A MEDICINAL PRODUCT CONTAINING A RADICAL FORMING CATALYST

Description

TECHNICAL FIELD

[0001] The present invention relates to a drug.BACKGROUND ART[Background Art of the Invention]

[0002] On the other hand, owing to its high reactivity, a radical is an important chemical species that is used widely. For example, sodium chlorite (NaClO 2 ) is a non-toxic inexpensive oxidizing reagent and has been used as a precursor of a chlorine dioxide radical (ClO 2 ˙) (Non Patent Literatures 1 to 4).

[0003] Diseases caused by infection with bacteria and the like have long been problems all over the world. At present, in order to avoid infection, bacteria are removed by, for example, spraying a bactericide on the bacteria. Various types of bactericides are used today, and example thereof include chlorine dioxide. Chlorine dioxide is used in hospitals, nursing facilities, etc.

[0004] Chlorine dioxide used as a bactericide is disclosed in Patent Literature 1, for example. Patent Literature 1 describes that the bactericide is produced by providing an aqueous solution containing a chlorite such as sodium chlorite and adjusting the pH of the aqueous solution by adding a buffer thereto to stabilize the aqueous solution.

[0005] Examples of bactericides used widely in Japan include ethanol for disinfection and hypochlorous acid. For example, Patent Literature 2 describes sterilizing water in swimming pools with hypochlorous acid.

[0006] When agricultural crops are infected with bacteria or the like, inhibition of the growth of the agricultural crops, reduction of the yield of the agricultural crops, etc. are caused. Thus, infection with bacteria or the like is prevented or treated by spreading a bactericide. Also, when bacteria and the like grow in the excrement of industrial animals, a foul odor is caused. Thus, deodorization or the like is performed by spreading a bactericide.

[0007] As a bactericide for preventing the infection and growth of bacteria and the like, chlorine dioxide and hypochlorous acid are used, for example. For example, Patent Literature 1 describes that a bactericide is produced by providing an aqueous solution containing a chlorite such as sodium chlorite and adjusting the pH of the aqueous solution by adding a buffer thereto to stabilize the aqueous solution. Patent Literature 2 describes that hypochlorous acid can be used for sterilization.

[0008] Non Patent Literature 5 describes the supramolecular reaction of lauroyl peroxide with tetralkylammonium bromides.

[0009] Non Patent Literature 6 describes the development of versatile oxidation systems based on the design of oxoammonium salts.

[0010] Patent Literature 5 describes a method for adding a slime control agent consisting a mixture of a hydantoin compound, ammonium halide, a hypohalous acid salt, and an alkaline aqueous solution to liquid to be treated, wherein (A) a first liquid consisting of an aqueous solution of a hypohalous acid salt is diluted and its temperature is maintained at 5-35°C, and a second liquid consisting of ammonium halide or a mixture of ammonium halide, a hypohalous acid salt, and an alkaline aqueous solution is mixed therein without dilution to be poured into the liquid to be treated, and (B) after mixing the first liquid and second liquid, the mixture is poured before its oxidation-reduction potential becomes 850 mV or more.

[0011] Patent Literature 6 describes the provision of an easily decomposable sterilizing composition with high safety and a reduced environmental load. According to the document, when the easily decomposable sterilizing composition is to be supplied, a request for supply of a sterilizing composition is received from a person to be supplied by phone, cellular phone, or a communication means via the internet. A blended sterilizing composition with a stable and highly safe composition, a valid term, suitable concentration and amount highly activated by controlling pH, etc. determined by a computer to which selections of sterilizing compositions with life extended by freezing, chemical equilibrium, etc. to be objects of the supply and decomposition rates of the sterilizing composition by sterilizing composition conditions are preliminarily inputted is supplied to the person to be supplied and the validity is monitored and reported to the person to be supplied. The person to be supplied uses the sterilizing composition within the highly active term.Citation ListPatent Literatures

[0012] Patent Literature 1: JP 2009-100850 A Patent Literature 2: JP 2014-091063 A Patent Literature 3: JP 2008-264615 A Patent Literature 4: JP 2005-305109 A Non Patent Literatures

[0013] [Non Patent Literature 1] H. Dodgen and H. Taube, J. Am. Chem. Soc., 1949, 71, 2501-2504. [Non Patent Literature 2] J. K. Leigh, J. Rajput, and D. E. Richardson, Inorg. Chem., 2014, 53, 6715-6727. [Non Patent Literature 3] C. L. Latshaw, Tappi J., 1994, 163-166. [Non Patent Literature 4] (a) J. J. Leddy, in Riegel's Handbook of Industrial Chemistry, 8th edn. Ed., J. A. Kent, Van Nostrand Reinhold Co. Inc, New York, 1983, pp. 212-235; (b) I. Fabian, Coord. Chem. Rev., 2001, 216-217, 449-472. [Non Patent Literature 5] N. A. Turovskij, E. N. Pasternak, E. K. Raksha, N. A. Golubitskaya, I. A. Opeida, and G. E. Zaikov, Oxidation Communications, 2010, 33, 485-501. [Non Patent Literature 6] S. Masatoshi, YAKUGAKU ZASSHI, 2012, 132, 1131-1143. SUMMARY OF INVENTIONTechnical Problem[Technical Problem to be Solved by the Invention]

[0014] However, high energy is generally required for generating radicals. Thus, heating or the like to raise the temperature is required, which causes problems in cost and reaction control. On this account, it is an object of the present invention to provide a drug comprising a radical generating catalyst that can generate (produce) radicals under mild conditions.[Technical Problem to be Solved ]

[0015] Chlorine dioxide has a very high sterilizing and deodorizing ability. However, it is a highly explosive gas, and in Japan, accidental explosions of chlorine dioxide have been reported several times. An aqueous solution of chlorine dioxide also is not preferable, because the chlorine dioxide is decomposed easily owing to change in conditions such as the pH or the temperature of the aqueous solution, thereby causing an unpleasant odor, and, in some cases, adversely affecting the human body. Accordingly, bactericides using chlorine dioxide have a problem in that they lack safety and storage stability.

[0016] Ethanol exhibits a low sterilizing effect, because it volatilizes immediately after being sprayed on hands or the like for sterilization.

[0017] Further, hypochlorous acid is decomposed immediately, so that the hypochlorous acid has a problem in that, while it has a temporary sterilizing effect, it cannot exhibit a sterilizing effect stably.

[0018] With the foregoing in mind, it is an object of the present invention to provide a drug that is highly safe and has a high sterilizing effect.

[0019] While chlorine dioxide has a very high sterilizing and deodorizing ability, it is highly explosive. Also, a chlorine dioxide aqueous solution is decomposed easily owing to the change in pH, temperature, or the like of the aqueous solution. Thus, bactericides using chlorine dioxide have a problem in that they lack safety and storage stability. Further, hypochlorous acid is decomposed immediately, so that the hypochlorous acid has a problem in that it only has a temporary sterilizing effect.

[0020] With the foregoing in mind, it is an object of the present invention to provide a drug for use in agriculture and livestock industry, that is highly safe and has a high sterilizing effect.Solution to Problem[Solution to Problem]

[0021] In order to achieve the above object, the present invention provides a drug comprising: (i) a radical generating catalyst comprising: an ammonium salt of formula (XI) and having a Lewis acidity of 0.4 eV or more where in the chemical formula (XI), R 11< , R 21< , R 31< , and R 41< are each a hydrogen atom or an alkyl group and may each comprise an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring, and R 11< , R 21< , R 31< , and R 41< may be the same or different from each other, and X -< is an anion selected from a halogen ion, an acetate ion, a nitrate ion and a sulfate ion, wherein said halogen atom is preferably a fluoride ion, a chloride ion, a bromide ion or an iodide ion; and (ii) a radical source that is at least one selected from the group consisting of chlorous acid, bromous acid, iodous acid and halite ions; and wherein the radical generating catalyst and the radical source are dissolved in a solvent.

[0022] Hereinafter, the radical generating catalyst may be referred to as "the radical generating catalyst of the drug of the present invention".

[0023] As discussed above, the present invention provides a drug. In one embodiment, the drug is for use in agriculture and livestock industry.Advantageous Effects of Invention[Advantageous Effects of Invention]

[0024] The invention makes it possible to provide a drug that is highly safe and has a high sterilizing effect. Further, the radical generating catalyst of the drug of the present invention makes it is possible to generate (produce) radicals under mild conditions.BRIEF DESCRIPTION OF DRAWINGS

[0025] [FIG. 1] FIG. 1 shows an ultraviolet-visible absorption spectrum of NaClO 2 (5.0 mM) collected 0, 4, and 16 hours after mixing with Sc(OTf) 3 (10 mM) in an aqueous solution at 298 K. [FIGs. 2A and 2B] FIG. 2A shows a time profile of UV-Vis absorption at 358 nm in formation of Sc 3+< (ClO 2 ˙) by a reaction between Sc(OTf) 3 (10 mM) and NaClO 2 (5.0 mM) in an aqueous solution (0.20 M acetate buffer having a pH of 2.9) at 298 K. FIG. 2B shows a secondary plot. [FIGs. 3A and 3B] FIG. 3A shows a time profile of UV-Vis absorption at 358 nm in consumption of Sc 3+< (ClO 2 ˙) in the presence of styrene (30 to 90 mM) in a MeCN / H 2 O (1 : 1 v / v) solution at 298 K. FIG. 3B shows a pseudo first-order rate-styrene concentration plot. [FIG. 4] FIG. 4 shows EPR spectra of MeCN solutions measured at 298 K. In FIG. 4, (a) shows a spectrum of a MeCN solution that contains NaClO 2 (0.10 mM) at 353 K after 1-hour reflux; (b) shows a spectrum of a MeCN solution that contains NaClO 2 (0.10 mM) and CF 3 COOH (10 mM); and (c) shows a spectrum of a MeCN solution that contains NaClO 2 (0.10 mM) and Sc(OTf) 3 (10 mM). [FIG. 5] FIG. 5 shows bond lengths (Å) of optimized structures calculated by DFT at the level of CAM-B3LYP / 6-311+G(d, p). In FIG. 5, (a) shows the result obtained regarding ClO 2 ; (b) shows the result obtained regarding H +< ClO 2 ; and (c) shows the result obtained regarding Sc 3+< ClO 2 . [FIG. 6] FIG. 6 is a spectral diagram showing the result of tracing the reaction of styrene (2.0 mM) by NaClO 2 (20 mM) in an aqueous MeCN solution (MeCN / H 2 O 1 : 1 v / v) at room temperature (25°C) utilizing 1< HNMR. [FIG. 7] FIG. 7 shows 1< HNMR spectra of CD 3 CN / D 2 O (4 : 1 v / v) that contains styrene (66 mM) and NaClO 2 (200 mM) at 60°C (333 K) collected 0 hours and 25 hours after mixing. The mark "*" indicates the peak derived from styrene oxide. [FIG. 8] FIG. 8 shows 1< HNMR spectra of CD 3 CN / D 2 O (1 : 1 v / v) that contains styrene (2.0 mM), NaClO 2 (20 mM), and Sc(OTf) 3 (30 mM) at 25°C collected 0.6 hours and 17 hours after mixing. The mark "*" and the mark "†" indicate the peak derived from 1-phenylethane-1,2-diol and the peak derived from 2-chloro-1-phenylethanol, respectively. [FIG. 9] FIG. 9 shows 1< HNMR spectra of CD 3 CN / D 2 O (1 : 1 v / v) that contains styrene (2.0 mM), NaClO 2 (20 mM), and CF 3 COOD (30 mM) collected 0.5 hours and 17 hours after mixing. The mark "*" and the mark "†" indicate the peak derived from 1-phenylethane-1,2-diol and the peak derived from 2-chloro-1-phenylethanol, respectively. [FIG. 10] FIG. 10 is a diagram showing spin distributions calculated by DFT at the level of CAM-B3LYP / 6-311+G(d, p). In FIG. 10, (a) shows a spin distribution of H +< ClO 2 ˙; and (b) shows a spin distribution of Sc 3+< ClO 2 ˙. [FIG. 11] In FIG. 11, (a) is a graph showing the time course of an ultraviolet-visible absorption spectrum of a solution obtained by adding benzethonium chloride(Bzn +< ) to an oxygen saturated solution of a cobalt (II) tetraphenylporphyrin complex Co(II)TPP ([CoTPP] = 9.0 × 10 -6< M, [O 2 ] = 13 mM) ([Bzn +< Cl -< ] = 30 mM); and (b) is a graph showing the time course of an increase in the absorption band at 433 nm shown in the graph (a). [FIG. 12] FIG. 12 show the structure of Bzn +< optimized by density functional calculation (B3LYP / 6-31G(d) level). [FIG. 13] FIG. 13 shows an ultraviolet-visible absorption spectrum of NaClO 2 (20 mM) collected after mixing with Sc(OTf) 3 (40 mM) in an aqueous solution at 298 K. [FIG. 14] In FIG. 14, (a) to (c) are graphs each showing the time course of a reaction when 10-methyl-9,10-dihydroacridine (AcrH 2 ) (1.4 mM) and sodium chlorite (NaClO 2 ) (2.8 mM) were added to a mixed solution containing deoxygenated acetonitrile and water (deoxygenated acetonitrile : water = 1 : 1 v / v). [FIG. 15] In FIG. 15, (a) and (b) are graphs each showing the time course of a reaction when the same mixed solution as in (a) to (c) of FIG. 14 was prepared and Bzn +< (0.56 mM) was further added thereto. [FIG. 16] In FIG. 16, (a) and (b) are graphs each showing the time course of a reaction when the same mixed solution as in (a) and (b) of FIG. 15 was prepared and Sc(OTf) 3 (3.0 mM) was further added thereto. [FIG. 17] FIG. 17 is a schematic view showing an example of a presumed reaction mechanism of an oxygenation (oxidation) reaction from AcrH 2 to 10-methylacridone. [FIG. 18] In FIG. 18, (a) is an ultraviolet-visible absorption spectrum showing the result of tracing an oxidation reaction of triphenylphosphine using NaClO 2 and scandium triflate; and (b) is a graph showing the relationship between an initial concentration of Ph 3 P and a concentration of generated Ph 3 P = O in the reaction shown in (a) of FIG. 18. [FIG. 19] FIG. 19 shows 1< HNMR spectra of CD 3 CN / D 2 O (1 : 1 v / v) that contains styrene (2.0 mM), NaClO 2 (6.0 mM), and Sc(OTf) 3 (5.6 mM) at 25°C in the Ar atmosphere collected 0 hours and 45 hours after mixing. [FIG. 20] FIG. 20 shows the yield etc. in an example where an oxidation reaction product (benzoic acid) was obtained by performing an oxidation reaction of a raw material aromatic compound (benzaldehyde) in acetonitrile in the presence of perchlorate (Acr +< -Mes ClO 4 -< ) of 9-mesityl-10-methylacridinium (Acr +< -Mes) and oxygen. [FIG. 21] FIG. 21 is a graph showing the Lewis acidities of benzethonium chloride [Bzn +< Cl -< ] and various metal complexes. [FIG. 22] In FIG. 22, (a) is an ultraviolet-visible absorption spectrum showing conversion of triphenylphosphine to triphenylphosphine oxide over time; and (b) is a graph showing the change of a triphenylphosphine (Ph 3 P) concentration over time in the presence and the absence of Sc(OTf) 3 (Sc 3+< ). DESCRIPTION OF EMBODIMENTS

[0026] The present invention will be described more specifically below with reference to illustrative examples.[Description of Embodiments][1. Drug]

[0027] As described above, the drug according to the present invention is a drug characterized in that it contains: (i) a radical generating catalyst comprising: an ammonium salt of formula (XI) and having a Lewis acidity of 0.4 eV or more where in the chemical formula (XI), R 11< , R 21< , R 31< , and R 41< are each a hydrogen atom or an alkyl group and may each comprise an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring, and R 11< , R 21< , R 31< , and R 41< may be the same or different from each other, and X -< is an anion selected from a halogen ion, an acetate ion, a nitrate ion and a sulfate ion, wherein said halogen atom is preferably a fluoride ion, a chloride ion, a bromide ion or an iodide ion; and (ii) a radical source that is at least one selected from the group consisting of chlorous acid, bromous acid, iodous acid and halite ions; and wherein the radical generating catalyst and the radical source are dissolved in a solvent. In the drug of the present invention, other configurations or conditions are not particularly limited.

[0028] As described above, the drug may be for use in agriculture and livestock industry In the drug for use in agriculture and livestock industry according to the present invention, other configurations or conditions are not particularly limited The drug for use in agriculture and livestock industry of the present invention is highly safe and has a high sterilizing effect. Thus, the drug for use in agriculture and livestock industry according to the present invention can be used widely for sterilization, deodorization, etc. in agriculture and livestock industry, for example. Further, the drug for use in agriculture and livestock industry according to present invention is less liable to cause corrosion, for example. Even when the drug is applied to metals, corrosion of the metals is less liable to occur. Thus, the drug for use in agriculture and livestock industry according to the present invention can be used for a target object containing a metal, for example.

[0029] The inventors of the present invention found out through research that ammonium serves as a radical generating catalyst. As a result of further research, the inventors of the present invention further found out that ammonium serving as a radical generating catalyst may have properties as a Lewis acid. That is, while the reason why the ammonium serves as a radical generating catalyst is not clear, it is presumably because the ammonium has a function as a Lewis acid. The "Lewis acid" refers to a substance that acts as a Lewis acid with respect to the radical source, for example.

[0030] The Lewis acidity of the radical generating catalyst contained in the drug of the present invention (may be referred to as "the radical generating catalyst of the drug of the present invention" hereinafter) is 0.4 eV or more. The upper limit of the Lewis acidity is not particularly limited, and is, for example, 20 eV or less. It is to be noted that the Lewis acidity can be measured, for example, by the method described in Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532, J. Am. Chem. Soc. 2002, 124, 10270-10271 or the method described in J. Org. Chem. 2003, 68, 4720-4726. Specifically, the Lewis acidity can be measured by the following method.(Measurement method of Lewis acidity)

[0031] As to acetonitrile (MeCN) that contains cobalt tetraphenylporphyrin, saturated O 2 , and an object whose Lewis acidity is to be measured (e.g., a cation of a metal or the like, represented by M n+< in the following chemical reaction formula (1a)) in the following chemical reaction formula (1a), the change of the ultraviolet-visible absorption spectrum is measured at room temperature. On the basis of the obtained reaction rate constant (k cat ), the ΔE value (eV), which is an indicator of the Lewis acidity, can be calculated. The higher the k cat , the stronger the Lewis acidity. Furthermore, the Lewis acidity of an organic compound can be estimated from the energy level of the lowest unoccupied molecular orbital (LUMO) calculated by the quantum chemical calculation. The higher the value at the positive side, the stronger the Lewis acidity.

[0032] Examples of the rate constant of reaction between CoTPP and oxygen in the presence of a Lewis acid, which is an indicator of the Lewis acidity measured (calculated) by the above-described measurement method, are shown below. In the following table, the numerical value expressed in the unit "k cat , M -2< s -1< " is a rate constant of reaction between CoTPP and oxygen in the presence of a Lewis acid. The numerical value expressed in the unit "LUMO, eV" is the energy level of LUMO. The "benzetonium chloride" means benzethonium chloride, "benzalkonium chloride" means benzalkonium chloride, "tetramethylammonium hexafluorophosphate" means tetramethylammonium hexafluorophosphate, "tetrabutylammonium hexafluorophosphate" means tetrabutylammonium hexafluorophosphate, and "ammonium hexafluorophosphate" means ammonium hexafluorophosphate (Note from translator: in the original text in Japanese, the above sentence explains the meanings of the English terms in the table in Japanese). [Table tpp]LUMO, eVk cat , M -2< s -1< benzetonium chloride-4.120.24benzalkonium chloride-4.020.18tetramethylammonium hexafluorophosphate-3.58> 0.1tetrabutylammonium hexafluorophosphate-2.07> 0.1ammonium hexafluorophosphate-5.7320

[0033] In the radical generating catalyst of the drug of the present invention, the ammonium may be quaternary ammonium, or may be tertiary ammonium, secondary ammonium, primary ammonium, or ammonium, for example.

[0034] In the radical generating catalyst of the drug of the present invention, the ammonium may be, for example, a cationic surfactant, which may be a quaternary ammonium-type cationic surfactant. Examples of the quaternary ammonium-type cationic surfactant include benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, hexadecyltrimethylammonium bromide, dequalinium chloride, edrophonium, didecyldimethylammonium chloride, tetramethylammonium chloride, tetrabutylammonium chloride, benzyltriethylammonium chloride, oxytropium, carbachol, glycopyrronium, safranin, sinapine, tetraethylammonium bromide, hexadecyltrimethylammonium bromide, suxamethonium, sphingomyelin, denatonium, trigonelline, neostigmine, paraquat, pyridostigmine, phellodendrine, pralidoxime methiodide, betaine, betanin, bethanechol, betalain, lecithin, and cholines (e.g., choline chlorides [such as benzoyl choline chloride and a lauroylcholine chloride hydrate], phosphocholine, acetylcholine, choline, dipalmitoylphosphatidylcholine, and choline bitartrate). It is to be noted, however, that, in the radical production method of the present invention, the quaternary ammonium is not limited to a surfactant. Also, in the radical generating catalyst of the drug of the present invention, one type of ammonium or a salt thereof may be used, or two or more types of ammonium or salts thereof may be used in combination, for example, , or one type of ammonium or a salt thereof may be used in combination one or more types of substances having Lewis acidic properties and / or Brønsted acidic properties, for example (the same applies hereinafter).

[0035] In the radical generating catalyst of the drug of the present invention, the ammonium is ammonium represented by the following chemical formula (XI), for example.

[0036] In the chemical formula (XI), R 11< , R 21< , R 31< , and R 41< are each a hydrogen atom or an alkyl group (e.g., a straight-chain or branched alkyl group having 1 to 40 carbon atoms) and may each include an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring. R 11< , R 21< , R 31< , and R 41< may be the same or different from each other. X -< is an anion selected from a halogen ion, an acetate ion, a nitrate ion and a sulfate ion, wherein said halogen atom is preferably a fluoride ion, a chloride ion, a bromide ion or an iodide ion.

[0037] The ammonium represented by the chemical formula (XI) may be ammonium represented by the following chemical formula (XII), for example.

[0038] In the chemical formula (XII), R 111< is an alkyl group having 5 to 40 carbon atoms and may comprise an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring, and R 21< and X -< are the same as those in the chemical formula (XI).

[0039] In the chemical formula (XII), R 21< may be a methyl group or a benzyl group, for example. In the benzyl group, one or more hydrogen atoms on the benzene ring may or may not be substituted with any substituent. The substituent may be, for example, an alkyl group, an unsaturated aliphatic hydrocarbon group, an aryl group, a heteroaryl group, a halogen, a hydroxy group (-OH), a mercapto group (-SH), or an alkylthio group (-SR, where R is an alkyl group).

[0040] The ammonium represented by the chemical formula (XII) may be ammonium represented by the following chemical formula (XIII), for example. In the chemical formula (XIII), R 111< and X -< are the same as those in the chemical formula (XII).

[0041] The ammonium represented by the chemical formula (XI) may be, for example, at least one selected from the group consisting of benzethonium chloride, benzalkonium chloride, hexadecyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, and tetrabutylammonium chloride. It is particularly preferable that the ammonium represented by the chemical formula (XII) is benzethonium chloride.

[0042] Benzethonium chloride (Bzn +< Cl -< ) can be represented by the following chemical formula, for example. Benzalkonium chloride can be, for example, a compound represented by the chemical formula (XIII) where R 111< is an alkyl group having 8 to 18 carbon atoms and X -< is a chloride ion.

[0043] In the chemical formulae (XI), (XII), and (XIII), when the anion is an anion with a plurality of electric charges, such as a divalent anion or a trivalent anion, the number of molecules of the ammonium (monovalent) in each of the chemical formulae (XI), (XII), and (XIII) is determined by, for example, [the number of molecules of the anion × the valence of the anion] (e.g., when the anion is divalent, the number of molecules of the ammonium (monovalent) is twice the number of molecules of the anion).

[0044] In the radical generating catalyst of the drug of the present invention, the acid dissociation constant pK a of the Brønsted acid is, for example, 5 or more. The upper limit of the pK a is not particularly limited and is, for example, 50 or less.

[0045] In the radical generating catalyst of the drug of the present invention, the optional substance having Lewis acidic properties and / or Brønsted acidic properties may be an organic compound (e.g., the above-described organic ammonium or cationic surfactant) or an inorganic substance. The inorganic substance may include one or both of metal ions and nonmetal ions. The metal ion may include one or both of typical metal ions and transition metal ions. The inorganic substance may be, for example, at least one selected from the group consisting of alkali earth metal ions, rare earth ions, Sc 3+< , Li +< , Fe 2+< , Fe 3+< , Al 3+< , silicate ions, and borate ions. Examples of the alkali earth metal ion include ions of calcium, strontium, barium, and radium. More specifically, examples of the alkali earth metal ion include Ca 2+< , Sr 2+< , Ba 2+< , and Ra 2+< . Furthermore the "rare earth metal" is a generic name of a set of seventeen elements, specifically, two elements such as scandium 21 Sc and yttrium 39 Y and fifteen elements (lanthanoids) from lanthanum 57 La to lutetium 71 Lu. Examples of the rare earth ion include corresponding trivalent cations of the seventeen elements.

[0046] The Lewis acid (including the counter ion) may be, for example, at least one selected from the group consisting of CaCl 2 , MgCl 2 , FeCl 2 , FeCl 3 , AlCl 3 , AlMeCl 2 , AlMe 2 Cl, BF 3 , BPh 3 , BMe 3 , TiCl 4 , SiF 4 , and SiCl 4 . It is to be noted that the "Ph" indicates a phenyl group and the "Me" indicates a methyl group.

[0047] In the radical generating catalyst of the drug of the present invention, the radical generating catalyst can be selected as appropriate depending on the intended use thereof, with consideration given to the reactivity, acidity, safety, etc.

[0048] In the drug of the present invention, the radical source is at least one selected from the group consisting of chlorous acid, bromous acid, iodous acid and halite ions. Particularly preferably, the radical source includes a chlorite ion, for example. One type of radical source may be used, or two or more types of radical sources may be used in combination, for example (the same applies hereinafter).

[0049] The radical source may be selected as appropriate depending on the use thereof, with consideration given to the intensity of reactivity of a radical species, etc., for example.

[0050] In the drug of the present invention, when the compound (e.g., the organic ammonium) has isomers such as tautomers and stereoisomers (e.g., a geometric isomer, a conformer, and an optical isomer), any isomer can be used in the present invention, unless otherwise stated.

[0051] Moreover, in the present invention, a chain substituent (e.g., an alkyl group, hydrocarbon groups such as an unsaturated aliphatic hydrocarbon group, etc.) may be straight-chain or branched, unless otherwise stated, and the number of carbons thereof is not particularly limited, and may be, for example, 1 to 40, 1 to 32, 1 to 24, 1 to 18, 1 to 12, 1 to 6, or 1 to 2 (at least 2 in the case of an unsaturated hydrocarbon group). Furthermore, in the present invention, as to a cyclic group (e.g., an aryl group, a heteroaryl group, etc.), the number of ring members (the number of atoms that compose a ring) is not particularly limited and may be, for example, 5 to 32, 5 to 24, 6 to 18, 6 to 12, or 6 to 10. When a substituent or the like has isomers, any isomer can be used, unless otherwise stated. For example, in the case of simply describing as a "naphthyl group", it may be a 1-naphthyl group or a 2-naphthyl group.

[0052] In the drug of the present invention, the content of the radical source is not particularly limited, and is, for example, 0.01 mass ppm or more, 0.05 mass ppm or more, 0.1 mass ppm or more, 1500 mass ppm or less, 1000 mass ppm or less, or 250 mass ppm or less. The amount of the radical source mixed in a drug preferably is from 0.01 to 1500 mass ppm, more preferably from 0.05 to 1000 mass ppm, and still more preferably from 0.1 to 250 mass ppm. The concentration of the radical source preferably is low, because it is considered that the safety level increases as the concentration becomes lower. However, if the concentration of the radical source is too low, the sterilizing effect or the like may not be obtained. From the viewpoint of the sterilizing effect and the like, the concentration of the radical source is not particularly limited, and preferably is set as high as possible.

[0053] In the drug of the present invention, the content of the radical generating catalyst is not particularly limited, and is, for example, 0.01 mass ppm or more, 0.05 mass ppm or more, 0.1 mass ppm or more, 1500 mass ppm or less, 1000 mass ppm or less, 500 mass ppm or less, or 250 mass ppm or less. The amount of the radical generating catalyst mixed in the drug preferably is from 0.01 to 1500 mass ppm, more preferably from 0.05 to 1000 mass ppm, still more preferably from 0.05 to 500 mass ppm, and yet more preferably from 0.1 to 250 mass ppm. The concentration of the radical generating catalyst preferably is low, because it is considered that the safety level increases as the concentration becomes lower. However, if the concentration of the radical generating catalyst is too low, the sterilizing effect or the like may not be obtained. From the viewpoint of preventing the risk that the sterilizing effect or the like may not be obtained owing to micelle formation, it is preferable that the concentration of the radical generating catalyst is equal to or lower than the critical micelle concentration.

[0054] In the drug of the present invention, the concentration ratio of the radical source and the radical generating catalyst (radical source / radical generating catalyst) in the drug is not particularly limited, and can be set as appropriate.

[0055] The drug of the present invention contains a solvent. The drug may further contain one or more other substances. Examples of the other substances include pH adjusters, and buffers. One type of them may be used, or two or more types of them may be used in combination (the same applies hereinafter).

[0056] The drug of the present invention preferably contains water and / or an organic solvent. In the present invention, the "solvent" dissolves the radical generating catalyst of the present invention, the radical source, and the like. Thus, after the mixing step, the radical generating catalyst of the present invention and the radical source are each in a state of being dissolved in the solvent. In the drug of the present invention, it is preferable to use water as a solvent for the radical generating catalyst of the present invention and the radical source from the viewpoint of safety, cost, etc. The water is not particularly limited, and preferably is purified water, ionexchange water, or pure water, for example. The organic solvent may be, for example, ketone such as acetone, a nitrile solvent such as acetonitrile, or an alcohol solvent such as ethanol. One type of solvent may be used alone, or two or more types of solvents may be used in combination. The type of the solvent may be selected as appropriate depending on the solubility of the solutes (e.g., the radical generating catalyst of the drug of the present invention, the radical source, and the like) etc., for example.

[0057] The drug of the present invention can be produced by, for example, mixing the radical source and the radical generating catalyst, and the solvent (preferably water and / or organic solvent). For example, the drug of the present invention can be obtained in manners described in the following examples. As described above, the drug further may contain one or more substances other than the radical source, the radical generating catalyst and the solvent.

[0058] The drug for use in agriculture and livestock industry according to t the present invention preferably contains water, for example. However, the drug may not necessarily contain water. The amount of the water mixed (the proportion of the water) in the drug for use in agriculture and livestock industry is not particularly limited. The proportion of the water may be the balance of the drug excluding the other components, for example. The drug for use in agriculture and livestock industry further may or may not contain, as the other substance(s), the pH adjuster, a buffer, and / or the like, for example.

[0059] In one aspect of the present invention, the drug is for use as a medicament and so may be for use in methods of treatment that are not particularly limited. For example, the drug of the present invention for use as a bactericide may be for use as a bactericide in the same manner as for conventional bactericides. Similarly, the drug for use as an oral care agent (i.e. when the drug is use for oral cavity) may be in the form of an aqueous solution so that it can be used for gargling and oral rinsing. When the drug is a drug for use in disinfection of a decubitus ulcer, the drug can be applied to an affected area. When for use in treating an affected area such as a self-destructive wound caused by cancer or a lesion caused by ringworm fungi or the like, absorbent cotton or gauze impregnated with the drug may be applied to the affected area. Further, the drug may be for use in the prevention of infection with bacteria or the like.

[0060] When the drug is used in a method which is not the treatment of the human or animal body by therapy, the method is not particularly limited. For example, the drug of the present invention can be used in the same manners as those for conventional bactericides and the like. Specifically, the drug of the present invention may be sprayed on or applied to a target object, for example. Specifically, for example, when the drug is used for deodorization of a space, the drug can be sprayed in the space. When the drug is use for oral cavity, the drug may be in the form of an aqueous solution so that it can be used for gargling and oral rinsing. When the drug is used for hand washing, it may be in the form of an aqueous solution so that it can be rubbed into hands. Medical instruments and the like can be washed with the drug by spraying the drug on them or immersing them in an aqueous solution containing the drug. Further, the drug may be applied to surroundings of beds, tables, doorknobs, and the like for the purpose of sterilization.(Bactericide)

[0061] In one embodiment, the drug of the present invention is for use as a bactericide. In another embodiment, the drug of the present invention is used as a bactericide wherein said use is not in a method for treatment of the human or animal body by therapy. Although various types of substances have been used as a bactericide conventionally, the sterilizing effects of these substances are not sufficient. Some of them can exhibit enhanced sterilizing effects by increasing their concentrations. However, this poses a problem in safety. A bactericide containing the drug of the present invention can exhibit a sufficient sterilizing effect while the concentration of the drug is low and is highly safe.(Bactericide for hand washing)

[0062] The drug of the present invention can be used as a bactericide for hand washing to disinfect hands, for example. The bactericide for hand washing containing the drug of the present invention can exhibit a sufficient sterilizing effect while the concentration of the drug is low and is highly safe.(Deodorizer)

[0063] The drug of the present invention can be used as a deodorizer, for example. Commonly used bactericides, such as ethanol, do not have a deodorizing effect. While chlorine dioxide has a deodorizing effect, the safety level thereof is very low. Some of other commercially available products purport to have sterilizing and deodorizing effects. For example, there are commercially available products purporting to exhibit sterilizing and deodorizing effects by spraying them onto clothes directly or spraying them in rooms, toilets, cars, or the like. Such commercially available products typically contain a quaternary ammonium salt as a sterilizing component. However, a commonly used quaternary ammonium salt is not used in combination with a radical source. Thus, in many cases, a sufficient sterilizing effect cannot be obtained unless the quaternary ammonium salt is contained at a high concentration, and this causes a problem of surface tackiness or the like after use. Further, since the quaternary ammonium salt does not have a deodorizing effect, the commercially available products contain a deodorant component as an additional component. While cyclodextrin typically is used as the deodorant component, the cyclodextrin is incapable of decomposing components causing offensive odors. The cyclodextrin merely masks the components causing offensive odors and cannot eliminate the offensive odors themselves. In contrast, the deodorizer containing the drug of the present invention, which has the above-described action mechanism, has a high sterilizing effect, for example, and also, is capable of decomposing substances that cause offensive odors and thus has a high deodorizing effect, for example.(Antibacterial agent for metals)

[0064] The drug of the present invention can be used as an antibacterial agent for metals, for example. An antibacterial agent containing the drug of the t present invention is highly safe, so that it can be sprayed on or applied to metal products in the kitchen, for example. Also, the antibacterial agent containing the drug of the present invention is less liable to cause corrosion. Thus, even when the antibacterial agent is used on metals, corrosion of the metals is less liable to occur.(Oral care agent)

[0065] In one embodiment, the drug of the present invention is for use as an oral care agent. In another embodiment, the drug of the present invention is used as an oral care agent wherein said use is not in a method for treatment of the human or animal body by therapy. An oral care agent containing the drug of the present invention is highly safe and thus suitable for use in the oral cavity.(Acne treatment agent)

[0066] The drug of the present invention can be for use as an acne treatment agent. An acne treatment agent containing the drug of the present invention is highly safe and thus can be applied to the face.(Disinfectant for decubitus ulcers)

[0067] The drug of the present invention can be for use as a disinfectant for decubitus ulcers. The disinfectant for decubitus ulcers containing the drug of the present invention is highly safe and thus can be applied to the body.(Fungicide)

[0068] The drug of the present invention can be for use as a fungicide for disinfecting an affected part caused by infection with fungi such as ringworm fungi, for example.(Bactericide for water purification)

[0069] The drug of the present invention can kill bacteria, such as Legionella bacteria, breeding in water in swimming pools and baths, for example. Besides, it does not corrode metals and does not generate gas. Therefore, the bactericide for water purification containing the drug of the present invention can be used safely.

[0070] As described above, the drug for use in agriculture and livestock industry according to the present invention is highly safe and has a high sterilizing effect. Thus, in one embodiment, the drug for use in agriculture and livestock industry can be used as a drug for use in agriculture or a drug for use in livestock industry, wherein said use is not in a method for treatment of the human or animal body. The drug for use in agriculture can be used as, for example, a bactericide for use in agriculture, an antiviral agent for use in agriculture, a deodorizer for use in agriculture, an insectcide for use in agriculture, a repellent for use in agriculture, or a soil conditioner for use in agriculture. The drug for use in livestock industry can be used as, for example, a bactericides for use in livestock industry, an antiviral agent for use in livestock industry, a deodorizer for use in livestock industry, an insecticide for use in livestock industry, a repellent for use in livestock industry, or a soil conditioners for use in livestock industry. The drug for use in agriculture and livestock industry may be applied to one use or two or more uses, for example.

[0071] In another embodiment, the drug may be a drug for use as a bactericide for use in livestock industry or antiviral agent for use in livestock industry.

[0072] Examples of the agriculture include rice farming and dry-field farming. Examples of the dry-field farming include production of: vegetables such as cucumbers, tomatoes, green onions, Chinese cabbages, and soybeans; tubers and roots, such as potatoes; flowers and ornamental plants, such as chrysanthemums grown with artificial light, clematis, and Lady Banks' roses (Rosa banksiae); fruits such as strawberries; and fertilizers. Examples of the livestock include industrial animals such as cows, pigs, and chickens.

[0073] When the drug for use in agriculture and livestock industry according to the present invention is used for the rice farming, the drug for use in agriculture and livestock industry can be used as a bactericide, an insectcide, a repellent, or a soil conditioner, for example. Specifically, for example, by using the drug for use in agriculture and livestock industry during soaking of rice seeds, it is possible to prevent the generation of slime and to reduce the burden of water replacement operations. Further, for example, by using the drug for use in agriculture and livestock industry during seed soaking, stimulation of germination, and seeding, it is possible to prevent rice blast, spot blight, false smut, bakanae disease, and the like. For example, by spreading the drug for use in agriculture and livestock industry over rice fields, it is possible to protect rice from shield bugs, pest insects, and the like. For example, by spreading the drug for use in agriculture and livestock industry during ploughing and irrigation of rice fields, it is possible to improve the soil.

[0074] When the drug for use in agriculture and livestock industry according to t the present invention is used for dry-field farming, the drug for use in agriculture and livestock industry can be used as a bactericide, an antiviral agent, a soil conditioner, or the like, for example. Specifically, for example, by spreading the drug for use in agriculture and livestock industry over leaves of cucumbers, tomatoes, or strawberries, it is possible to prevent powdery mildew, mosaic disease, and the like. For example, by spreading the drug for use in agriculture and livestock industry over leaves of tomatoes, it is possible to prevent gray mold, leaf mold, and the like. For example, by spreading the drug for use in agriculture and livestock industry over leaves of green onions, it is possible to prevent brown leaf rust and the like. For example, by spreading the drug for use in agriculture and livestock industry over leaves of Chinese cabbages, it is possible to prevent root-knot disease and the like. For example, by spreading the drug for use in agriculture and livestock industry over a potato field after being cultivated using a tractor or the like and then cultivating the field again, it is possible to prevent replant failure and the like. For example, by immersing seed potatoes in the drug for use in agriculture and livestock industry, it is possible to disinfect (sterilize) the seed potatoes. For example, by spreading the drug for use in agriculture and livestock industry over leaves of potatoes a plurality of times in a period from germination to harvest of the potatoes, it is possible to prevent common scab and the like. For example, by spreading the drug for use in agriculture and livestock industry over chrysanthemums grown with artificial light, clematis, and Lady Banks' roses (Rosa banksiae), it is possible to prevent powdery mildew and the like.

[0075] When the drug for use in agriculture and livestock industry according to present invention is used for the livestock industry, the drug for use in agriculture and livestock industry can be used as a bactericide, a deodorizer, or the like, for example, wherein said use is not in a method for treatment of the human or animal body. For example, by spraying the drug for use in agriculture and livestock industry in a livestock barn or the like for cows, pigs, or chickens with a sprayer or the like, it is possible to deodorize the livestock barn or the like. For example, by using the drug for use in agriculture and livestock industry for hen eggs, it is possible to disinfect (sterilize) the hen eggs.

[0076] Alternatively, the drug may be for use in the treatment of the human or animal body. Specifically, for example, the drug for use in agriculture and livestock industry may be for use in the prevention of mastitis and the like, for instance as a dipping agent for cows. For example, the drug for use in agriculture and livestock industry may be for use in the treatment or prevention of hoof disease, for instance in a hoof bath for a cow or by applying the drug for use in agriculture and livestock industry to an affected area of a cow infected with a hoof disease. For example, the drug for use in agriculture and livestock industry may before use in the prevention of respiratory diseases, foot-and-mouth disease, and the like, for instance by spraying on a cow with a sprayer or the like.

[0077] The drug for use in agriculture and livestock industry according to the present invention may be sprayed on, applied to, or spread over a target object, or the target object may be immersed in the drug for use in agriculture and livestock industry, for example. Specifically, when the drug is used to deodorize a space, the drug may be sprayed in the space, for example. When the drug is for use in treating a hoof disease in an affected area of a hoof disease or the like, absorbent cotton, gauze, or the like impregnated with the drug may be applied to the affected area, for example. When the drug is used for hand washing, the drug may be in the form of an aqueous solution so that it can be rubbed into hands, for example. Medical instruments and the like can be washed with the drug by spraying the drug on them or immersing them in an aqueous solution containing the drug. When the drug for use in agriculture and livestock industry is used for a machine used in livestock barns, such as an automobile, an agricultural machine, or a forklift, the drug may be sprayed on the machine, or the machine may be washed with the drug, for example. When the drug for use in agriculture and livestock industry is used for deodorization of the above-described industrial animals, the drug may be sprayed with a sprayer or the like or may be spread with a spreader or the like, for example. Hen eggs can be sterilized by applying the drug to the hen eggs, for example.<Disinfectant for use in agriculture and livestock industry>

[0078] A bactericide for use in agriculture and livestock industry according to the present invention is characterized in that it contains the drug for use in agriculture and livestock industry according to the present invention. The drug for use in agriculture and livestock industry according to the present invention can be used as a bactericide, for example. Although various types of substances have been used as a bactericide conventionally, the sterilizing effects of these substances are not sufficient. Some of them can exhibit enhanced sterilizing effects by increasing their concentrations. However, this poses a problem in safety. A bactericide for use in agriculture and livestock industry containing the drug for use in agriculture and livestock industry according to the present invention can exhibit a sufficient sterilizing effect while the concentration of the drug is low and is highly safe.<Bactericide for hand washing for use in agriculture and livestock industry>

[0079] The hand-washing bactericide for use in agriculture and livestock industry according to the present invention is characterized in that it contains the drug for use in agriculture and livestock industry according to the present invention. The drug for use in agriculture and livestock industry according to the present invention can be used as a bactericide for hand washing for use in agriculture and livestock industry to disinfect hands, for example. The hand-washing bactericide for use in agriculture and livestock industry including the drug for use in agriculture and livestock industry according to the present invention can exhibit a sufficient sterilizing effect while the concentration of the drug is low and is highly safe.<Deodorizer for use in agriculture and livestock industry>

[0080] The deodorizer for use in agriculture and livestock industry according to the present invention is characterized in that it contains the drug for use in agriculture and livestock industry according to the present invention. The drug for use in agriculture and livestock industry according to the present invention can be used as a deodorizer for use in agriculture and livestock industry, for example. As a commonly used sterilizing component, a quaternary ammonium salt typically is used. In many cases, a sufficient sterilizing effect cannot be obtained unless the quaternary ammonium salt is contained at a high concentration. This causes a problem in safety. Further, since the quaternary ammonium salt does not have a deodorizing effect, the commercially available products contain a deodorant component as an additional component. While cyclodextrin typically is used as the deodorant component, the cyclodextrin is incapable of decomposing components causing offensive odors. The cyclodextrin merely masks the components causing offensive odors and cannot eliminate the offensive odors themselves. The deodorizer for use in agriculture and livestock industry including the drug for use in agriculture and livestock industry according to the present invention has a high sterilizing effect, and also, is capable of removing substances that cause offensive odors and thus has a high deodorizing effect, for example.<Fungicide for use in agriculture and livestock industry>

[0081] A fungicide for use in agriculture and livestock industry according to the present invention is characterized in that it contains the drug for use in agriculture and livestock industry according to the present invention. The fungicide for use in agriculture and livestock industry according to the present invention may be for use as a fungicide for disinfecting an affected part caused by infection with fungi such as ringworm fungi, for example.<Water purifying agent for use in agriculture and livestock industry>

[0082] The water purifying agent for use in agriculture and livestock industry according to the present invention is characterized in that it contains the drug for use in agriculture and livestock industry according to the present invention. The water purifying agent for use in agriculture and livestock industry according to the present invention can kill bacteria, such as Legionella bacteria, breeding in water used in agriculture and livestock industry, for example. The drug for use in agriculture and livestock industry according to the present invention does not corrode metals and does not generate gas. Therefore, the water purifying agent for use in agriculture and livestock industry containing the drug for use in agriculture and livestock industry according to the present invention can be used safely. The water purifying agent for use in agriculture and livestock industry according to the present invention can be used to kill bacteria contained in water or to improve quality of water, for example. Thus, the water purifying agent for use in agriculture and livestock industry according to the present invention also can be referred to as a bactericide for water for use in agriculture and livestock industry or a water quality improving agent for water for use in agriculture and livestock industry, for example.<Method of using drug for use in agriculture and livestock industry>

[0083] The method of using the drug for use in agriculture and livestock industry according to the present invention is characterized in that it includes the step of bringing the drug for use in agriculture and livestock industry according to the present invention into contact with a target object. By the method of using the drug for use in agriculture and livestock industry according to the present invention, it is possible to perform sterilization, deodorization, or the like of the target object, for example.Examples

[0084] Next, examples of the present invention will be described.[Examples][Example 1 (Reference Example)]

[0085] In the present example, it was confirmed that efficient dihydroxylation of styrene can be performed by scandium triflate and sodium chlorite. Specifically, by the dihydroxylation of styrene by scandium triflate and chlorite ions (ClO 2 -< ) at ordinary temperature and atmospheric pressure, 1-phenylethane-1,2-diol could be produced efficiently. It was confirmed that the scandium triflate working as a strong Lewis acid generates chlorine dioxide radicals (ClO 2 ·< ) from the chlorite ions (ClO 2 -< ) and increases the reactivity of the chlorine dioxide radicals (ClO 2 ˙).

[0086] Oxidization of an olefin to a 1,2-diol is an important industrial process for producing precursors of various types of chemical substances such as resins, pharmaceutical agents, dyes, insecticides, and perfume compounds in the fields of fine chemicals and speciality chemicals. Several methods for converting olefins to corresponding epoxides and alcohols by oxidization using inorganic metal oxo complexes and metallic oxides having heavy atoms have been reported. High-valent Os VIII< O 4 is an effective and selective reagent for oxidizing an olefin to a 1,2-diol (References, etc. 1 to 8). However, the toxicity, sublimation property, and waste of the osmium compound cause serious problems. Sodium chlorite (NaClO 2 ) is a non-toxic inexpensive oxidizing reagent and has been used as a precursor of a chlorine dioxide radical (ClO 2 ·< ) (References, etc. 9 to 12 [the same as Non Patent Literatures 1 to 4]). ClO 2 ˙ is known as a reactive stable radical. ClO 2 ˙, however, is an explosive gas which is yellow at room temperature. ClO 2 ˙ can be experimentally prepared by oxidization of NaClO 2 by Cl 2 and reaction of chloric acid potassium (KClO 3 ) and oxalic acid (Reference, etc. 13). These methods cause serious problems such as the toxicity of Cl 2 and the explosivity of ClO 3 -< . There has been an attempt on epoxidation of an olefin using NaClO 2 as a precursor of ClO 2 ˙. However, because the oxidization ability of ClO 2 ˙ was not strong enough to oxidize an olefin to a diol in the absence of an acid, a 1,2-diol product could not be obtained (References, etc. 14 to 17). The activation of Cl=O double bond of ClO 2 ˙ is a key for selectively dihydroxylating an olefin in one step.

[0087] The present example reports an efficient synthesis method of a dihydroxylated product of styrene at ordinary temperature and atmospheric pressure by the activation of ClO 2 ˙ using scandium triflate [Sc(OTf) 3 ] as a Lewis acid (Reference, etc. 18). The mechanism of dihydroxylation was disclosed on the basis of the detection of a radical intermediate by the EPR and UV-Vis absorption spectroscopy.

[0088] In the reaction of styrene (2.0 mM) by NaClO 2 (20 mM) in an aqueous MeCN solution (MeCN / H 2 O 1 : 1 v / v) at room temperature (25°C), dihydroxylation of the styrene was not caused (see FIG. 6). FIG. 6 shows the results obtained by performing the above-described reaction using a 1< HNMR spectrum measurement solvent CD 3 CN / D 2 O (1 : 1 v / v) as MeCN / H 2 O and tracing the reaction utilizing 1< HNMR. FIG. 6 shows the 1< HNMR spectra of CD 3 CN / D 2 O (1 : 1 v / v) collected 0.3 hours and 17 hours after the start of the reaction. When the temperature was increased to 333 K, a dihydroxylated product was not formed but epoxidation was caused (FIG. 7) (References, etc. 14 and 19). FIG. 7 shows the 1< HNMR spectra of CD 3 CN / D 2 O (4 : 1 v / v) that contains styrene (66 mM) and NaClO 2 (200 mM) at 60°C (333 K) collected 0 hours and 25 hours after mixing. The mark "*" indicates the peak derived from styrene oxide. In contrast, in the case where CF 3 COOH (30 mM) as a Brønsted acid was added as an additive, an epoxide was not formed at all 17 hours after mixing, instead, 1-phenylethane-1,2 diol (1) and 2-chloro-1-phenylethanol (2) were produced at the yield of 15% and 69%, respectively [reaction formula (1)]. They were measured utilizing the 1< HNMR spectrum (FIG. 8) (Reference, etc. 20). FIG. 8 shows the 1< HNMR spectra of CD 3 CN / D 2 O (1 : 1 v / v) that contains styrene (2.0 mM), NaClO 2 (20 mM), and Sc(OTf) 3 (30 mM) at 25°C collected 0.6 hours and 17 hours after mixing. The mark "*" and the mark "†" indicate the peak derived from 1-phenylethane-1,2-diol and the peak derived from 2-chloro-1-phenylethanol, respectively. When Sc(OTf) 3 (30 mM), which is a strong Lewis acid, was used instead of CF 3 COOH, the yield of diol (1) increased remarkably to 51% [see the following reaction formula (1)] (FIG. 19) (Reference, etc. 21). FIG. 9 shows the 1< HNMR spectra of CD 3 CN / D 2 O (1 : 1 v / v) that contains styrene (2.0 mM), NaClO 2 (20 mM), and CF 3 COOD (30 mM) collected 0.5 hours and 17 hours after mixing. The mark "*" and the mark "†" indicate the peak derived from 1-phenylethane-1,2-diol and the peak derived from 2-chloro-1-phenylethanol, respectively. AdditiveConversion1 2 3 none3000CF 3 COOH10015690Sc(OTf) 3 10051300

[0089] The UV-Vis absorption spectroscopy was adopted for clarifying the reaction mechanism and the detection of a reactive intermediate. As shown in FIG. 1, NaClO 2 showed the absorption band at 260 nm in an aqueous solution. The absorption band was quenched by adding Sc(OTf) 3 (10 mM), and in accordance with this, a new absorption band was increased at 358 nm, and it was identified (assigned) that this absorption band was based on ClO 2 ˙ (References, etc. 22, 23). Also in the presence of CF 3 COOH, a similar change of the absorption spectrum was measured (Reference, etc. 24). FIG. 1 shows the change of occurrence of the absorption band at 358 nm with time. FIG. 1 shows the ultraviolet-visible absorption spectrum of NaClO 2 (5.0 mM) collected 0, 4, and 16 hours after mixing with Sc(OTf) 3 (10 mM) in an aqueous solution at 298 K. In FIG. 1, the horizontal axis indicates the wavelength (nm) and the vertical axis indicates the absorbance. FIG. 2A shows a time profile of UV-Vis absorption at 358 nm in the same reaction as shown in FIG. 1 (formation of Sc 3+< (ClO 2 ˙) by a reaction between Sc(OTf) 3 (10 mM) and NaClO 2 (5.0 mM) in an aqueous solution (0.20 M acetate buffer having a pH of 2.9) at 298 K). In FIG. 2A, the horizontal axis indicates the time (second) and the vertical axis indicates the absorbance at 358 nm. FIG. 2B shows the secondary plot of the measurement result of FIG. 2A. The time profile (FIG. 2A) meets the secondary plot (FIG. 2B) well. In generation of ClO 2 ˙ using Sc(OTf) 3 , two molecules of ClO 2 -< are involved in the rate-determining step (see below). The rate constant of the two molecules was determined as 0.16 M -1< s -1< based on the slope of the straight line.

[0090] In the absence of a substrate, no decay of the absorbance at 358 nm based on ClO 2 ˙ generated from NaClO 2 using Sc(OTf) 3 was observed in MeCN at 298 K. FIG. 3A shows the time profile of UV-Vis absorption at 358 nm in consumption of Sc 3+< (ClO 2 ˙) in the presence of styrene (30 to 90 mM) in a MeCN / H 2 O (1 : 1 v / v) solution at 298 K. In FIG. 3A, the horizontal axis indicates the time (second), and the vertical axis indicates the ClO 2 ˙ concentration. FIG. 3B shows the pseudo first-order rate-styrene concentration plot. In the presence of an excessive amount of styrene, the rate of decay was in accordance with the pseudo first order (FIG. 3B). The pseudo first-order rate (k obs ) observed on the increase in dihydroxyl was increased linearly with the increase in a styrene concentration (FIG. 3B). The two-molecule rate constant of the consumption of ClO 2 ˙ and styrene was determined as 1.9 × 10 -2< M -1< s -1< (Reference, etc. 25). For clarifying the radical structure, electronic paramagnetic resonance (EPR) was performed. Pure ClO 2 ˙ was prepared by refluxing a MeCN solution containing NaClO 2 at 353 K for 1 hour. The EPR spectrum of the thus-obtained pure ClO 2 ˙ was measured after being cooled to 298 K. As a result, a distinctive isotropic signal was observed with g = 2.0151 (±0.0002) together with four hyperfine lines derived from an unpaired electron of a Cl nucleus (I = 3 / 2 in 35< Cl and 37< Cl, each having the same type of magnetic moment of 0.821 and 0.683 ((a) of FIG. 4) (Reference, etc. 26). The G value was remarkably changed by addition of CF 3 COOH (g = 2.0106) and Sc(OTf) 3 (g = 2.0103) ((b) and (c) of FIG. 4). The hyperfine binding constant of ClO 2 ˙ was decreased in the presence of CF 3 COOH (15.78 G) and Sc(OTf) 3 (15.56 G) (a(Cl) = 16.26 G) (Reference, etc. 27). This shows that proton and Sc 3+< bind to ClO 2 ˙ to form H +< ClO 2 ˙ and Sc 3+< ClO 2 ˙ as reaction intermediates for strongly dihydroxylating styrene (Reference, etc. 28).

[0091] As shown in FIG. 5, properties of ClO 2 ˙, H +< ClO 2 ˙, and Sc 3+< ClO 2 ˙ were calculated on the basis of the density functional theory (DFT), and the reaction mechanism for dihydroxylation was predicted. The optimization of a structure was performed by the theoretical calculation at the level of DFT CAM-B3LYP / 6-311+G(d, p). FIG. 5 shows the bond lengths (Å) of the DFT-optimized structures obtained by the theoretical calculation at the level of CAM-B3LYP / 6-311+G(d, p). In FIG. 5, (a) shows the result obtained regarding ClO 2 ˙; (b) shows the result obtained regarding H +< ClO 2 ˙; and (c) shows the result obtained regarding Sc 3+< ClO 2 ˙. The bond length of the Cl-O double bond of ClO 2 ˙ was calculated as 1.502 Å ((a) of FIG. 5). The bond length of the Cl-O double bond of H +< ClO 2 ˙ was calculated as 1.643 Å ((b) of FIG. 5). (c) of FIG. 5 shows that, as compared to ClO 2 , the bond strength of Sc 3+< ClO 2 ˙ is also remarkably weakened (Cl-O: 1.818 Å). There is a possibility that the cleavage of the Cl-O bond may affect advantageously on generation of ClO· as a strong oxidizing agent in the presence of a substrate. FIG. 10 shows spin distributions obtained by the theoretical calculation at the level of CAM-B3LYP / 6-311+G(d, p). In FIG. 10, (a) shows the spin distribution of H +< ClO 2 ˙ and (b) shows the spin distribution of Sc 3+< ClO 2 ˙.

[0092] On the basis of the above-described results, the dihydroxylation mechanism of styrene by ClO 2 ˙ is shown in the following reaction formulae (2) to (5) and scheme 1. The disproportionation reaction of NaClO 2 is caused in the presence of H +< or Sc 3+< , thereby forming ClO -< and ClO 3 -< [reaction formula (2)] (Reference, etc. 29). ClO -< easily reacts with ClO 2 -< and protons, thereby generating Cl 2 O 2 [reaction formula (3)]. Subsequently, Cl 2 O 2 is reduced by ClO 2 -< , thereby generating a reactive species ClO 2 ˙ [reaction formula (4)]. An overall stoichiometry is given by the reaction formula (5). ClO 2 ˙ is activated by binding to acids such as H +< and Sc 3+< . When ClO 2 binds to H +< , on the basis of the DFT calculation (see above), the Cl-O bond is not cleaved. The oxidization of styrene by H +< proceeds by addition of ClO 2 ˙ to the styrene double bond. In contrast, the dihydroxylation of styrene by Sc 3+< is caused, as shown in scheme 1, by addition of ClO· and Sc 3+< O· generated by homolytic fission of Sc 3+< Cl-O bond of a Sc 3+< ClO 2 ˙ complex to the styrene double bond. Subsequently, a scandium complex is hydrolyzed for obtaining a diol and Sc 3+< ClO· as end products (scheme 1). Sc 3+< ClO· can be reused by adding a large excessive amount of ClO 2 -< to cause Sc 3+< ClO 2 ˙ to be formed through oxidization. Also, ClO -< can be regenerated by ClO 2 -< as shown in reaction formula (2). Addition of ClO· formed by cleaving the Cl-O bond of Sc 3+< ClO 2 ˙ to β carbon of styrene gave two isomers. When the β carbon-ClO bond is formed, as shown in scheme 1, a chlorine compound was obtained as a minor end product.         ClO -< + ClO 2 -< + 2H +< → Cl 2 O 2 + H 2 O     (3)         Cl 2 O 2 + ClO 2 -< → 2ClO 2 · + Cl -<      (4)         4ClO 2 -< + 2H +< → 2ClO 2 ˙ + ClO 3 -< + Cl -< + H 2 O     (5)

[0093] As described above, it was confirmed by the present example that ClO 2 ˙ is an effective dihydroxylation reagent for styrene as a Lewis acid in the presence of Sc 3+< . The present invention can provide a unique dihydroxylation pathway of an olefin without causing hazardous wastes such as heavy metals.[References, etc.]

[0094] 1. M. Schroeder, Chem. Rev., 1980, 80, 187-213. 2. (a) E. N. Jacobsen, I. Marko, W. S. Mungall, G. Schroeder and K. B.Sharpless, J. Am. Chem. Soc., 1988, 110, 1968-1970; and (b) S. G.Hentges and K. B. Sharpless, J. Am. Chem. Soc., 1980, 102, 4263-4265. 3. W. Yu, Y. Mei, Y. Kang, Z. Hua and Z. Jin, Org. Lett., 2004, 6, 3217-3219. 4. (a) A. J. DelMonte, J. Haller, K. N. Houk, K. B. Sharpless, D. A. Singleton, T. Strassner, and A. A. Thomas, J. Am. Chem. Soc., 1997, 119, 9907-9908; and (b) J. S. M. Wai, I. Marko, J. S. Svendsen, M. G.Finn, E. N. Jacobsen and K. B. Sharpless, J. Am. Chem. Soc., 1989, 111, 1123-1125. 5. (a) S. Kobayashi, M. Endo and S. Nagayama, J. Am. Chem. Soc., 1999, 121, 11229-11230; and (b) S. Kobayashi, T. Ishida and R. Akiyama, Org. Lett., 2001, 3, 2649-2652. 6. H. C. Kolb, P. G. Andersson and K. B. Sharpless, J. Am. Chem. Soc., 1994, 116, 1278-1291. 7. E. J. Corey and M. C. Noe, J. Am. Chem. Soc., 1996, 118, 11038-11053. 8. S. Y Jonsson, K. Faernegrdh and J.-E. Baeckvall, J. Am. Chem. Soc., 2001, 123, 1365-1371. 9. H. Dodgen and H. Taube, J. Am. Chem. Soc., 1949, 71, 2501-2504. 10. J. K. Leigh, J. Rajput, and D. E. Richardson, Inorg. Chem., 2014, 53, 6715-6727. 11. C. L. Latshaw, Tappi J., 1994, 163-166. 12. (a) J. J. Leddy, in Riegel's Handbook of Industrial Chemistry, 8th edn. Ed., J. A. Kent, Van Nostrand Reinhold Co. Inc, New York, 1983, pp. 212-235; and (b) I. Fabian, Coord. Chem. Rev., 2001, 216-217, 449-472. 13. M. J. Masschelen, J. Am. Works Assoc., 1984, 76, 70-76. 14. X.-L. Geng, Z. Wang, X.-Q. Li, and C. Zhang J. Org. Chem., 2005, 70, 9610-9613. 15. A. Jangam and D. E. Richardson, Tetrahedron Lett., 2010, 51, 6481-6484. 16. J. J. Kolar and B. O. Lindgren, Acta Chem. Scand. B, 1982, 36, 599-605. 17. B. O. Lindgren, T. Nilsson, Acta Chem. Scand. B, 1974, 28, 847-852. 18. (a) S. Fukuzumi and K. Ohkubo, J. Am. Chem. Soc., 2002, 124, 10270-10271; and (b) S. Fukuzumi and K. Ohkubo, Chem.-Eur. J., 2000, 6, 4532-4535. 19. Epoxidation of styrene (66 mM) by NaClO 2 (200 mM) was checked in a MeCN / H 2 O mixture solution (4 : 1 v / v) at 333 K (Reference, etc. 14). The yield of styrene oxide was 44% and the conversion ratio of styrene was 61%. 20. E. V. Bakhmutova-Albert, D. W. Margerum, J. G. Auer and B. M. Applegate, Inorg. Chem., 2008, 47, 2205-2211. 21. As a result of measurement utilizing 1< HNMR, styrene epoxide as an intermediate in reaction by CF 3 COOH or Sc(OTf) 3 was not observed. 22. C. Rav-Acha, E. Choushen (Goldstein) and S. Sarel, Helv. Chim. Acta, 1986, 69, 1728-1733. 23. There is a possibility that ClO 2 ˙ generated from acetic anhydride and NaClO 2 (Reference, etc. 22) is in the protonated form (H +< ClO 2 ˙) in a ClO 2 ˙ aqueous solution. 24. W. Masschelein, Ind. Eng. Chem. Prod. Res. Devel., 1967, 6, 137-142. 25. This numerical value is slightly greater than the value of the conversion of styrene to epoxide by ClO 2 ˙ (1.17 × 10 -2< M -1< s -1< ) (Reference, etc. 10). 26. (a) T. Ozawa and T. Kwan, Chem. Pharm. Bull., 1983, 31, 2864-2867; and (b) T. Ozawa, T. Trends Org. Chem., 1991, 2, 51-58. 27. The calculated values of the spin distribution of Sc 3+< ClO 2 ˙ and H +< ClO 2 ˙ are shown in FIG. 10. According to this, each of Sc and H nuclei does not show a spin density. This means that the EPR spectrum does not show the hyperfine splitting derived from Sc (I = 7 / 2) or H (I = 1 / 2). 28. As to the bond between Sc 3+< and an oxo group of a metal oxo complex, see the following references: (a) J. Chen, X. Wu, K. M. Davis, Y-M. Lee, M. S. Seo, K.-B. Cho, H. Yoon, Y. J. Park, S. Fukuzumi, Y. N. Pushkar and W. Nam, J. Am. Chem. Soc., 2013, 135, 6388-6391; (b) H. Yoon, Y-M. Lee, X. Wu, K.-B. Cho, Y. N. Pushkar, W. Nam and S. Fukuzumi, J. Am. Chem. Soc., 2013, 135, 9186-9194; and (c) S. Fukuzumi, K. Ohkubo, Y.-M. Lee and W. Nam, Chem.-Eur. J., 2015, 21, 17548-17559. 29. As to the disproportionation of a neutral radical by Sc 3+< , see the following reference: I. Nakanishi, T. Kawashima, K. Ohkubo, T. Waki, Y. Uto, T. Kamada, T. Ozawa, K. Matsumoto and S. Fukuzumi, S. Chem. Commun., 2014, 50, 814-816. [Example 2 (Reference Example)]

[0095] In the present example, an oxygen reduction reaction was activated by benzethonium chloride. Research and development of Lewis acids have been carried out widely in various organic synthesis reactions. In most of the researches, a metal ion or a metal complex was used as a Lewis acid site, and the ligand design around the Lewis acid site was the main focus of the researches. In the present example, benzethonium chloride was used as an ammonium derivative having strong Lewis acidic properties, and whether the benzethonium chloride is widely useful in an oxygenation reaction of an aromatic organic compound using sodium chlorite was examined.

[0096] In acetonitrile, electron transfer does not proceed at all between cobalt (II) tetraphenylporphyrin complex Co(II)TPP (TPP = 5,10,15,20-tetraphenylporphyrin) (Eox = 0.35V vs SCE) and molecular oxygen (E red = -0.86 V vs SCE). However, when benzethonium chloride (Bzn +< ) was added to this oxygen saturated solution ([CoTPP] = 9.0 × 10 -6< M, [O 2 ] = 13 mM) ([Bzn +< Cl -< ] = 30 mM), accompanying decay of the absorption band derived from Co(II)TPP at 411 nm, an increase in absorption band characteristic of Co(III)TPP +< at 433 nm was observed with an isosbestic point ((a) of FIG. 11). In FIG. 11, (a) is a graph showing the time course of the ultraviolet-visible absorption spectrum of the solution. The horizontal axis indicates the wavelength (nm), and the vertical axis indicates the absorbance. It is considered the above behavior indicates that an electron transfer reaction from Co(II)TPP to molecular oxygen proceeded and Co(III)TPP +< was generated. The time constant of the change in decay of the absorption band at 411 nm with time was substantially the same as the time constant of the change in increase in the absorption band at 433 nm, and the rate constant was determined to be 9.3 × 10 -5< s -1< by pseudo-first-order curve fitting ((b) of FIG. 11). In the graph of (b) of FIG. 11, the horizontal axis indicates the time, and the vertical axis indicates the absorbance. This rate constant exhibited first-order dependence on the oxygen concentration and the Bzn +< concentration, and the catalytic transfer rate constant (k cat ) was determined to be 0.24 M -2< s -1< from the slope of the plot. Previous research (Ohkubo, K.; Fukuzumi, S. Chem. Eur. J., 2000, 6, 4532) has revealed that the electron transfer reaction from Co(II)TPP to molecular oxygen proceeds efficiently in the presence of a Lewis acid such as metal ions. In the case of Bzn +< used in the present research, it is considered that the reaction proceeded in a manner similar to the Lewis acid catalyzed reaction. The catalyst rate constant of Bzn +< (0.24 M -2< s -1< ) obtained in the present example was slightly lower than that of lithium perchlorate (0.36) and larger than that of strontium perchlorate (0.10 M -2< s -1< ) and barium perchlorate (0.051 M -2< s -1< ). From these results, it is considered that Bzn +< has a relatively strong Lewis acidity. From this catalyst rate constant, the ΔE value as the indicator of the Lewis acidity was determined to be 0.53 eV according to the method described in the literature. Indeed, it has been reported that ammonium salts served as Lewis acids. For example, from the fact that the ΔE value of the ammonium salt in the present example was larger than the ΔE value (0.32 eV) of ammonium hexafluorophosphate (NH 4 PF 6 ) (e.g., References, etc. 33), it was confirmed that the ammonium salt in the present example exhibits strong Lewis acidity among various types of ammonium. The graph of FIG. 21 shows the Lewis acidities of benzethonium chloride [Bzn +< Cl -< ] and various metal complexes. In FIG. 21, the horizontal axis indicates the ΔE value (eV), and the vertical axis indicates the logarithm of the rate constant (log(k cat ,M -2< s -1< )).

[0097] The structure of Bzn +< was optimized by density functional calculation (B3LYP / 6-31G(d) level). The obtained structure is shown in FIG. 12. As can be seen from FIG. 12, from the localization of Mulliken charges and LUMO in the vicinity of ammonium nitrogen, it is expected that Bzn +< exhibits Lewis acidity.[Example 3 (Reference Example)]

[0098] The present example examined the acceleration effect of a disproportionation reaction of NaClO 2 by a Lewis acid.

[0099] As confirmed in Example 1 of the present invention, degradation of sodium chlorite (NaClO 2 ) is not observed because it is very stable in a mixed solution containing a neutral aqueous solution and acetonitrile. When Sc(OTf) 3 (40 mM) was added to this 20 mM solution, accompanying the decay of the absorption band of NaClO 2 , an increase in absorption band characteristic of ClO 2 radicals (ClO 2 ·< ) was observed at 358 nm immediately (FIG. 13). In FIG. 13, the horizontal axis indicates the wavelength (nm), and the vertical axis indicates the absorbance. The increase in this absorption band could be observed as a change over time by decreasing the concentration of Sc(OTf) 3 , as confirmed in Example 1 of the present invention (FIG. 1). By conducting similar studies on magnesium ions, lithium ions, and the like having lower Lewis acidities than scandium ions, the reaction rate constants of the respective ions were determined. It is known that Lewis acids catalyze various disproportionation reactions. In this reaction, it is considered that ClO 2 -< is disproportionated to ClO -< and ClO 3 -< according to the reaction formula (2) of Example 1 of the the present invention by a similar mechanism. Thereafter, it is considered that the generated ClO -< reacts with ClO 2 -< , which is present in a large excessive amount, in the presence of an acid and gives Cl 2 O 2 (the reaction formula (3) of Example 1 of the present invention). Thereafter, it is considered that Cl 2 O 2 further reacts with ClO 2 -< and gives ClO 2 radicals as active radical species (the reaction formula (4) of Example 1 of the present invention).[Example 4 (Reference Example)]

[0100] The present example examined the generation of ClO 2 radicals and acceleration of an oxidation reaction using benzethonium chloride.

[0101] ClO 2 radicals are considered to exhibit strong oxygenation reaction activity. Thus, first, in a mixed solution containing deoxygenated acetonitrile and water (deoxygenated acetonitrile : water = 1 : 1 v / v), 10-methyl-9,10-dihydroacridine (AcrH 2 ) (1.4 mM) and sodium chlorite (NaClO 2 ) (2.8 mM) were added. In this case, there was almost no progress in an oxygenation reaction of AcrH 2 (FIG. 14). In FIGs. 14, (a) to (c) are graphs each showing the time course of the reaction. In the graph (a) of FIG. 14, the horizontal axis indicates the wavelength (nm), and the vertical axis indicates the absorbance. The graph (b) of FIG. 14 shows the time course of the absorbance at a wavelength of 358 nm. In the graph (b) of FIG. 14, the horizontal axis indicates the time (second), and the vertical axis indicates the absorbance. The graph (c) of FIG. 14 shows the time course of the absorbance at a wavelength of 387 nm. In the graph (c) of FIG. 14, the horizontal axis indicates the time (second), and the vertical axis indicates the absorbance.

[0102] Next, the same mixed solution as that shown in FIG. 14 was prepared. When Bzn +< (0.56 mM) was further added to the mixed solution, an oxygenation reaction from AcrH 2 to 10-methylacridone proceeded (FIG. 15). In FIG. 15, (a) and (b) are graphs each showing the time course of the reaction. In the graph (a) of FIG. 15, the horizontal axis indicates the wavelength (nm), and the vertical axis indicates the absorbance. The graph (b) of FIG. 15 shows the time course of the absorbance at a wavelength of 387 nm. In the graph (b) of FIG. 15, the horizontal axis indicates the time (second), and the vertical axis indicates the absorbance. As can be seen from the graphs (a) and (b) of FIG. 15, an increase in absorption derived from 10-methylacridone (λmax = 382 nm) with time was observed. This demonstrates that the oxygenation (oxidation) reaction from AcrH 2 to 10-methylacridone proceeded.

[0103] Also, when scandium trifluoromethanesulfonate (Sc(OTf) 3 ,3.0 mM) was further added to the same mixed solution as that shown in FIG. 15, an oxygenation reaction from AcrH 2 to 10-methylacridone proceeded (FIG. 16). In FIG. 16, (a) and (b) are graphs each showing the time course of the reaction. In the graph (a) of FIG. 16, the horizontal axis indicates the wavelength (nm), and the vertical axis indicates the absorbance. The graph (b) of FIG. 16 shows the time course of the absorbance at a wavelength of 430 nm. In the graph (b) of FIG. 16, the horizontal axis indicates the time (second), and the vertical axis indicates the absorbance. As can be seen from the graphs (a) and (b) of FIG. 16, an increase in absorption derived from 10-methylacridone with time was observed. This demonstrates that the oxygenation (oxidation) reaction from AcrH 2 to 10-methylacridone proceeded. It is considered that this oxygenation reaction proceeds through the chain reaction mechanism shown in FIG. 17. That is, it is considered that, in this reaction, ClO 2 ˙ abstracts hydrogen from 10-methylacridone and add oxygen to the 10-methylacridone at the same time, thereby forming acridone. On the other hand, it is considered that ClO 2 ˙, which is a product obtained after the addition of the oxygen, caused an electron transfer reaction with ClO 2 -< and regenerates while giving ClO -< and ClO 2 ˙.[Example 5 (Reference Example)]

[0104] In the present example, an oxygenation reaction of a substrate by NaClO 2 using a Lewis acid was used for an oxygenation reaction from triphenylphosphine to triphenylphosphine oxide in order to examine whether it works. More specifically, the oxygenation reaction from triphenylphosphine to triphenylphosphine oxide by NaClO 2 was performed in the presence and the absence of scandium triflate Sc(OTf) 3 , which is a Lewis acid in order to examine whether the Lewis acid promotes the reaction.

[0105] First, under the following conditions, in the presence or absence of Sc(OTf) 3 , the reaction was performed at ordinary temperature and atmospheric pressure (no light irradiation), and the reaction was traced by the ultraviolet-visible absorption spectrum. The ultraviolet-visible absorption spectrum shown in (a) of FIG. 22 shows the conversion of triphenylphosphine to triphenylphosphine oxide over time. In (a) of FIG. 22, the horizontal axis indicates the wavelength (nm), and the vertical axis indicates the absorbance. The graph shown in (b) of FIG. 22 shows the changes of a triphenylphosphine (Ph 3 P) concentration over time in the presence and the absence of Sc(OTf) 3 (Sc 3+< ). In (b) of FIG. 22, the horizontal axis indicates the time (second), and the vertical axis indicates the triphenylphosphine (Ph 3 P) concentration (mM). As shown in (b) of FIG. 22, while the reaction rate constant k calculated from the curve in the absence of Sc 3+< was 9.8 × 10 -4< S -1< , the reaction rate constant k calculated from the curve in the presence of Sc 3+< was increased to 1.7 × 10 -3< S -1< . Thus, it was confirmed that Sc 3+< (a Lewis acid) promoted the reaction. Ph 3 P = 0.4 mM NaClO 2 = 0.4 mM Sc OTf 3 = 0 or 10 mM 0.12M acetate buffer, pH5.3 MeCN / H 2 O (4 : 6)

[0106] The reaction did not proceed at all by mixing triphenylphosphine and NaClO 2 (4.0 mM) in deoxygenated acetonitrile MeCN / H 2 O (0.9 ml / 0.1 ml). By adding scandium triflate Sc(OTf) 3 (30 mM) thereto, oxygenated products were produced efficiently. The initial concentration of triphenylphosphine was set to 1.0 mM, 2.0 mM, 4.0 mM, or 8.0 mM, and each reaction was performed at 25°C for 15 minutes. The reaction was traced by monitoring the change in the ultraviolet-visible absorption spectrum ((a) of FIG. 18). In (a) of FIG. 18, the horizontal axis indicates the wavelength (nm), and the vertical axis indicates the absorbance. As can be seen from (a) of FIG. 18, it can be considered that ClO 2 radicals as active radical species were generated by scandium ions Sc 3+< , and Ph 3 P was oxygenated to Ph 3 P=O. The stoichiometry is as represented by the following reaction formula (6), and it was confirmed that the reaction proceeds almost quantitatively ((b) of FIG. 18). In (b) of FIG. 18, the horizontal axis indicates the initial concentration of Ph 3 P, and the vertical axis indicates the concentration of the generated Ph 3 P = O .         2Ph 3 P + NaClO 2 → 2Ph 3 P=O + NaCl     (6) [Example 6 (Reference Example)]

[0107] In the present example, an oxidation reaction of a raw material aromatic compound (benzaldehyde) was performed in acetonitrile in the presence of perchlorate (Acr +< -Mes ClO 4 -< ) of 9-mesityl-10-methylacridinium (Acr +< -Mes) and oxygen, thereby obtaining an oxidation reaction product (benzoic acid) (FIG. 20). The reaction was performed in the presence or absence of Bzn +< Cl -< .

[0108] As a reaction solvent, 0.6 ml of CD 3 CN saturated with oxygen gas was used. As shown in FIG. 20, 1 mM of Acr +< -Mes ClO 4 -< , 5 mM of benzaldehyde (PhCHO), and 0 or 1 mM of Bzn +< Cl -< were added thereto, and the resultant mixture was or was not irradiated with light at a wavelength of 390 nm emitted from a xenon lamp. The reaction was traced by 1< HNMR. The results obtained are shown in the table in FIG. 20. In the table, "×" means the reagent was not added or light irradiation was not performed; "∘" means light irradiation was performed; "conversion" indicates the conversion rate of the raw material aromatic compound (benzaldehyde); "yield" indicates the yield of the benzoic acid; and "time" indicates the reaction time. As can be seen from FIG. 20, in the case where Bzn +< Cl -< was not added, the yield of the benzoic acid was a trace amount. In the case where Bzn +< Cl -< was added, the yield of the benzoic acid was 60%, and the conversion rate of the benzaldehyde was 63%. It is considered this result indicates that, while the reactivity of Acr +< -Mes was low in the absence of the Lewis acid (Bzn +< Cl -< ), generation of radicals from Acr +< -Mes was promoted in the presence of the Lewis acid (Bzn +< Cl -< ), which suggests that the Lewis acid (Bzn +< Cl -< ) served as a strong reaction promoter.[Example 7 (Reference Example)]

[0109] In the present example, according to the measurement method described in the above section "Measurement method of Lewis acidity", oxidation reaction products of cobalt tetraphenylporphyrin were produced using various types of ammonium as radical generating catalysts and oxygen molecules as a radical source (also serving as an oxidizing agent). More specifically, as to acetonitrile (MeCN) that contains cobalt tetraphenylporphyrin in the following chemical reaction formula (1a), saturated O 2 , and an object whose Lewis acidity is to be measured (e.g., a cation of a metal or the like, represented by M n+< in the following chemical reaction formula (1a)), the change of the ultraviolet-visible absorption spectrum was measured at room temperature, and whether CoTPP +< was obtained as an oxidation reaction product was examined.

[0110] The oxidation reaction was performed using each type of ammonium shown in the following table as a radical generating catalyst. In the following table, the numerical value expressed in the unit "k cat ,M -2< s -1< " is a rate constant of reaction between CoTPP and oxygen in the presence of Lewis acid, which is an indicator of the Lewis acidity of each ammonium. The numerical value expressed in the unit "LUMO, eV" is the energy level of LUMO. The "benzetonium chloride" means benzethonium chloride, "benzalkonium chloride" means benzalkonium chloride, "tetramethylammonium hexafluorophosphate" means tetramethylammonium hexafluorophosphate, "tetrabutylammonium hexafluorophosphate" means tetrabutylammonium hexafluorophosphate, and "ammonium hexafluorophosphate" means ammonium hexafluorophosphate (Note from translator: in the original text in Japanese, the above sentence explains the meanings of the English terms in the table in Japanese). [Table tpp]LUMO, eVk cat , M -2< s -1< benzetonium chloride-4.120.24benzalkonium chloride-4.020.18tetramethylammonium hexafluorophosphate-3.58> 0.1tetrabutylammonium hexafluorophosphate-2.07> 0.1ammonium hexafluorophosphate-5.7320 [Examples of Drug]

[0111] Next, specific examples of the drug of the present invention will be described. Drugs used in the following examples of the present invention and comparative examples were produced in the following manners.Example 1 of the drug of the present invention:

[0112] 5 g of sodium chlorite was dissolved in purified water to obtain 100 ml of an aqueous solution. Thus, the 40,000 ppm sodium chlorite aqueous solution was obtained (solution A). 0.1 g of benzethonium chloride was dissolved in 100 ml of purified water to prepare a 100 ml of 1000 ppm aqueous solution (solution B). 0.1 M phosphate-NaOH buffer (pH = 9.5) was provided. To 600 ml of purified water at pH 7, 20 ml of the solution A diluted 10-fold and 80 ml of the buffer were added, and then 80 ml of the solution B was added. Purified water was further added to make the total amount 800 ml. In this manner, the drug according to Example 1 of the drug of the present invention was obtained.Example 2 of the drug of the present invention:

[0113] 5 g of sodium chlorite was dissolved in purified water to obtain 100 ml of an aqueous solution. Thus, the 40,000 ppm sodium chlorite aqueous solution was obtained. 0.1 g of benzethonium chloride was dissolved in 100 ml of purified water to prepare a 1000 ppm aqueous solution. The 40,000 ppm sodium chlorite aqueous solution was diluted 40-fold to obtain a 1000 ppm aqueous solution. 10 ml of the sodium chlorite aqueous solution and 10 ml of the benzethonium chloride aqueous solution were added to 80 ml of purified water to obtain a 100 ppm aqueous solution. In this manner, a drug according to Example 2 of the drug of the present invention was obtained.

[0114] Comparative Example 1 of the drug of the present invention: a bactericide containing sodium hypochlorite and water (commercially available product) Comparative Example 2 of the drug of the present invention: a sterilizing deodorizer containing sodium hypochlorite (commercially available product) Comparative Example 3 of the drug of the present invention: a sterilizing deodorizer containing hypochlorous acid and water (commercially available product) Comparative Example 4 of the drug of the present invention: a sterilizing deodorizer containing sodium hypochlorite and water (commercially available product) Comparative Example 5 of the drug of the present invention: a sterilizing deodorizer containing sodium hypochlorite and water (commercially available product) Comparative Example 6 of the drug of the present invention: a sodium chlorite standard solution 1000 ppm (test product) Comparative Example 7 of the drug of the present invention: 5 g of sodium chlorite (Wako Pure Chemical Industries, Ltd.) was dissolved in 100 ml of purified water to prepare a 40,000 ppm aqueous solution. The 40,000 ppm aqueous solution was further diluted with purified water to obtain a 100 ppm aqueous solution. In this manner, a test product according to Comparative Example 7 of the drug of the present invention was obtained. Comparative Example 8 of the drug of the present invention: a benzethonium chloride aqueous solution (test product) (Experimental Example 1 of Drug of Invention)

[0115] In Experimental Example 1 of the drug of the present invention, the following were provided first.

[0116] Bacterial strains to be used: Staphylococcus aureus Escherichia coli MV1184 Bacterial solution:

[0117] Bacteria cultured in a BHI agar medium were collected with a platinum loop and placed in a BHI liquid medium, and the BHI liquid medium was shaken. The bacteria were allowed to grow in the BHI liquid medium for a whole day and night. 50 µl of the resultant culture solution was diluted 190-fold with a BHI liquid medium, and mixed well with the BHI liquid medium by stirring. The resultant mixture was used as a bacterial solution.

[0118] Using each bacterial strain and bacterial solution, the effect was examined in the following manner.

[0119] A microplate (with a lid) was sterilized for 10 minutes with a UV sterilization lamp. Next, a BHI liquid medium, the bacterial solution, and the drug according to Example 1 of the drug of the present invention were injected in this order into each well with a micropipette. The bacteria were cultured at 37°C for 24 hours. Thereafter, the bacteria were examined using a microplate reader, and the minimum inhibitory concentration (MIC) was determined. As a control, the same examination was performed using the liquid medium only. Further, 10 µl of the culture solution was collected from the well in the vicinity of the MIC, and inoculated in a petri dish. The bacteria were cultured at 37°C for 24 hours, and the minimum bactericidal concentration (MBC) was determined. The results obtained are shown in Table 4.

[0120] Using the bactericide according to Comparative Example 1 of the drug of the present invention instead of the drug according to Example 1 of the drug of the present invention, the MIC and MBC were determined in the same manner. The results obtained are shown in Table 4.

[0121] Using each of the sterilizing deodorizers according to Comparative Examples 2 to 5 of the drug of the present invention instead of the drug according to Example 1 of the drug of the present invention, the MIC of the Staphylococcus aureus was determined in the same manner. The results obtained are shown in Table 4.

[0122] Using the test product according to Comparative Example 6 of the drug of the present invention instead of the drug according to Example 1 of the drug of the present invention, the MIC of the Staphylococcus aureus and the MIC and MBC of the Escherichia coli were determined in the same manner. The results obtained are shown in Table 4. [Table 4]Ex. 1Comp. Ex. 1Comp. Ex. 2Comp. Ex. 3Comp. Ex. 4Comp. Ex. 5Comp. Ex. 6S. aureusMIC (ppm)1.56300ineffectiveineffectiveineffectiveineffective40MBC (ppm)3.12300E. coliMIC (ppm)12.522030MBC (ppm)20.022050 (Experimental Example 2 of Drug of Invention)

[0123] Using the drug according to Example 2 or Comparative Example 7 or 8 of the drug of the present invention instead of the drug according to Example 1 of the drug of the present invention, the MIC of the Escherichia coli was determined in the same manner. The results obtained are shown in Table 5. [Table 5]Ex. 2Comp. Ex. 7Comp. Ex. 8E. coliMIC (ppm)12.5 >25 <17.5 (Experimental Example 3 of Drug of Invention)

[0124] In Experimental Example 3 of the drug of the present invention, the following were provided first. Bacterial strain to be used: Streptococcus pyogenesBacterial solution:

[0125] A bacterial solution was obtained in the same manner as in Experimental Example 1 of the drug of the present invention.

[0126] Using the above bacterial strain and bacterial solution and the drug according to Example 1 of the drug of the present invention, the MIC and MBC were determined in the same manner as in Experimental Example 1 of the drug of the present invention. The results obtained are shown in Table 6. [Table 6]Ex. 3Streptococcus pyogenesMIC (ppm)0.1MBC (ppm)1.0 (Experimental Example 4 of Drug of Invention)

[0127] In Experimental Example 4 of the drug of the present invention, the following were provided first. Bacterial strains to be used: Streptococcus mutansBacterial solution:

[0128] Bacteria cultured in a BHI agar medium were collected with a platinum loop and placed in a BHI liquid medium, and the BHI liquid medium was shaken. The bacteria were allowed to grow in the BHI liquid medium for a whole day and night. 50 µl of the resultant culture solution was diluted 190-fold with a BHI liquid medium, and mixed well with the BHI liquid medium by stirring. The resultant mixture was used as a bacterial solution.

[0129] Using each bacterial strain and bacterial solution, the effect was examined in the following manner.

[0130] The bacterial solution was injected with a micropipette into a BHI liquid medium placed in each of two test tubes. Saccharose was added thereto so that the concentration thereof was 0.2%. The bacteria were cultured at 37°C for 18 hours to allow them to form a biofilm. The medium in each test tube was discarded in a beaker, and the biofilm was washed twice with PBS. The drug according to Example 1 of the drug of the present invention was injected into one of the test tube, and PBS was injected into the other test tube. Then, the test tubes were shaken at 37°C for 30 minutes. The liquid in each test tube was discarded in a beaker, and the biofilm was washed twice with PBS. A BHI liquid medium was injected into the test tubes, and the bacteria were cultured at 37°C for 24 hours. 10 µl of the medium collected from each test tube was inoculated into a nutrient agar medium, and the bacteria were cultured at 37°C for 24 hours. The presence or absence of colonies was checked through visual observation. As a result, while no colony was observed in the test tube to which the drug according to Example 1 of the drug of the present invention had been injected, many colonies were observed in the test tube to which PBS had been injected.

[0131] In order to examine the effect of the drug on the bacterial cells in the biofilm, the following test was conducted further.

[0132] The bacterial solution was injected with a micropipette into a BHI liquid medium placed in microtubes. Saccharose was added thereto so that the concentration thereof was 0.2%. The bacteria were cultured at 37°C for 18 hours to allow them to form a biofilm. The medium in each microtube was discarded in a beaker, and the biofilm was washed twice with PBS. The drug according to Example 1 of the drug of the present invention was injected into one of the microtubes, and PBS was injected into the other microtube. The bacteria in the former microtube and the bacteria in the latter microtube were aged at 37°C for 15 minutes and 30 minutes, respectively. The liquid in each microtube was discarded in a beaker, and the biofilm was washed twice with PBS. A BHI liquid medium was injected into the test tubes and homogenized. Thereafter, the bacteria were cultured at 37°C for 24 hours. 10 µl of the medium collected from each microtube was inoculated into a nutrient agar medium, and the bacteria were cultured at 37°C for 24 hours. The presence or absence of colonies was checked through visual observation. As a result, while no colony was observed in the microtube to which the drug according to Example 1 of the drug of the present invention had been injected, many colonies were observed in the microtube to which PBS had been injected. These results demonstrate that, by impregnating a biofilm with the drug according to Example 1 of the drug of the present invention, the drug acts on bacteria deep inside the biofilm to exhibit the sterilizing effect.(Experimental Example 5 of Drug of Invention)

[0133] In Experimental Example 5 of the drug of the present invention, the following bacterial strains were used. Except for this, the MIC and MBC were determined using the drug according to Example 1 of the drug of the present invention in the same manner as in Experimental Example 1 of the drug of the present invention. The results obtained are shown in Table 7. Bacterial strains to be used: Bacteria 1 (Porphyromonas gingivalis) Bacteria 2 (Treponema denticola) Bacteria 3 (Tannerella forsythensis) Bacteria 4 (Aggregatibacter actinomycetemcomitans) [Table 7] Ex. 1Bacteria 1MIC (ppm)20.0MBC (ppm)20.0Bacteria 2MIC (ppm)25.0MBC (ppm)25.0Bacteria 3MIC (ppm)12.5MBC (ppm)12.5Bacteria 4MIC (ppm)35-45MBC (ppm)35-50 (Experimental Example 6 of Drug of Invention)

[0134] Test pieces (25.4 mm × 25.4 mm) respectively made of iron, aluminum, tin plate, and stainless steel were washed. Thereafter, the test pieces made of each material were immersed in resin containers containing the drug according to Example 1 of the drug of the present invention, a 1.2% sodium hypochlorite aqueous solution, and tap water, respectively, and then, the resin containers were covered with a lid. The test pieces were taken out on a nonwoven fabric after a lapse of each time period shown in Tables 8 and 9, and the conditions of the test pieces were examined through visual observation. In the examination, pictures were taken when necessary, and a microscope was used when the change was subtle. The evaluation was made using the following evaluation criteria.

[0135] -: no corrosion ±: generation of rust +: fairly large amount of rust ++: vary large amount of rust +++: corrosion of metal surfaces [Table 8] Test piece10 min30 min1 hr3 hr6 hrIronExample 1+++++Hypochlorous acid++++++++++Tap water+++++AluminumExample 1-----Hypochlorous acid+++++Tap water-----Tin plateExample 1-----Hypochlorous acid---++Tap water-----Stainless steelExample 1-----Hypochlorous acid-----Tap water----- [Table 9] Test piece1 day3 days1 week2 weeks3 weeks4 weeksIronExample 1++++++Hypochlorous acid++++++++++++++++++Tap water++++++AluminumExample 1------Hypochlorous acid+++++++++++++++Tap water------Tin plateExample 1-±±±±±Hypochlorous acid+++++++++++++++Tap water-±±+++Stainless steelExample 1------Hypochlorous acid------Tap water------ (Experimental Example 7 of Drug of Invention)

[0136] The deodorizing performance test was conducted in accordance with JEM 1467 "domestic air cleaner" in the Standards of the Japan Electrical Manufacturers' Association. In the measurement, cigarettes were burned while operating a circulator in an acrylic container (1 m in height × 1 m in width × 1 m in depth) with an internal volume of 1 m 3< to fill the container with smoke. After all the cigarettes were burned, the circulator was stopped, and the drug according to Example 1 of the drug of the present invention was sprayed in the container by operating a sprayer. The concentrations of three components, namely, ammonia, acetaldehyde, and acetic acid, in the container were measured over 2 hours at regular intervals to trace the change in concentrations. Similarly, formaldehyde vapor was injected into an acrylic container and the formaldehyde concentration in the container was measured over 2 hours at regular intervals to trace the change in concentration. The sprayer was operated in "Manual" mode. As a control, a blank test in which the sprayer was not operated was also conducted. The results obtained are shown in Tables 10 to 13. The malodorous components were measured using detector tubes (Gastec Corporation). The detector tubes used for the measurement are shown below.Detector tubes used for measurement

[0137] ammonia:No. 3Lacetaldehyde:No. 92Lacetic acid:No. 81Lformaldehyde:No. 91 [Table 10] Elapsed timeAmmonia concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start3032-5 min8327310 min5328320 min4328730 min2329345 min1319760 min1>3197 <90 min1>3197 <120 min1>2697 < [Table 11] Elapsed timeAcetaldehyde concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start1414-5 min12141410 min10142920 min10142930 min7145045 min7145060 min7145090 min71450120 min61457 [Table 12] Elapsed timeAcetic acid concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start1210-5 min0.5 >1096 <10 min0.5 >1096 <20 min0.5 >1096 <30 min0.5 >1096 <45 min0.5 >1096 <60 min0.5 >9.596 <90 min0.5 >9.096 <120 min0.5 >9.096 < [Table 13] Elapsed timeFormaldehyde concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start2020-5 min10205010 min8206020 min5207530 min3208545 min2209060 min2209090 min21890120 min21890 (Experimental Example 8 of Drug of Invention)

[0138] The drug according to Example 1 of the drug of the present invention was sprayed using a sprayer to measure the deodorizing performance for cigarette odor. First, cigarettes were burned in a room with a 6-tatami mat size to fill the room with smoke at a predetermined concentration. Next, a sprayer was set in the room, and the odor intensity in the room was measured three times, namely, before operating the sprayer, one hour after operating the sprayer, and two hours after operating the sprayer. The sprayer was set near a wall in the room, and the odor was collected at a height of 1 m in the middle of the room. Two circulation fans were set in the room, and they were operated at all times to maintain the air-circulating conditions. The sprayer was operated in "Manual" mode. As a control, a blank test in which the sprayer was not operated was also conducted. The odor intensity was determined as follows according to the six-grade odor intensity measurement method. The results obtained are shown in Table 14.

[0139] The odor intensity was evaluated by six testers (test panel). The results were calculated by determining the average value of the odor intensities given by the respective testers. The six-grade odor intensity measurement method is a method for converting odor intensity to a numerical value using human olfaction. The members of the test panel who had joined the test were those who had taken the legally-required olfactometry and had been admitted as having normal olfaction.

[0140] In the six-grade odor intensity measurement method, the following numerical values are used as evaluation criteria. 0: odorless 1: barely perceivable odor (detection threshold concentration) 2: weakly perceivable odor (recognition threshold concentration) 3: easily perceivable odor 4: strong odor 5: very strong odor [Table 14] Elapsed timeOdor intensityExample 1Blank testStart4.64.51 h3.54.52 h2.94.2 (Experimental Example 9 of Drug of Invention)

[0141] The drug according to Example 1 of the drug of the present invention was sprayed with a sprayer to measure the performance thereof to remove airborne bacteria (general bacteria, fungi). First, a sprayer was set in a room with a 6-tatami mat size, and the concentration of airborne bacteria in the air was measured three times, namely, before operating the sprayer, one hour after operating the sprayer, and two hours after operating the sprayer. The sprayer was set near a wall in the room, and the airborne bacteria were collected at a height of 1 m in the middle of the room. Two circulation fans were set in the room, and they were operated at all times to maintain the air-circulating conditions. The airborne bacteria were measured by a filtration method using a membrane filter. The sprayer was operated in "Manual" mode. As a control, a blank test in which the sprayer was not operated was also conducted. The results obtained are shown in Tables 15 and 16.Measurement conditions etc. in Experimental Example 9 of the drug of the present invention

[0142] Filter to be used:Toyo Roshi Kaisha, Ltd., 37 mm MonitorsAmount of sucked air:300 l (sucked for 15 minutes at 20 l / min)Medium to be used:m-TGE Broth liquid medium for general bacteria (Toyo Seisakusho Kaisha, Ltd.)m-Green Y & M Broth liquid medium for fungi (Toyo Seisakusho Kaisha, Ltd.)Culture conditions:30°C for 72 hours for general bacteria30°C for 5 days for fungi [Table 15] Elapsed timeThe number of airborne general bacteria (the number of bacteria / 300 l)Example 1Example 1Blank testRemoval rate (%)Start1311-1 h0111002 h011100 [Table 16] Elapsed timeThe number of airborne fungi (the number of fungi / 300 l)Example 1Example 1Blank testRemoval rate (%)Start1011-1 h0101002 h09100 (Experimental Example 10 of Drug of Invention)

[0143] In Experimental Example 10 of the drug of the present invention, the following bacterial strains were used. Except for this, the MIC or MBC was determined using the drug according to Example 1 of the drug of the present invention in the same manner as in Experimental Example 1 of the drug of the present invention. The results obtained are shown in Table 17. Bacterial strains to be used: Streptococcus mutans hemolytic streptococcus Bacillus subtilis Candida albicans [Table 17] Example 1Streptococcus mutansMIC (ppm)5MBC (ppm)15Hemolytic streptococcusMIC (ppm)0.1MBC (ppm)1.0Bacillus subtilisMIC (ppm)12.5MBC (ppm)Candida albicansMIC (ppm)5 >MBC (ppm) (Experimental Example 11 of Drug of Invention)

[0144] Using the drug according to Example 1 of the drug of the present invention, a deodorization test was performed in accordance with an instrumental analysis implementation manual; a detector tube method, a gas chromatography method (the Certification Standards of Antibacterial Finished Textile Products of Japan Textile Evaluation Technology Council were applied with necessary modifications). The results obtained are shown in Table 18. [Table 18]Odor componentImpression of odorConcentration 1 (ppm)Concentration 2 (ppm)Gas reduction rate (%)ammoniaexcrement100793acetic acidvinegar50198hydrogen sulfiderotten egg4.000.1297methyl mercaptanrotten onion8.004.9638tritylaminerotten fish28.003.0889isovaleric acidmusty socks38.000.3899Concentration 1: initial gas concentration Concentration 2: gas concentration after a lapse of 2 hours Gas reduction rate: ([concentration 1 - concentration 2] / concentration 1) × 100 (Experimental Example 12 of Drug of Invention)

[0145] The drug according to Example 1 of the drug of the present invention was applied to acne lesions for 14 consecutive days (a few times a day, about 2 ml / time). As a result, it was clear that the acne was healed by the application of the drug. This result demonstrates that the drug of the present invention is useful as an acne treatment agent.[Further Examples of Drug of Invention]

[0146] Next, specific examples of the drug of the present invention will be described.. In examples of the present invention to be described below, drugs for use in agriculture and livestock industry according to the examples also may be referred to simply as "drugs".

[0147] First, as drugs to be used in the following experimental examples of the drug of the invention, drugs according to examples of the drug of the present invention and comparative examples were produced in the following manners.Further Example 1 of the drug of the present invention:

[0148] 5 g of sodium chlorite was dissolved in purified water to obtain 100 ml of an aqueous solution. Thus, the 40,000 ppm sodium chlorite aqueous solution was obtained (solution A). 0.1 g of benzethonium chloride was dissolved in 100 ml of purified water to prepare a 100 ml of 1000 ppm aqueous solution (solution B). 0.1 mol / l phosphate-NaOH buffer (pH = 9.5) was provided. To 600 ml of purified water at pH 7, 20 ml of the solution A diluted 10-fold and 80 ml of the buffer were added, and then 80 ml of the solution B was added. Purified water was further added to make the total amount 800 ml. In this manner, the drug according to Further Example 1 of the drug of the present invention was obtained.Further Example 2 of the drug of the present invention:

[0149] 5 g of sodium chlorite was dissolved in purified water to obtain 100 ml of an aqueous solution. Thus, the 40,000 ppm sodium chlorite aqueous solution was obtained. 0.1 g of benzethonium chloride was dissolved in 100 ml of purified water to prepare a 1000 ppm aqueous solution. The 40,000 ppm sodium chlorite aqueous solution was diluted 40-fold to obtain a 1000 ppm aqueous solution. 10 ml of the sodium chlorite aqueous solution and 10 ml of the benzethonium chloride aqueous solution were added to 80 ml of purified water to obtain a 100 ppm aqueous solution. In this manner, a drug according to Further Example 2 of the drug of the present invention was obtained.

[0150] Further Comparative Example 1 of the drug of the present invention: a bactericide containing sodium hypochlorite and water (commercially available product) Further Comparative Example 2 of the drug of the present invention: a sterilizing deodorizer containing sodium hypochlorite (commercially available product) Further Comparative Example 3 of the drug of the present invention: a sterilizing deodorizer containing hypochlorous acid and water (commercially available product) Further Comparative Example 4 of the drug of the present invention: a sterilizing deodorizer containing sodium hypochlorite and water (commercially available product) Further Comparative Example 5 of the drug of the present invention: a sterilizing deodorizer containing sodium hypochlorite and water (commercially available product) Further Comparative Example 6 of the drug of the present invention: a sodium chlorite standard solution 1000 ppm (test product) Further Comparative Example 7 of the drug of the present invention: 5 g of sodium chlorite (Wako Pure Chemical Industries, Ltd.) was dissolved in 100 ml of purified water to prepare a 40,000 ppm aqueous solution. The 40,000 ppm aqueous solution was further diluted with purified water to obtain a 100 ppm aqueous solution. In this manner, a test product according to Comparative Example 7 of the drug of the present invention was obtained. Further Comparative Example 8 of the drug of the present invention: a benzethonium chloride aqueous solution (test product) (Further Experimental Example 1 of Drug of Invention)

[0151] In Further Experimental Example 1 of the drug of the present invention, the following were provided first. Bacterial strains to be used: Staphylococcus aureus Escherichia coli MV1184 Bacterial solution:

[0152] Bacteria cultured in a BHI agar medium were collected with a platinum loop and placed in a BHI liquid medium, and the BHI liquid medium was shaken. The bacteria were allowed to grow in the BHI liquid medium for a whole day and night. 50 µl of the resultant culture solution was diluted 190-fold with a BHI liquid medium, and mixed well with the BHI liquid medium by stirring. The resultant mixture was used as a bacterial solution.

[0153] Using each bacterial strain and bacterial solution, the effect was examined in the following manner.

[0154] A microplate (with a lid) was sterilized for 10 minutes with a UV sterilization lamp. Next, a BHI liquid medium, the bacterial solution, and the drug according to Further Example 1 of the drug of the present invention were injected in this order into each well with a micropipette. The bacteria were cultured at 37°C for 24 hours. Thereafter, the bacteria were examined using a microplate reader, and the minimum inhibitory concentration (MIC) was determined. As a control, the same examination was performed using the liquid medium only. Further, 10 µl of the culture solution was collected from the well in the vicinity of the MIC, and inoculated in a petri dish. The bacteria were cultured at 37°C for 24 hours, and the minimum bactericidal concentration (MBC) was determined. The results obtained are shown in Table 19.

[0155] Using the bactericide according to Further Comparative Example 1 of the drug of the present invention instead of the drug according to Further Example 1 of the drug of the present invention, the MIC and MBC were determined in the same manner. The results obtained are shown in Table 19.

[0156] Using each of the sterilizing deodorizers according to Further Comparative Examples 2 to 5 of the drug of the present invention instead of the drug according to Further Example 1 of the drug of the present invention, the MIC of the Staphylococcus aureus was determined in the same manner. The results obtained are shown in Table 19.

[0157] Using the test product according to Further Comparative Example 6 of the drug of the present invention instead of the drug according to Further Example 1 of the drug of the present invention, the MIC of the Staphylococcus aureus and the MIC and MBC of the Escherichia coli were determined in the same manner. The results obtained are shown in Table 19. [Table 19]Ex. 1Comp. Ex. 1Comp. Ex. 2Comp. Ex. 3Comp. Ex. 4Comp. Ex. 5Comp. Ex. 6S. aureusMIC (ppm)1.56300ineffectiveineffectiveineffectiveineffective40MBC (ppm)3.12300E. coliMIC (ppm)12.522030MBC (ppm)20.022050 (Further Experimental Example 2 of Drug of Invention)

[0158] Using the drug according to Further Example 2 or Further Comparative Example 7 or 8 of the drug of the present invention instead of the drug according to Further Example 1 of the drug of the present invention, the MIC of the Escherichia coli was determined in the same manner. The results obtained are shown in Table 20. [Table 20]Ex. 2Comp. Ex. 7Comp. Ex. 8E. coliMIC (ppm)12.5 >25 <17.5 (Further Experimental Example 3 of Drug of Invention)

[0159] In Further Experimental Example 3 of the drug of the present invention, the following were provided first. Bacterial strain to be used: Streptococcus pyogenesBacterial solution:

[0160] A bacterial solution was obtained in the same manner as in Further Experimental Example 1 of the drug of the present invention.

[0161] Using the above bacterial strain and bacterial solution and the drug according to Further Example 1 of the drug of the present invention, the MIC and MBC were determined in the same manner as in Further Experimental Example 1 of the drug of the present invention. The results obtained are shown in Table 21. [Table 21]Ex. 1Streptococcus pyogenesMIC (ppm)0.1MBC (ppm)1.0 (Further Experimental Example 4 of Drug of Invention)

[0162] In Further Experimental Example 4 of the drug of the present invention, the following were provided first. Bacterial strains to be used: Streptococcus mutansBacterial solution:

[0163] Bacteria cultured in a BHI agar medium were collected with a platinum loop and placed in a BHI liquid medium, and the BHI liquid medium was shaken. The bacteria were allowed to grow in the BHI liquid medium for a whole day and night. 50 µl of the resultant culture solution was diluted 190-fold with a BHI liquid medium, and mixed well with the BHI liquid medium by stirring. The resultant mixture was used as a bacterial solution.

[0164] Using each bacterial strain and bacterial solution, the effect was examined in the following manner.

[0165] The bacterial solution was injected with a micropipette into a BHI liquid medium placed in each of two test tubes. Saccharose was added thereto so that the concentration thereof was 0.2%. The bacteria were cultured at 37°C for 18 hours to allow them to form a biofilm. The medium in each test tube was discarded in a beaker, and the biofilm was washed twice with PBS. The drug according to Further Example 1 of the drug of the present invention was injected into one of the test tube, and PBS was injected into the other test tube. Then, the test tubes were shaken at 37°C for 30 minutes. The liquid in each test tube was discarded in a beaker, and the biofilm was washed twice with PBS. ABHI liquid medium was injected into the test tubes, and the bacteria were cultured at 37°C for 24 hours. 10 µl of the medium collected from each test tube was inoculated into a nutrient agar medium, and the bacteria were cultured at 37°C for 24 hours. The presence or absence of colonies was checked through visual observation. As a result, while no colony was observed in the test tube to which the drug according to Further Example 1 of the drug of the present invention had been injected, many colonies were observed in the test tube to which PBS had been injected.

[0166] In order to examine the effect of the drug on the bacterial cells in the biofilm, the following test was conducted further.

[0167] The bacterial solution was injected with a micropipette into a BHI liquid medium placed in microtubes for BioMasher. Saccharose was added thereto so that the concentration thereof was 0.2%. The bacteria were cultured at 37°C for 18 hours to allow them to form a biofilm. The medium in each microtube was discarded in a beaker, and the biofilm was washed twice with PBS. The drug according to Further Example 1 of the drug of the present invention was injected into one of the microtubes, and PBS was injected into the other microtube. The bacteria in the former microtube and the bacteria in the latter microtube were aged at 37°C for 15 minutes and 30 minutes, respectively. The liquid in each microtube was discarded in a beaker, and the biofilm was washed twice with PBS. A BHI liquid medium was injected into the test tubes and homogenized. Thereafter, the bacteria were cultured at 37°C for 24 hours. 10 µl of the medium collected from each microtube was inoculated into a nutrient agar medium, and the bacteria were cultured at 37°C for 24 hours. The presence or absence of colonies was checked through visual observation. As a result, while no colony was observed in the microtube to which the drug according to Further Example 1 of the drug of the present invention had been injected, many colonies were observed in the microtube to which PBS had been injected. These results demonstrate that, by impregnating a biofilm with the drug according to Further Example 1 of the drug of the present invention, the drug acts on bacteria deep inside the biofilm to exhibit the sterilizing effect.(Further Experimental Example 5 of Drug of Invention)

[0168] In Further Experimental Example 5 of the drug of the present invention, the following bacterial strains were used. Except for this, the MIC and MBC were determined using the drug according to Further Example 1 of the drug of the present invention in the same manner as in Further Experimental Example 1 of the drug of the present invention. The results obtained are shown in Table 22. Bacterial strains to be used: Bacteria 1 (Porphyromonas gingivalis) Bacteria 2 (Treponema denticola) Bacteria 3 (Tannerella forsythensis) Bacteria 4 (Aggregatibacter actinomycetemcomitans) [Table 22] Ex. 1Bacteria 1MIC (ppm)20.0MBC (ppm)20.0Bacteria 2MIC (ppm)25.0MBC (ppm)25.0Bacteria 3MIC (ppm)12.5MBC (ppm)12.5Bacteria 4MIC (ppm)35-45MBC (ppm)35-50 (Further Experimental Example 6 of Drug of Invention)

[0169] Test pieces (25.4 mm × 25.4 mm) respectively made of iron, aluminum, tin plate, and stainless steel were washed. Thereafter, the test pieces made of each material were immersed in resin containers containing the drug according to Further Example 1 of the drug of the present invention, a 1.2% sodium hypochlorite aqueous solution, and tap water, respectively, and then, the resin containers were covered with a lid. The test pieces were taken out on a nonwoven fabric after a lapse of each time period shown in Tables 23 and 24, and the conditions of the test pieces were examined through visual observation. In the examination, pictures were taken when necessary, and a microscope was used when the change was subtle. The evaluation was made using the following evaluation criteria.

[0170] -: no corrosion ±: generation of rust +: fairly large amount of rust ++: vary large amount of rust +++: corrosion of metal surfaces [Table 23] Test piece10 min30 min1 hr3 hr6 hrIronExample 1+++++Hypochlorous acid++++++++++Tap water++++AluminumExample 1-----Hypochlorous acid+++++Tap water-----Tin plateExample 1-----Hypochlorous acid---++Tap water-----Stainless steelExample 1-----Hypochlorous acid-----Tap water----- [Table 24] Test piece1 day3 days1 week2 weeks3 weeks4 weeksIronExample 1++++++Hypochlorous acid++++++++++++++++++Tap water++++++AluminumExample 1------Hypochlorous acid+++++++++++++++Tap water------Tin plateExample 1-+++++Hypochlorous acid+++++++++++++++Tap water-+++++Stainless steelExample 1------Hypochlorous acid------Tap water------ (Further Experimental Example 7 of Drug of Invention)

[0171] The deodorizing performance test was conducted in accordance with JEM 1467 "domestic air cleaner" in the Standards of the Japan Electrical Manufacturers' Association. In the measurement, cigarettes were burned while operating a circulator in an acrylic container (1 m in height × 1 m in width × 1 m in depth) with an internal volume of 1 m 3< to fill the container with smoke. After all the cigarettes were burned, the circulator was stopped, and the drug according to Further Example 1 of the drug of the present invention was sprayed in the container by operating a sprayer. The concentrations of three components, namely, ammonia, acetaldehyde, and acetic acid, in the container were measured over 2 hours at regular intervals to trace the change in concentrations. Similarly, formaldehyde vapor was injected into an acrylic container and the formaldehyde concentration in the container was measured over 2 hours at regular intervals to trace the change in concentration. The sprayer was operated in "Manual" mode. As a control, a blank test in which the sprayer was not operated was also conducted. The results obtained are shown in Tables 25 to 28. The malodorous components were measured using detector tubes (Gastec Corporation). The detector tubes used for the measurement are shown below.Detector tubes used for measurement

[0172] ammonia:No. 3Lacetaldehyde:No. 92Lacetic acid:No. 81Lformaldehyde:No. 91 [Table 25] Elapsed timeAmmonia concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start3032-5 min8327310 min5328320 min4328730 min2329345 min1319760 min1>3197 <90 min1>3197 <120 min1>2697 < [Table 26] Elapsed timeAcetaldehyde concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start1414-5 min12141410 min10142920 min10142930 min7145045 min7145060 min7145090 min71450120 min61457 [Table 27] Elapsed timeAcetic acid concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start1210-5 min0.5 >1096 <10 min0.5 >1096 <20 min0.5 >1096 <30 min0.5 >1096 <45 min0.5 >1096 <60 min0.5 >9.596 <90 min0.5 >9.096 <120 min0.5 >9.096 < [Table 28] Elapsed timeFormaldehyde concentration (ppm)Example 1Example 1Blank testRemoval rate (%)Start2020-5 min10205010 min8206020 min5207530 min3208545 min2209060 min2209090 min21890120 min21890 (Further Experimental Example 8 of Drug of Invention)

[0173] The drug according to Further Example 1 of the drug of the present invention was sprayed using a sprayer to measure the deodorizing performance for cigarette odor. First, cigarettes were burned in a room with a 6-tatami mat size to fill the room with smoke at a predetermined concentration. Next, a sprayer was set in the room, and the odor intensity in the room was measured three times, namely, before operating the sprayer, one hour after operating the sprayer, and two hours after operating the sprayer. The sprayer was set near a wall in the room, and the odor was collected at a height of 1 m in the middle of the room. Two circulation fans were set in the room, and they were operated at all times to maintain the air-circulating conditions. The sprayer was operated in "Manual" mode. As a control, a blank test in which the sprayer was not operated was also conducted. The odor intensity was determined as follows according to the six-grade odor intensity measurement method. The results obtained are shown in Table 29.

[0174] The odor intensity was evaluated by six testers (test panel). The results were calculated by determining the average value of the odor intensities given by the respective testers. The six-grade odor intensity measurement method is a method for converting odor intensity to a numerical value using human olfaction. The members of the test panel who had joined the test were those who had taken the legally-required olfactometry and had been admitted as having normal olfaction.

[0175] In the six-grade odor intensity measurement method, the following numerical values are used as evaluation criteria. 0: odorless 1: barely perceivable odor (detection threshold concentration) 2: weakly perceivable odor (recognition threshold concentration) 3: easily perceivable odor 4: strong odor 5: very strong odor [Table 29] Elapsed timeOdor intensityExample 1Blank testStart4.64.51 h3.54.52 h2.94.2 (Further Experimental Example 9 of Drug of Invention)

[0176] The drug according to Further Example 1 of the drug of the present invention was sprayed with a sprayer to measure the performance thereof to remove airborne bacteria (general bacteria, fungi). First, a sprayer was set in a room with a 6-tatami mat size, and the concentration of airborne bacteria in the air was measured three times, namely, before operating the sprayer, one hour after operating the sprayer, and two hours after operating the sprayer. The sprayer was set near a wall in the room, and the airborne bacteria were collected at a height of 1 m in the middle of the room. Two circulation fans were set in the room, and they were operated at all times to maintain the air-circulating conditions. The airborne bacteria were measured by a filtration method using a membrane filter. The sprayer was operated in "Manual" mode. As a control, a blank test in which the sprayer was not operated was also conducted. The results obtained are shown in Tables 30 and 31.Measurement conditions etc. in Further Experimental Example 9 of the drug of the present invention

[0177] Filter to be used:Toyo Roshi Kaisha, Ltd., 37 mm MonitorsAmount of sucked air:300 l (sucked for 15 minutes at 20 l / min)Medium to be used:m-TGE Broth liquid medium for general bacteria (Toyo Seisakusho Kaisha, Ltd.)m-Green Y & M Broth liquid medium for fungi (Toyo Seisakusho Kaisha, Ltd.)Culture conditions:30°C for 72 hours for general bacteria30°C for 5 days for fungi [Table 30] Elapsed timeThe number of airborne general bacteria (the number of bacteria / 300 l)Example 1Example 1Blank testRemoval rate (%)Start1311-1 h0111002 h011100 [Table 31] Elapsed timeThe number of airborne fungi (the number of fungi / 300 l)Example 1Example 1Blank testRemoval rate (%)Start1011-1 h0101002 h09100 (Further Experimental Example 10 of Drug of Invention)

[0178] In Further Experimental Example 10 of the drug of the present invention, the following bacterial strains were used. Except for this, the MIC or MBC was determined using the drug according to Further Example 1 of the drug of the present invention in the same manner as in Further Experimental Example 1 of the drug of the present invention. The results obtained are shown in Table 32. Bacterial strains to be used: Streptococcus mutans hemolytic streptococcus Bacillus subtilis methicillin-resistant Staphylococcus aureus (MRSA) [Table 32] Example 1Streptococcus mutansMIC (ppm)5MBC (ppm)15Hemolytic streptococcusMIC (ppm)0.1MBC (ppm)1.0Bacillus subtilisMIC (ppm)12.5MBC (ppm)MRSAMIC (ppm)2MBC (ppm) (Further Experimental Example 11 of Drug of Invention)

[0179] Using the drug according to Further Example 1 of the drug of the present invention, a deodorization test was performed in accordance with an instrumental analysis implementation manual; a detector tube method, a gas chromatography method (the Certification Standards of Antibacterial Finished Textile Products of Japan Textile Evaluation Technology Council were applied with necessary modifications). The results obtained are shown in Table 33. [Table 33]Odor componentImpression of odorConcentration 1 (ppm)Concentration 2 (ppm)Gas reduction rate (%)ammoniaexcrement100793acetic acidvinegar50198hydrogen sulfiderotten egg4.000.1297methyl mercaptanrotten onion8.004.9638tritylaminerotten fish28.003.0889isovaleric acidmusty socks38.000.3899Concentration 1: initial gas concentration Concentration 2: gas concentration after a lapse of 2 hours Gas reduction rate: ([concentration 1 - concentration 2] / concentration 1) × 100 (Further Experimental Example 12 of Drug of Invention)

[0180] The drug according to the present invention was administered to mice in order to examine whether the drug according to the present invention is highly safe.

[0181] Using the drug according to Further Example 1 of the drug of the present invention, an acute oral toxicity test was performed on mice in accordance with OECD TG 420 (fixed dose procedure). The test was conducted by Japan Food Research Laboratories. As a result, LD50 of the drug was 2000 mg / kg or more in both the female and male mice. This result demonstrates that that the drug according to the present invention is highly safe.(Further Experimental Example 13 of Drug of Invention)

[0182] The drug according to the present invention was administered to rabbits in order to examine whether the drug according to the the present invention is highly safe.

[0183] Using the drug according to Further Example 1 of the drug of the present invention, an eye irritation test was performed on rabbits in accordance with OECD TG 405 Acute Eye Irritation / Corrosion. The test was conducted by Japan Food Research Laboratories. As a result, it was found that the drug was non-irritating. From this result, it was found that that the drug according to the present invention is highly safe.(Further Experimental Example 14 of Drug of Invention)

[0184] The drug according to the present invention was administered to rabbits in order to examine whether the drug according to the present invention is highly safe.

[0185] Using the drug according to Further Example 1 of the drug of the present invention, a primary skin irritation test was performed on rabbits in accordance with OECD TG 404 Acute Skin Irritation / Corrosion. The test was conducted by Japan Food Research Laboratories. As a result, it was found that the drug was slightly irritating. This result demonstrates that the drug according to the present invention is highly safe.(Further Experimental Example 15 of Drug of Invention)

[0186] The drug according to the present invention was administered to guinea pigs in order to examine whether the drug according to the present invention is highly safe.

[0187] Using the drug according to Further Example 1 of the drug of the present invention, a continuous skin irritation test was performed on guinea pigs by applying the drug on their skin for 14 consecutive days. The test was conducted by Life Science Laboratories, Ltd. As a result, it was found that the drug was non-irritating. This demonstrates that that the drug according to the present invention is highly safe.(Further Experimental Example 16 of drug of Invention)

[0188] The drug according to the present invention was administered to guinea pigs in order to examine whether the drug according to the present invention is highly safe.

[0189] Using the drug according to Further Example 1 of the drug of the present invention, a skin sensitization test was performed on guinea pigs by the maximization test method. The test was conducted by Life Science Laboratories, Ltd. As a result, it was found that the drug did not cause skin sensitization. This result demonstrates that the drug according to the present invention is highly safe.(Further Experimental Example 17 of Drug of Invention)

[0190] The drug according to the present invention was administered to humans in order to examine whether the drug according to the present invention is highly safe.

[0191] Using the drug according to Further Example 1 of the present invention, a human patch test was conducted by attaching patches impregnated with the drug to humans for 24 hours. The test was conducted by Life Science Laboratories, Ltd. As a result, it was found that the drug was non-irritating. This result demonstrates that the drug according to the present invention is highly safe.(Further Experimental Example 18 of Drug of Invention)

[0192] The present example examined whether the drug according to the present invention can inhibit the occurrence of rice blast.

[0193] Seeds of Koshihikari (rice cultivar) were subjected to seed selection with a salt solution, and diseased seeds were removed by removing floating seeds. The thus-selected seeds were washed with water, drained, and packed in a coarse saran fiber bag. Next, a diluted solution was prepared by diluting the drug according to Further Example 1 of the drug of the present invention 200-fold (also referred to as "200-fold dilution" hereinafter). Then, the seeds packed in the saran fiber bag were immersed in the 200-fold dilution twice as heavy as the seeds for 24 hours. During the immersion treatment, water replacement was not performed. After the immersion treatment, the seeds were air-dried, and then subjected to the immersion treatment again for 6 days. During the immersion treatment, water replacement was not performed. After the immersion treatment, the seeds were further subjected to the immersion treatment again for 6 days.

[0194] Next, the seeds were seeded in seedling boxes, and further, the 200-fold dilution was sprayed (500 ml / seedling box). Thereafter, the seeds were grown. The obtained seedlings were planted in a rice field, and cultivated by an ordinary method. Then, occurrence of rice blast during the cultivation was examined. As a control, the occurrence of rice blast was examined in the same manner, except that seeds of Hitomebore (rice cultivar) were used instead of the seeds of Koshihikari, the immersion treatments in the 200-fold dilution were not performed, and seedlings of Hitomebore were planted in a rice field adjacent to the rice field where the seedlings of Koshihikari were planted.

[0195] As a result, the occurrence of rice blast was not observed in the rice field where the seedlings obtained from the seeds subjected to the immersion treatments with the 200-fold dilution were planted. In contrast, in the control, the occurrence of rice blast was observed. These results demonstrate that the drug according to the present invention can inhibit the occurrence of rice blast.(Further Experimental Example 19 of Drug of Invention)

[0196] The present example examined whether the drug according to the present invention can restrict the spread of rice blast.

[0197] A rice field with a high incidence of rice blast was ploughed and irrigated while adding a diluted solution obtained by diluting the drug according to Further Example 1 of the drug of the present invention 10-fold (also referred to as "10-fold dilution" hereinafter) to the rice field (10 l of the 10-fold dilution per 10 a of the rice field). Next, the seedlings of Koshihikari used in Further Experimental Example 18 of the drug of the invention were planted in a rice field after being ploughed and irrigated, and cultivated. Then, when the occurrence of rice blast was observed during the cultivation, stalks infected with rice blast were removed, and the 10-fold dilution was sprayed around areas where the stalks infected with rice blast had been cultivated (1 l of the 10-fold dilution per 10 a of the rice field). As a control, instead of the seedlings of Koshihikari obtained in Further Experimental Example 18 of the drug of the invention, the control seedlings in Further Experimental Example 18 of the drug of the invention were cultivated in the same manner, except that the control seedlings were planted in a rice field adjacent to the rice field where the seedlings of Koshihikari were planted, without adding or spraying the 10-fold dilution to the rice field. Then, whether the rice blast that had occurred in the rice field where the control seedlings were planted spread out to the rice field where the seedlings of Koshihikari were planted during the cultivation was examined.

[0198] As a result, in the rice field where the control seedlings were planted, the occurrence and spread of rice blast were observed. In contrast, in the rice field where the seedlings of Koshihikari were planted, while the occurrence of rice blast was observed slightly above primary rachis-branches in an area within about 2 to 3 m from the boundary to the rice field where the control seedlings were planted, the spread of the rice blast to the remaining area of the rice field was not observed. These results demonstrate that the drug according to the present invention can restrict the spread of rice blast.(Further Experimental Example 20 of Drug of Invention)

[0199] The present example examined whether the drug according to the present invention can repel shield bugs and pest insects.

[0200] The seedlings of Koshihikari obtained in Further Experimental Example 18 of the drug of the invention were planted in rice fields owned by 23 farmers and cultivated in the same manner as in the Further Experimental Example 19 of the drug of the invention, except that the rice fields were treated one by one by the respective farmers. Then, after the cultivation, each of the farmers was interviewed about the extent to which shield bugs and pest insects approached the rice field as compared with previous years.

[0201] As a result, eight farmers commented that repelling of shield bugs and pest insects was observed. These results demonstrate that the drug according to the present invention can repel shield bugs and pest insects.Industrial Applicability[Industrial Applicability]

[0202] As specifically described above, according to the present invention, it is possible to provide a drug that is highly safe and has a high sterilizing effect. Said drug may be a drug for use in agriculture and livestock industry that is highly safe and has a high sterilizing effect. The drug of the present invention is not particularly limited, and is applicable to a wide variety of uses. The drug of the present invention is very useful in the fields of agriculture, livestock industry, etc., for example.

Claims

1. A drug comprising: (i) a radical generating catalyst comprising: an ammonium salt of formula (XI) and having a Lewis acidity of 0.4 eV or more where in the chemical formula (XI), R11, R21, R31, and R41 are each a hydrogen atom or an alkyl group and may each comprise an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring, and R11, R21, R31, and R41 may be the same or different from each other, and X- is an anion selected from a halogen ion, an acetate ion, a nitrate ion and a sulfate ion, wherein said halogen atom is preferably a fluoride ion, a chloride ion, a bromide ion or an iodide ion; and (ii) a radical source that is at least one selected from the group consisting of chlorous acid, bromous acid, iodous acid and halite ions; and wherein the radical generating catalyst and the radical source are dissolved in a solvent.

2. The drug according to claim 1, wherein: (a) the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XII): where in the chemical formula (XII), R111 is an alkyl group having 5 to 40 carbon atoms and may comprise an ether bond, a ketone (carbonyl group), an ester bond, or an amide bond, or an aromatic ring, and R21 and X- are the same as those in the chemical formula (XI); or (b) the ammonium salt represented by the chemical formula (XI) is an ammonium salt represented by the following chemical formula (XIII): where in the chemical formula (XIII), R111 and X- are the same as those in the chemical formula (XII); or (c) the ammonium is at least one selected from the group consisting of benzethonium chloride, benzalkonium chloride, hexadecyltrimethylammonium chloride, tetramethylammonium chloride, ammonium chloride, tetrabutylammonium chloride, cetylpyridinium chloride, hexadecyltrimethylammonium bromide, dequalinium chloride, edrophonium, didecyldimethylammonium chloride, benzyltriethylammonium chloride, oxytropium, carbachol, glycopyrronium, safranin, sinapine, tetraethylammonium bromide, hexadecyltrimethylammonium bromide, suxamethonium, sphingomyelin, denatonium, trigonelline, neostigmine, paraquat, pyridostigmine, phellodendrine, pralidoxime methiodide, betaine, betanin, bethanechol, betalain, lecithin, and cholines; or (d) the ammonium salt represented by the chemical formula (XI) is benzethonium chloride.

3. The drug according to claim 1 or claim 2, wherein: (a) the amount of the radical source mixed in the drug is from 0.1 to 250 mass ppm, and / or (b) the amount of the radical generating catalyst mixed in the drug is from 0.1 to 250 mass ppm.

4. The drug according to any one of claims 1 to 3, wherein the solvent is water and / or an organic solvent, wherein the organic solvent is preferably acetone, acetonitrile or ethanol.

5. The drug according to any one of claims 1 to 4 for use as a medicament.

6. The drug according to claim 5 for use as: (a) a bactericide, (b) an oral care agent, (c) an acne treatment agent, (d) a disinfectant for decubitus ulcers, or (e) a fungicide.

7. The drug according to claim 6, for use as a bactericide for use in livestock industry or an antiviral agent for use in livestock industry.

8. Use of the drug according to any one of claims 1 to 4 as: (a) a bactericide, (b) a bactericide for hand washing, (c) a deodorizer, (d) an antibacterial agent for metals, (e) an oral care agent, (f) a fungicide, or (g) a bactericide for water purification; wherein said use is not in a method for treatment of the human or animal body by therapy.

9. Use of the drug according to any one of claims 1 to 4 in agriculture or livestock industry, wherein said use is not in a method for treatment of the human or animal body by therapy.

10. Use according to claim 9, wherein said use is as: (i) a bactericide for use in agriculture, an antiviral agent for use in agriculture, a deodorizer for use in agriculture, an insecticide for use in agriculture, a repellent for use in agriculture, or a soil conditioner for use in agriculture; or (ii) a bactericide for use in livestock industry, an antiviral agent for use in livestock industry, a deodorizer for use in livestock industry, an insecticide for use in livestock industry, a repellent for use in livestock industry, or a soil conditioners for use in livestock industry