Abstract:
This invention relates to fungicidal compositions comprising triforine and carbendazim as active ingredients, wherein the composition comprises carbendazim suspended in a solution of a triforine in dimethylformamide, N-methylpyrrolidone, or a mixture thereof and contains a stabilizer selected from the group consisting of saccharides, polyethylene glycol, polyvinylpyrrolidone/polyvinylacetate mixtures, and mixtures thereof.

Description:
This is a continuation, of Ser. No. 219,246, filed Dec. 22, 1980. 
    
    
     FIELD OF THE INVENTION 
     The invention is related to novel fungicidal compositions and their production. More specifically, the invention is related to stabilized fungicidal compositions comprised of triforine and carbendazim. 
     BACKGROUND OF THE INVENTION 
     For biological reasons, it is desirable to employ together the two systemic fungicides 1,1&#39;-piperazine-1,4-diyldi-[N-(2,2,2-trichloroethyl)-formamide] and methylbenzimidazole-2-ylcarbamate, also known as triforine and carbendazim, respectively, for control of fungal diseases in plants. Preparations containing both active substances are desired to facilitate better handling of the active substance combinations. 
     Triforine develops its full activity only if it is used in dissolved form. To obtain good stability of triforine concentrates, they are formulated with addition of salts of dodecyclbenzene sulfonic acid (DBS), in particular, amine salts. Carbendazim is preferably used in the form of wettable powders. 
     In accordance with the prior art, the problem of producing a combined liquid formulation of the active substances sufficient for practical requirements seemed to be unsolvable. Triforine is sufficiently soluble only in very few solvents. In these solvents, however, the solubility of carbendazim is too low, between 0.7 percent and 0.35 percent at room temperature, to produce solution concentrates. On the other hand, this solubility is too high for assuming that carbendazim solid substance might be processed to a sufficiently stable suspension in these solvents. When such preparations are stored, or shelved, crystal growth due to the Ostwald-ripening would be expected, according to the present level of knowledge. Such crystal growth would make the preparations unfit for use as fungicidal agents. 
     Carbendazim itself forms soluble DBS salts. Employment of the DBS salt, which salts are, according to German Offenlegungsschrift No. 25 21 284, important for the stability of triforine preparations, increases solubility of the carbendazim. This reduces the chance of impeding the growth of crystals. Also, carbendazim cannot be used directly in form of the soluble DBS salts of carbendazim (German Offenlegungsschrift No. 24 17 008), as these salts are unstable, hydrolyze within a short time, and lead to non-reversible precipitation of carbendazim in large crystals. 
     In addition, the carbendazim adducts disclosed in German Offenlegungsschrift No. 22 19 174 are unstable in the mixtures with triforine and DBS salts. Furthermore, liquid preparations of carbendazim are disclosed in German Offenlegungsschrift Nos. 19 57 712, 21 54 020, 23 03 757, and 23 54 467 and in Japanese patent application No. 72 40 060. However, these liquid preparations cannot be considered for use in fungicidal compositions with triforine since, for example, metal salts catalyze decomposition of triforine and triforine is insoluble in mineral oils and cannot exhibit fungicidal activity. 
     OBJECTS OF THE INVENTION 
     It is an object of the invention to provide novel fungicidal compositions. 
     It is a further object of the invention to provide a method of using such novel fungicides. 
     It is yet a further object of the invention to provide fungicidal compositions comprising suspensions of carbendazim and solutions of triforine in dimethylformamide and/or N-methylpyrrolidine, which compositions also comprise saccharides and/or polyethylene glycol and/or mixtures of polyvinylpyrrolidone/polyvinylacetate. 
     These and other objects of the invention will become more apparent in the discussion below. 
     DETAILED DESCRIPTION OF THE INVENTION 
     Applicant has found a practical manner in which to provide stable suspensions of carbendazim in solutions of triforine. Accordingly, Applicant&#39;s invention relates to compositions comprising suspensions of carbendazim in solutions of triforine in dimethylformamide and/or N-methylpyrrolidone, optionally having a content of DBS salts, wherein the compositions are stabilized by the addition of saccharides and/or polyethylene glycol (PEG) and/or mixtures of polyvinylpyrrolidone/polyvinylacetate (PVP/PVA). The result is that, on the one hand, the finely dispersed carbendazim does not precipitate in suspensions of this type and, on the other hand, there is only a slight tendency to recrystallize. 
     The basic formulation comprises a solution of triforine in N-methylpyrrolidine, dimethylformamide, or mixtures of these solvents, whereby the triforine content is from about 1 to 20, preferably from about 5 to 15, percent by weight, based on the total weight of the final composition. The carbendazim content is from about 1 to 40, preferably from about 5 to 15, percent by weight. 
     The stabilization agents useful according to the invention may be employed alone or in combination. Useful saccharides include oligo- and polysaccharides in quantities of from about 1 to 40, preferably from about 3 to 10, percent by weight, based on the weight of the final composition. Saccharose, maltose, lactose, raffinose, dextrin, starch, and cellulose are examples of suitable saccharides. In general, good stabilization is obtained more easily with polysaccharides than with di- or trisaccharides. 
     Polyethylene glycols suitable as stabilizers are those having a molecular weight greater than 2000, preferably of from about 6000 to 35,000. The content of polyethylene glycol, including mixtures of polyethylene glycols, in the final formulation amounts to from about 5 to 15, preferably from about 10 to 15, percent by weight. 
     Polyvinylpyrrolidone and polyvinylacetate are employed in the form of mixtures in the proportion by weight of from about 4:1 to 1:4, preferably from about 1:1 to 2:1. The mixtures are added to the final formulations in quantities of from about 1 to 15, preferably from about 1 to 5, percent by weight. 
     If a combination of two useful stabilizers according to the invention is employed, it is practical to use combinations of saccharides and PVP/PVA mixtures in a proportion by weight of from about 1:15 to 40:1, preferably from about 5:1 to 10:1, and combinations of saccharides and PEG in a proportion of from about 1:5 to 5:1, preferably from about 2:5 to 1:1. If combinations of three stabilizers are employed, it is advantageous to use mixtures of PEG, saccharides, and PVP/PVA in proportions of from about 1:1:1 to 5:1:1 to 1:5:1 to 5:5:1, that is, in proportions of from about 1-5:1-5:1. Proportions of from about 2:2:1 to 3:3:1 are preferred. 
     When a combination of two or three stabilizers is used, the combination is present in the final composition in an amount of from about 1 to 25, preferably from about 5 to 20, percent by weight. 
     The following examples are intended to illustrate the invention and are not to be construed as limiting the invention thereto. 
    
    
     EXAMPLES 
     EXAMPLE I 
     Triforine is dissolved, perhaps with further excipients, in a mixture of solvents, PVA/PVP and DBS amine salts. Finely ground saccharide, ground in a pearl or ball mill until the saccharide has a particle size of 5μ, is added to the solution, and then the solution is well chilled. Subsequently, carbendazim is added to the cooled mixture, preferably after the mixture has been subjected to an air jet grinding and substantially no particles remain bigger than 5μ. Then it is dispersed or finely ground in a pearl or ball mill again. The product thus obtained possesses an excellent sedimentation and shelving stability. 
     EXAMPLE II 
     Micronized carbendazim, together with polyethylene glycols having an average molecular weight of 6000, is stirred into a solution of triforine and DBS amine salts in dimethylformamide. The mixture thus obtained is ground by means of a pearl or ball mill while being well chilled. 
     EXAMPLE III 
     A mixture of polyethylene glycol and saccharide, preferably dextrin, is suspended in dimethylformamide. This suspension is subjected to a wet grinding in a ball mill. A solution of triforine, DBS amine salt, and antifoaming agent, prepared separately, is thoroughly mixed into the mixture. Then, micronized carbendazim is suspended in the mixture. 
     Using the procedures set forth in Examples I to III, the following testing was performed: 
     EXAMPLE IV 
     Stabilization with Polyethylene Glycol 
     The concentrates prepared had the following composition: 
     
         ______________________________________             AmountComponent         (percent by weight)______________________________________Triforine         10.0Carbendazim       10.0Emulsifier (DBS amine salt)             10.0Polyethylene glycol             10.0Dimethylformamide to 100.0______________________________________ 
    
     Several similar compositions having different polyethylene glycol contents were tested for stability, and the results are set forth in the following table: 
     
                       TABLE 1______________________________________  Molecular Weight  Percent of SupernatantSample of Polyethylene Glycol                    Liquid After 20 Days______________________________________Control  --                74A       6,000            0B      20,000            17C      35,000            0______________________________________ 
    
     EXAMPLE V 
     Stabilization with Saccharides 
     The concentrated prepared had the following composition: 
     
         ______________________________________             AmountComponent         (percent by weight)______________________________________Triforine         10.0Carbendazim       10.0Emulsifier (DBS amine salt)             10.0Saccharide        3-20Dimethylformamide to 100.0______________________________________ 
    
     Compositions having different saccharide contents were tested for stability, and the results are set forth in the following table: 
     
                       TABLE 2______________________________________            Concentration            of Saccharide                        Percent of SupernatantSample Saccharide            (% by wt.)  Liquid After 20 Days______________________________________Control  --        --          74A      Cane Sugar            20          31B      Starch    10          12C      Starch    20          3D      Cellulose  3          0E      Dextrin   10          1F      Dextrin   15          0______________________________________ 
    
     EXAMPLE VI 
     Stabilization with Dextrin and PVP/PVA 
     The concentrates prepared had the following composition: 
     
         ______________________________________             AmountComponent         (percent by weight)______________________________________Triforine         10.0Carbendazim       10.0Triethylamine salt of DBS             12.0Antifoam agent     2.0Dextrin           5-15Mixture of PVP/PVA             0-5Dimethylformamide to 100.0______________________________________ 
    
     Compositions having different dextrin and PVP/PVA concentrations were tested for stability, and the results are set forth in the following table: 
     
                       TABLE 3______________________________________  Dextrin   PVP/PVA  (percent  (percent    Percent of SupernatantSample by weight)            by weight)  Liquid After 20 Days______________________________________Control  0         0           75A      5         0           37B      5         1           28C      5         5           9D      10        0           7E      15        5           0______________________________________ 
    
     EXAMPLE VII 
     Stabilization with PEG, Dextrin, and, Optionally, PVP/PVA 
     Concentrates prepared had the following composition: 
     
         ______________________________________                AmountComponent            (percent by weight)______________________________________Triforine            10.0Carbendazim          10.0Polyethylene glycol (MW = 6000)                5Dextrin              0-10PVP/PVA (30:70)      0-5Dimethylformamide    to 100.0______________________________________ 
    
     Compositions having different stabilizer contents were tested for stability, and the results were as follows: 
     
                       TABLE 5______________________________________ Polyethylene                 Percent of Glycol     Dextrin   PVP/PVA Supernatant (percent   (percent  (percent                              LiquidSample by weight) by weight)                      by weight)                              After 20 Days______________________________________A     5          0         0       10B     5          2         0       2C     5          2         2       0D     5          5         0       0E     5          5         2       0F     5          10        0       0G     5          10        5       0______________________________________ 
    
     The preceding specific embodiments are illustrative of the practice of the invention. It is to be understood, however, that other expedients known to those skilled in the art or disclosed herein, may be employed without departing from the spirit of the invention or the scope of the appended claims.