JP5593013B2 - Solid-type disinfectant and human body composition - Google Patents

Description

  The present invention relates to a solid fungicide that has a high bactericidal power and a wide bactericidal spectrum and can be easily blended in cosmetics, and a human body composition containing the solid fungicide.

  Parabens, benzoic acid and its salts, salicylic acid and its salts, etc. are generally used as antiseptic fungicides in compositions applied to the human body such as cosmetics, topical pharmaceuticals, and quasi drugs.

  However, these antiseptic disinfectants have the disadvantage that the range of use is limited because of their high skin irritation and low safety. For example, the use limit concentration of parabens and benzoates is 1%, and the use restriction concentration of benzoic acid and salicylic acid is 0.2%. In addition, these antiseptic disinfectants have problems that their disinfecting effects are easily affected by pH and are not stabilized, and that when used in combination with other compounding agents such as surfactants, the disinfecting power is significantly reduced. Furthermore, even various cosmetics containing these antiseptic disinfectants within the limited range may cause skin disorders and allergic reactions due to their cumulative use, which has become a major social problem.

  Therefore, in order to respond to the consumer's safety orientation, it has been demanded that no antiseptic disinfectant is added to cosmetics or the like, and that the amount of the additive is extremely reduced. Attempts have been made.

  Specifically, a method of producing a synergistic effect by using a plurality of solid-type disinfectants and reducing the amount of the antiseptic disinfectant used can be exemplified. In addition, since the effect of these antiseptic disinfectants depends on the amount present in the aqueous phase, polyhydric alcohols such as 1,3-butylene glycol and dipropylene glycol are added to the antiseptic disinfectant into the aqueous phase. A method for increasing the distribution can also be exemplified.

  However, although the bactericidal effect is improved by the combined use of the antiseptic disinfectant and the polyhydric alcohol, the effect cannot be exhibited unless a large amount of the polyhydric alcohol is blended. For example, the antiseptic and sterilizing effect cannot be exhibited unless 1,3-butylene glycol and dipropylene glycol are mixed at 10% by weight or more and glycerin at 30% by weight or more. However, it was practically impossible to add such an amount considering the balance with other ingredients.

  By the way, quaternium salts such as quaternium 73, quaternium 51, and quaternium 45, and some styryl compounds (for example, INCI name dimethylamino) are shown as substances having a stable bactericidal effect even in a small amount and having low skin irritation and high safety. Conventionally, styryl heptylmethyl thiazolium iodide) is used.

  In addition, quaternium 73 and a styryl compound have already been reported as many excellent bactericides, and although the bactericidal action is somewhat inferior to these, it has been reported that quaternium 51 has both hair growth and hair growth action. It has been reported that it has a skin conditioning effect for skin.

  In addition, although these quaternium salts show an effect in a small amount, the solubility in water and alcohol is extremely low because of the cationic salt, but unlike other antiseptic disinfectants, they are effective in a trace amount, so an ethanol solution, The solubility is improved by using solubilizers such as polyhydric alcohols such as 1,3-butylene glycol, dipropylene glycol and glycerin. These quaternium salts have a legal upper limit of 0.002% by weight for cosmetics and 0.005% by weight for quasi-drugs in terms of action and effect.

  Furthermore, although quaternium salts and the like have a broad bactericidal spectrum, they are slightly inferior in bactericidal properties against gram-negative bacteria compared to bactericidal properties against gram-positive bacteria. Therefore, conventionally, the bactericidal property against Gram-negative bacteria has been enhanced by using it together with a solid-type bactericide such as paraben. However, in this case, the preservative disinfectant such as parabens cannot be greatly reduced or completely eliminated (for example, Patent Document 1).

  On the other hand, the inventors have mixed solid sterilization obtained by mixing quaternary salt and the like with polyethylene glycol, which is generally used as a cosmetic raw material, with stirring at a high temperature of 90 to 100 ° C. for a certain period of time, and cooling and solidifying the mixture. Attempts have already been made to use the agent in cosmetics.

  However, although this solid-type disinfectant is clear during mixing, it becomes dark after solidification, and since many of quaternium salts and the like are decomposed from the measurement of absorptiometry, disinfecting power cannot be expected. Use for was not practical.

Japanese Patent Laid-Open No. 11-322591

  Therefore, the present invention provides a highly safe human body application composition that has excellent bactericidal properties, a wide bactericidal spectrum, and aesthetics without greatly reducing or completely using harmful preservative fungicides such as parabens. It is an object of the present invention to provide a solid-type disinfectant capable of easily preparing this human body application composition.

  The inventors dissolved the quaternium salt etc. in alcohol under heating, then mixed this with polyethylene glycol under heating, and then cooled and solidified, so that the quaternium salt etc. and polyethylene glycol were easily It is possible to prepare a chemically stable solid-type disinfectant and use this solid-type disinfectant to easily prepare a highly safe human application composition with excellent bactericidal properties and a wide bactericidal spectrum. The present invention was completed by finding out what can be done.

  That is, the solid-type disinfectant according to claim 1 is (1) a high-concentration solution obtained by dissolving at least one of a specific quaternium salt and a styryl compound in an alcohol having 2 to 3 carbon atoms with heating. (2) Polyethylene glycol is mixed under heating and then solidified by cooling.

  Moreover, the human body application composition of Claim 2 contains the solid-type disinfectant of Claim 1. The composition applied to the human body means a composition that is applied directly to the outside of the human body, such as cosmetics, quasi drugs, and external quasi drugs.

  The solid-type disinfectant of the present invention contains a quaternium salt or the like excellent in bactericidal activity in a small amount and polyethylene glycol, and by containing this in a human body application composition such as cosmetics, It has become possible to easily prepare a composition for applying to the human body having a wide sterilization spectrum and aesthetics and high safety. Moreover, since this human body composition does not contain conventional antiseptic fungicides such as parabens, there is almost no possibility of causing skin damage or allergic reaction due to cumulative use. Therefore, even those who could not make up because of the occurrence of these illnesses can now make up.

1. Solid-type disinfectant The solid-type disinfectant according to the present invention is obtained by mixing (1) a high concentration solution and (2) polyethylene glycol (PEG) under heating. The details will be described below.

(1) High-concentration solution At least one or more of a specific quaternium salt and a specific styryl compound are dissolved in an alcohol having 2 to 3 carbon atoms with heating.

(I) Quaternium salt and styryl compound The quaternium salt used in the present invention has the following quaternium 73 (Chemical Formula 1), quaternium 51 (Chemical Formula 2) and quaternium 45 (Chemical Formula) whose sterilizing properties and safety are confirmed. 3). The styryl compound used in the present invention is the INCI name dimethylaminostyryl heptylmethylthiazolium iodide (Chemical Formula 4). In addition, a quaternium salt and a styryl compound may be used individually by 1 type according to a use, and may be used in combination of multiple.

(Ii) Alcohol having 2 to 3 carbon atoms The alcohol having 2 to 3 carbon atoms used in the present invention is ethanol or propanol, and among these, the solubility of the quaternium salt and the styryl compound is high, and safety. Ethanol is preferred because of its versatility. In addition, according to the use, these alcohols may be used alone or in combination.

(Iii) Dissolution method The quaternium salt and styryl compound are dissolved in an alcohol having 2 to 3 carbon atoms under heating. Here, although the heating temperature varies depending on the quaternium salt, styryl compound and alcohol having 2 to 3 carbon atoms to be used, it is preferably 75 ° C. or lower in order to suppress decomposition of the quaternium salt or styryl compound, and 65 ° C. or higher in order to increase the solubility. Is preferred.

  In addition, the concentration of the quaternium salt and styryl compound in the high-concentration solution is such that the content of the high-concentration solution in the solid-type disinfectant and the solid in the human-body application composition so that the human-body application composition described later produces its effect. It may be set in consideration of the content of the mold disinfectant. However, since the high-concentration solution is diluted and used, it is preferable that the concentration is as high as possible, preferably close to the saturation concentration.

  In addition, quaternium salts and styryl compounds have been used for many years as a material for substances that have bactericidal activity against a wide range of bacterial species at low concentrations such as cosmetics, quasi drugs, etc. It has been confirmed that its safety is extremely high.

  Therefore, the content of quaternium salt and the like in the solid-type disinfectant can be freely changed according to its use and is not particularly limited. However, in view of the bactericidal effect, 0.01 wt% to 2.00 wt% Is preferable, and 0.01% by weight to 1.00% by weight is more preferable.

  More specifically, when only quaternium 73 is used, its content is preferably 0.02 to 1.00% by weight based on the total content of PEG 4,000 and PEG 6,000. This is because the amount dissolved in the alcohol is made as high as possible and the quaternium salt or the like is not reprecipitated from the solid-type fungicide.

  Further, when the combination of quaternium 51, quaternium 45, or dimethylaminostyryl heptylmethylthiazolium iodide is used, the total content thereof is 0.02 to 0.02 to the total content of PEG 4,000 and PEG 6,000. It is preferably 2.00% by weight. This is because the solubility in alcohol is better than that of Kutanium 73.

  When the quaternium 51 and the quaternium 73 are used in combination, the total content is preferably 0.02 to 2.00% by weight based on the total content of PEG 4,000 and PEG 6,000. This is because the amount used as a single product can be reduced.

  When the quaternium 45 and the quaternium 73 are used in combination, the total content is 0.02 to 2.00% by weight with respect to the total content of PEG 4,000 and PEG 6,000 for the same reason as described above. Is preferred.

  When quaternium 51, quaternium 45, quaternium 73 and dimethylaminostyryl heptylmethyl thiazolium iodide are used in combination, the total content is 0.02 to 4,000 with respect to the total content of PEG 4,000 and PEG 6,000. It is preferably 2.00% by weight. This is because, when four products are mixed, the amount used as a single product can be reduced.

  The content of the quaternium salt and styryl compound in the human body application composition is preferably 0.002% by weight to 0.005% by weight for legal reasons.

(2) Polyethylene glycol Polyethylene glycol is a water-soluble polymer synthesized by radical polymerization with alkali of ethylene oxide and cationic polymerization by proton initiation. Polyethylene glycol can be classified into PEG 6,000, PEG 4,000, etc., depending on the molecular weight of the polymer contained, more precisely, the Gaussian-like molecular weight distribution of the polymer contained. For example, the average molecular weight of PEG 6,000 is 7,300-9,300, and the average molecular weight of PEG 4,000 is 2,700-3,400.

  Among these polyethylene glycols, use of PEG 6,000 or PEG 4,000 is preferable. This is because the melting point and freezing point of PEG 6,000 and PEG 4,000 are most suitable for the present invention.

(3) Mixing method (i) Mixing method The above (1) high-concentration solution and (2) polyethylene glycol are mixed under heating by a conventional method and then solidified by cooling. Here, the shape after solid may have a fixed shape such as a tablet shape, or may have fluidity such as powder or granule.

  Moreover, although the heating temperature at the time of mixing varies depending on the quaternium salt, styryl compound and alcohol having 2 to 3 carbon atoms to be used, it is preferably 75 ° C. or lower in order to suppress decomposition of the quaternium salt and styryl compound, such as quaternium salt In order to increase the solubility of polyethylene glycol in polyethylene glycol and mix uniformly, a temperature of 70 ° C. or higher is preferable. After mixing, the solidified product that has been cooled may be pulverized and vacuum suctioned at a temperature of about 40 ° C. or around 40 ° C. to remove the alcohol used in the preparation of the high-concentration solution.

  The solid-type disinfectant prepared in this way is extremely easy to handle, stable without deterioration or decomposition at room temperature, and can be stored at room temperature if placed in a light-shielding bottle as well as in a refrigerator. It is a convenient material. Moreover, since this solid-type disinfectant is solid, it is easy to handle and weigh, and has high solubility, so it can be easily blended when preparing a human body application composition.

2. Human body application composition The human body application composition of the present invention includes the solid-type fungicide. Specifically, liquid solids, lotions, creams, ointments, jellies, gels, etc. prepared by known methods together with known active ingredients and absorption promoters, and more Specifically, cosmetics for skin and hair such as facial cleansers, lotions, emulsions, creams, shampoos, hair treatments, quasi-drugs for external use for specific purposes such as whitening, spots and freckles prevention, and acne And pharmaceuticals for the treatment of atopy.

  Below, the solid-type disinfectant and human body composition of this invention were specifically prepared as examples, and the characteristics were tested. In addition, this invention is not limited to a following example in any meaning.

(1) Stability test over time (i) Preparation of calibration curve Quotanium 73 5 mg was precisely weighed and dissolved in 200 ml of ethanol while heating at 70 ° C. to prepare a solution, and 10 ml of this solution was diluted in 100 ml of purified water. . Next, a diluted solution train was prepared by serially diluting this solution. Further, Abs. Max 411 ± 2 nm of this diluted solution row was measured with a spectrophotometer to prepare a calibration curve.

  Similarly, calibration curves were prepared for quaternium 51, quaternium 45, and dimethylaminostyryl heptylmethylthiazolium iodide. Note that the Abs.Max of quaternium 51 is 404 ± 2 nm, the Abs.Max of quaternium 45 is 363 ± 2 nm, and the Abs.Max of dimethylaminostyryl heptylmethylthiazolium iodide is 480 ± 2 nm. It was created.

(Ii) Preparation of solid-type disinfectant A solid-type disinfectant containing alcohol and polyethylene glycol such as quaternium salt was prepared. Specifically, for example, 0.2 g of quaternium 73 was dissolved in 5.0 ml of isopropanol under heating at 70 to 75 ° C. to obtain a high concentration solution, and this high concentration solution was mixed with polyethylene glycol under heating at 70 ° C. Then, it prepared by cooling and solidifying at normal temperature. In addition, the solid-type disinfectant was prepared in a fixed form (tablet form, mold frame form), powder, and granular form. In addition, “PEG 4,000” has a pH of 6.8 (5% Aq), a freezing point of 56 ° C. and an average molecular weight of 3360, and “PEG 6,000” has a pH of 6.8 (5% Aq), a freezing point of 60 ° C. and an average molecular weight of 8360. I used something.

  In addition, it confirmed before starting a stability test that the density | concentrations, such as a quaternium salt, in the solid type fungicide produced in this way can be measured with a spectrophotometer and the said calibration curve. For example, 1 g of a solid-type fungicide powder containing 0.02% by weight of quaternium 73 was placed in a volumetric flask, 50 ml of ethanol was added, and the volume was made up to 100 ml with purified water and dissolved. This dissolved solution was diluted stepwise with purified water so as to be within the measurement range. Absorbance of these diluted solutions at Abs. Max 411 ± 2 nm was measured with a spectrophotometer, and the content was calculated from a calibration curve. As a result, it was found that the concentration of quaternium 73 was in the range of 0.02% ± 0.001% by weight. From this result and similar results in other solid-type fungicides, it was confirmed that the concentration of quaternium salt and the like can be accurately measured by using the calibration curve.

(iii) Measurement of stability over time The concentration of quaternium salt in the solid fungicide prepared in this way was stored at room temperature in the room for half a month, 1 month, 3 months, 6 months at the time of preparation, The stability test was performed separately for those stored in a cool and dark place. In addition, each solid-type disinfectant is stored in a constant temperature chamber with a temperature of 37 ° C, humidity of 60%, and two 20w fluorescent lamps mounted on the wall, and the concentration of quaternium salt is 1 month, 3 months, and 6 months at the time of preparation. A forced aging stability test was also conducted.

  As a result, when solid sterilizer containing only quaternium 45 was subjected to a forced aging stability test, the absorbance decreased except that the concentration decreased to 99.70 ± 0.20 at the start of the test after 6 months. No change in absorbance curve due to alteration was observed, confirming that the solid fungicide was stable for a long time.

(2) Irritation test
(i) Preparation of Solid Type Bactericide A solid type bactericide containing a quaternium salt, alcohol, and polyethylene glycol was prepared at the blending ratio shown in Table 1 below (value in the table is W / W%). Specifically, a quaternium salt is dissolved in alcohol at a temperature of 70 to 75 ° C. to make a high concentration solution, and this high concentration solution is mixed with polyethylene glycol under a temperature of 75 ° C. and then cooled and solidified at room temperature. Each example was prepared by:

(Ii) Irritation test The test was carried out using 15 guinea pigs, 5 for each of the solid-type fungicides of Examples 1 to 3. Specifically, the solid fungicides of Examples 1 to 3 were diluted 10-fold with physiological saline, and this diluted solution was applied to the back of a guinea pig to examine skin inflammation. As a result, there was almost no irritation | stimulation with respect to skin about any solid-type disinfectant.

(3) Bactericidal test A plurality of solid-type bactericides were prepared, and their bactericidal activity was tested by measuring their minimum inhibitory concentration (MIC).

(i) Preparation of Solid Type Bactericide A solid type bactericide containing alcohol, polyethylene glycol, etc., such as a quaternium salt, was prepared at the blending ratio shown in Table 2 below (value in the table is W / W%). Specifically, a quaternium salt is dissolved in alcohol at a temperature of 70 ° C. to make a high concentration solution, and this high concentration solution is mixed with polyethylene glycol at a temperature of 70 to 75 ° C., and then cooled and solidified at room temperature. Each example was prepared by:

(ii) Measurement of MIC First, each of the six types of solid-type fungicides was diluted with physiological saline to prepare an aqueous solution (normal solution) having a quaternium salt concentration of 0.02%. Each defined solution was further diluted stepwise with physiological saline to prepare a serial dilution series (quantum salt concentration of 0.02 to 0.0005%). In addition, the culture solution in which the test bacteria were pre-cultured twice in bouillon medium for about 18 hours was measured with a turbidimeter and assumed to be 10 ⁸ cells / ml, and diluted with SCD medium to about 10 ⁵ cells / ml. Prepared as a fungal suspension. In addition, Escherichia coli IFO3972 (Escherichia coli) and Staphylococcus aureus IFO13276 (Staphylococcus aureus) were used as test bacteria. The number of bacteria was confirmed by the colony count method.

Next, in a 15 ml test tube that has been sterilized by dry heat, put 1.4 ml each of the diluted solution and SCD medium adjusted to various concentrations, inoculate 70 μl of the bacterial suspension to 10 ³ cells / ml, 35 Culturing was carried out at 24 ° C. for 24 hours. After the completion of the culture, the growth of the bacteria was judged visually, and 1 g of a sample having a concentration at which the growth of the bacteria was completely inhibited was collected and cultured in an agar medium for 24 hours to confirm complete inhibition, thereby obtaining a MIC. The results are shown in Table 3.

  From the results of Table 3, Example 4 containing quaternium 73 is 0.0005 to 0.005%, Example 5 containing quaternium 51 is 0.001 to 0.01%, and Example 6 containing quaternium 45 is 0.005 to 0.015%, which is a styryl compound. Example 7 containing (Chemical Formula 4) was found to be able to suppress the growth of S. aureus and E. coli at 0.00025-0.0025%. It was also found that the MIC of each solid fungicide showed a value almost equal to the MIC value of quaternium salt etc. contained in each solid fungicide. Furthermore, sufficiently high bactericidal activity was also obtained with solid type bactericides (Examples 8 and 9) in which quaternium 51 and 45 having relatively weak bactericidal activity were mixed with quaternium 73 and a styryl compound (Chemical Formula 4).

  From these results, it was confirmed that each solid-type fungicide has high bactericidal properties and that the bactericidal power of quaternium salts and the like contained therein does not decrease even when prepared in a solid-type fungicide. Moreover, since a bactericidal power can be improved by mixing a plurality of quaternium salts, etc., when producing a human body application composition containing a plurality of quaternium salts, each of the quaternium salts and the like is added to the human body composition. It was confirmed that it was easier to prepare a solid-type disinfectant containing a plurality of quaternium salts, and to blend the prepared solid-type disinfectant, instead of individually mixing.

(4) Solubility test After changing the dissolution method of quaternium salt to prepare solid-type disinfectant, the concentration of quaternium salt contained in the solid-type disinfectant is measured. The effect of quaternium salt on the concentration was investigated.

(I) Quotanium 73
First, 0.01 g of quaternium 73, dissolved in 5 g of ethanol under heating at 70 ° C., and then mixed with PEG 6,000, 94.99 g under heating at 70-75 ° C. Was prepared. Also, quaternium 73, 0.01 g was forcibly heated and mixed with PEG 6,000, 99.99 g under heating at 90-95 ° C. to prepare a solid-type fungicide as a comparative control.

  Next, 1.0 g of the prepared solid fungicide was dissolved in 100 ml of ethanol, and the absorbance of the diluted solution was measured while changing the measurement wavelength. The result is shown in FIG. In addition, (a) is the result of measuring the absorbance of the solid fungicide of the present invention, and (b) is the result of measuring the absorbance of the solid fungicide as a comparative control.

  From FIG. 1, when the absorbance near 411 nm, which is the maximum absorption wavelength, was compared between (a) and (b), a decrease in concentration was clearly observed in (b) compared to (a). From this result, it was confirmed that the solid-type disinfectant of the present invention was not decomposed compared to the solid-type disinfectant as a comparative control. The solution of (a) is light yellow, whereas (b) is dark brown yellow, and it is confirmed that the solid fungicide of this invention is superior also in terms of aesthetics. did it.

  Using quaternium 51, the effect of the difference in dissolution method on the concentration of quaternium salt in the solid-type fungicide was examined by the same method.

(Ii) Quaternium 51
First, 51 g of quaternium, 0.01 g, was dissolved in 5 g of ethanol under heating at 70 ° C., and then mixed with PEG 6,000, 94.99 g under heating at 70 to 75 ° C. Was prepared. Also, quaternium 51, 0.01 g was forcibly heated and mixed with PEG 6,000, 99.99 g at 90-95 ° C. to prepare a solid-type fungicide as a comparative control.

  Next, 1.0 g of the prepared solid fungicide was dissolved in 100 ml of ethanol, and the absorbance of the diluted solution was measured while changing the measurement wavelength. The result is shown in FIG. In addition, (a) is the result of measuring the absorbance of the solid fungicide of the present invention, and (b) is the result of measuring the absorbance of the solid fungicide as a comparative control.

  From FIG. 2, a significant difference was recognized when the absorbance at around 404 nm, which is the maximum absorption wavelength, was compared between (a) and (b). In other words, it was found that the solid-type fungicide used as a comparison control with the solid-type fungicide of the present invention had a significant difference in the concentration of onium 51. From this result, it was confirmed that the solid-type disinfectant of the present invention was not decomposed compared to the solid-type disinfectant as a comparative control. The solution of (a) is light yellow, whereas (b) is dark brown yellow, and it is confirmed that the solid fungicide of this invention is superior also in terms of aesthetics. did it.

(5) Test of feeling of use etc. (i) Preparation of human body application composition The human body application composition was prepared by the usual method according to prescription of the following Tables 4-9.

(Ii) Usability test etc. The prepared hair tonic (listed in Table 5) is sprinkled on the head once a day for 3 weeks for 5 males and 5 females, and then immediately massaged. I was asked to evaluate the use feeling, cool feeling, presence or absence of irritation, and the occurrence of itching. In addition, O / W type cream (listed in Table 7) was applied to the face of 10 women once a day for 2 weeks and tried in the form of rubbing, feeling of use, moist feeling, itching I was asked to evaluate the sensitivity of the stimulus.

  As a result, it was answered that none of the subjects suffered from problems such as redness or inflammation due to use, and the feeling of use was good. As for irritation, most people answered that they did not feel much irritation. However, one of the subjects who used the O / W type cream responded that they felt irritation in the mouth and submandibular region, although it was extremely low. From the above results, it was confirmed that the hair tonic and O / W type cream were excellent in use feeling and low in irritation.

It is a figure which shows the influence which the difference in a melt | dissolution method has on decomposition | disassembly of quaternium 73 contained in a solid-type disinfectant. In addition, (a) is the result of measuring the absorbance of the solid fungicide of the present invention, and (b) is the result of measuring the absorbance of the solid fungicide as a comparative control. It is a figure which shows the influence which the difference in a melt | dissolution method has on decomposition | disassembly of the quaternium 51 contained in a solid-type disinfectant. In addition, (a) is the result of measuring the absorbance of the solid fungicide of the present invention, and (b) is the result of measuring the absorbance of the solid fungicide as a comparative control.

Claims (2)

(1) Quotanium 73 represented by the following formula 1 (Chemical formula 1), quaternium 51 represented by the following formula 2 (Chemical formula 2), quaternium 45 represented by the following formula 3 (Chemical formula 3), and Formula 4 (Chemical formula 4) 0.001 to 2.00 parts by weight of at least one fungicide selected from the group consisting of the styryl compounds shown is dissolved in 5 to 10 parts by weight of alcohol having 2 to 3 carbon atoms under heating at 65 to 75 ° C. A highly concentrated solution;
(2) 88 to 94.999 parts by weight of polyethylene glycol having an average molecular weight of 2,700 to 9,300 ,
Is a solid-type disinfectant obtained by mixing at 70 to 75 ° C. and then solidifying by cooling.

        A human body composition containing the solid fungicide according to claim 1.

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