecanol The mixture is homogenized with a high-speed Ultra Turrax stirrer.

Example 12 For preparation, see Example 11; fenbendazole particle size: 50% of particles 6 pm.

strength fenbendazole pour-on formulation 7.50% by weight fenbendazole, 99.98% pure 10.00% by weight ®Span 82.50% by weight 2-octyldodecanol The mixture is homogenized with a high-speed Ultra Turrax stirrer.

Example 13 Preparation method as described in Example 4 and Fenbendazole particle size 50% 6 pm.

strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure 1.00% by weight "Texapon K12 24.00% by weight water ,i 1.00% by weight "Span 64.00% by weight 2-octyldodecanol A formulation which can be administered satisfactorily is obtained.

Example 14 Aluminum monostearate is dissolved in 2-octyldodecanol at 140-150*C and kept at this temperature for 30 minutes -14with stirring. After cooling to about 50°C, fenbendazole is added and homogenized with a high-speed Ultra-Turrax stirrer.

Fenbendazole particle size: 50% of particles 6 pm.

10% strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure S1.00% by weight aluminum monostearate 89.00% by weight 2-octyldodecanol A suspension which ca.n easily be poured is obtained.

Example Aluminum monostearate is dissolved in 2-octyldodecanol at 140-150 C and kept at this temperature for 30 minutes with stirring. After cooling to about 100°C, "Span 60 is added and, at 50 0 C, fenbendazole, both likewise with stirring. Homogenization is subsequently carried out with a high-speed Ultra-Turrax stirrer.

Fenbendazole particle size: 50% of particles 6 pm.

strength fenbendazole pour-on formulation 10.00% by weight fenbendazole, 99.98% pure .1.00% by weight "Span 2.50% by weight aluminum monostearate 86.50% by weight 2-octyldodecanol A formulation with good storage stability and good pourability is obtained.

Example 16 Preparation method as described for Example Fenbendazole particle size: 50% of particles 6 pm.

strength fenbendazole pour-on formulation 20.00% by weight fenbendazole, 99.98% pure 15 15 1.00% by weight ®Span 1.50% by weight aluminum monostearate 77.50% by weight 2-octyldodecanol Example 17 Preparation method as described for Example Fenbendazole particle size: 50% of particles 6 pm.

11.37% strength fenbendazole pour-on formulation 11.37% by weight fenbendazole, 99.98% pure 100 g/l I 1.14% by weight *Span 2.85% by weight aluminum monostearate 84.64% by weight 2-octyldodecanol Example 18 8.53% strength fenbendazole pour-on formulation 8.53% by weight fenbendazole, 99.98% pure 75 g/l 1.14% by weight "Span 2.85% by weight aluminum monostearate 87.48% by weight 2-octyldodecanol Example 19 5.75% strength fenbendazole pour-on formulation 20 5.75% by weight fenbendazole, 99.98% pure 50 g/1 .1.15% by weight ®Span SO S° 2.88% by weight aluminum monostearate 90.22% by weight 2-octyldodecanol The products prepared in Examples 16 to 19 have good storage stability with regard to phase separation and constancy of active ingredient content. They can easily be poured and can therefore be administered as pour-on formulations satisfactorily.

S16- Example 11.37% strength fenbendazole pour-on formulation 11.37% by weight fenbendazole, 99.98% pure S100 g/1 2.30% by weight Span 600 1.70% by weight aluminum monostearate j 84.62% by weight 2-octyldodecanol The process is as described in Example 15. The fenbendazole used is previously milled in a spiral jet mill until 50% of the particles have a particle size 2.8 pm.

Examples 21-26 For preparation method, see Example 11 10.00% by weight anthelmintic agent (see Tab. I) 10.00% by weight ®Span 80.00% by weight 2-octyldodecanol A 5% strength formulation of thiabendazole was prepared: 5.00% by weight thiabendazole 10.00% by weight ®Span 85.00% by weight 2-octyldodecanol '1 17 Table I 06 b a 0 1 0 0

SI

I 11

(IS.

Example Anthelmintic agent Formula 21 Oxibendazole Ia 22 Parbendazole Ia 23 Albendazole Ia 24 Mebendazole Ia Thiabendazole Ib 26 Febantel III Biological activity The investigations were carried out on cattle which had been artificially infected with the economically important gastrointestinal nematodes of ruminants Ostertagia ostertagi, Trichostrongylus axei, Trichostrongylus colubriformis and Cooperia oncophora. The activity was measured by dissection with determination of the worm burden compared with untreated control animals. The 25 treatment by pouring on the formulations along the dorsal line of the livestock usually takes place 14 days after infection; at this time the nematodes are still immature and particularly difficult to influence by anthelmintics.

The investigations were carried out in accordance with 30 the guidelines of the WAAVP (World Association for the Advancement of Veterinary Parasitology; Powers, K.G et al., Vet. Parasitol. (1982) 10, 265-284).

Individual investigations and results are compiled in the following Table II.

i-i,:ii l- ~CI~

R

7 1 18 Table II Activity of fenbendazole in various pour-on preparations against immature stages of gastrointestinal nematodes of cattle Amerage panttage nmEtion in the wnm hrdb, ampred ith antrils I I OstMtU&ia ou"Urtagi Trichostrongylus ai colubriformiz Coaperia onaphora 1 3.75 7.50 100 94 3.75 7.50 tage cct n to rd c( the omtrol gra (rr-9) 98 99 3922 1 78 91 36 99 2610 100 100 100 99 98 100 1067 99,8 100 100 99 100 100 1957 Bj 12 aaraip wxm hx-dmn (f the cmntini grup (rF-3) 4rr 44 7.50 7 99 99 100 99 11 7.50 7 98 99 99 1 99 gB w~im 1iti ci 6573 649 479 J 2279 tne Otrl qin 11 5.0 7 82 92 100 99 7.5 7 70 93 99 98 13 5.0 7 66 86 100 98 7 91 99 99 99 14 5.0 7 68 97 99 99 7 84 98 99 99 5.0 7 >80 >90 98 98 7 90 95 98 98 ,avazge rwzI bu m cf 5763 490 1589 3867 the acrtrol grnp (n-7) i il L I An indicative test was carried out to establish the activity of pour-on formulations of fenbendazole, oxibendazole, parbendazole, albendazole, mebendazole, thiabendazole and febantel (preparation examples 20-25) on Trichostrongylus colubriformis in rodents: ji :ds (Meriones unguiculatus).

The dosage was in each case 0.2 ml per animal, and 0.4 ml with thiabendazole and additionally 0.1 and 0.05 ml with fenbendazole; this volu m. was dripped onto the shaven area of the back of the neck of the jirds. The possibility of intake of active ingredient by licking was prevented by the location of the administration site and the housing of the animals singly.

The results are listed in Table III.

Table III Activit1y of pour-on formulations agrainst T. colubriformis in lirds Active Preparation Concentration Amount admin. Dose Number of Number of Effect ingredient example (mi/animal) mg/kg worms animals in Ferbendazole 11 10% 0.2 ca. 300 0 11 100 Fenbendazole 11 10% 0.1 ca. 150 0 5 100 enbendazole 11 10% 0.05 ca. 75 0 4 100 bendazole 23 1CQ- 0.2 ca. 300 0 5 100 ebantel 26 10% 0.2 ca. 300 0 5 100 Aebendazole 24 10% 0.2 ca. 300 0 5 100 3xibendazole 21 10% 0.2 ca. 300 0 5 100 r arbendazole22_10%_0.2_c,_300_0_5_10 habendazole 22 10% 0.2 ca. 300 0 5 100 Control without treatment 67 9 I.

Claims

1. A pour on preparation which has an anthelmintic activity and contains as active ingredient at least one benzimidazole with anthelmintic activity in fine- particle dispersion in a long chain alcohol as dermal penetration-promoting agent, wherein the particles of the active ingredient have a particle size of 0.05 p~m.

2. A pour on preparation as claimed in claim 1 or 2, in which the content of active ingredient is 1-60% by weight, preferably 5-20% by weight.

3. A pour on preparation as claimed in any of claims 1 to 3, in which are employed a penetration-promoting oil as penetration-promoting agent in a content of 5-95% by weight, together with auxiliaries such as emulsifiers, wetting agents and/or dispersants in total contents of 0.5-30% by weight.

4. A pour on preparation as claimed in any of claims 1 to 4, containing the active ingredient fenbendazole.

A method for the transdermal control of helminths in livestock comprising administering to livestock requiring such treatment an effective amount of a pour on preparation as claimed in any one of claims 1 to 4.

6. A process for the preparation of an agent as claimed in any of claims 1 to 4, which comprises converting the fine-particle active ingredient into a suitable administration form. DATED this 9th day of February, 1995 HOECHST AKTIENGESELLSCHAFT WATERMARK PATENT TRADEMARK ATTORNEYS 290 BURWOOD ROAD HAWTHORN VICTORIA 3122 AUSTRALIA f .u