Use of dithiocarbamic acid derivatives having the structure ##STR1## in which R.sub.1, R.sub.2 and R.sub.3 are various organic radicals as preventive and curative agents against mycoplasmosis. These derivatives are prepared from the starting materials having the structure ##STR2## by reaction with carbon disulfide or from the starting materials having the structure ##STR3## BY REACTION WITH R.sub.3 -halide.
Description
This invention relates to a new use of certain dithiocarbamic acid derivatives as preventive and curative agents against mycoplasmosis. More particularly, it is concerned with a preventive and curative composition against mycoplasmosis which comprises as an active ingredient a dithiocarbamic acid derivative of the formula ##STR4## wherein R.sub.1 and R.sub.2 may be the same or different and each represents an alkyl group of 1 to 4 carbon atoms, cyclohexyl group or an aralkyl group having 6 or 10 carbon atoms in the aryl moiety and 1 to 3 carbon atoms in the alkyl moiety or they may, jointly with the nitrogen atom to which they are attached, form a 5-7 membered heteroalicyclic ring which may further contain as another hetero atom one of nitrogen atom and oxygen atom other than the nitrogen atom linked with R.sub.1 and R.sub.2 and may have as substituent an alkyl group of 1 to 4 carbon atoms, carboxyl group or a carboxylic acid ester group; and R.sub.3 is a group --CH.sub.2 --R.sub.4 in which R.sub.4 is a 5-7 membered 2-oxocycloalkyl group optionally substituted with 1-3 C.sub.1 -C.sub.4 alkyl groups; A group ##STR5## in which n is an integer of 1 or 2 and R.sub.5 is naphthyl group, a phenyl group optionally substituted with 1-2 groups selected from the group consisting of hydroxy, C.sub.1 -C.sub.12 alkyl, C.sub.1 -C.sub.4 alkoxy, nitro and halogen or a 5-7 membered heterocyclic group which has as hetero atom 1 or 2 atoms of oxygen atom, nitrogen atom and sulfur atoms and may be substituted with 1-3 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, hydroxy, hydroxymethyl, halogenomethyl, dihalogenomethyl, trihalogenomethyl, nitro and halogen; A group ##STR6## in which R.sub.6 is an alkyl group of 1 to 12 carbon atoms, a 5-6 membered cycloalkyl group, an aralkyl group which has 6 or 10 carbon atoms in the aryl moiety and 1 to 4 carbon atoms in the alkyl moiety and may be substituted with C.sub.1 -C.sub.4 alkyl, hydroxy, nitro, C.sub.1 -C.sub.4 alkoxy or halogen or an alkenyl group of 2 to 5 carbon atoms which may be substituted with cycloalkenyl or phenyl, said phenyl being optionally substituted with C.sub.1 -C.sub.4 alkyl, hydroxy, nitro, C.sub.1 -C.sub.4 alkoxy or halogen and X is a group ##STR7## wherein R.sub.7 is hydrogen, C.sub.1 -C.sub.12 alkyl, cyclohexyl, aralkyl of C.sub.6 or C.sub.10 in the aryl moiety and C.sub.1 -C.sub.4 in the alkyl moiety, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.3 alkynyl or phenyl or a group ##STR8## wherein R.sub.8 is hydrogen, C.sub.1 -C.sub.12 alkyl, cyclohexyl, aralkyl of C.sub.6 or C.sub.10 in the aryl moiety and C.sub.1 -C.sub.4 in the alkyl moiety, said aryl moiety being optionally substituted with C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy or halogen, or phenyl optionally substituted with C.sub.2 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy or halogen; or a group ##STR9## in which R.sub.9 is hydrogen atom, an alkyl group of 1 to 4 carbon atoms, cyclohexyl group or phenyl group and R.sub.10 is a phenyl group which has one hydroxy group at the o- or p-position and 2-4 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.4 alkenyl hydroxyalkyl of C.sub.1 -C.sub.4, a group ##STR10## wherein R.sub.1 and R.sub.2 are as defined above and a group ##STR11## wherein R.sub.1 and R.sub.2 are as defined above, a naphthyl group which has one hydroxy group at the 1- or 2-position and optionally halogen or a group ##STR12## wherein R.sub.1 and R.sub.2 are as defined above, a group ##STR13## or a group ##STR14## or a pharmaceutically acceptable salt thereof. In the above formula (I), R.sub.1 and R.sub.2 may be exemplified by methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, cyclohexyl, benzyl, phenethyl, phenylpropyl, morpholino, piperidino, pyrrolidino, hexamethyleneimino, 3-oxazolidino, 4-methyl-1-piperazino, 2-methoxycarbonyl-1-pyrrolidino, 2-benzyloxycarbonyl-1-pyrrolidino, 2-carboxy-1-pyrrolidino. With respect to the definition of R.sub.3, R.sub.4 represents a 5-7 membered 2-oxocycloalkyl group unsubstituted or substituted with 1-3 lower alkyl groups such as methyl, ethyl, propyl and butyl. R.sub.5 represents a naphthyl group, a phenyl group unsubstituted or substituted with 1 or 2 groups selected from the group consisting of an alkyl group such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, dodecyl, etc., alkoxy group such as methoxy, ethoxy, propoxy, butoxy, etc., hydroxy group, nitro group and a halogen atom, or a 5-7 membered monovalent heterocyclic group having as ring members 1 or 2 (the same or different) atoms of oxygen, nitrogen and sulfur, said heterocyclic group being unsubstituted or substituted with 1-3 groups selected from the group consisting of a lower alkyl group such as methyl, ethyl, propyl, butyl, etc., hydroxy group, hydroxymethyl group, a halogenomethyl group, a dihalogenomethyl group, a trihalogenomethyl group, nitro group and a halogen atom. R.sub.6 represents a straight-chain or branched alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, hexyl, 3-methylhexyl, octyl, tert-octyl, undecyl, ect.; a 5-6 membered cycloalkyl group; an aralkyl group (in which the aryl may be unsubstituted or substituted with an alkyl group, hydroxy group, nitro group, an alkoxy group or a halogen atom) such as benzyl, phenethyl, o-, m-, p-nitrobenzyl, o-, m-, p-hydroxyphenethyl, o-, m-, p-methylphenethyl, o-, m-, p-methoxyphenethyl, o-, m-, p-chlorophenethyl, o-, m-, p-nitrophenethyl, etc.; an alkenyl group (which may be unsubstituted or substituted with a cycloalkenyl group or with an unsubstituted or substituted phenyl group, the substituent of which is an alkyl group, hydroxy group, nitro group, an alkoxy group or a halogen atom) such as 1-propenyl, allyl, styryl, 1,3-pentadienyl, o-, m-, p-hydroxystyryl, o-, m-, p-methylstyryl, o-, m-, p-methoxystyryl, o-, m-, p-chlorostyryl, o-, m-, p-nitrostyryl, 2-(2,6,6-trimethyl-1-cyclohexenyl)-vinyl. X represents a group ##STR15## or a group ##STR16## wherein R.sub.7 represents a hydrogen atom; a straight-chain or branched alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, octyl, decyl, etc.; cyclohexyl group; an aralkyl group such as benzyl, phenethyl, etc.; an alkenyl group as vinyl, allyl, 1-butenyl, 2-butenyl, etc.; an alkynyl group such as 1-propynyl, 2-propynyl, etc., and R.sub.8 represents a hydrogen atom; a straight-chain or branched alkyl group such as methyl, ethyl, isopropyl, butyl, pentyl, 2-methylpentyl, decyl, etc.; cyclohexyl group; an aralkyl group (in which the aryl may be unsubstituted or substituted with an alkyl group, hydroxy group, an alkoxy group or a halogen atom) such as benzyl, phenethyl, o-, m-, p-hydroxybenzyl, o-, m-, p-methylbenzyl, o-, m-, p-methoxybenzyl, o-, m-, o-chlorobenzyl, etc.; an unsubstituted or substituted phenyl group (as the substituents may be mentioned an alkyl group, hydroxy group, an alkoxy group or a halogen atom) such as phenyl, o-, m-, p-tolyl, o-, m-, p-hydroxyphenyl, o-, m-, p-methoxyphenyl, o-, m-, p-chlorophenyl, etc. R.sub.9 represents hydrogen atom, an alkyl group such as methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, cyclohexyl group or phenyl group. R.sub.10 may be exemplified by 4-hydroxy-3,5-dimethylphenyl, 4-hydroxy-2-isopropyl-5-methylphenyl, 4-hydroxy-3-tert-butyl-5-methylphenyl, 4-hydroxy-3,5-di-tert-butylphenyl, 4-hydroxy-3,5-diisopropylphenyl, 2-hydroxy-3,5-dimethylphenyl, 2-hydroxy-3,5-di-tert-butylphenyl, 4-hydroxy-3,5-dimethoxyphenyl, 4-hydroxy-3,5-dichlorophenyl, 4-hydroxy-3-dimethylaminomethyl-5-methylphenyl, 4-hydroxy-3-(4-methyl-1-piperazinomethyl)-5-methylphenyl, 4-hydroxy-3-dimethylaminomethyl-5-n-propylphenyl, 4-hydroxy-3-dimethylaminomethyl-5-sec.-butylphenyl, 2-hydroxy-3-methoxy-5-hydroxymethylphenyl, 2-hydroxy-3-methoxy-5-propenylphenyl, 4-hydroxy-5-dimethylamino-thiocarbamoylthiomethyl-2-methylphenyl, 4-hydroxy-5-dimethylaminothiocarbamoylthiomethyl-3-tert-butylphenyl, 4-hydroxy-5-(4-methyl-1-piperazinothiocarbonylthiomethyl)-3-n-propylphenyl, 2-hydroxy-5-(1-piperidinothiocarbonylthiomethyl)-3-tert -butylphenyl, 2-hydroxy-5-(4-methyl-1-piperazinothiocarbonylthiomethyl)-3-tert-butylphenyl, 4-chloro-1-hydroxy-2-naphthyl, 4-dimethylaminothiocarbamoylthiomethyl-1-hydroxy-2-naphthyl, 2-hydroxy-1-naphthyl, 4-morpholinothiocarbonylthiomethyl-2-hydroxy-1-naphthyl, 5-hydroxy-2-hydroxymethyl-4-oxo- 4H-pyran-6-yl or a group of formula ##STR17## As the salts of the derivatives of dithiocarbamic acid represented by the formula (I), there are mentioned acid addition salts of the amine group and alkali or alkaline earth metal salts of the carboxyl group. As the acid addition salt of the amine group, there may be mentioned such pharmaceutically acceptable non-toxic salts are those with hydrochloric acid, sulfuric acid, oxalic acid, maleic acid, tartaric acid, malonic acid, citric acid, phthalic acid or naphthalene-disulfonic acid and the like. As the alkali or alkaline earth metal salts of the carboxyl group, there may be mentioned pharmaceutically acceptable non-toxic salts as those of, for example, lithium, sodium, potassium, magnesium, calcium and the like. Mycoplasmosis is a disease of poultry and domestic animals caused by mycoplasma or a group of microorganisms belonging to PPLO (Pleuro-pneumonia-like organisms). Frequently pigs, chickens and turkeys suffer from this disease, which causes chronic respiratory disorder or arthritis and causes heavy damage on poultry and stock breeding industry. Mycoplasma-infected disease affects poultry in particular, and causes the stoppage of egg-laying and extreme fall of fertilization ratio or hatching ratio. This disease further causes fatal damage such as the decrease of the body weight of a chicken for broiler. An outbreak of these symptoms caused by this disease shows a tendency to increase year by year. The symptoms caused by the infection (mixed-infection) show complicated aspect. It was reportedly observed that mycoplasma is sensitive in vitro to antibiotics such as tetracycline, macrolide, aminoglyco-side and the like. Recently, tylosin, an antibiotic belonging to macrolide came to be applied as a preventive and curative agent against this disease. But, in spite of the various studies on the chemotherapy by antibiotics or antibacterial pharmaceuticals, the perfect extinguishment of mycoplasma from the interior of animal body can hardly be accomplished. As a result of our research to develop a more effective preventive and curvative agent against mycoplasmosis, it has been found that the dithiocarbamic acid derivatives (I) or salts thereof show a strong inhibition against various kinds of mycoplasmosis in an extremely low concentration. It is, accordingly, a primary object of this invention to provide a new and more effective preventive and curvative composition against mycoplasmosis which comprises as an active ingredient the dithiocarbamic acid derivative (I) or a salt thereof. Other subjects and advantages of this invention will be apparent from the following description. Of the dithiocarbamic acid derivatives (I) which may be effectively employed in the present composition, there can be mentioned, as a preferable group in view of a biological activity, those derivatives of the formula (I) wherein R.sub.1 and R.sub.2 individually represent an alkyl group of 1 to 4 carbon atoms, cyclohexyl group or benzyl group or they may, jointly with the nitrogen atom to which they are attached, form a 5-7 membered heteroalicyclic ring which may further contain as another hetero atom one of nitrogen atom and oxygen atom other than the nitrogen atom linked with R.sub.1 and R.sub.2 and may have as substituent an alkyl group of 1 to 4 carbon atoms: and R.sub.4 is a 5-6 membered 2-oxocycloalkyl group optionally substituted with 1-2 C.sub.1 -C.sub.4 alkyl groups; n is 2 and R.sub.5 is naphthyl group, a phenyl group optionally substituted with 1-2 groups selected from the group consisting of hydroxy, C.sub.1 -C.sub.8 alkyl, nitro and halogen or a 5-6 membered heterocyclic group which has as hetero atom 1 to 2 atoms of oxygen atom and nitrogen atom; R.sub.6 is an alkyl group of 1 to 12 carbon atoms, a phenethyl group which may be substituted with methyl, hydroxy, methoxy or halogen, an alkenyl group of 3 carbon atoms or a styryl group which may be substituted with methyl, hydroxy, methoxy or halogen and X is a group ##STR18## wherein R.sub.8 is hydrogen, C.sub.1 -C.sub.12 alkyl, cyclohexyl, benzyl optionally substituted with methyl, hydroxy or methoxy or phenyl; or R.sub.9 is hydrogen atom, methyl group cyclohexyl group or phenyl group and R.sub.10 is a phenyl group which has one hydroxy group at the o- or p-position and 2-4 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, chlorine, methoxy, propenyl, hydroxymethyl, a group ##STR19## wherein R.sub.1 and R.sub.2 are as defined above and a group ##STR20## wherein R.sub.1 and R.sub.2 are as defined above, naphthyl group, a group ##STR21## or a group ##STR22## Moreover, the most preferable group of the dithiocarbamic acid derivatives (I) includes those derivatives of the formula (I) wherein R.sub.1 and R.sub.2 individually represent an alkyl group of 1 to 4 carbon atoms or benzyl group or they may, jointly with the nitrogen atom to which they are attached, form a 6-7 membered heteroalicyclic ring which may further contain as another hetero atom one of nitrogen atom and oxygen atom other than the nitrogen atom linked with R.sub.1 and R.sub.2 and may be substituted with methyl; and R.sub.4 is a 5-6 membered 2-oxocycloalkyl group; n is 2 and R.sub.5 is naphthyl group, a phenyl group optionally substituted with 1-2 groups selected from the group consisting of hydroxy, C.sub.1 -C.sub.8 alkyl, nitro and chlorine or a 5-6 membered heterocyclic group which has as hetero atom one of oxygen atom and nitrogen atom; R.sub.6 is alkyl group of 1 to 12 carbon atoms, a phenethyl group which may be substituted with methyl, hydroxy or methoxy or a styryl group which may be substituted with methyl, hydroxy or methoxy and X is a group ##STR23## wherein R.sub.8 is hydrogen, C.sub.1 -C.sub.12 alkyl or phenyl; or R.sub.9 is hydrogen atom or phenyl group and R.sub.10 is a phenyl group which has one hydroxy group at the o- or p-position and 2-4 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, hydroxymethyl, a group ##STR24## wherein R.sub.1 and R.sub.2 are as defined above and a group ##STR25## wherein R.sub.1 and R.sub.2 are as defined above, a group ##STR26## or a group ##STR27## Representatives of the dithiocarbamic acid derivatives (I) in this invention are illustratively shown herinbelow. The Compound Nos. for designation of particular compounds frequently referred to hereinafter. 1. 2-Oxocyclopentylmethyl dimethyldithiocarbamate 2. 2-Oxocyclopentylmethyl diethyldithiocarbamate 3. 2-Oxocyclopentylmethyl 4-morpholinecarbodithioate 4. 2-Oxocyclopentylmethyl 1-piperidinecarbodthioate 5. 2-Oxocyclohexylmethyl dimethyldithiocarbamate 6. 2-Oxocyclohexylmethyl diethyldithiocarbamate 7. 2-Oxocyclohexylmethyl n-butylmethyldithiocarbamate 8. 2-Oxocyclohexylmethyl 1-pyrrolidinecarbodithioate 9. 2-Oxocyclohexylmethyl 1-piperidinecarbodithioate 10. 2-Oxocyclohexylmethyl 1-hexamethyleneiminecarbodithioate 11. 2-Oxocyclohexylmethyl 3-oxazolidinecarbodithioate 12. 2-Oxocyclohexylmethyl 4-morpholinecarbodithioate 13. 2-Oxocyclohexylmethyl 4-methyl-1-piperazinecarbodithioate 14. 2-Methyl-6-oxocyclohexylmethyl diethyldithiocarbamate 15. 2,2-Dimethyl-6-oxocyclohexylmethyl dimethyldithiocarbamate 16. 2,4,4-Trimethyl-6-oxocyclohexylmethyl dimethyldithiocarbamate 17. 2,4,4-Trimethyl-6-oxocyclohexylmethyl 1-piperidinecarbodithioate 18. 2,4,4-Trimethyl-6-oxocyclohexylmethyl 4-morpholinecarbodithioate 19. 3-Isopropyl-6-methyl-2-oxocyclohexylmethyl dimethyldithiocarbamate 20. 2-Oxocycloheptylmethyl diethyldithiocarbamate 21. Phenacyl dimethyldithiocarbamate 22. Phenacyl diethyldithiocarbamate 23. 2-Benzoylethyl dimethyldithiocarbamate 24. 2-Benzoylethyl diethyldithiocarbamate 25. 2-Benzoylethyl n-butylmethyldithiocarbamate 26. 2-Benzoylethyl cyclohexylmethyldithiocarbamate 27. 2-Benzoylethyl benzylmethyldithiocarbamate 28. 2-Benzoylethyl phenethylmethyldithiocarbamate 29. 2-Benzoylethyl 2-pyrrolidinecarbodithioate 30. 2-Benzoylethyl 1-piperidinecarbodithioate 31. 2-Benzoylethyl 1-hexamethyleneiminecarbodithioate 32. 2-Benzoylethyl 3-oxazolidinecarbodithioate 33. 2-Benzoylethyl 4-morpholinecarbodithioate 34. 2-Benzoylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride 35. 2-Benzoylethyl L-2-methoxycarbonyl-1-pyrrolidinecarbodithioate 36. 2-Benzoylethyl L-2-benzyloxycarbonyl-1-pyrrolidinecarbodithioate 37. Sodium salt of 2-benzoylethyl L-2-carboxy-1-pyrrolidinecarbodithioate 38. 2-(.beta.-naphthoyl)ethyl dimethyldithiocarbamate 39. 2-(.alpha.-naphthoyl)ethyl dimethyldithiocarbamate 40. 2-(o-Hydroxybenzoyl)ethyl dimethyldithiocarbamate 41. 2-(o-Hydroxybenzoyl)ethyl 1-piperidinecarbodithioate 42. 2-(o-Hydroxybenzoyl)ethyl 4-morpholinecarbodithioate 43. 2-(o-Hydroxybenzoyl)ethyl 4-methyl-1-piperazinecarbodithioate 44. 2-(p-Hydroxybenzoyl)ethyl diethyldithiocarbamate 45. 2-(p-Hydroxybenzoyl)ethyl 4-morpholinecarbodithioate 46. 2-(p-Methoxybenzoyl)ethyl dimethyldithiocarbamate 47. 2-(p-Methoxybenzoyl)ethyl 1-pyrrolidinecarbodithioate 48. 2-(p-Methoxybenzoyl)ethyl 4-morpholinecarbodithioate 49. 2-(p-Chlorobenzoyl)ethyl 4-morpholinecarbodithioate 50. 2-(p-Bromobenzoyl)ethyl dimethyldithiocarbamate 51. 2-(p-Bromobenzoyl)ethyl 4-morpholinecarbodithioate 52. 2-(3,4-Dichlorobenzoyl)ethyl dimethyldithiocarbamate 53. 2-(3,4-Dichlorobenzoyl)ethyl 1-piperidinecarbodithioate 54. 2-(3,4-Dichlorobenzoyl)ethyl b 4-morpholinecarbodithioate 55. 2-(p-Toluoyl)ethyl dimethyldithiocarbamate 56. 2-(m-Toluoyl)ethyl dimethyldithiocarbamate 57. 2-(o-Toluoyl)ethyl dimethyldithiocarbamate 58. 2-(p-n-Octylbenzoyl)ethyl dimethyldithiocarbamate 59. 2-(o-Nitrobenzoyl)ethyl dimethyldithiocarbamate 60. 2-(o-Nitrobenzoyl)ethyl 4-methyl-1-piperazinecarbodithioate 61. 2-(o-Nitrobenzoyl)ethyl 4-morpholinecarbodithioate 62. 2-(m-Nitrobenzoyl)ethyl 1-piperidinecarbodithioate 63. 2-(m-Nitrobenzoyl)ethyl 4-morpholinecarbodithioate 64. 2-(p-Nitrobenzoyl)ethyl 4-morpholinecarbodithioate 65. 2-(2-Furoyl)ethyl dimethyldithiocarbamate 66. 2-(2-Furoyl)ethyl 4-methyl-1-piperazinecarbodithioate 67. 2-(2-Furoyl)ethyl 4-morpholinecarbodithioate 68. 2-(2-Thenoyl)ethyl 4-morpholinecarbodithioate 69. 2-Nicotinoyl dimethyldithiocarbamate 70. 2-Nicotinoylethyl 4-methyl-1-piperazinecarbodithioate 71. 2(2-Chloromethyl-5-nitronicotinoyl)ethyl dimethyldithiocarbamate 72. 2(2-Dichloromethyl-5-nitronicotinoyl)ethyl dimethyldithiocarbamate 73. 2-(6-Trichloromethyl-2-methyl-5-nitronicotinoyl)ethyl dimethyldithiocarbamate 74. 2-(5-Thiazolcarbonyl)ethyl dimethyldithiocarbamate 75. 2-(1-Methyl-5-imidazolcarbonyl)ethyl 4-methyl-1-piperazinecarbodithioate 76. 2-(5-Pyrimidinecarbonyl)ethyl dimethyldithiocarbamate 77. 2-(5-Pyridazinecarbonyl)ethyl dimethyldithiocarbamate 78. 2-Acetylethyl dimethyldithiocarbamate 79. 2-Acetylethyl diethyldithiocarbamate 80. 2-Acethylethyl butylmethyldithiocarbamate 81. 2-Acetylethyl cyclohexylmethyldithiocarbamate 82. 2-Acetylethyl benzylmethyldithiocarbamate 83. 2-Acetylethyl 1-pyrrolidinecarbodithioate 84. 2-Acetylethyl 2-carboxy-1-pyrrolidinecarbodithioate 85. Sodium salt of 2-acetylethyl 2-carboxy1-pyrrolidinecarbodithioate 86. 2-Acetylethyl 2-methoxycarbonyl-1-pyrrolidinecarbodithioate 87. 2-Acetylethyl 2-benzyloxycarbonyl-1-pyrrolidinecarbodithioate 88. 2-Acetylethyl 1-piperidinecarbodithioate 89. 2-Acetylethyl 1-hexamethyleneiminecarbodithioate 90. 2-Acetylethyl 3-oxazolidinecarbodithioate 91. 2-Acetylethyl 4-morpholinecarbodithioate 92. 2-Acetylethyl 4-methyl-1-piperazinecarbodithioate 93. 2-Acetylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride 94. Acetonyl dimethyldithiocarbamate 95. Acetonyl diethyldithiocarbamate 96. 3-Phenylacetonyl dimethyldithiocarbamate 97. Cyclohexylcarbonylmethyl dimethyldithiocarbamate 98. 2-Propionylethyl dimethyldithiocarbamate 99. 2-Propionylethyl diethyldithiocarbamate 100. 2-Propionylethyl 1-piperidinecarbodithioate 101. 2-Propionylethyl 4-morphonlinecarbodithioate 102. 2-Propionylethyl 4-methyl-1-piperazinecarbodithioate 103. 2-Propionylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride 104. 2-Isobutyrylethyl dimethyldithiocarbamate 105. 2-Isobutyrylethyl diethyldithiocarbamate 106. 2-Isobutyrylethyl 1-piperidinecarbodithioate 107. 2-Isobutyrylethyl 4-methyl-1-piperazinecarbodithioate 108. 2-Pivaroylethyl dimethyldithiocarbamate 109. 2-Pivaroylethyl diethyldithiocarbamate 110. 2-Pivaroylethyl 1-piperidinecarbodithioate 111. 2-Pivaroylethyl 4-morpholinecarbodithioate 112. 2-Pivaroylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride 113. 2-Heptanoylethyl dimethyldithiocarbamate 114. 2-(4-methylheptanoyl)ethyl dimethyldithiocarbamate 115. 2-Lauroylethyl dimethyldithiocarbamate 116. 2-Lauroylethyl diethyldithiocarbamate 117. 2-(2,2,4,4-Tetramethylvaleryl)ethyl dimethyldithiocarbamate 118. 2-Cyclopentylcarbonylethyl dimethyldithiocarbamate 119. 2-Phenylacetylethyl dimethyldithiocarbamate 120. 2-Phenylacetylethyl diethyldithiocarbamate 121. 2-Phenylacetylethyl 1-piperidinecarbodithioate 122. 2-Phenylacetylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride 123. 2-Hydrocinnamoylethyl dimethyldithiocarbamate 124. 2-(p-Nitrophenylacetyl)ethyl dimethyldithiocarbamate 125. 2-(o-Hydroxyhydrocinnamoyl)ethyl diethyldithiocarbamate 126. 2-(p-Hydroxyhydrocinnamoyl)ethyl diethyldithiocarbamate 127. 2-(m-Methylhydrocinnamoyl)ethyl dimethyldithiocarbamate 128. 2-(p-Methylhydrocinnamoyl)ethyl diethyldithiocarbamate 129. 2-(p-Methoxyhydrocinnamoyl)ethyl diethyldithiocarbamate 130. 2-(o-Chlorohydrocinnamoyl)ethyl dimethyldithiocarbamate 131. 2-(o-Nitrohydrocinnamoyl)ethyl dimethyldithiocarbamate 132. 2-(2-Butenoyl)ethyl dimethyldithiocarbamate 133. 2-(2-Butenoyl)ethyl diethyldithiocarbamate 134. 2-Cinnamoylethyl dimethyldithiocarbamate 135. 2-Cinnamoylethyl diethyldithiocarbamate 136. 2-Cinnamoylethyl 1-piperidinecarbodithioate 137. 2-Cinnamoylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride 138. 2-(2,4-Hexadienoyl)ethyl dimethyldithiocarbamate 139. 2-(o-Hydroxycinnamoyl)ethyl diethyldithiocarbamate 140. 2-(p-Hydroxycinnamoyl)ethyl diethyldithiocarbamate 141. 2-(m-Methylcinnamoyl)ethyl dimethyldithiocarbamate 142. 2-(p-Methylcinnamoyl)ethyl diethyldithiocarbamate 143. 2-(p-Methoxycinnamoyl)ethyl diethyldithiocarbamate 144. 2-(o-Chlorocinnamoyl)ethyl dimethyldithiocarbamate 145. 2-(o-Nitrocinnamoyl)ethyl dimethyldithiocarbamate 146. 2-[.beta.-(2,6,6-Trimethylcyclohexene-1-yl)acryloyl]-ethyl dimethyldithiocarbamate 147.2-Acetylpropyl dimethyldithiocarbamate 148. 2-Acetylpropyl diethyldithiocarbamate 149. 2-Acetylpropyl 1-piperidinecarbodithioate 150. 2-Acetylpropyl 4-methyl-1-piperazinecarbodithioate hydrochloride 151. 2-Acetylheptyl dimethyldithiocarbamate 152. 2-Acetyldodecyl dimethyldithiocarbamate 153. 2-Acetyldodecyl diethyldithiocarbamate 154. 2-Acetyl-4-methylheptyl dimethyldithiocarbamate 155. 2-Acetyl-2-cyclohexylethyl dimethyldithiocarbamate 156. 2-Acetyl-2-benzylethyl dimethyldithiocarbamate 157. 2-Acetyl-2-benzylethyl diethyldithiocarbamate 158. 2-Acetyl-2-(p-hydroxybenzyl)ethyl dimethyldithiocarbamate 159. 2-Acetyl-2-salicylethyl diethyldithiocarbamate 160. 2-Acetyl-2-(m-methylbenzyl)ethyl dimethyldithiocarbamate 161. 2-Acetyl-2-(p-methylbenzyl)ethyl diethyldithiocarbamate 162. 2-Acetyl-2-(p-anisyl)ethyl diethyldithiocarbamate 163. 2-Acetyl-2-(o-chlorobenzyl)ethyl dimethyldithiocarbamate 164. 2-Acetyl-2-phenylethyl dimethyldithiocarbamate 165. 2-Acetyl-2-phenylethyl diethyldithiocarbamate 166. 2-Acetyl-2-phenylethyl 1-piperidinecarbodithioate 167. 2-Acetyl-2-phenylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride 168. 2-Acetyl-2-(o-tolyl)ethyl dimethyldithiocarbamate 169. 2-Acetyl-2-(m-tolyl)ethyl diethyldithiocarbamate 170. 2-Acetyl-2-(p-tolyl)ethyl dimethyldithiocarbamate 171. 2-Acetyl-2-(p-methoxyphenyl)ethyl dimethyldithiocarbamate 172. 2-Acetyl-2-(o-chlorophenyl)ethyl dimethyldithiocarbamate 173. 2-Acetyl-2-(p-hydroxyphenyl)ethyl dimethyldithiocarbamate 174. 1-Methylacetonyl dimethyldithiocarbamate 175. 1-Methylacetonyl diethyldithiocarbamate 176. 1-Decylacetonyl diethyldithiocarbamate 177. 1-Isopropylacetonyl dimethyldithiocarbamate 178. 1-Cyclohexylacetonyl dimethyldithiocarbamate 179. 1-Benzylacetonyl diethyldithiocarbamate 180. 1-Vinylacetonyl 1-piperidinecarbodithioate 181. 1-Ethynylacetonyl dimethyldithiocarbamate 182. 1-Phenylacetonyl diethyldithiocarbamate 183. 4-Hydroxy-3,5-dimethylbenzyl dimethyldithiocarbamate 184. 4-Hydroxy-3,5-dimethylbenzyl n-butylmethyldithiocarbamate 185. 4-Hydroxy-3,5-dimethylbenzyl cyclohexylmethyldithiocarbamate 186. 4-Hydroxy-3,5-dimethylbenzyl benzylmethyldithiocarbamate 187. 4-Hydroxy-3,5-dimethylbenzyl 1-pyrrolidinecarbodithioate 188. 4-Hydroxy-3,5-dimethylbenzyl 2-carboxy-1-pyrrolidinecarbodithioate 189. 4-Hydroxy-3,5-dimethylbenzyl 2-carboxy-1-pyrrolidinecarbodithioate sodium salt 190. 4-Hydroxy-3,5-dimethylbenzyl 2-methoxycarbonyl-1-pyrrolidinecarbodithioate 191. 4-Hydroxy-3,5-dimethylbenzyl 2-benzyloxycarbonyl-1-pyrrolidinecarbodithioate 192. 4-Hydroxy-3,5-dimethylbenzyl 1-piperidinecarbodithioate 193. 4-Hydroxy-3,5-dimethylbenzyl 3-oxazolidinecarbodithioate 194. 4-Hydroxy-3,5-dimethylbenzyl 4-morpholinecarbodithioate 195. 4-Hydroxy-3,5-dimethylbenzyl 4-methyl-1-piperazinecarbodithioate 196. 4-Hydroxy-3,5-dimethylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 197. 2-Hydroxy-3,5-dimethylbenzyl dimethyldithiocarbamate 198. 2-Hydroxy-3,5-dimethylbenzyl diethyldithiocarbamate 199. 2-Hydroxy-3,5-dimethylbenzyl diethyldithiocarbamate 200. 2-Hydroxy-3,5-dimethylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 201. 4-Hydroxy-2-isopropyl-5-methylbenzyl dimethyldithiocarbamate 202. 4-Hydroxy-2-isopropyl-5-methylbenzyl diethyldithyldithiocarbamate 203. 4-Hydroxy-2-isopropyl-5-methylbenzyl 1-piperidinecarbodithioate 204. 4-Hydroxy-2-isopropyl-5-methylbenzyl 4-morpholinecarbodithioate 205. 4-Hydroxy-2-isopropyl-5-methylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 206. 4-Hydroxy-3-t-butyl-5-methylbenzyl dimethyldithiocarbamate 207. 4-Hydroxy-3-t-butyl-5-methylbenzyl 1-piperidinecarbodithioate 208. 4-Hydroxy-3-t-butyl-5-methylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 209. 4-Hydroxy-3,5-di-isopropylbenzyl dimethyldithiocarbamate 210. 4-Hydroxy-3,5-di-isopropylbenzyl 4-morpholinecarbodithioate 211. 4-Hydroxy-3,5-di-t-butylbenzyl dimethyldithio carbamate 212. 4-Hydroxy-3,5-di-t-butylbenzyl diethyldithiocarbamate 213. 4-Hydroxy-3,5-di-t-butylbenzyl n-butylmethyldithiocarbamate 214. 4-Hydroxy-3,5-di-t-butylbenzyl di-ni-propyldithiocarbamate 215. 4-Hydroxy-3,5di-t-butylbenzyl di-n-butyldithiocarbamate 216. 4-Hydroxy-3,5-di-t-butylbenzyl cyclohexylmethyldithiocarbamate 217. 4-Hydroxy-3,5-di-t-butylbenzly benzylmethyldithiocarbamate 218. 4-Hydroxy-3,5-di-t-butylbenzyl 1-piperidinecarbodithioate 219. 4-Hydroxy-3,5-di-t-butylbenzyl 4-morpholinecarbodithioate 220. 4-Hydroxy-3,5-di-t-butylbenzyl 1-hexamethyleneiminecarbodithioate 221. 4-Hydroxy-3,5-di-t-butylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 222. 4-Hydroxy-3,5-di-t-butyl-.alpha.-methylbenzyl dimethyldithiocarbamate 223. 4-Hydroxy-3,5-di-t-butyl-.alpha.-cyclohexylbenzyl dimethyldithiocarbamate 224. 4-Hydroxy-3,5-di-t-butyl-.alpha.- phenylbenzyl dimethyldithiocarbamate 225. 4-Hydroxy-3,5-di-t-butyl-.alpha.-phenylbenzyl 1-piperidinecarbodithioate 226. 4-Hydroxy-3,5-di-t-butyl-.alpha.-phenylbenzyl 4-methyl-1-piperazinecarbondithioate hydrochloride 227. 2-Hydroxy-3,5-di-t-butylbenzyl dimethyldithiocarbamate 228. 4-Hydroxy-3,5-dimethoxybenzyl dimethyldithiocarbamate 229. 4-Hydroxy-3,5-dimethoxybenzyl 1-piperidinecarbodithioate 230. 4-Hydroxy-3,5-dimethoxybenzyl 4-morpholinecarbodithioate 231. 4-Hydroxy-3,5-dimethoxybenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 232. 4-Hydroxy-3,5-dichlorobenzyl dimethyldithiocarbamate 233. 4-Hydroxy-3,5-dichlorobenzyl diethyldithiocarbamate 234. 4-Hydroxy-3,5-dichlorobenzyl 1-piperidinecarbodithioate 235. 4-Hydroxy-3,5-dichlorobenzyl 4-morpholinecarbodithioate 236. 4-Hydroxy-3-dimethylaminomethyl-5-methylbenzyl dimethyldithiocarbamate 237. 4-Hydroxy-3-(methyl-1-piperazinomethyl)-5-methylbenzyl 4-methyl-1-piperazinecarbodithioate dihydrochloride 238. 4-Hydroxy-3-dimethylaminomethyl5-n-propylbenzyl dimethyldithiocarbamate hydrochloride 239. 4-Hydroxy-3-(;b 4-methyl-1-piperazinomethyl)-5-n-propylbenzyl 4-metyl-1-piperazinecarbodithioate dihydrochloride 240. 4-Hydroxy-3-dimethylaminomethyl-5-sec-butylbenzyl dimethyldithiocarbamate hydrochloride 241. 4-Hydroxy-3-dimethylaminomethyl-5-t-butylbenzyl diethyldithiocarbamate 242. 2-Hydroxy-3-methoxy-5-hydroxymethylbenzyl diethyldithiocarbamate 243. 2-Hydroxy-3-methoxy-5-hydroxymetylbenzyl 1-piperidinecarbodithioate 244. 2-Hydroxy-3-methoxy-5-hydroxymethylbenzyl 4-morpholinecarbodithioate 245. 2-Hydroxy-3-methoxy-5-hydroxymethylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 246. 2-Hydroxy-3-methoxy-5-propenylbenzyl diethyldithiocarbamate 247. 4-Hydroxy-5-dimethylthiocarbamoylthiomethyl-2-methylbenzyl dimethyldithiocarbamate 248. 4-Hydroxy-5-dimethylthiocarbamoylthiomethyl-3-n-propylbenzyl dimethyldithiocarbamate 249. 4-Hydroxy-5-(4-methyl-1-piperazinethiocarbonylthiomethyl)-3-n-propylbenzyl 4-methyl-1-piperazinecarbodithioate dihydrochloride 250. 4-Hydroxy-5-dimethylthiocarbamoylthiomethyl-3-sec-butylbenzyl dimethyldithiocarbamate 251. 2-Hydroxy-5-dimethylthiocarbamoylthiomethyl-3-t-butylbenzyl dimethyldithiocarbamate 252. 2-Hydroxy-5-(1-piperidinethiocarbonylthiomethyl)-3-t-butylbenzyl 1-piperidinecarbodithioate 253. 2-Hydroxy-5-(4-methyl-1-piperzonethiocarbonylthiomethyl)-3-t-butylbenzyl 4-methyl-1-piperazinecarbodithioate dihydrochloride 254. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl dimethyldithiocarbamate 255. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl diethyldithiocarbamate 256. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl n-butylmethyldithiocarbamate 257. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl benzylmethyldithiocarbamate 258. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-1-pyrrolidinecarbodithioate 259. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-2-methoxycarbonyl-1-pyrrolidinecarbodithioate 260. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran6-ylmethyl-2-carboxy-1-pyrrolidinecarbodithioate sodium salt 261. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-1-piperidinecarbodithioate 262. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-4-morpholinecarbodithioate 263. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-4-methyl-1-piperazinecarbodithioate 264. 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-4-methyl-1-piperazinecarbodithioate hydrochloride 265. 16-Dimethylthiocarbamoylthiomethylsiccanin 266. 16-Diethylthiocarbamoylthiomethylsiccanin 267. 16-n-Butylmethylthiocarbamoylthiomethylsiccanin 268. 16-Cyclohexylmethylthiocarbamoylthiomethylsiccanin 269. 16-(1-Pyrrolidinethiocarbonylthiomethyl)siccanin 270. 16-(1-Piperidinethiocarbonylthiomethyl)siccanin 271. 16-(4-Morpholinethiocarbonylthiomethyl)siccanin 272. 16-(4-Methyl-1-piperazinethiocarbonylthiomethyl)-siccanin 273. 16-(4-Methyl-1-piperazinethiocarbonylthiomethyl)siccanin hydrochloride 274. 4-Hydroxy-2,3-dimethyl-5-t-butylbenzyl dimethyldithiocarbamate 275. 4-Hydroxy-2,3-dimethyl-5-t-butylbenzyl diethyldithiocarbamate 276. 4-Hydroxy-2,3-dimethyl-5-t-butylbenzyl 4-morpholinecarbodithioate 277. 4-Hydroxy-2,5-dimethyl-3-dimethylthiocarbamoylthiomethylbenzyl dimethyldithiocarbamate 278. 4-Hydroxy-2,5-dimethyl-3-dimethylaminomethylbenzyl dimethyldithiocarbamate 279. 4-Hydroxy-2,5-dimethyl-3-diethylthiocarbamoylthiomethylbenzyl diethyldithiocarbamate 280. 4-Hydroxy-2,5-dimethyl-3-(4-moropholinothiocarbonylthiomethyl)benzyl 4-morpholinecarbodithioate 281. 4-Hydroxy-5,6-dimethyl-3-dimethylaminomethylbenzyl dimethyldithiocarbamate hydrochloride 282. 4-Hydroxy-5,6-dimethyl-3-diethylthiocarbamoylthiomethylbenzyl diethyldithiocarbamate 283. 4-Hydroxy-5,6-dimethyl-3-(4-methyl-1-piperazinothiocarbonylthiomethyl)benzyl 4-methyl-1-piperazinocarbodithioate dihydrochloride 284. 4-Hydroxy-2,3,5,6-tetramethylbenzyl dimethyldithiocarbamate 285. 4-Hydroxy-2,3,5,6-tetramethylbenzyl diethyldithiocarbamate 286. 4-Hydroxy-2,3,5,6-tetramethylbenzyl 1-piperidinecarbodithioate 287. 4-Hydroxy-2,3,5,6-tetramethylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride 288. 4-Hydroxy-2,3,5,6-tetramethylbenzyl 4-morpholinecarbodithioate 289. 4-Chloro-2-dimethylthiocarbamoylthiomethyl-1-naphthol 290. 4-Chloro-2-diethylthiocarbamoylthiomethyl-1-naphthol 291. 4-Chloro-2-(1-piperidinothiocarbonylthiomethyl)-1-naphthol 292. 3-Chloro-2-(4-methyl-1-piperazinothiocarbonylthiomethyl)-1-naphthol hydrochloride 293. 2,4-Bis(dimethylthiocarbamoylthiomethyl-1-naphthol 294. 2,4-Bis(diethylthiocarbamoylthiomethyl)-1-naphthol 295. 2,4-Bis(4-methyl-1-piperazinothiocarbonylthiomethyl)-1-naphthol 296. 1-Dimethylthiocarbamoylthiomethyl-2-naphthol 297. 1-Diethylthiocarbamoylthiomethyl-2-naphthol 298. 1-(4-Methyl-1-piperazinothiocarbonylthiomethyl)-2-naphthol 299. 2-(1-Piperidinothiocarbonylthiomethyl)-1-naphthol 300. 2,4-Bis(4-moropholinothiocarbonylthiomethyl)-1-naphthol 301. 1-(1-Piperidinothiocarbonylthiomethyl)-2-naphthol 302. 1-(4-Morpholinothiocarbonylthiomethyl)-2-naphthol Of the above-listed compounds, there are mentioned the following compounds as a preferable group in view of their activities. Compound Nos. 1, 2, 3, 5, 6, 7, 9, 12, 23, 24, 30, 31, 34, 42, 55, 56, 57, 61, 69, 78, 79, 80, 81, 82, 88, 89, 91, 92, 93, 99, 101, 104, 108, 123, 125, 129, 134, 135, 142, 146, 147, 148, 149, 152, 156, 164, 176, 178, 183, 187, 192, 197, 198, 199, 202, 207, 210, 211, 218, 219, 225, 229, 232, 236, 238, 240, 241, 242, 246, 248, 250, 251, 254, 255, 265, 266, 272. The most preferable group of the above-listed compounds are as shown below. Compound Nos. 1, 2, 3, 5, 6, 7, 9, 12, 23, 24, 30, 31, 34, 42, 55, 56, 57, 69, 78, 79, 80, 81, 82, 88, 89, 91, 92, 93, 99, 101, 104, 108, 123, 125, 129, 134, 135, 142, 147, 148, 149, 152, 156, 164, 176, 178, 183, 202, 207, 219, 232, 236, 238, 242, 248, 250, 251, 255, 266. Of the above-listed compounds, some of them, manely those having Compound Nos. 21, 22, 23, 24, 33, 34, 78, 94, 95, 174, 175, 183, 192, 194, 197, 207, 211, 212, 218, 219, 225, 227, 229, 236, 238, 240, 241, 248, 250, 251, 274, 277, 278, 284 are known as such, but other derivatives are new substances. The dithiocarbamic acid derivatives of the present invention represented by the formula (I) can be prepared by either of the following methods. Process A: A method according to the procedures described in Archiv der pharmazie, 304, 649 (1971). Starting material ##STR28## (R.sub.1, R.sub.2 and R.sub.3 have the same meanings as above), which is synthesized in a conventional manner by Mannich's reaction, is subjected to reaction with a slight excess of carbon disulfide at a temperature of from room temperature to reflux temperature for 0.5 to 20 hours. After cooling, the desired compound ##STR29## in many cases precipitates. The precipitate is collected by decantation or by filtration and purified by recrystallization from a suitable solvent or by silica gel chromatography. Alternatively, the desired compound may be recovered and purified by removing the solvent, dissolving the residue in benzene and washing the resulting solution successively with a mineral acid and water. The solution is dried over anhydrous sodium sulfate and, if necessary, decolorized with Florisil (trade name of silica gel available from Floridin Co., Ltd,. U.S.A.) and then the solvent is distilled off to give the desired compound (I) as a viscous oil or crystalline substance in a substantially pure state. In case the starting material is synthesized from an unsymmetric ketone, the material is a mixture of straight-chain and branched isomers. At this time, each of the desired compounds can be obtained from the said mixture by separating each of the isomers and then subjecting each to reaction with carbon disulfide or by treating the mixture as shown below, the treatment being based on the difference of the reaction rate of the isomers with carbon disulfide. The isomeric mixture (which is previously the approximate ratio of the isomers by thin layer chromatography and nuclear magnetic resonance absorpiton) is dissolved in alcohol. About 1/3-1/2 of the theoretical amount of carbon disulfide is added thereto and the mixture is subjected to reaction under boiling for about 1-3 hours. The alcohol is removed and the residue is dissolved in benzene, washed with a diluted mineral acid. After washing with water, the benezene layer is dried over anhydrous sodium sulfate and, if necessary, decolorized with Florisil. Thereafter, benzene is removed by evaporation to give a pure straight-chain-type dithiocarbamate. (For example, compound No. 98-107, 113-116, 119-131). The diluted acid washing is made basic and extracted with benzene. After dissolving the extract in alcohol, the theoretical amount of carbon disulfide is added and the mixture is boiled for 3-10 hours. After removing alcohol by evaporation, the residue is dissolved in benzene, and washed with diluted mineral acid and subsequently with water. The benzene layer is dried over anhydrous sodium sulfate and, if necessary, decolorized with Florisil. After removing benzene by evaporation, almost pure branched-type dithiocarbamate (For example, Compound No. 147-173) is obtained. Process B: A method according to the procedure described in Chem. Ber., 106, 1483 (1973) or in J. Indian Chem. Soc., 51, 440 (1974). A compound ##STR30## (wherein R.sub.1 and R.sub.2 have the same meanings as above) and a compound R.sub.3 --X.sub.1 (R.sub.3 is the same as described above and X.sub.1 represents a halogen atom) are subjected to reaction at a temperature of from room temperature to boiling temperature for 3-7 hours in a suitable solvent such as dioxane, ethanol, aqueous ethanol, etc. After removing the solvent, the residue is extracted with benzene, washed with water and dried over anhydrous sodium sulfate. The solvent is removed by evaporation to give the desired compound as an almost pure viscous oil or crystalline substance. According to the above Process A or B, the following compounds were synthesized. In case the compound is a viscous oil, its property is shown by a R.sub.f value. The characterization by chromatography was conducted by using Eastman-chromatogram-sheet-silica gel No 6060 and by developing the chromatogram by 6 cm. As the developing solvents, 1 benzene-ethyl acetate (1:1), 2 benzene and 3 n-hexane-benzene (4:1) were used. The R.sub.f value of each case was shown at 1, 2 or 3, respectively. 2-Oxocyclopentylmethyl dimethyldithiocarbamate mp: 68.degree.-72.degree. C 2-oxocyclopentylmethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.80, 2 0.45 2-Oxocyclopentylmethyl 4-morpholinecarbodithioate mp: 46.degree.-52.degree. C 2-oxocyclohexylmethyl demethyldithiocarbamate viscous oil, R.sub.f :1 0.75, 2 0.50 2-Oxocyclohexylmethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.80 2 0.55 2-Oxocyclohexylmethyl n-butylmethyldithiocarbamate viscous oil, R.sub.f :1 0.90, 2 0.48 2-Oxocyclohexylmethyl 1-piperidinecarbodithioate mp: 32.degree. C 2-oxocyclohexylmethyl 4-morpholinecarbodithioate mp: 94.5.degree.-98.degree. C 2,4,4-trimethyl-6-oxocyclohexylmethyl 1-piperidinecarbodithioate mp: 78.degree.-82.degree. C 2,4,4-trimethyl-6-oxocyclohexylmethyl 4-morpholinecarbodithioate mp: 90.degree.-92.degree. C 3-isopropyl-6-methyl-2-oxocyclohexylmethyl dimethyldithiocarbamate viscous oil, R.sub.f :1 0.78, 2 0.59 Phenacyl dimethyldithiocarbamate mp: 108.degree.-110.degree. C Phenacyl diethyldithiocarbamate mp: 110.degree.-102.degree. C 2-benzoylethyl dimethyldithiocarbamate mp: 45.degree.-47.degree. C 2-benzoylethyl diethyldithiocarbamate mp: 35.degree.-37.degree. C 2-benzoylethyl n-butylmethyldithiocarbamate viscous oil, R.sub.f : 1 0.85, 2 0.64 2-Benzoylethyl cyclohexylmethyldithiocarbamate viscous oil, R.sub.f :1 0.83, 2 0.64 2-Benzoylethyl benzylmethyldithiocarbamate mp: 58.degree.-61.degree. C 2-benzoylethyl 1-pyrrolidinecarbodithioate mp: 103.degree.-104.degree. C 2-benzoylethyl 4-morpholinecarbodithioate mp: 105.degree.-106.degree. C 2-benzoylethyl 4-methyl-1-piperazinecarbodithioate mp: 86.5.degree.-87.5.degree. C 2-benzoylethyl 4-methyl-1-piperazinecarbodithioate hydrochloride mp: 144.degree.-145.degree. C (decomp.) 2-Benzoylethyl L-2-methoxycarbonyl-1-pyrrolidinecarbodithioate viscous oil, R.sub.f :1 0.79, 2 0.48 2-Benzoylethyl L-2-benzyloxycarbonyl-1-pyrrolidinecarbodithioate mp: 57.degree.-58.degree. C Sodium salt of 2-benzoylethyl L-2-carboxy-1-pyrrolidinecarbodithioate mp: 110.degree.-114.degree. C 2-(.beta.-naphthoyl) ethyl dimethyldithiocarbamate mp: 94.degree.-96.degree. C 2-(.alpha.-naphthoyl)ethyl dimethyldithiocarbamate mp: 83.degree.-88.degree. C 2-(o-Hydroxybenzoly)ethyl dimethyldithiocarbamate mp: 132.degree.-133.degree. C 2-(o-Hydroxybenzoyl)ethyl 4-morpholinecarbodithioate mp: 123.degree.-124.degree. C 2-(p-Hydroxybenzoyl)ethyl 4-morpholinecarbodithioate mp: 155.degree.-157.degree. C 2-(p-Methoxybenzoyl)ethyl 1-pyrrolidinecarbodithioate mp: 102.degree.-104.degree. C 2-(p-Methoxybenzoyl)ethyl 4-morpholinecarbodithioate mp: 126.degree.-127.degree. C 2-(p-Chlorobenzoyl)ethyl 4-morpholinecarbodithioate mp: 124.5;20 -125.5.degree. C 2-(p-Bromobenzoyl)ethyl 4-morpholinecarbodithioate mp: 122.degree.-123.degree. C 2-(3,4-dichlorobenzoyl)ethyl dimethyldithiocarbamate mp: 104.degree.-106.degree. C 2-(3,4-dichlorobenzoyl)ethyl 4-moropholinecarbodithioate mp: 131.5.degree.-132.5.degree. C 2-(p-Toluoyl)ethyl dimethyldithiocarbamate mp: 104.degree.-106.degree. C 2-(m-Toluoyl)ethyl dimethyldithiocarbamate mp: 41.degree.-43.degree. C 2-(o-Toluoyl)ethyl dimethyldithiocarbamate mp: 58.degree.-62.degree. C 2-(o-Nitrobenzoyl)ethyl 4-morpholinecarbodithioate mp: 101.degree.-102.degree. C 2-(m-Nitrobenzoyl)ethyl 4-morpholinecarbodithioate mp: 106.degree.-108.degree. C 2- (p-Nitrobenzoyl)ethyl 4-morpholinecarbodithioate mp: 135.degree.-136.degree. C 2-(2-furoyl)ethyl 4-morpholinecarbodithioate mp: 127.degree.-128.degree. C 2-(2-thenoyl)ethyl 4-morpholinecarbodithioate mp: 106.degree.-107.degree. C 2-nicotinoylethyl dimethyldithiocarbamate mp: 88.degree.-89.degree. C 2-acetylethyl dimethyldithiocarbamate viscous oil, R.sub.f :1 0.78 2 0.43 2-Acetylethyl diethyldithiocarbamate viscous oil, R.sub.f :1 0.83 2 0.63 2-Acetylethyl butylmethyldithiocarbamate viscous oil, R.sub.f :1 0.83 2 0.63 2-Acetylethyl cyclohexylmethyldithiocarbamate viscous oil, R.sub.f :1 0.88 2 0.62 2-Acetylethyl benzylmethyldithiocarbamate viscous oil, R.sub.f :1 0.83 2 0.58 2-Acetylethyl 2-carboxy-1-pyrrolidinecarbodithioate mp: 118.degree.-120.degree. C sodium salt of 2-acetylethyl 2-carboxy-1-pyrroldinecarbodithioate mp: 80.degree.-130.degree.C (decomp.) 2-Acetylethyl 2-benzyloxycarbonyl-1- pyrrolidinecarbodithioate viscous oil, R.sub.f : 1 0.83 2 0.32 2-Acetylethyl 1-piperidinecarbodithioate viscous oil, R.sub.f :1 0.78 2 0.47 2-Acetylethyl 1-hexamethyleneiminecarbodithioate viscous oil, R.sub.f : 1 0.83 2 0.59 2-Acetylethyl 4-morpholinecarbodithioate viscous oil, R.sub.f : 1 0.75 2 0.26 2-Acetylethyl 1-methyl-4-piperazinecarbodithioate viscous oil, R.sub.f : 1 0.37 2 0.08 2-Acetylethyl 1-methyl-4-piperazinecarbodithioate hydrochloride mp: 130.degree.-132.degree. C Acetonyl dimethyldithiocarbamate mp: 55.degree.-56.degree. C Acetonyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.70 2 0.57 2-Propionylethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.84 2 0.63 2-Propionylethyl 4-morpholinecarbodithioate viscous oil, R.sub.f : 1 0.87 2 0.30 2-Isobutyrylethyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.87 2 0.60 2-Pivaroylethyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.83 2 0.63 2-Lauroylethyl dimethyldithiocarbamate mp: 47.degree.-48.degree. C 2-hydrocinnamoylethyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.83 2 0.57 2-(p-Methoxyhydrocinnamoyl)ethyl diethyldithiocarbamate viscous oil R.sub.f : 1 0.83 2 0.52 2-Cinnamoylethyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.80 2 0.58 2-(p-Methoxycinnamoyl)ethyl diethyldithiocarbamate mp: 76.degree.-79.degree. C 2-[.beta.-(2,6,6-trimethylcyclohexene-1-yl)acryloyl]ethyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.90 2 0.49 2-Acetylpropyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.79 2 0.40 2-Acetylpropyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.87 2 0.59 2-Acetylpropyl 1-piperidinecarbodithioate viscous oil, R.sub.f : 1 0.81 2 0.41 2-Acetyldodecyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.87 2 0.64 2-Acetyl-2-benzylethyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.79 2 0.58 2-Acetyl-2-(p-anisyl)ethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.81 2 0.48 2-Acetyl-2-phenylethyl dimethyldithiocarbamate mp: 88.degree.-89.degree. C 1-methylacetonyl dimethyldithiocarbamate viscous oil, R.sub.f : 1 0.80 2 0.58 1-Methylacetonyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.84 2 0.67 2-Cinnamoylethyl diethyldithiocarbamate mp: 40.degree.-45.degree. C 2-(o-Hydroxyhydrocinnamoyl)ethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.81 2 0.35 2-(p-Methylhydrocinnamoyl)ethyl diethyldithiocarbamate viscous oil, R.sub.f 1 0.86 2 0.66 2-(o-Hydroxycinnamoyl)ethyl diethyldithiocarbamate mp: 120.degree.-121.degree. C 2-(p-Methylcinnoamoyl)ethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.81 2 0.58 2-Acetyl-2-salicylethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.81 2 0.23 2Acetyl-2-(p-methylbenzyl)ethyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.89 2 0.67 1-Phenylacetonyl diethyldithiocarbamate viscous oil, R.sub.f : 1 0.82 2 0.57 4-Hydroxy-3,5-dimethylbenzyl dimethyldithiocarbamate mp: 93.degree.-94.degree. C 4-hydroxy-3,5-dimethylbenzyl 1-pyrrolidinecarbodithioate mp: 153.degree.-155.degree. C 4-hydroxy-3,5-dimethylbenzyl 2-benzyloxycarbonyl-1-pyrrolidinecarbodithioate viscous oil, R.sub.f : 1 0.77 2 0.38 4-Hydroxy-3,5-dimethylbenzyl 1-piperidinecarbodithioate mp: 108.degree.-109.degree. C 4-hydroxy-3,5-dimethylbenzyl 4-morpholinecarbodithioate mp: 125.degree.-127.degree. C 4-hydroxy-3,5-dimethylbenzyl 4-methyl-1-piperazinecarbodithioate hydrochloride mp: 174.degree.-176.degree. C (decomp.) 2-Hydroxy-3,5-dimethylbenzyl dimethyldithiocarbamate mp: 121.degree.-123.degree. C 2-hydroxy-3,5-dimethylbenzyl diethyldithiocarbamate mp: 79.degree.-81.degree. C 2-hydroxy-3,5-dimethylbenzyl 1-piperidinocarbodithioate mp: 115.degree.-118.degree. C 4-hydroxy-2-isopropyl-5-methylbenzyl diethyldithiocarbamate mp: 71.degree.-73.degree. C 4-hydroxy-2-isopropyl-5-methylbenzyl 4-morpholinecarbodithioate mp: 139.degree.-141.degree. C 4-hydroxy-3-t-butyl-5-methylbenzyl 1-piperidinecarbodithioate mp: 103.degree.-105.degree. C 4-hydroxy-3,5-di-isopropylbenzyl 4-morpholinecarbodithioate mp: 116.5.degree.-118.5.degree. C 4-hydroxy-3,5-di-t-butylbenzyl dimethyldithiocarbamate mp: 139.degree.-141.degree. C 4-hydroxy-3,5-di-t-butylbenzyl diethyldithiocarbamate viscous oil, R.sub.f : 2 0.83 4-Hydroxy-3,5-di-t-butylbenzyl n-butylmethylditiocarbamate viscous oil, R.sub.f : 3 0.23 4-Hydroxy-3,5-di-t-butylbenzyl di-n-propyldithiocarbamate viscous oil, R.sub.f : 3 0.40 4-Hydroxy-3,5-di-t-butylbenzyl di-n-butyldithiocarbamate viscous oil, R.sub.f : 3 0.47 4-Hydroxy-3,5-di-t-butylbenzyl cyclohexylmethyldithiocarbamate viscous oil, R.sub.f : 3 0.30 4-Hydroxy-3,5-di-t-butylbenzyl benzylmethyldithiocarbamate mp: 103.degree.-107.degree. C 4-hydroxy-3,5-di-t-butylbenzyl 1-piperidinecarbodithioate mp: 109.5.degree.-110.5.degree. C 4-hydroxy-3,5-di-t-butylbenzyl 4-morpholinecarbodithioate mp: 114.degree.-115.degree. C 4-hydroxy-3,5-di-t-butylbenzyl 1-hexamethyleneiminecarbodithioate viscous oil, R.sub.f : 1 0.89 2 0.83 4-Hydroxy-3,5-di-t-butyl-.alpha.-phenylbenzyl 1-piperidinecarbodithioate mp: 112.degree.-114.degree. C 2-hydroxy-3,5-di-t-butylbenzyl dimethyldithiocarbamate mp: 193.degree.-195.degree. C 4-hydroxy-3,5-dimethoxybenzyl 1-piperidinecarbodithioate mp: 99.degree.-98.degree. C 4-hydroxy-3,5-dimethoxybenzyl 4-morpholinecarbodithioate mp: 132.degree.-134.degree. C 4-hydroxy-3,5-dichlorobenzyl dimethyldithiocarbamate mp: 134.degree.-136.degree. C 4-hydroxy-3,5-dichlorobenzyl 1-piperidinecarbodithioate mp: 177.degree.-178.degree. C (decomp.) 4-Hydroxy-3,5-dichlorobenzyl 4-morpholinecarbodithioate mp: 156.degree.-157.degree. C 4-hydroxy-3-dimethylaminomethyl-5-methylbenzyl dimethyldithiocarbamate mp: 98.degree.-101.degree. C 4-hydroxy-3-dimethylaminomethyl-5-n-propylbenzyl dimethyldithiocarbamate hydrochloride mp: 133.degree.-135.degree. C 4-hydroxy-3-dimethylaminomethyl-5-sec-butylbenzyl dimethyldithiocarbamate hydrochloride mp: 148.degree.-149.degree. C 4-hydroxy-3-dimethylaminomethyl-5-t-butylbenzyl dimethyldithiocarbamate hydrochloride mp: 223.degree.-224.degree. C 2-hydroxy-3-methoxy-5-hydroxymethylbenzyl diethyldithiocarbamate mp: 108.degree.-110.degree. C 2-hydroxy-3-methoxy-5-hydroxymethylbenzyl 4-morpholinecarbodithioate mp: 140.degree.-142.degree. C 2-hydroxy-3-methoxy-5-propenylbenzyl diethyldithiocarbamate mp: 98.5.degree.-100.5.degree. C 4-hydroxy-5-dimethylthiocarbamoylthiomethyl-2-methylbenzyl dimethyldithiocarbamate mp: 140.degree.-143.degree. C 4-hydroxy-5-dimethylthiocarbamoylthiomethyl-3-n-propylbenzyl dimethyldithiocarbamate mp: 97.degree.-98.degree. C 4-hydroxy-5-dimethylthiocarbamoylthiomethyl-3-sec-butylbenzyl dimethyldithiocarbamate mp: 140.degree.-142.degree. C 2-hydroxy-5-dimethylthiocarbamoylthiomethyl-3-t-butylbenzyl dimethyldithiocarbamate mp: 135.degree.-137.degree. C 5-hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl dimethyldithiocarbamate mp: 148.degree.-149.degree. C (decomp.) 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl diethyldithiocarbamate mp: 109.degree.-111.degree. C (decomp.) 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-1-pyrrolidinecarbodithioate mp: 167.5.degree.-168.5.degree. C (decomp.) 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-yimethyl-1-piperidinecarbodithioate mp: 158.degree.-158.5.degree. C (decomp.) 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-4-morpholinecarbodithioate mp: 141.degree.-142.degree. C (decomp.) 5-Hydroxy-2-hydroxymethyl-4-oxo-4H-pyran-6-ylmethyl-4-methyl-1-piperazinecarbodithioate mp: 166.degree.-167.degree. C (decomp.) 16-Dimethylthiocarbamoylthiomethylsiccanin mp: 216.degree.-218.degree. C (decomp.) 16-Diethylthiocarbamoylthiomethylsiccanin mp: 202.degree.-203.degree. C (decomp.) 16-(1-Pyrrolidinethiocarbonylthiomethyl)siccanin mp: 227.degree.-229.degree. C 16-(4-morpholinethiocarbonylthiomethyl)siccanin mp: 178.degree.-179.degree. 16-(4-Methyl-1-piperazinethiocarbonylthiomethyl)siccanin mp: 155.degree.-156.degree. C 16-(4-methyl-1-piperazinethiocarbonylthiomethyl)siccanin hydrochloride mp: 150.degree.-160.degree. C 4-hydroxy-2,5-dimethyl-3-dimethylthiocarbamoylthiomethylbenzyl dimethyldithiocarbamate mp: 163.degree.-165.degree. C 4-hydroxy-2,5-dimethyl-3-dimethylaminomethylbenzyl dimethyldithiocarbamate mp: 143.degree.-145.degree. C 4-hydroxy-5,6-dimethyl-3-dimethylaminomethylbenzyl dimethyldithiocarbamate hydrochloride mp: 139.degree.-141.degree. C 4-hydroxy-2,3,5,6-tetramethylbenzyl dimethyldithiocarbamate mp: 177.degree.-178.degree. C 4-chloro-2-(1-piperidinothiocarbonylthiomethyl)-1-naphthol mp: 115.degree.-116.degree. C 2-(1-piperidinothiocarbonylthiomethyl)-1-naphthol viscous oil, R.sub.f : 2 0.67 2,4-Bis(4-morpholinothiocarbonylthiomethyl)-1-naphthol mp: 158.degree.-159.degree. C 1-(1-piperidinothiocarbonylthiomethyl)-2-naphthol mp: 130.degree.-134.degree. C 1-(4-morpholinothiocarbonylthiomethyl)-2-naphthol mp: 123.degree.-124.degree. C According to one aspect of this invention, there is provided a preventive and curative composition against mycoplasmosis which comprises as an active ingredient the dithiocarbamic acid derivative (I) and an inert carrier. The term "inert carrier" as used herein means one that is substantially non-reactive with the active ingredient, orally ingestable and tolerated by the poultry and domestic animals. Representative examples of the carriers to be employed in this invention are solid oral carriers such as distillers dried grains, corn starch, potato starch, fermentation residues, ground oyster shells, Attapulgus clay, rice bran, wheat bran, wheat middling, molasses solubles, corn husks, corn meal, edible vegetable substances, soybean cake, soybean meal, antibiotic mycelis, crushed lime stone and the like. The amount of dithiocarbamic acid derivative required for control of mycoplasmosis in poultry will vary somewhat with the specific compound employed, the species of animals, the method or the object of application or with the symptoms. Generally, the dithiocarbamic acid derivatives (I) are effective in preventing the disease without undesirable side effect and toxic effect when administered at a level of more than about 0.005% by weight of the feed. For good prophylactic results, it is preferred that the feed contains between about 0.005 and 0.02% by weight of the active ingredient, more preferably between about 0.0075 and 0.01%. When the dithiocarbamic acid derivatives are to be employed for therapeutic purpose, the higher levels are used for a shorter period of time. Thus, the concentrations of about 0.01 to about 0.1% by weight, preferably 0.02 to 0.05% by weight, of the feed may be advantageously administered for treatment of mycoplasmosis. When these compounds are to be employed for therapeutic purpose, it is desirable to employ the lowest levels that exhibit anti-mycoplasmosis activities, in order to eliminate any risk of side effects that may appear on prolonged feeding. In preparing solid compositions, a uniform dispersion of the active ingredient throughout the carrier can be readily accomplished by the conventional methods of grinding, stirring or milling. Many of these dithiocarbamic acid derivatives are advantageously administered to poultry by way of the drinking water of the birds. This method of treatment may often be employed in the therapeutic use, since poultry with mycoplasmosis are apt to consume less solid feed than normal birds. According to still another aspect of this invention, novel compositions are provided in which active ingredient is present in relatively large amounts and which are suitable for addition to the poultry feed directly or after intermediate dilution step. Such compositions which are a preferred feature of this invention are the so-called feed supplements or premix. Formulations containing from about 5% to about 30% by weight, and preferably from about 10-25% by weight, of the active ingredient are particularly suitable for this purpose. It is preferable in the industry to use about 1-3 kg. of such a supplement per ton of feed. The present composition as prepared above may include other preventive and curative agents against mycoplasmosis, for example, chlorotetracycline, streptomycin, spiramycin, erythromycin, taylocin, etc., or more than one compound of the above formula (I). When two compounds of the formula (I) are synthesized as a mixture, for example, a mixture of a straight-chain and branched isomers, it is unnecessary to separate the isomers and the mixture itself can be added to a feed as a preventive and curative agent. The concentration to be administered of the preventive and curative agent against mycoplasmosis in the present invention may vary upon the species of poultry or domestic animals, the method or purpose of administration, the severity of the symptom, etc., but 20-400 ppm may be used for preventive and curative purposes in admixture with a feed. Some examples of the formulation for feed supplements according to this invention are shown below. In these examples, all parts are given by weight unless otherwise indicated. ______________________________________Formulation A Parts______________________________________Compound No. 12 25wheat bran 75Formulation B Parts______________________________________Compound No. 92 20rice bran 80Formulation C Parts______________________________________Compound No. 202 10wheat bran 60soybean meal 30______________________________________ In order to demonstrate the excellent antimicrobial activity against mycoplasmosis of the dithiocarbamic acid derivatives (I) in this invention, there are given below the two Experiments and the results therefrom. EXPERIMENT 1 ANTIMICROBIAL TEST AGAINST THREE STRAINS OF MYCOPLASMA The test was effected by a conventional agar plate dilution method using the indicated strains of mycoplasma. The dithiocarbamic acid derivatives as shown below with Compound Nos. were employed in the test. The results are summarized in Table 1. Table 1__________________________________________________________________________Minimum Inhibitory Concentration (mcg/ml) Species submittedTest to the Mycoplasma Mycoplasma Mycoplasmacompound(No.) test gallisepticum pulmonis hyorhinis__________________________________________________________________________1 0.05 0.05 0.052 0.10 0.10 0.103 0.20 0.10 0.205 0.05 0.10 0.056 0.10 0.10 0.057 0.20 0.20 0.209 0.20 0.39 0.2012 0.05 0.20 0.3923 0.05 0.025 0.0524 0.05 0.20 0.3930 0.20 0.20 0.2031 0.20 0.20 0.2034 0.05 0.05 0.0542 0.20 0.20 0.3955 0.20 0.39 0.2056 0.10 0.10 0.0557 0.10 0.20 0.1061 0.10 0.39 1.5669 0.10 0.10 0.1078 0.05 0.05 0.02579 0.012 0.012 0.01280 0.10 0.10 0.1081 0.20 0.20 0.2082 0.20 0.20 0.2088 0.05 0.05 0.02589 0.20 0.10 0.1091 0.20 0.20 0.02592 0.20 0.20 0.02593 0.10 0.10 0.0599 0.05 0.05 0.05101 0.10 0.10 0.10104 0.20 0.20 0.20108 0.20 0.20 0.20123 0.20 0.20 0.20125 0.20 0.20 0.20129 0.20 0.20 0.20134 0.20 0.20 0.20135 0.20 0.20 0.20142 0.20 0.20 0.20146 0.39 0.39 0.39147 0.05 0.05 0.05148 0.05 0.05 0.05149 0.20 0.20 0.05152 0.10 0.10 0.39156 0.20 0.20 0.20164 0.10 0.10 0.10183 0.20 0.20 0.20187 0.78 0.78 0.78191 1.56 1.56 3.13192 0.39 0.39 0.10194 1.56 1.56 0.78196 1.56 1.56 0.39197 0.39 0.39 0.20198 0.39 0.39 0.20199 0.39 0.39 0.39202 0.10 0.10 0.10207 0.10 0.10 0.10210 0.39 0.39 0.39211 0.78 0.78 0.39212 1.56 1.56 1.56218 0.78 0.39 0.39219 0.20 0.20 0.10220 0.78 0.78 0.78225 0.39 0.20 0.39229 0.39 0.39 0.39230 1.56 1.56 0.78232 0.39 0.39 0.20234 3.13 3.13 1.56235 1.56 1.56 1.56236 0.20 0.20 0.20238 0.20 0.20 0.20240 0.39 0.39 0.20241 0.78 0.39 0.39242 0.10 0.10 0.10246 0.39 0.20 0.39247 0.78 0.78 0.39248 0.10 0.10 0.20250 0.20 0.20 0.20251 0.20 0.10 0.20254 0.39 0.39 0.39255 0.05 0.10 0.05258 0.78 0.78 0.39261 3.13 3.13 3.13262 0.20 0.78 0.78263 1.56 3.13 3.13265 0.39 0.39 0.39266 0.10 0.10 0.10271 1.56 1.56 1.56272 0.39 0.39 0.39273 0.78 0.78 0.78__________________________________________________________________________ Though the sensitivity of the species to these compounds varies slightly depending upon the kind of the species, all of these compounds have a strong antimicrobial activity against mycoplasma gallisepticum which has been considered to cause the chronic respiratory disorders of chicken in particular. EXPERIMENT 2 Each of the dithiocarbamic acid derivatives as indicated below with Compound No. was added to a feed and administered orally to mice infected artificially with MRL-4 strain of mycoplasma pulmonis. The effectiveness of the treatment was evaluated. Six groups, each group consisting of ten female mice which were negative in the test for mycoplasmosis, were used. After MRL-4 strain of mycoplasma pulmonis was cultured in PPLO agar medium, the colonies of the surface of the medium were diluted with a phosphate buffer solution to prepare a solution containing about 10.sup.9 /ml of mycoplasma. 0.1 ml of the microbe-containing solution was injected intravenously to the tail of each mouse. For consecutive 10 days from the next day of the injection, the mice were fed with a powdery feed containing the active compound at respective concentrations of 0.04, 0.02, 0.01 and 0.005%, respectively. During the experiment period, all the procedures were conducted in a vinyl isolater. After one month from the starting of the experiment, the presence of arthritis was visually investigated and at the same time the presence of pneumonia was also investigated after dissection. Recovery tests of mycoplasma and general bacteria were conducted using the joints and lungs of host subjects as the testing materials. The results are summarized in Table 2. Table 2__________________________________________________________________________Curative effect of dithiocarbamic acid derivativesin mice by oral administration in feed(i)Compound No. 12 24Con-centra- Recovery of Recovery oftion of Attack rate mycoplasma Attack rate mycoplasmaagent arthritis pneumonia joint lung arthritis pneumonia joint lung__________________________________________________________________________0.04% 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/100.02 1/10 0/10 1/10 0/10 2/10 0/10 2/10 0/100.01 4/10 0/10 4/10 0/10 3/10 0/10 3/10 0/100.005 6/10 0/10 6/10 0/10 4/10 0/10 4/10 0/10Non-infected 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10controlInfectedcontrol 10/10 0/10 10/10 0/10 10/10 0/10 10/10 0/10__________________________________________________________________________(ii)Compound No. 88 79Con-centra- Recovery of Recovery oftion of Attack rate mycoplasma Attack rate mycoplasmaagent arthritis pneumonia joint lung arthritis pneumonia joint lung__________________________________________________________________________0.04% 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/100.02 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/100.01 1/10 0/10 1/10 0/10 0/10 0/10 0/10 0/100.005 3/10 0/10 3/10 0/10 2/10 0/10 2/10 0/10non-infect-ed control 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10infectedcontrol 10/10 0/10 10/10 0/10 10/10 0/10 10/10 0/10__________________________________________________________________________ As shown in Table 2, the appearance of arthritis on the mice to which the active compounds in this invention was administered is sufficiently low in comparison with that of the control groups. Microbe was entirely negative except in the joint affected by arthritis. In all of the infected non-medicated control, arthritis was observed. But, in the group to which 0.04% of each of the present compounds, arthritis was not detected. Even in the group to which 0.005% of the compounds, 70-80% was effectively treated with the present compounds.
Claims
1. A preventive and curative composition against mycoplasmosis which comprises an effective amount of an active ingredient a compound having the formula ##STR31## wherein R.sub.1 and R.sub.2 form, jointly with the nitrogen atom to which they are attached, a 6-membered heteroalicyclic ring which also contains oxygen as another hetero atom and which may be substituted with alkyl of 1 to 4 carbon atoms; and
R.sub.3 is a group --CH.sub.2 --R.sub.4 in which R.sub.4 is a 5-7 membered 2-oxocycloalkyl group optionally substituted with 1-3 C.sub.1 -C.sub.4 alkyl groups;
a group ##STR32## in which n is an integer of 1 or 2 and R.sub.5 is naphthyl group, a phenyl group optionally substituted with 1-2 groups selected from the group consisting of hydroxy, C.sub.1 -C.sub.12 alkyl, C.sub.1 -C.sub.4 alkoxy, nitro and halogen or a 5-7 membered heterocyclic group which has as hetero atom 1 or 2 atoms of oxygen atom, nitrogen atom and sulfur atoms and may be substituted with 1-3 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, hydroxy, hydroxymethyl, halogenomethyl, dihalogenomethyl, trihalogenomethyl, nitro and halogen;
a group ##STR33## in which R.sub.6 is an alkyl group of 1 to 12 carbon atoms, a 5-6 membered cycloalkyl group, an aralkyl group which has 6 or 10 carbon atoms in the aryl moiety and 1 to 4 carbon atoms in the alkyl moiety and may be substituted with C.sub.1 -C.sub.4 alkyl, hydroxy, nitro, C.sub.1 -C.sub.4 alkoxy or halogen or an alkenyl group of 2 to 5 carbon atoms which may be substituted with cycloalkenyl or phenyl, said phenyl being optionally substituted with C.sub.1 -C.sub.4 alkyl, hydroxy, nitro, C.sub.1 -C.sub.4 alkoxy or halogen and X is a group ##STR34## wherein R.sub.7 is hydrogen, C.sub.1 -C.sub.12 alkyl, cyclohexyl, aralkyl of C.sub.6 or C.sub.10 in the aryl moiety and C.sub.1 -C.sub.4 in the alkyl moiety, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.3 alkynyl or phenyl or a group ##STR35## wherein R.sub.8 is hydrogen, C.sub.1 -C.sub.12 alkyl, cyclohexyl, aralkyl of C.sub.6 or C.sub.10 in the aryl moiety and C.sub.1 -C.sub.4 in the alkyl moiety, said aryl moiety being optionally substituted with C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy or halogen, or phenyl optionally substituted with C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkoxy or halogen; or
a group ##STR36## in which R.sub.9 is hydrogen atom, an alkyl group of 1 to 4 carbon atoms, cyclohexyl group or phenyl group and R.sub.10 is a phenyl group which has one hydroxy group at the o- or p-position and 2-4 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, halogen, C.sub.1 -C.sub.4 alkoxy, C.sub.2 -C.sub.4 alkenyl, hydroxyalkyl of C.sub.1 -C.sub.4, a group ##STR37## wherein R.sub.1 and R.sub.2 are as defined above and a group ##STR38## wherein R.sub.1 and R.sub.2 are as defined above, a naphthyl group which has one hydroxy group at the 1- or 2-position and optionally halogen or a group ##STR39## wherein R.sub.1 and R.sub.2 are as defined above, a group ##STR40## or a group ##STR41## or a salt thereof and an inert carrier.
2. A composition according to claim 1 wherein
R.sub.1 and R.sub.2 form, jointly with the nitrogen atom to which they are attached, a 6-membered heteroalicyclic ring which also contains oxygen as another hetero atom and which may be substituted with alkyl of 1 to 4 carbon atoms; and R.sub.4 is a 5-6 membered 2-oxocycloalkyl group optionally substituted with 1-2 C.sub.1 -C.sub.4 alkyl groups;
n is 2 and R.sub.5 is naphthyl group, a phenyl group optionally substituted with 1-2 groups selected from the group consisting of hydroxy, C.sub.1 -C.sub.8 alkyl, nitro and halogen or a 5-6 membered heterocyclic group which has as hetero atom 1 or 2 atoms of oxygen atom and nitrogen atom;
R.sub.6 is an alkyl group of 1 to 12 carbon atoms, a phenethyl group which may be substituted with methyl, hydroxy, methoxy or halogen, an alkenyl group of 3 carbon atoms or a styryl group which may be substituted with methyl hydroxy, methoxy or halogen and X is a group ##STR42## wherein R.sub.8 is hydrogen, C.sub.1 -C.sub.12 alkyl, cyclohexyl, benzyl optionally substituted with methyl, hydroxy or methoxy or phenyl; or
R.sub.9 is hydrogen atom, methyl group cyclohexyl group or phenyl group and R.sub.10 is a phenyl group which has one hydroxy group at the o- or p-position and 2-4 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, chlorine, methoxy, propenyl, hydroxymethyl, a group ##STR43## wherein R.sub.1 and R.sub.2 are as defined above and a group ##STR44## wherein R.sub.1 and R.sub.2 are as defined above, naphthyl group, a group ##STR45## or a group ##STR46##
3. A composition according to claim 1 wherein
R.sub.1 and R.sub.2 form; jointly with the nitrogen atom to which they are attached, a 6-membered heteroalicyclic ring which also contains oxygen as another hetero atom and which may be substituted with methyl; and
R.sub.4 is a 5-6 membered 2-oxoxcycloalkyl group;
n is 2 and R.sub.5 is naphthyl group, a phenyl group optionally substituted with 1-2 groups selected from the group consisting of hydroxy, C.sub.1 -C.sub.8 alkyl, nitro and chlorine or a 5-6 membered heterocyclic group which has as hetero atom one of oxygen atom and nitrogen atom;
R.sub.6 is an alkyl group of 1 to 12 carbon atoms, a phenethyl group which may be substituted with methyl, hydroxy or methoxy or a styryl group which may be substituted with methyl, hydroxy or methoxy and X is a group ##STR47## wherein R.sub.8 is hydrogen, C.sub.1 -C.sub.12 alkyl or phenyl; or R.sub.9 is hydrogen atom or phenyl group and R.sub.10 is a phenyl group which has one hydroxy group at the o- or p-position and 2-4 groups selected from the group consisting of C.sub.1 -C.sub.4 alkyl, hydroxymethyl, a group ##STR48## wherein R.sub.1 and R.sub.2 are as defined above, and a group ##STR49## wherein R.sub.1 and R.sub.2 are as defined above, a group ##STR50## or a group ##STR51##
4. A composition according to claim 1, wherein the compound is 4-hydroxy-3,5-di-6-butylbenzyl 4-morpholinecarbodithioate.
5. A composition according to claim 1, wherein the compound is 2-oxocyclopentylmethyl 4-morpholinecarbodithioate.
6. A composition according to claim 1, wherein the compound is 2-oxocyclohexylmethyl 4-morpholinecarbodithioate.
7. A composition according to claim 1, wherein the compound is 2-(o-hydroxybenzoyl)ethyl 4-morpholinecarbodithioate.
8. A composition according to claim 1, wherein the compound is 2-(o-nitrobenzoyl)ethyl 4-morpholinecarbodithioate.
9. A composition according to claim 1, wherein the compound is 2-acetylethyl 4-morpholinecarbodithioate.
10. A composition according to claim 1, wherein the compound is 2-propionylethyl 4-morpholinecarbodithioate.
11. A composition according to claim 1, wherein the compound is 4-hydroxy-3,5-di-isopropylbenzyl 4-morpholinecarbodithioate.
12. A composition according to claim 1, wherein the compound is 4-hydroxy-3,5-di-t-butylbenzyl 4-morpholinecarbodithioate.
Priority Claims (2)
Number
Date
Country
Kind
50-69324
Jun 1975
JA
50-118580
Oct 1975
JA
Non-Patent Literature Citations (2)
Entry
kasugai et al. - Chem. Abst., vol. 80 (1974) p. 44679j.
Chem. Abst. 8th Cumulative Index (1967-1971) p. 19775s.