Abstract:
The present invention relates to novel compacted granular larvicidal feed premix compositions of N[[(4-chlorophenyl)amino]carbonyl]-2,6-difluorobenzamide, a method for their preparation and an improved method for the control of larvae utilizing these compositions.

Description:
The present application is a continuation-in-part application of pending parent application for U.S. Letter Patent, Ser. No. 731,578, filed May 9, 1985, now abandoned. 
    
    
     BACKGROUND OF THE INVENTION 
     The control of fly larval infestation is important in agricultural in order to avoid the illnesses and economic losses associated with such insect pest infestation. A method of controlling fly larval by direct application to the larval breeding medium is widely known in the industry. The method involves such direct utilization of the compound, N[[4-chlorophenyl)amino]carbonyl]-2,6-difluorobenzamide, sold under the tradename of DIMILIN® insecticide, a registered trademark of Duphar BV of Amsterdam, Holland (hereinafter referred to as diflubenzuron, the generally recognized generic chemical name). 
     Due to the effectiveness of diflubenzuron when used against fly larvae, the search for a more beneficial manner to control such fly larvae has spurred and continues to spur new research efforts. One attractive method for fly larvae control is to utilize diflubenzuron in feeds for controlling fly larvae in excreted feces. This method is commonly referred to as feed-through application. For instance diflubenzuron at levels of 0.5 to 1.0 mg/kg animal body weight, has been mixed directly into the feed of calves and dairy cattle and has shown effective control of house fly and face fly larval in the feces (R. W. Baker et al, J. Georgia Entomol. Soc., 11 (1976) 1: 67-71 and R. W. Miller, J. Economic Entomol. 67 (1974) 5: 697). 
     In addition to this direct feed addition method, diflubenzuron has been encapsulated and tested for insecticidal activity, F. W. Knapp et al., Symp. Int. Meeting Controlled Release Soc. (Academic Press, 1980), as well as being applied in mineral blocks and delivered in a sustained-release bolus form (U.S. Pat. No. 4,166,107, issued to J. A. Miller et al on AUg. 28, 1979). 
     SUMMARY OF THE INVENTION 
     The present invention relates to novel compacted granular feed premix compositions containing diflubenzuron. These granular feed premix compositions provide enhanced larvicidal effectiveness and fly control of surprisingly low doses of diflubenzuron. 
     It is an object of the present invention therefore to provide novel such compacted granular feed premix compositions with improved larvicidal effectivness and fly control. 
     It also is an object of the present invention to provide a method for preparing the novel compacted granular feed premix compositions of the invention. 
     These and further objects of the present invention will become more apparent by the more detailed description of the invention provided herein. 
     DETAILED DESCRIPTION OF THE INVENTION 
     The present invention relates to compacted granular feed premix compositions comprising, on a weight basis, about 0.5% to 84.0% diflubenzuron; about 0% to 10% whole dried whey; about 0% to 2% water and the remainder of a compactable, insoluble carrier to total the composition of 100%. 
     Compactable, insoluble carriers suitable for use in the compositions of the present invention include clays and mineral salts, such as CaSO 4 , BaSO 4  or other mineral salts, CaCl 2 . The preferred carrier, however, is CaSO 4  dihydrate. Preferred compacted granular premix compositions of this invention have a granular particle size of 10 mesh to 100 mesh, with a particle size range of 20 mesh to 60 mesh being preferred. 
     This invention also relates to methods for the preparation of these compacted granular compositions. It unexpectedly has been discovered that compositions of the present invention, prepared by the compaction and granulation process of the invention, provide compositions which provide effective control of larvae when administering doses in animal feeds of diflubenzuron at rates as low as 0.025 mg/kg of animal body weight. Surprisingly, the compacted granulated compositions of the invention are more efficacious than diflubenzuron alone, the uncompacted composition or an alfalfa feed premix of diflubenzuron administered in animal feed for the feed through control of fly larvae and resulting fly control (see Table I). This invention also provides an improved method for controlling fly larvae and flies in the feces of animals. This is accomplished by orally administering, in an animal feedstuff or feed supplement, sufficient quantities of the present compositions to provide about 0.025 mg/kg to 10 mg/kg per animal per day of diflubenzuron. 
     
                       TABLE I______________________________________% Fly control obtained by various feed through compositions                           4.0% Compacted             4.0%          granularDiflubenzuron             Alfalfa premix                           CaSO.sub.4 premixDay  0.5 mg/kg/day a.i.             0.5 mg/kg/day a.i.                           0.5 mg/kg/day a.i.______________________________________ 7   64.5         44.0          85.614   84.5         69.5          97.021   76.5         97.5          100.0______________________________________ 
    
     The compositions of the invention may be administered by addition to animal feeds, protein concentrates or supplements and other feed ingredient compositions such as vitamin or mineral supplements. 
     The feed premix compositions of the present invention may readily be prepared by compacting a mixture of the compactable carrier and diflubenzuron. Alternatively, an appropriate amount of water may be sprayed onto the carrier and mixed until homogeneous, and then diflubenzuron is added, mixed with the homogeneous mixture and the resulting blend compacted on serrated compaction rolls. The compacted blend is then ground to the desired particle size range of about 10 to 100 mesh, with a preferred range of 20 to 60 mesh. This is then packaged. 
     Material of smaller particle size is recycled through the compaction procedure and reground in order to obtain the optimum particle size, while larger particles also may be recycled or merely reground. 
    
    
     The compositions of the invention are further illustrated by the following non-limiting examples. 
     EXAMPLE 1 
     Preparation of compacted granular larvicidal premix compositions 
     Water (200 g) is sprayed into CaSO 4  (9.335 kg) while blending the mixture. After ten minutes, diflubenzuron (465 g,) is added, and blending is continued until the mixture is homogeneous. A portion of this mixture (5.0 kg) is compacted using 2&#34; compaction rolls, with a roll speed of 5.5, a feeder speed of 1.5 and pressure of 1500 psig. 
     The resulting compacted material is ground, and the ground material classified on a shaker equipped with two sieves (20 and 60 mesh), to give the desired compacted granular premix composition. Material less than 60 mesh is blended with 2.5 kg of the remaining mixture, and the compaction, grinding and classification steps repeated. This is continued through three cycles or until greater than 90% of the original mixture is converted to the preferred particle size. Material greater than 20 mesh is ground and classified directly into the preferred size range. 
     EXAMPLE 2 
     Efficacy of compacted granular larvicidal feed premix compositions 
     Twenty-one Hereford steers weighing approximately 250 to 450 kg each are provided with 1.0 kg of dairy concentrate daily plus free choice silage and water ad libitum. Each steer individually housed is acclimatized to these conditions and observed until all animals are consuming the silage-concentrate mixture and their manure appears normal. 
     Then the compacted granular feed premix is added to the daily ration of concentrate and fed daily for 14 days at the different rates indicated in Table II. Two manure samples (200 g) are collected from each animal on days 0, 4, 7 and 14 after treatment commences. Each sample is seeded with 25 WHO strain house fly first instar larvae and the number of pupae and emerged adult flies are recorded. 
     The results of these experiments, which are summarized in Table II below, demonstrate the improved efficacy of the compacted granular premix compositions of the invention compared to diflubenzuron alone and a diflubenzuron and CaSO 4  mixture which has not been compacted and granulated. 
     EXAMPLE 3 
     Water (200 g) is sprayed onto CaSO 4  (5.67 kg) while blending the mixture. After ten minutes diflubenzuron (4.122 kg) is added and the blending continued until the mixture is homogeneous. One-half of this mixture (5.0 kg) is compacted using a two inch compaction rolls, with a roll speed of 5.5, a feeder speed of 1.5 and pressure of 1500 psig. 
     The resulting compacted material is ground and classified in a shaker equipped with two sieves (20 and 60 mesh), to the desired particle size. Material less than 60 mesh is blended with 2.5 kg (one-half of remaining) mixture and compacted/ground/classified. This is continued through three cycles or until greater than 90% of the original mixture is converted to the preferred particle size. Material greater than 20 mesh is ground and classified directly into the preferred particle size range. 
     
                                           TABLE II__________________________________________________________________________                Average % pupae recovered*                                Average % fly control*            Rate                Day Day Day Day Day Day DayTreatment        mg/kg                0   4   7   14  4   7   14__________________________________________________________________________A Controls       None                91  93  87  83  --  --  --B                0.05                87  43  46  51  97  97  95C                0.10                83  30  10  17  99  100 100D                0.25                86   9   1   2  100 100 100E                0.50                92   4   1   2  100 99  100F Diflubenzuron  0.10                92  93  73  61  95  82  89G Diflubenzuron + CaSO.sub.4 not as            0.10                83  78  35  57  88  97  83  compacted granular premix__________________________________________________________________________ *Average of three animals per group and two samples per animal. 
    
     EXAMPLE 4 
     Diflubenzuron (12.6 g) is blended with 9.874 kg CaSO 4  and mixed. One-half of this uncompacted blend (5.0 kg) is compacted using a two inch compaction rolls, with a roll speed of 5.0, a feeder speed of 2.5 and a pressure of 1500 psig. 
     The resulting compacted material is ground and classified on a shaker equipped with screens ranging from 12 to 60 mesh. Material less than 60 mesh is blended with 2.5 kg (one-half of remaining) original blend and the compaction/grinding/classification cycle repeated. This sequence is continued for at least three cycles or until greater than 90% of the original blend is converted to the desired particle size range. Material greater than 12 mesh is ground/classified directly into the preferred particle size range. 
     EXAMPLE 5 
     Water (200 g) is blended with 9.335 kg CaCl 2  and mixed. To this mixture, 465 g of diflubenzuron is added, and blending is continued until the mixture is homogeneous. A portion of this uncompacted blend (5.0 kg) is compacted using two inch compaction rolls, with a roll speed of one roll speed 7.0 and pressure of 1000 psig. 
     The resulting compacted material is ground and classified as described in Example 4. Again at least three cycles of blending/compaction/grinding and classification are used. 
     EXAMPLES 6-8 
     Compositions which have been or can be prepared in accordance with the present invention are listed below. The components are thoroughly blended, and this blended composition is transferred to a holding bin that feeds a set of serrated rolls (e.g. Fitzpatrick chillsonator). The composition is fed to the rolls and compacted into a ribbon of materials. Thereafter, it is granulated and sieved for size, with the procedure repeated, if necessary, to obtain the appropriate mesh sizes. 
     
         ______________________________________PREMIX COMPOSITIONS      % (w/w)Components   Example 6  Example 7  Example 8______________________________________diflubenzuron        41.2       55.5       83.33(95-100% technical)whey         2.0        4.5        8.0water        1.5        0.5        0.0CaSO.sub.4 dihydrate        55.3       39.0       8.67______________________________________