Clethodim composition, emulsifiable concentrate and parent drug containing the composition

Abstract

The present application relates to a clethodim composition comprising clethodim or an agriculturally acceptable salt thereof and thioglycolic acid or a thioglycolic acid ester. The present application also relates to the use of thioglycolic acid or a thioglycolic acid ester as a stabilizer for clethodim or an agriculturally acceptable salt thereof. The present application further relates to a clethodim emulsifiable concentrate and a parent drug containing the composition of the present invention.

Description

Technical Field

[0001] The present invention relates to a clethodim composition, which contains clethodim or an agriculturally acceptable salt thereof and thioglycolic acid or thioglycolic acid ester. The present invention further relates to a clethodim emulsifiable concentrate and a parent drug containing the composition. Background Art

[0002] Clethodim is an important cyclohexanedione oxime herbicide with the following structure:

[0003]

[0004] Clethodim boasts broad spectrum, high efficacy, and low toxicity. However, due to the presence of functional groups such as hydroxyl groups, double bonds, and oximes in its molecular structure, it is unstable and easily degraded. Environmental factors such as moisture, oxygen, ultraviolet light, and temperature can all cause clethodim to degrade. Therefore, effective measures are urgently needed to mitigate its degradation during long-distance transportation and storage.

[0005] Currently, there are attempts to improve transportation or storage stability by dissolving the clethodim technical in a solvent to prepare a parent drug form.

[0006] The commonly used preparation of clethodim is emulsifiable concentrate. Summary of the Invention

[0007] The present invention aims to provide a stable clethodim composition, which contains clethodim or an agriculturally acceptable salt thereof and thioglycolic acid or thioglycolic acid ester.

[0008] Specifically, the present invention provides:

[0009] (1) A clethodim composition comprising clethodim or an agriculturally acceptable salt thereof and thioglycolic acid or a thioglycolic acid ester.

[0010] (2) The composition according to (1) above, wherein the thioglycolate is thioglycolate C 1-20 Alkyl ester, more preferably thioglycolic acid C 1-10 Alkyl esters.

[0011] (3) The composition according to (1) or (2) above, wherein the thioglycolate is one or more selected from the group consisting of isooctyl thioglycolate, ethyl thioglycolate, 1,4-butylene bis(thioglycolate), and ethylene glycol bis(thioglycolate).

[0012] (4) The composition according to any one of (1) to (3) above, wherein the weight of the thioglycolic acid or thioglycolic acid ester is 0.001-20%, preferably 0.001-10%, more preferably 0.005-5%, relative to the weight of clethodim or its agriculturally acceptable salt, and specifically can be, for example, about 0.005%, 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 3%, 4%, 5%, etc.

[0013] (5) Clethodim emulsifiable concentrate containing the composition according to any one of (1) to (4) above; preferably, the content of the composition of the present invention is 10-70% by weight, preferably 10-40% by weight, and specifically can be, for example, about 10-15% by weight, 25-30% by weight, 35-40% by weight, or 50-60% by weight, relative to the total weight of the emulsifiable concentrate.

[0014] (6) A parent drug of clethodim, which contains the composition according to any one of the above (1) to (4); preferably, the weight ratio of the composition to the solvent in the parent drug is (5-90):(95-10), preferably (20-50):(80-50), more preferably (30-60):(70-40), and specifically can be, for example, 37:63 or 50:50.

[0015] (7) Use of thioglycolic acid or thioglycolic acid esters as stabilizers for clethodim or its agriculturally acceptable salts.

[0016] (8) The use according to (7) above, wherein the thioglycolate is thioglycolate C 1-20 Alkyl ester, more preferably thioglycolic acid C 1-10 Alkyl esters.

[0017] (9) The use according to (8) above, wherein the thioglycolate is one or more selected from the group consisting of isooctyl thioglycolate, ethyl thioglycolate, 1,4-butylene bis(thioglycolate), and ethylene glycol bis(thioglycolate).

[0018] (10) The use according to any one of (7) to (9) above, wherein the amount of thioglycolic acid or thioglycolic acid ester is 0.001-20%, preferably 0.001-10%, more preferably 0.005-5%, relative to the weight of clethodim or its agriculturally acceptable salt, and specifically can be, for example, about 0.005%, 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, or 1.5%. DETAILED DESCRIPTION

[0019] In this application, unless otherwise specified, "%" refers to percentage by weight, and "about" refers to the range of ±10%, preferably ±5%.

[0020] The degradation rate is an important indicator used to measure the stability of clethodim or its agriculturally acceptable salt. The initial content of clethodim or its agriculturally acceptable salt is recorded as w1, and the content at the time of measurement is recorded as w2. The degradation rate is calculated as (w1-w2) / w1×100%. The content can be measured by well-known methods such as high-performance liquid chromatography.

[0021] In the present invention, the stability of clethodim or its agriculturally acceptable salt is improved by adding thioglycolic acid or thioglycolic acid ester to clethodim as a stabilizer.

[0022] The thioglycolate used in the present invention is preferably thioglycolate C 1-20 Alkyl ester, more preferably thioglycolic acid C 1-10 Alkyl alcohol esters. The alkanol can be a monohydric alcohol, a dihydric alcohol or a polyhydric alcohol.

[0023] Specific examples of the thioglycolate include isooctyl thioglycolate, ethyl thioglycolate, 1,4-butylene bis(thioglycolate), and ethylene glycol bis(thioglycolate). These may be used alone or in combination of two or more.

[0024] In some specific embodiments, any one of isooctyl thioglycolate, ethyl thioglycolate, 1,4-butylene bis(thioglycolate), and ethylene glycol bis(thioglycolate) is used as the stabilizer.

[0025] In the composition of the present invention, the weight of the thioglycolic acid or thioglycolic acid ester is 0.001-20%, preferably 0.001-10%, and more preferably 0.005-5%, relative to the weight of clethodim or its agriculturally acceptable salt. Specifically, it can be, for example, about 0.005%, 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, 2%, 3%, 4%, 5%, etc., but is not limited to these specific values.

[0026] The composition of the present invention can be prepared into a formulation suitable for clethodim by a known method with suitable adjuvants or auxiliaries allowed for use in pesticides. The formulations of clethodim are known, including but not limited to emulsifiable concentrates.

[0027] The present invention first discovered that thioglycolic acid or thioglycolic acid esters have a stabilizing effect on clethodim or its agriculturally acceptable salts, reducing or delaying its degradation. Therefore, the present application also relates to the use of thioglycolic acid or thioglycolic acid esters as stabilizers for clethodim or its agriculturally acceptable salts. In this use, specific examples and amounts of thioglycolic acid or thioglycolic acid esters are as described above.

[0028] The present application also relates to a clethodim emulsifiable concentrate containing the composition of the present invention as described above, which can be prepared by combining the composition of the present invention with adjuvants and additives for preparing emulsifiable concentrates permitted on pesticides by a known method for preparing emulsifiable concentrates. Relative to the total weight of the emulsifiable concentrate, the amount of the composition of the present invention is preferably 10-70% by weight, more preferably 10-60% by weight, and further preferably 10-40% by weight. In some specific embodiments, the amount of the composition of the present invention is about 10-15% by weight, 25-30% by weight, 35-40% by weight, or 50-60% by weight.

[0029] The present application also relates to a parent drug of clethodim containing the composition of the present invention as described above. The parent drug can be prepared by mixing the composition of the present invention with a solvent, and the weight ratio of the composition of the present invention to the solvent is (5-50): (95-50), preferably (20-50): (80-50), more preferably (30-60): (70-40). In some specific embodiments, the weight ratio of the composition of the present invention to the solvent is about 37: 63 or 50: 50. Specific examples of the solvent include, but are not limited to, solvent oil, etc., and examples thereof include 150# solvent oil, 200# solvent oil, etc.

[0030] Example

[0031] The present invention will be described in more detail below by way of specific examples, but the present invention is not limited to these examples. Any modifications or changes without departing from the gist of the present invention fall within the scope of the present invention.

[0032] Example 1 Inhibition of Clethodim Degradation by 1% 2-Ethylthioglycolate at 35°C

[0033] Isooctyl thioglycolate (JS) was added to clethodim technical (produced by Hebei Lansheng Biotechnology Co., Ltd.) at a weight ratio of 100:1. The mixture was placed in a 35°C incubator, and the clethodim content was determined by high-performance liquid chromatography at the times shown in Table 1. The detection method was as follows: the sample was dissolved in anhydrous acetone and petroleum ether (1:1 by volume), and the mobile phase was acetonitrile:water (80:20) (the pH of the mixture was adjusted to approximately 4.0-4.5 with formic acid). Separation was performed on a C18 column, and detection was performed with a UV detector at a wavelength of 254 nm. Quantification was performed using an external standard method.

[0034] The same batch of clethodim technical without the addition of isooctyl thioglycolate was used as a blank control.

[0035] The results are shown in Table 1. Compared with the blank control, the addition of 1% isooctyl thioglycolate can effectively inhibit the degradation of clethodim.

[0036] Table 1

[0037]

[0038]

[0039] *1: Day 0 refers to the day of drug addition; *2: refers to the content measured on the day after the addition of 2-ethylhexyl thioglycolate.

[0040] Example 2 Inhibition of Clethodim Degradation by 0.1% 2-ethylhexyl thioglycolate at 25°C

[0041] To clethodim technical (produced by Hebei Lansheng Biotechnology Co., Ltd.), isooctyl thioglycolate was added at a weight ratio of clethodim:isoctyl thioglycolate of 100:0.1. The mixture was placed in a constant temperature box at 25°C, and the clethodim content was detected by high performance liquid chromatography at the times shown in Table 2. The detection method was the same as in Example 1.

[0042] The same batch of clethodim technical without the addition of isooctyl thioglycolate was used as a blank control.

[0043] The results are shown in Table 2. Compared with the blank control, the addition of 0.1% isooctyl thioglycolate can effectively inhibit the degradation of clethodim.

[0044] Table 2

[0045]

[0046] *1: Day 0 refers to the day of drug addition; *2: refers to the content measured on the day after the addition of 2-ethylhexyl thioglycolate.

[0047] Example 3 Inhibition of Clethodim Degradation by Other Addition Amounts of Isooctyl Thioglycolate

[0048] Isooctyl thioglycolate was added to clethodim technical (produced by Hebei Lansheng Biotechnology Co., Ltd.) in the amounts shown in Table 3, and the mixture was placed in a constant temperature box at 40° C. The clethodim content was detected by high performance liquid chromatography at the times shown in the table, using the same detection method as in Example 1.

[0049] The same batch of clethodim technical without the addition of isooctyl thioglycolate was used as a blank control.

[0050] The results are shown in Table 3. Compared with the blank control, other added amounts of isooctyl thioglycolate can also effectively inhibit the degradation of clethodim.

[0051] Table 3

[0052] JS addition amount (%) <![CDATA[Content at 0 days *1 (%)]]> 8-day content (%) Degradation rate (%) 0 95.18 87.49 8.08 0.2 94.06 88.61 5.79 0.3 94.37 89.04 5.65 0.8 93.74 89.49 4.53

[0053] *1: Content measured on the day after adding 2-ethylhexyl thioglycolate.

[0054] Example 4 Inhibition of Clethodim Degradation by Bis(Mercaptoacetic Acid)-1,4-Butanediol

[0055] Bis(thioglycolic acid)-1,4-butylene glycol (JSD) was added to clethodim technical (produced by Hebei Lansheng Biotechnology Co., Ltd.) in the amounts shown in Table 4. The mixture was placed in a 40°C incubator, and the clethodim content was detected by high performance liquid chromatography on day 0 and day 8, respectively, using the same detection method as in Example 1.

[0056] The same batch of clethodim technical without the addition of 1,4-butylene bis(thioglycolate) was used as a blank control.

[0057] The results are shown in Table 4. Compared with the blank control, all added amounts of 1,4-butanediol bis(thioglycolate) can effectively inhibit the degradation of clethodim.

[0058] Table 4

[0059] JSD addition amount (%) <![CDATA[Content at 0 days *1 (%)]]> 8-day content (%) Degradation rate (%) 0 95.18 87.49 8.08 0.06 94.35 89.02 5.65 0.1 94.28 89.38 5.20 0.2 93.94 89.51 4.72 0.5 93.19 89.42 4.05

[0060] *1: Content measured on the day after adding 1,4-butylene bis(mercaptoacetate).

[0061] Example 5 Inhibition of Clethodim Degradation by Ethyl Mercaptoacetate

[0062] Ethyl mercaptoacetate (JSY) was added to clethodim technical (produced by Hebei Lansheng Biotechnology Co., Ltd.) in the amounts shown in Table 5. The mixture was placed in a 40°C incubator, and the clethodim content was measured by high performance liquid chromatography on day 0 and on days 7, 14, and 21, respectively, using the same detection method as in Example 1.

[0063] The same batch of clethodim technical without ethyl mercaptoacetate was used as a blank control.

[0064] The results are shown in Table 5. Compared with the blank control, the added amounts of ethyl mercaptoacetate can effectively inhibit the degradation of clethodim.

[0065] Table 5

[0066]

[0067] *1: Content measured on the day after adding ethyl thioglycolate.

[0068] Example 6 Inhibition of Clethodim Degradation by Ethylene Glycol Bis(Mercaptoacetic Acid)

[0069] To clethodim technical (produced by Hebei Lansheng Biotechnology Co., Ltd.), ethylene glycol bis(thioglycolate) (JSS) was added at a weight ratio of 100:0.3. The mixture was placed in a 40°C incubator, and the clethodim content was determined by high-performance liquid chromatography on day 0 and on days 7, 14, 21, and 28, using the same method as in Example 1.

[0070] The same batch of clethodim technical without ethylene glycol bis(thioglycolate) was used as a blank control.

[0071] The results are shown in Table 6. Compared with the blank control, ethylene glycol bis(thioglycolate) can effectively inhibit the degradation of clethodim.

[0072] Table 6

[0073]

[0074] *1: Content measured on the day after adding ethylene glycol bis(thioglycolate).

[0075] As can be seen from the above, thioglycolate or thioglycolic acid is an effective clethodim stabilizer, which can reduce the degradation rate of clethodim, thereby solving the stability problem of clethodim during storage or transportation and improving the quality.

[0076] Comparative Example 1 Inhibition of Clethodim Degradation by 2-Mercaptobenzothiazole

[0077] To clethodim technical (produced by Hebei Lansheng Biotechnology Co., Ltd.), a solution of 2-mercaptobenzothiazole (0.1%, relative to the weight of clethodim) in propylene carbonate (2%, relative to the weight of clethodim) was added, or 2% propylene carbonate alone (as a solvent control) was added. The mixture was placed in a 30°C incubator, and the clethodim content was determined by high performance liquid chromatography at the times shown in Table 7, using the same method as in Example 1. The results are shown in Table 7.

[0078] Table 7

[0079]

[0080] *1: Content measured on the day after adding propylene carbonate or 2-mercaptobenzothiazole and propylene carbonate.

[0081] From the results in Table 7, it can be seen that the degradation rate of 2-mercaptobenzothiazole is higher than that of the solvent control, so it can be considered that it has no inhibitory effect on the degradation of clethodim.

Claims

1. A clethodim composition comprising clethodim or an agriculturally acceptable salt thereof and thioglycolate, wherein the thioglycolate is one or more selected from the group consisting of isooctyl thioglycolate, ethyl thioglycolate, 1,4-butylene bis(thioglycolate), and ethylene glycol bis(thioglycolate), and the weight of the thioglycolate is 0.01-10% relative to the weight of clethodim or its agriculturally acceptable salt.

2. The composition of claim 1, wherein the weight of the thioglycolate is 0.05-5% relative to the weight of clethodim or its agriculturally acceptable salt.

3. Clethodim emulsifiable concentrate, comprising the composition according to claim 1 or 2; the content of the composition of the present invention is 10-70 wt % relative to the total weight of the emulsifiable concentrate.

4. The clethodim emulsifiable concentrate according to claim 3, wherein the content of the composition of the present invention is 10-40 wt % relative to the total weight of the emulsifiable concentrate.

5. A parent drug of clethodim, comprising the composition according to claim 1 or 2; wherein the weight ratio of the composition to the solvent in the parent drug is (5-90):(95-10).

6. The clethodim mother drug according to claim 5, wherein the weight ratio of the composition to the solvent in the mother drug is (20-50):(80-50).

7. The clethodim mother drug according to claim 6, wherein the weight ratio of the composition to the solvent in the mother drug is (30-60):(70-40).

8. Use of a thioglycolate as a stabilizer for clethodim or an agriculturally acceptable salt thereof, wherein the thioglycolate is one or more selected from the group consisting of isooctyl thioglycolate, ethyl thioglycolate, 1,4-butylene bis(thioglycolate), and ethylene glycol bis(thioglycolate), and the amount of the thioglycolate is 0.01-10% relative to the weight of clethodim or its agriculturally acceptable salt.

9. The use according to claim 8, wherein the amount of the thioglycolate is 0.05-5% relative to the weight of clethodim or its agriculturally acceptable salt.

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