Abstract:
Diaminoguanidine derivatives in preparation of animal growth promoters used in feed. The diaminoguanidine derivatives have a structural formula as shown in formula (I), wherein R 1  is methyl, ethyl, isopropyl, n-butyl, n-propyl, n-pentyl, n-octyl, n-tetradecyl, sec-butyl, 3-pentyl, cyclopentyl or benzyl. The diaminoguanidine compounds significantly improve the productivity of ducks if they are fed with the diaminoguanidine compounds. Productivity of pigs or chickens is also improved with such diaminoguanidine compounds.

Description:
FIELD OF THE INVENTION: 
       [0001]    The present invention relates to the field of feed for poultry and livestock, specifically to diaminoguanidine derivatives and application thereof in preparation of an animal growth promoter used in feed. 
       BACKGROUND OF THE INVENTION 
       [0002]    Growth promoters used in feed, which cover bioactive substances and preparations thereof with various effective mechanisms and various chemical structures, have contributed significantly to the improvement of feed conversion efficiency and productivity of pastoral industry. However, a great amount of antibiotic growth promoters have been or are about to be banned due to the transfer of drug resistance. 
         [0003]    Therefore, it is an issue that how to screen out safe and efficient growth promoters used in feed, which are not for human medical use and exhibit no cross resistance with antibiotic for human use, especially non-antibiotic and non-hormonal growth promoters. And the present invention has solved this issue. 
       SUMMARY OF THE INVENTION 
       [0004]    The first object of the present invention is to provide diaminoguanidine derivatives which can promote the growth of animals. 
         [0005]    The diaminoguanidine derivatives of the present invention have a structural formula as shown in formula (I). 
         [0000]    
       
                 
         
             
             
         
       
     
         [0006]    Wherein, R 1  is methyl, ethyl, isopropyl, n-butyl, n-propyl, n-pentyl, n-octyl, n-tetradecyl, sec-butyl, 3-pentyl, cyclopentyl or benzyl. 
         [0007]    The second object of the present invention is to provide an application of the diaminoguanidine derivatives, which are as shown in formula (I), in preparation of animal growth promoters used in feed. 
         [0008]    Said animal includes ducks, pigs, chickens, or the like, in all growth stages. 
         [0009]    Dosage of the diaminoguanidine derivative in animal feeds is 0.1˜200 ppm, and the feed can be complete formula feed. 
         [0010]    The diaminoguanidine derivatives of the present invention as shown in formula (I) show low toxicity or non-toxicity to animals, which make it more suitable to be applied as a growth promoters used in feed and has a very good application prospect in cultivation industry. 
         [0011]    Via feeding experiments, it has been discovered for the first time by the inventors that, productivity of ducks is improved significantly if they are fed with the diaminoguanidine compounds. It has also been discovered via feeding experiments that productivity of pigs or chickens is improved with such diaminoguanidine compounds. 
     
    
     DETAILED DESCRIPTION OF THE EMBODIMENTS 
       [0012]    The present invention is described in farther detail with reference to embodiments Which shall not be regarded as limits to the present invention. 
         [0013]    Structural formulas and marks of the diaminoguanidine derivatives of the present invention are as shown below. 
         [0000]    
       
                 
         
             
             
         
       
       
                 
         
             
             
         
       
     
       Embodiment 1 
       [0014]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0015]    Preparation of 1,3-bis[(4-methoxybenzylidene)amino]guanidine hydrochloride (IST_007_001). 
         [0016]    4-Methoxybenzaldehyde (30 g, 0.22 mol, 2 eq) was dissolved in about 300 ml of ethanol. Then the resulting solution Was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), refluxed until complete dissolution, and then reaction proceeded at a constant temperature for 1-5 hours with stirring until TLC (thin layer chromatography) showed that the 4-methoybenzaldehyde had been reacted completely. The solution was cooled to −10° C. with stirring t amount of white precipitate, and then filtrated. Filter cake was washed with cold ethanol for 2˜3 times, and subjected to rotary evaporation to remove the solvent and give a product, i.e., 1,3-bis[(4-methoxybenzylidene)amino]guanidine hydrochloride. 
         [0017]      1 H-NMR: δH (DMSO, 500 MHz) 12.2 (2H, 5), 8.38(41-1, s), 7.88(4H, d), 7.03(4H, d), 3.8(6H, s). 
       Embodiment 2 
       [0018]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0019]    Preparation of 1,3-bis[(4-ethoxybenzylidene)amino]guanidine hydrochloride (IST_007_002). 
         [0020]    4-Ethoxybenzaldehyde (24.77 g, 0.165 mol, 2 eq) was dissolved in about 300 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5eq), refluxed until complete dissolution, and then reaction proceeded at a constant temperature for 1-5 hours with stifling until TLC showed that the 4-ethoxybenzaldehvde had been reacted completely. The solution was cooled to −10° C. with stirring to give a great amount of white precipitate, and then filtrated. Filter cake was washed with cold ethanol for 2˜3 times, and subjected to rotary evaporation to remove the solvent and give a product, i.e., 1.3-bis[(4-ethoxybenzylidene)amino]guanidine hydrochloride. 
         [0021]      1 H-NMR: δH (DMSO, 500 MHz) 8.35(4H, s), 7.86(4H, d), 7.02(4H, d), 4.1(4H, m), 1.34(6H, m). 
       Embodiment 3 
       [0022]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0023]    Preparation of 1,3-bis[(4-isopropoxybenzylidene)amino]guanidine hydrochloride (IST_007_003). 
         [0024]    4-n-butoxybenzaldehyde (25 g, 0.153 mol, 2 eq) was dissolved in about 300 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), refluxed until complete dissolution, and then reaction proceeded at a constant temperature for 1˜5 hours with stirring until TLC showed that the 4-isopropoxybenzaldehyde had been reacted completely. The solution was cooled to −10° C. with stifling to give a great amount of white precipitate, and then filtrated. Filter cake was washed with cold ethanol for 2˜3 times, and subjected to rotary evaporation to remove the solvent and give a product, i.e., 1,3-bis[(4-isopropoxybenzylidene)amino]guanidine hydrochloride. 
         [0025]      1 H-NMR: δH (DMSO, 500 MHz) 11.77(2H, s). 8.29(4H s), 7.85(4H, d), 7.01(4H, d), 4.72(2H, m), 1.29(12H, d). 
       Embodiment 4 
       [0026]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0027]    Preparation of 1,3-bis[(4-butoxybenzylidene)amino]guanidine hydrochloride (IST_007_005). 
         [0028]    4-n-butoxylenzaldehyde (25 g, 0.14 mol, 2 eq) was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), refluxed until complete dissolution, and then reaction proceeded at a constant temperature for 1˜5 hours with stirring until TLC showed that the 4-n-butoxybenzaldehyde had been reacted completely. The solution was cooled to −10° C. with stirring to give a great amount of white precipitate, and then filtrated. Filter cake was washed with cold ethanol for 2˜3 times, and subjected to rotary evaporation to remove the solvent and give a product, i.e., 1,3-bis[(4-butoxybenzylidene)amino]guanidine hydrochloride. 
         [0029]      1 H-NMR: δH (DMSO, 500 MHz) 12.15(2H, s), 8.38(4H, d) 7.86(4H, d), 7.02(4H, d), 4.0(4H, m), 1.7(4H, m) 1.44(4H, m), 0.93(6H, m). 
       Embodiment 5 
       [0030]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0031]    Preparation of 1,3-bis[(4-pentoxybenzylide)amino]guanidine hydrochloride (IST_007_019). 
         [0032]    Step 1: 
         [0033]    A mixture of 4-hydroxybenzaldehyde (12.2 g. 100 mmol, 1 eq), 1-bromopentane (0.8˜1.5 eq) and potassium carbonate (1˜3 eq) was added with 30 ml of DMF, and stirred at 50˜100° C. for 5˜16 hours, wherein TLC (PE:EA=5:1) gave a new spot with low polarity, and showed that a little amount of 4-hydroxybenzaldehyde had not been reacted. The resulting solution was cooled to room temperature, and then added with 100 ml of dichloromethane and 100 ml of water, and the layers were separated. The resulting organic phase was washed with water twice, dried over 20 g of anhydrous sodium sulfate for about 30 minutes, filtrated to remove the inorganic salt, and subjected to a gradient elution from 100% petroleum ether to petroleum ether/ethyl acetate (5:1) over a 200˜300 mesh silica gel column to give pure 4-n-pentoxybenzaldehyde. 
         [0034]    Step 2: 
         [0035]    4-n-pentoxybenzaldehyde (15.36 g, 0.08 mol, 2 eq) was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochimide (0.7˜1.5 eq), stirred at 10-70° C. for 17 hours to give clear liquid. The liquid was subjected to rotary evaporation to remove the solvent, added into 150 ml of ethyl acetate, stirred at room temperature for 2˜5 hours to give a great amount of precipitate, and then filtrated. The filter cake was washed with cold ethyl acetate (50 ml×3), and dried via rotary evaporation in a 40° C. water bath to give a product, i.e., 1,3-bis[(4-pentoxybenzylidene)amino]guanidine hydrochloride. 
         [0036]      1 H-NMR: H (DMSO, 500 MHz) 12.133(2H, s), 8.350(4H, s), 7.845-7.863(4H, d, J=9), 7.003-7.021 (4H, d, J=9), 4.011-4.037(4H, in), 1,700-1.756(4H, m), 1.342-1.432(8H, m), 0.89-0.092(6H, m). 
       Embodiment 6 
       [0037]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0038]    Preparation of 1,3-bis[(4-octoxybenzylidene)amino]guanidine hydrochloride (IST_007_020). 
         [0039]    Step 1: 
         [0040]    A mixture of 4-hydroxybenzaldehyde (12.2 g, 100 mmol, 1 eq), 1-bromooctane (0.8˜1.5 eq) and potassium carbonate (1˜3eq) was added with 30 ml of DMF, and stirred at 50˜100° C. for 5˜16 hours, wherein TLC (PE: EA=5:1) gave a new spot with low polarity, and showed that a little amount of 4-hydroxybenzaldehyde had not been reacted. The resulting solution was cooled to room temperature, and then added with 100 ml of dichloromethane and 100 ml of water, and the layers were separated. The resulting organic phase was washed with water twice, dried over 20 g of anhydrous sodium sulfate for about 30 minutes, filtrated to remove the inorganic salt, and subjected to a gradient elution from 100% petroleum ether to petroleum ether/ethyl acetate (5:1) over a 200˜300 mesh silica gel column to give pure 4-n-octoxybenzaldehyde. 
         [0041]    Step 2: 
         [0042]    4-n-octoxybenzaldehyde (15.53 g, 0.045 mol, was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5eq), stirred at 10˜70° C. for 17 hours to give a great amount of white precipitate, and then filtrated. The filter cake was washed with ethanol (50 ml×3) for 2˜3 times, and dried via rotary evaporation in a 40° C. water bath to give a product, i.e., 1,3-bis[(4-octoxybenzylidene)amino]guanidine hydrochloride. 
         [0043]      1 H-NMR: δH (CDCl 3 , 500 MHz) 12.411 (2H, s), 8.033 (2H, s), 7.532-7.547 (4H, d, J=7.5), 6.863-6.879 (4H, d, J=8), 6.675 (2H, s), 3.945-3.969 (4H, m), 1.750-1.805 (4H, m), 1.433-1.460 (4H, m), 1.289-1.340 (16H. m), 0.873-0.901 (6H, m). 
       Embodiment 7 
       [0044]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0045]    Preparation of 1,3-bis[(4-sec-butoxybenzylidene)amino]guanidine hydrochloride (IST_007_022). 
         [0046]    Step 1: 
         [0047]    A mixture of 4-hydroxybenzaldehyde (12.2 g, 100 mmol, 1 eq), 2-bromobutane (0.8˜1.5 eq) and potassium carbonate (1˜3 eq) was added with 30 ml of DMF, and stirred at 50˜100° C. for 5˜16 hours, wherein TLC (PE: EA=5:1) gave a new spot with low polarity, and showed that a little amount of 4-hydroxybenzaldehyde had not been reacted. The resulting solution was cooled to room temperature, and then added with 100 ml of dichloromethane and 100 ml of water, and the layers were separated. The resulting organic phase was washed with water twice, dried over about 20 g of anhydrous sodium sulfite for about 30 minutes, filtrated to remove the inorganic salt, and subjected to a gradient elution from 100% petroleum ether to petroleum ether/ethyl acetate (5:1) over a 200˜300 mesh silica gel column to give pure 4-sec-butoxybenzaldehyde. 
         [0048]    Step 2: 
         [0049]    4-sec-butoxybenzaldehyde (14.24 g, 0.08 mol, 2 eq) was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), and stirred at 10˜70° C. for 17 hours. The diaminoguanidine monohydrochloride was dissolved gradually and no precipitate was observed. Then the solution was subjected to rotary evaporation in a 40° C. water bath to remove the solvent and thereby gave a residual as yellowish viscous solids. The solids were washed with about 200 ml of petroleum ether with stirring at room temperature for 2 hours to give a great amount of precipitate, and then filtrated. The filter cake was washed with petroleum ether (50 ml×2) for 2˜3 times, and subjected to rotary evaporation to give a crude product. The crude product was washed with about 150 ml of ethyl acetate with stirring at room temperature for 3˜5 hours, and then filtrated. The filter cake was washed with ethyl acetate (50 ml×2), then subjected to rotary evaporation to give a white solid product, i.e., 1.3-bis[(4-sec-butoxybenzylidene)amino]guanidine hydrochloride. 
         [0050]      1 H-NMR: δH (CDCl 3 , 500 MHz) 12.571 (2H, s), 8.071 (2H, s), 7.545-7.562 (4H, d, J=8.5), 6.875-6.892 (4K, d, J=8.5), 6.589 (2H, s), 4.333-4.367 (2H, m), 1.712-1.781 (2H, m), 1.610-1.679 (2H, m), 1.302-1.314 (6H, d, J=6), 0.961-0.991 (6H, m). 
       Embodiment 8 
       [0051]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0052]    Preparation of 1,3-bis[[4-(3-pentoxy)benzyhdene]amino]guanidine hydrochloride (IST_007_023). 
         [0053]    Step 1: 
         [0054]    A mixture of 4-hydroxybenzaldehyde (12.2 g, 100 mmol, 1 eq), 3-bromopentane (0.8˜1.5 eq) and potassium carbonate (1-3 eq) was added with 30 ml of DMF, and stirred at 50˜100t for 5˜16 hours, wherein TLC (PE:EA=5:1) gave a new spot with low polarity, and showed that a little amount of 4-hydroxybenzaldehyde had not been reacted. The resulting solution was cooled to room temperature, and then added with 100 ml of dichloromethane and 100 ml of water, and the layers were separated. The resulting organic phase was washed with water twice, dried over about 20 g of anhydrous sodium sulfate for about 30 minutes, filtrated to remove the inorganic salt, and subjected to a gradient elution from 100% petroleum ether to petroleum ether/ethyl acetate (5:1) over a 200˜300 mesh silica gel column to give pure 4-(3-pentoxy)benzaldehyde. 
         [0055]    Step 2: 
         [0056]    4-(3-Pentoxy)benzaldehyde (15.36 g, 0.08 mol, 2 eq) was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), and stirred at 10˜70° C. for 17 hours. The diaminoguanidine monohydrochloride was dissolved gradually and no precipitate was observed. Then the solution was subjected to rotary evaporation in a 40° C. water bath to remove the solvent and thereby gave a residual as yellowish viscous solids. The solids were washed with about 200 ml of petroleum ether with stirring at room temperature for 2 hours to give a great amount of precipitate, and then filtrated. The filter cake was washed with petroleum ether (50 ml×2) for 2˜3 times, and subjected to rotary evaporation to give a crude product. The crude product was washed with about 150 ml of ethyl acetate with stirring at room temperature for 3˜5 hours, and then filtrated. The filter cake was washed with ethyl acetate (50 ml×2), then subjected to rotary evaporation to give a white solid product, i.e., 1,3-bis[[4-(3-pentoxy)benzylidene]amino]guanidine hydrochloride. 
         [0057]      1 H-NMR: δH (CDCl 3 , 500 MHz) 12.514 (2H, s), 8.075 (2H, 7.545-7.561 (4H, d, J=8), 6.884-6.901 (4H, d, J=8.5), 6.593 (2H, s), 4.162-4.184 (2H, in), 1.664-1.719 (8H, m), 0.940-0.970 (12H, m). 
       Embodiment 9 
       [0058]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0059]    Preparation of 1,3-bis[(4-benzyloxybenzylidene)amino]guanidine hydrochloride IST_007_025). 
         [0060]    Step 1: 
         [0061]    A mixture of 4-hydroxybenzaldehyde (6.1 g, 50 mmol, 1 eq), benzyl bromide (0.8˜1.5 eq) and potassium carbonate (1˜3 eq) was added with 30 ml of DMF, and stirred at 50˜100° C. for 5˜16 hours, wherein TLC (PE:EA=5:1) gave a new spot with low polarity, and showed that a little amount of 4-hydroxybenzaldehyde had not been reacted. The resulting solution was cooled to room temperature, and then added with 100 ml of dichloromethane and 100 ml of water, and the layers were separated. The resulting organic phase was washed with water twice, dried over about 20 g of anhydrous sodium sulfate for about 30 minutes, filtrated to remove the inorganic salt, and subjected to a gradient elution from 100% petroleum ether to petroleum ether/ethyl acetate (5:1) over a 200˜300 mesh silica gel column to give pure 4-benzyloxybenzaldehyde. 
         [0062]    Step 2: 
         [0063]    4-Benzyloxybenzaldehyde (9.75 g, 46 mmol, 2 eq) was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), stirred at 10˜70° C. for 17 hours to give a great amount of white precipitate while the diaminoguanidine monohydrochloride was dissolved gradually, and then filtrated. The filter cake was washed with ethanol (50 ml×2), and dried via rotary evaporation in a 40° C. water bath to give a product, i.e., 1,3 -bis[(4-benzyloxybenzylidene)amino]guanidine hydrochloride. 
         [0064]      1 H-NMR: δH (DMSO, 500 MHz) 12.013 (2H, s), 8.338 (4H, s), 7.872-7.889 (4H, d, J=8.5), 7.467-7.481 (4H, d, J=7), 7.393-7.423 (4H, m), 7.333-7.362 (2H, m), 7.110-7.128 (4H, in, J=9), 5.184 (4H, s). 
       Embodiment 10 
       [0065]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0066]    Preparation of 1,3-bis[(4-cyclopentoxybenzylidene)amino]guanidine hydrochloride (IST_007_024). 
         [0067]    Step 1: 
         [0068]    A mixture of 4-hydroxybenzaldehyde (12.2 g, 100 mmol, 1 eq), cyclopentyl bromide (0.8˜1.5 eq) and potassium carbonate (1˜3 eq) was added with 30 ml of DMF, and stirred at 50˜100° C. for 5˜16 hours, wherein TLC (PE:EA=5:1) gave a new spot with low polarity, and showed that a little amount of 4-hydroxybenzaldehyde had not been reacted. The resulting solution was cooled to room temperature, and then added with 100 ml of dichloromethane and 100 ml of water, and the layers were separated. The resulting organic phase was washed with water twice, dried over about 20 g of anhydrous sodium sulfate for about 30 minutes, filtrated to remove the inorganic salt, and subjected to a gradient elution from 100% petroleum ether to petroleum ether/ethyl acetate (5:1) over a 200˜300 mesh silica gel column to give pure 4-cyclopentoxybenzaldehyde. 
         [0069]    Step 2: 
         [0070]    4-Cyclopentoxybenzaldehyde (15.2 g, 0.08 mol, 2 eq) was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), stirred at 10-70° C. for 17 hours to give a great amount of white precipitate while the diaminoguanidine monohydrochloride was dissolved gradually, and then filtrated. The filter cake was washed with ethanol (50 ml×2), and dried via rotary evaporation in a 40° C. water bath to give a product, i.e., 1,3-bis[(4-cyclopentoxybenzylidene)amino]guanidine hydrochloride. 
         [0071]      1 H-NMR: δH (CDCl 3 , 500 MHz) 12.428 (2H, s), 8.048 (2H, s), 7.524-7.538 (4H, d, J=7), 6.844-6.858 (4H, d, J=7), 6.677 (2H, m), 4.768 (2H, in). 1.798-1.912 (14H, m), 1.629 (2H, m). 
       Embodiment 11 
       [0072]    Structural Formula: 
         [0000]    
       
                 
         
             
             
         
       
     
         [0073]    Preparation of 1,3-bis[(4-propoxybenzylidene)amino]guanidine hydrochloride (IST_007 —028 ). 
         [0074]    Step 1: 
         [0075]    A mixture of 4-hydroxybenzaldehyde (12.2 g, 100 mol, 1 eq), 1-bromopropane 0.8˜1.5 eq) and potassium carbonate (1˜3 eq) was added with 30 ml of DMF, and stirred at 50˜100° C. for 5˜16 hours, wherein TLC (PE:EA=5:1) gave a new spot with low polarity and showed that a little amount of 4-hydroxybenzaldehyde had not been reacted. The resulting solution was cooled to room temperature, and then added with 100 ml of dichloromethane and 100 ml of water, and the layers were separated. The resulting organic phase was washed with water twice, dried over about 20 g of anhydrous sodium sulfate for about 30 minutes, filtrated to remove the inorganic salt, and subjected to a gradient elution from 100% petroleum ether to petroleum ether/ethyl acetate (5:1) over a 200˜300 mesh silica gel column to give pure 4-propoxybenzaldehyde. 
         [0076]    Step 2: 
         [0077]    4-Propoxybenzaldehyde (12.4 g, 0.09 mol, 2 eq) was dissolved in about 150 ml of ethanol. Then the resulting solution was added with diaminoguanidine monohydrochloride (0.7˜1.5 eq), stirred at 10˜70° C. for 17 hours to give a great amount of white precipitate while the diaminoguanidine monohydrochloride was dissolved gradually, and then filtrated. The filter cake was washed with ethanol (50 ml×2), and dried via rotary evaporation in a 40° C. water bath to give a product, 1,3-bis[(4-propoxybenzylidene)amino]guanidine hydrochloride. 
         [0078]      1 H-NMR: δH (CDCl 3 , 500 MHz) 12.541 (2H, s), 8.085 (2H, s), 7.562-7.577 (4H, d, J=7.5), 6.897-6.913 (4H, d, J=8), 6.571 (2H, s), 3.953 (4H, m), 1.805-1.845 (4H, m), 1.033-1.062 (6H, m). 
       Embodiment 12: Minimum Inhibitory Concentration Against  Clostridium  Perfringens in Vitro (MICs, ppm) 
       [0079]      
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 1 
               
             
             
               
                   
               
               
                 Minimum inhibitory concentration of diaminoguanidine derivatives against 
               
               
                   clostridium perfringens  in vitro 
               
             
          
           
               
                 Sample 
                 CP-JM-1210-B 
                 CP-JM-1210-E 
                 CP-JM-1208-H 
               
               
                   
               
             
          
           
               
                 IST_007_001 
                 1.56 
                 50 
                 12.5 
               
               
                 IST_007_003 
                 3.13 
                 12.5 
                 12.5 
               
               
                 IST_007_002 
                 0.2 
                 &gt;100 
                 &gt;100 
               
               
                 IST_007_005 
                 0.78 
                 25 
                 12.5 
               
               
                 IST_007_019 
                 &gt;200 
                 &gt;200 
                 &gt;200 
               
               
                 IST_007_020 
                 &gt;200 
                 &gt;200 
                 &gt;200 
               
               
                 IST_007_022 
                 12.5 
                 12.5 
                 12.5 
               
               
                 IST_007_023 
                 12.5 
                 12.5 
                 12.5 
               
               
                 IST_007_024 
                 1.56 
                 3.13 
                 1.56 
               
               
                 IST_007_025 
                 100 
                 &gt;200 
                 &gt;200 
               
               
                 IST_007_028 
                 1.56 
                 1.56 
                 1.56 
               
               
                   
               
             
          
         
       
     
       Embodiment 13: Minimum Inhibitory Concentration Against Riemerella Anatipestifer in Vitro (MICs, ppm) 
       [0080]      
         [0000]    
       
         
               
             
               
               
               
               
             
               
               
               
               
             
           
               
                 TABLE 2 
               
             
             
               
                   
               
               
                 Minimum inhibitory concentration of diaminoguanidine derivatives against 
               
               
                   riemerella anatipestifer  in vitro 
               
             
          
           
               
                 Sample 
                 RA-HN-1211-C 
                 RA-FS-1308-1 
                 RA-GD-1211-D 
               
               
                   
               
             
          
           
               
                 IST_007_001 
                 3.13 
                 6.25 
                 3.13 
               
               
                 IST_007_003 
                 1.56 
                 1.56 
                 1.56 
               
               
                 IST_007_002 
                 &gt;100 
                 &gt;100 
                 &gt;100 
               
               
                 IST_007_005 
                 1.56 
                 1.56 
                 1.56 
               
               
                 IST_007_019 
                 &gt;200 
                 &gt;200 
                 0.39 
               
               
                 IST_007_020 
                 &gt;200 
                 &gt;200 
                 &gt;200 
               
               
                 IST_007_022 
                 1.56 
                 1.56 
                 0.2 
               
               
                 IST_007_023 
                 1.56 
                 1.56 
                 0.78 
               
               
                 IST_007_024 
                 0.39 
                 0.39 
                 0.78 
               
               
                 IST_007_025 
                 &gt;200 
                 &gt;200 
                 0.39 
               
               
                 IST_007_028 
                 0.39 
                 1.56 
                 0.39 
               
               
                   
               
             
          
         
       
     
       Embodiment 14: Feeding Trial (Ducks) 
       [0081]    800 1-day-old cherry valley ducks were divided into 8 groups, 100 ducks in each group. The ducks were fed with food and water ad libitum for 30 days, each group being fed with the same basal diet mixed with different compound of the IST_007 series, and productivity and survival rate of the ducks were obtained. Table 3 shows the grouping and dosages, and table 4 shows the productivity. The compounds of IST_007 series can substantially enhance the productivity of the ducks, concluded from the results. 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 3 
               
             
             
               
                   
               
               
                 Grouping of the ducks of the IST_007_series, and dosages of additives 
               
             
          
           
               
                 Group 
                 Compound 
                 Dosage (ppm) 
               
               
                   
               
             
          
           
               
                 1 
                 — 
                 0 
               
               
                 2 
                 IST_007_028 
                 20 
               
               
                 3 
                 IST_007_001 
                 20 
               
               
                 4 
                 IST_007_022 
                 20 
               
               
                 5 
                 IST_007_023 
                 20 
               
               
                 6 
                 IST_007_003 
                 20 
               
               
                 7 
                 IST_007_005 
                 20 
               
               
                 8 
                 IST_007_024 
                 20 
               
               
                   
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 4 
               
             
             
               
                   
               
               
                 Feeding trial results of the IST_007_series compounds in ducks 
               
             
          
           
               
                   
                   
                   
                 Average feed 
                   
               
               
                   
                 Average initial 
                 Average weight 
                 conversion 
                 Survival 
               
               
                 Group 
                 weight 
                 gain 
                 efficiency 
                 rate (%) 
               
               
                   
               
               
                 1 
                 51.6 
                 55.8 
                 2.16 
                 100 
               
               
                 2 
                 51.6 
                 61.6 
                 2.04 
                 100 
               
               
                 3 
                 51.6 
                 62.1 
                 2.01 
                 100 
               
               
                 4 
                 51.6 
                 61.3 
                 2.08 
                 100 
               
               
                 5 
                 51.6 
                 62.4 
                 2.05 
                 100 
               
               
                 6 
                 51.6 
                 63.6 
                 2.03 
                 100 
               
               
                 7 
                 51.6 
                 62.4 
                 2.07 
                 100 
               
               
                 8 
                 51.6 
                 63.1 
                 2.09 
                 100 
               
               
                   
               
             
          
         
       
     
       Embodiment 15: Feeding Trial (Broilers) 
       [0082]    400 1-day-aged, healthy, fast-grown yellow feather broilers (female) in the same growing state and similar in weight were randomly divided into eight groups according to table 5, 50 broilers in each group. Broilers in each group were fed with different dosage of the IST_007 series compounds. The broilers were kept in cages and fed with food and water ad libitum for 30 days, wherein weight gain and feed conversion efficiency of the broilers fed with IST_007 series compounds had been significantly improved (table 6). 
         [0000]    
       
         
               
             
               
               
               
             
               
               
               
             
           
               
                 TABLE 5 
               
             
             
               
                   
               
               
                 Grouping of the animals, and dosages of additives 
               
             
          
           
               
                 Group 
                 Compound 
                 Dosage (ppm) 
               
               
                   
               
             
          
           
               
                 1 
                 — 
                 0 
               
               
                 2 
                 — 
                 0 
               
               
                 3 
                 IST_007_001 
                 20 
               
               
                 4 
                 IST_007_001 
                 20 
               
               
                 5 
                 IST_007_003 
                 20 
               
               
                 6 
                 IST_007_003 
                 20 
               
               
                 7 
                 IST_007_005 
                 20 
               
               
                 8 
                 IST_007_005 
                 20 
               
               
                   
               
               
                 —: control blank, wherein IST_007 series compounds were not added 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
               
             
               
               
               
               
               
               
               
             
           
               
                 TABLE 6 
               
             
             
               
                   
               
               
                 Feeding trial results of the IST_007_series compounds in broilers 
               
             
          
           
               
                   
                   
                   
                 Average 
                   
                 Average 
                   
               
               
                   
                 Initial 
                   
                 weight 
                   
                 daily 
                 Feed 
               
               
                   
                 weight 
                 Survival 
                 gain 
                 Consumption 
                 weight 
                 conversion 
               
               
                 Group 
                 (g) 
                 rate (%) 
                 (g) 
                 (kg) 
                 gain (g) 
                 efficiency 
               
               
                   
               
             
          
           
               
                 1 
                 39.7 
                 100 
                 713 
                 76.6 
                 23.7 
                 2.15 
               
               
                 2 
                 38.5 
                 100 
                 712 
                 75.2 
                 23.7 
                 2.11 
               
               
                 3 
                 39.8 
                 100 
                 764 
                 71.7 
                 25.5 
                 1.88 
               
               
                 4 
                 39.1 
                 100 
                 775 
                 73.8 
                 25.8 
                 1.91 
               
               
                 5 
                 39 
                 100 
                 791 
                 73.7 
                 26.3 
                 1.86 
               
               
                 6 
                 39.6 
                 100 
                 795 
                 72.3 
                 26.5 
                 1.82 
               
               
                 7 
                 39.4 
                 100 
                 796 
                 74.1 
                 26.5 
                 1.86 
               
               
                 8 
                 40.2 
                 100 
                 787 
                 72.5 
                 26.2 
                 1.84 
               
               
                   
               
             
          
         
       
     
       Embodiment 16: Feeding Trial (Pigs) 
       [0083]    90 65-day-aged. Duroc-YorkShire-Landrace crossbred lean pigs similar in weight were randomly divided into six groups, 15 pigs in each group. Pigs in each group were fed with the IST_007 series compounds with the dosages listed in table 7. The pigs were fed with food and water ad libitum for 14 days, wherein weight gain and feed conversion efficiency of the pigs fed with IST_007 series compounds had been significantly improved. Grouping and results of the trial were as shown in table 7 and table 8. 
         [0000]    
       
         
               
             
               
               
               
               
               
             
           
               
                 TABLE 7 
               
             
             
               
                   
               
               
                 Grouping of the animals, and dosages of additives 
               
             
          
           
               
                   
                 Quantity 
                   
                 Dosage 
                   
               
               
                 Group 
                 of the pigs 
                 Compound 
                 (mg/kg) 
                 Administration 
               
               
                   
               
               
                 1 
                 15 
                 — 
                 — 
                 — 
               
               
                 2 
                 15 
                 — 
                 — 
                 — 
               
               
                 3 
                 15 
                 IST_007_003 
                 25 
                 Mixed with feed 
               
               
                 4 
                 15 
                 IST_007_003 
                 25 
                 Mixed with feed 
               
               
                 5 
                 15 
                 IST_007_028 
                 25 
                 Mixed with feed 
               
               
                 6 
                 15 
                 IST_007_028 
                 25 
                 Mixed with feed 
               
               
                   
               
               
                 —: control blank, wherein neither IST_007_003 nor IST_007_028 was added 
               
             
          
         
       
     
         [0000]    
       
         
               
             
               
               
               
               
               
               
             
           
               
                 TABLE 8 
               
             
             
               
                   
               
               
                 Feeding trial results of the IST_007_series compounds in pigs 
               
             
          
           
               
                   
                   
                 Average 
                 Average 
                   
                   
               
               
                   
                 Average 
                 weight 
                 daily 
                   
                 Feed 
               
               
                   
                 initial 
                 gain 
                 weight gain 
                 Consumption 
                 conversion 
               
               
                 Group 
                 weight (kg) 
                 (kg) 
                 (kg/day) 
                 (kg) 
                 efficiency 
               
               
                   
               
               
                 1 
                 15.7 
                 6.2 
                 0.44 
                 198.3 
                 2.13 
               
               
                 2 
                 16.2 
                 6.1 
                 0.43 
                 192.9 
                 2.11 
               
               
                 3 
                 16.3 
                 7.8 
                 0.56 
                 215.3 
                 1.84 
               
               
                 4 
                 15.4 
                 8.2 
                 0.58 
                 203.4 
                 1.65 
               
               
                 5 
                 15.3 
                 7.7 
                 0.55 
                 201.3 
                 1.75 
               
               
                 6 
                 16.4 
                 7.3 
                 0.52 
                 202.5 
                 1.85