CN106380500A - Extraction method for improving output and internal quality of avermectin B1a fine powder - Google Patents
Extraction method for improving output and internal quality of avermectin B1a fine powder Download PDFInfo
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- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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Abstract
The invention relates to an extraction method for improving the output and internal quality of avermectin B1a fine powder. The method comprises the following steps: adding hyphae of avermectin into a methanol solvent with a temperature of 40 to 45 DEG C and a mass concentration of 95 to 97%, carrying out extraction, then cooling to a temperature lower than 0 DEG C, maintaining the temperature for 2 to 4 hours, concentrating and purifying filtrate, and finally carrying out crystallization and recrystallization to obtain the avermectin B1a crystals. The hyphae of avermectin is added into methanol with a temperature of 40 to 45 DEG C and a mass concentration of 95 to 97% to obtain an extract; as the extract cools down, the solubility of higher fatty acid grease in the methanol is reduced quickly, the higher fatty acid grease is precipitated, after filtering, the crystallization and recrystallization will remove grease residues from the fine powder, thus the content of avermectin B1a is increased, and the internal quality of fine powder is improved therefore.
Description
Technical field：
The present invention relates to a kind of preparation method of biological pesticide, especially a kind of improve Avermectin B1a fine powder production capacity and
The leach extraction method of inherent quality, belongs to preparation technique of pesticide field.
Background technology：
AVM is in ten hexa-atomic big rings being similar to by one group of structure that tunning separation and Extraction in streptomycete obtains
Esters antibiotic, is made up of one group of 8 close homologue of structure, B1 and B2 is two big components in this homologue.Avermectin
To nematode, insect, mite class has high Biocidal activity to plain B class component.
AVM is as one of insecticide maximally efficient in the world at present, domestic year usage amount about 4100 tons of left sides
The right side, becomes the main product in agricultural chemical insecticide.AVM is a kind of wide spectrum, efficient, safe and stable insecticidal materials,
There is the very strong activity killing off acarid, insect and parasite it is also possible to be used for people, animal and crops, and it is to people and the food in one's mouth
Newborn animal safe, be a kind of good biological pesticide.
At present, the production process of avermectin extracting is as follows：By zymotic fluid through plate compression, abandon filtrate, obtain bacterium
Filament filter cake, obtains AVM after drying and dries mycelia, then use methyl alcohol soak extraction, extracting technology is normal using 8 times
Warm methyl alcohol soak extraction, the leaching liquor potency that this method is extracted is low, and methyl alcohol usage amount is big, therefore, existing avermectin extracting
The disadvantage that presence yields poorly, high energy consumption, process time length, production cost are high.
Higher fatty acids grease, as the inevitable product in abamectin fermenting process, extracted in AVM
Also together will be extracted in leaching liquor with AVM as impurity in journey, and in the follow-up dedoping step of AVM,
Although multiple recrystallization can using mother liquor take away wherein most, but still some fat residue shadow among fine powder
Ring the inherent quality of fine work.CN102060901A " a kind of method that petroleum ether deoils " is although the method announced can be in subsequent wash
Grease can be removed, but petroleum ether has unit consumption height, and petroleum ether flash-point is relatively low, there is very big potential safety hazard.
Content of the invention：
Extract for existing avermectin extracting technique that potency is low, methyl alcohol usage amount is big；Leading to AVM hereinafter grease in fine powder more
The technical problem that rhzomorph B1a content is low, inherent quality is poor, the present invention is a kind of to improve Avermectin B1a fine powder production capacity and inherent matter
The leach extraction method of amount.
Technical scheme is as follows：
A kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality, as follows including step：
(1) AVM mycelia is added to 40～45 DEG C of temperature, mass concentration is in 95～97% methanol solvate, Ah
Tieing up rhzomorph mycelia with the mass volume ratio of methanol solvate is：1: (3～5), unit g/mL, insulated and stirred 20～30 minutes, filter
Obtain avermectin extracting liquid；
(2) avermectin extracting liquid is cooled to less than 0 DEG C, is incubated 2～4 hours, filtrate is then collected by filtration；
(3) filtrate of step (2) is warming up to 60～70 DEG C, concentrates under vacuum condition, obtain the thick material of ointment, thick to ointment
Add 75～85 DEG C of hot water in material, stir 20～30 minutes, then stratification, remove upper water, obtain ointment after purification thick
Material；
(4) the thick material of ointment adds in methanol solvate after purification, is warming up to 65～75 DEG C of dissolvings, adjusts mixing speed, slow fall
Temperature is crystallized to 20～30 DEG C, and insulation carries out growing the grain in 1～2 hour, and suction filtration obtains B1a crude product,
(5) B1a crude product is added methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that B1a crude product is complete
After CL, it is incubated 30 minutes, carries out suction filtration, reclaim filtrate normal pressure and be concentrated into 2～4 times of B1a crude product weight and recrystallized,
Filter, obtain Avermectin B1a crystal.
Currently preferred, the method for the present invention also includes step (6), by the Avermectin B1a crystal of step (5) according to
The method of step (5) repeats 1～3 time, then carries out suction filtration, drying, obtains Avermectin B1a fine powder.
Currently preferred, step (1), methanol solvate temperature used during extraction is 40 DEG C, and the quality of methanol solvate is dense
Spend for 95%, AVM mycelia with the mass volume ratio of methanol solvate is：1: 5, unit g/mL.
Currently preferred, step (2), avermectin extracting liquid is cooled to 0 DEG C, and temperature retention time is 4 hours.
Currently preferred, step (3), vacuum concentrated in vacuo is -0.05～-0.07Mpa, the addition of hot water with
The volume ratio of the thick material of ointment is 1：(1～4), it is preferred that the temperature of hot water is 80 DEG C, mixing time is 30 minutes.
Currently preferred, step (3), the stratification time is 10-18min.
Currently preferred, the thick material of ointment and the volume ratio of methanol solvate are (8～12) to step (4) after purification：(6～8),
Preferably, the thick material of ointment and the volume ratio of methanol solvate are 10: 8 after purification, and the mass concentration of methanol solvate is 95～97%, excellent
Choosing, the mass concentration of methanol solvate is 95%.
Currently preferred, step (4), mixing speed is 10～20r/min, and slow cooling speed is 3～5 DEG C often little
When, slow cooling is crystallized to 25 DEG C.The B1a crude product obtaining is through methyl alcohol dissolving freezing no floccule.
Currently preferred, step (5), the mass volume ratio of B1a crude product and methyl alcohol：1：(10～20), unit g/mL, excellent
Choosing, the mass volume ratio of B1a crude product and methyl alcohol：1：15, unit g/mL, the mass concentration of methyl alcohol is 99%.
Currently preferred, step (5), activated carbon dosage is the 1% of B1a crude product quality.
AVM solubility in methyl alcohol is as the rising of methanol concentration and raises, higher fatty acids grease conduct
Inevitable product in abamectin fermenting process, after being leached into leaching liquor, though in later crystallization and recrystallization process
So mother liquor can be taken away a part but take away not exclusively and stay in fine powder, present inventors have unexpectedly found that, AVM mycelia is through temperature
40～45 DEG C, mass concentration be 95～97% the leaching liquor that obtains of methyl alcohol, after low temperature, higher fatty acids grease is with temperature
Reduction, solubility in methyl alcohol can reduce rapidly and separate out in a large number, after filtration, can be made by follow-up crystallization and recrystallization
Grease residual is not had to improve content, thus improving the inherent quality of fine powder in fine powder.
The technological progress that the present invention obtains：
1st, the method for the present invention, soaks AVM using the methyl alcohol that 40～45 DEG C of temperature, mass concentration are 95～97%
Mycelia, methyl alcohol usage amount has been reduced to present 5 times by 8 times of original dry powder weight, and potency is improved by 12000 original μ/ml
To 20000 μ/more than ml, yield increased 30%, thus overcome that prior art extraction yield is low, high energy consumption, the process time
Disadvantage long, that production cost is high.
2nd, the method for the present invention, removes grease therein using leaching liquor low temperature, production of high purity fine powder of making a living provides must
Ensure, be also the follow-up guarantee reducing recrystallization number of times；Fine work quality is significantly improved, after drying no longer occurs in product
Yellowing phenomenon, does downstream product and also no longer occurs because AVM oil content is too high and can not use situation, the containing of Avermectin B1a
Amount can bring up to more than 94.5% by original 93%.
Brief description：
The leaching liquor that Fig. 1 a obtains for the embodiment of the present invention 1 step (1) is cooled to -20 DEG C, leaching liquor photo figure；
The leaching liquor that Fig. 1 b obtains for comparative example 1 step (1) is cooled to -20 DEG C, leaching liquor photo figure；
Fig. 2 a is that the B1a fine powder that the embodiment of the present invention 1 is obtained is dissolved with 50 times of methyl alcohol, and prepared fine work lysate will obtain
Fine work lysate be cooled to -20 DEG C, lysate photo figure；
Fig. 2 b is that the B1a fine powder that comparative example 1 is obtained is dissolved with 50 times of methyl alcohol, and prepared fine work lysate, by the fine work obtaining
Lysate is cooled to -20 DEG C, lysate photo figure.
Specific embodiment：
Below by specific embodiment, the present invention will be further described, but not limited to this.AVM hereinafter used in embodiment
It is to be prepared in accordance with the following steps that rhzomorph dries mycelia：
Abamectin fermented dry mycelium：AVM produces bacterial classification A Foman streptomycete through 280～300 hours aerobics
Fermentation, after zymotic fluid potency reaches certain standard, stops fermentation, by this abamectin fermented liquid after plate and frame filter press filtration
Obtain moisture content 70% about zymotic fluid filter cake and the useless fermentation aqueous solution, then again 70% about zymotic fluid filter cake is done through flash distillation
Dry use as the raw material of the embodiment of the present invention to moisture content 8～10% fermentation dry bacterium filament.
Equipment used by embodiment is conventional existing equipment.
Embodiment 1：
A kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality, as follows including step：
(1) take AVM to dry mycelia 2000g (mycelia potency is 10230 μ/g), add 40 DEG C of 10000mL temperature, matter
Measure in the methyl alcohol that concentration is 95% and stir 30 minutes, be filtrated to get avermectin extracting liquid 9900ml, with HPLC, gained is extracted
Liquid is detected, leaching liquor potency：20842μ/ml.
(2) take leaching liquor 5L, freeze 4 hours under conditions of 0 DEG C, after separating out floccule, suction filtration obtains filtrate, and filtrate is put
It is incubated under conditions of being placed in 0 DEG C, no floccule separates out.
(3) filtrate of step (2) is warming up to 65 DEG C, concentrates under vacuum condition, obtain the thick material of ointment, in the thick material of ointment
Add 80 DEG C of hot water, the addition of hot water is 1 with the volume ratio of the thick material of ointment：2, stir 30 minutes, then stand 15min and divide
Layer, removes upper water, obtains the thick material of ointment after purification；
(4) the thick material of ointment adds in methanol solvate after purification, and the thick material of ointment and the volume ratio of methanol solvate are 10 after purification：8,
The mass concentration of methanol solvate is 95%.It is warming up to 70 DEG C of dissolvings, adjustment mixing speed is 10～20r/min, with 5 DEG C per hour
Rate of temperature fall slow cooling crystallized to 25 DEG C, insulation carry out growing the grain within 2 hours, suction filtration obtains B1a crude product 226g, with HPLC pair
This step gained crude product, the B1a content of mother liquor carry out detecting content in crude product：68.87%；This step gained crude product is cold after methyl alcohol dissolving
Freeze and observe no floccule.
(5) by above-mentioned crude product with 99% methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that crude product is complete
After CL, it is incubated 30 minutes, carries out suction filtration, reclaim filtrate to crystallizing tank, then normal pressure concentrates filtrate to 3 times of crude product weight
Filter, obtain Avermectin B1a crystal.Wherein, recrystallize methanol solvate used：Crude product=15ml：1g；Activated carbon dosage is
The 1% of coarse crystallization quality；
(6) by the Avermectin B1a crystal 76g of step (5), the method according to step (5) repeats 3 times, Ran Houjin
Row suction filtration, drying, are detected to this step gained B1a fine powder content with HPLC：B1a content 95.03%, fine work dissolves through methyl alcohol
Freezing no floccule, qualified product.
Comparative example 1：
A kind of preparation method improving Avermectin B1a fine powder yield and content, step is as follows：
(1) take AVM to dry mycelia 2000g (mycelia potency is 10230 μ/g), add 25 DEG C of 10000mL temperature, matter
Measure in the methyl alcohol that concentration is 92% and stir 30 minutes, be filtrated to get avermectin extracting liquid 9900ml, with HPLC, gained is extracted
Liquid is detected, leaching liquor potency：12561μ/ml.
(2) leaching liquor is warming up to 70 DEG C of vacuum distillations 2 hours, and solution is condensed into paste, obtains the thick material of ointment, during concentration
Vacuum is -0.07Mpa.Add 80 DEG C of hot water in the thick material of ointment, the addition of hot water with the volume ratio of the thick material of ointment is
1：2, stir 30 minutes, then standing 15min layering, removes upper water, obtain the thick material of ointment after purification；
(3) the thick material of ointment adds in methanol solvate after purification, and the thick material of ointment and the volume ratio of methanol solvate are 10 after purification：8,
The mass concentration of methanol solvate is 95%.It is warming up to 70 DEG C of dissolvings, adjustment mixing speed is 10～20r/min, with 5 DEG C per hour
Rate of temperature fall slow cooling crystallized to 25 DEG C, insulation carry out growing the grain within 2 hours, suction filtration obtains B1a crude product crude product 233g, use
HPLC carries out to the B1a content of this step gained crude product, mother liquor detecting content in crude product：64.11%；This step gained crude product is molten through methyl alcohol
After solution, floccule is obvious.
(4) by above-mentioned crude product with 99% methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that crude product is complete
After CL, it is incubated 30 minutes, carries out suction filtration, reclaim filtrate to crystallizing tank, then normal pressure concentrates filtrate to 3 times of crude product weight
Filter, obtain Avermectin B1a crystal.Wherein, recrystallize methanol solvate used：Crude product=15ml：1g；Activated carbon dosage is
The 1% of coarse crystallization quality；
(5) by the Avermectin B1a crystal 76g of step (4), the method according to step (4) repeats 3 times, Ran Houjin
Row suction filtration, drying, are detected to this step gained B1a fine powder content with HPLC：B1a content 93.02%, fine work is through 50 times of methyl alcohol
Dissolving cooling freezing, floccule is obvious.
The impact such as table 1 below to leaching liquor potency, fine powder b1a content for the process of the embodiment of the present invention 1 and comparative example 1
Shown.
Table 1
| Methanol usage | Leaching liquor potency μ/ml | Fine powder b1a content | |
| The embodiment of the present invention 1 | 5 times | 20842 | 95.03% |
| Comparative example 1 | 8 times | 12561 | 93.02% |
Embodiment 2：
A kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality, as follows including step：
(1) take AVM to dry mycelia 2000g (mycelia potency is 10230 μ/g), add 42 DEG C of 10000mL temperature, matter
Measure in the methyl alcohol that concentration is 96% and stir 30 minutes, be filtrated to get avermectin extracting liquid 9900ml, with HPLC, gained is extracted
Liquid is detected, leaching liquor potency：20143μ/ml.
(2) take leaching liquor 5L, freeze 3 hours under conditions of 0 DEG C, after separating out floccule, suction filtration obtains filtrate, and filtrate is put
It is incubated under conditions of being placed in 0 DEG C, no floccule separates out.
(3) filtrate of step (2) is warming up to 70 DEG C, concentrates under vacuum condition, obtain the thick material of ointment, in the thick material of ointment
Add 78 DEG C of hot water, the addition of hot water is 1 with the volume ratio of the thick material of ointment：3, stir 30 minutes, then stand 15min and divide
Layer, removes upper water, obtains the thick material of ointment after purification；
(4) the thick material of ointment adds in methanol solvate after purification, and the thick material of ointment and the volume ratio of methanol solvate are 10 after purification：7,
The mass concentration of methanol solvate is 95%.It is warming up to 72 DEG C of dissolvings, adjustment mixing speed is 10～20r/min, with 5 DEG C per hour
Rate of temperature fall slow cooling crystallized to 25 DEG C, insulation carry out growing the grain within 2 hours, suction filtration obtains B1a crude product 223.05g, use
HPLC carries out to the B1a content of this step gained crude product, mother liquor detecting content in crude product：64.32%；This step gained crude product is molten through methyl alcohol
After solution, no floccule is observed in freezing.
(5) by above-mentioned crude product with 99% methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that crude product is complete
After CL, it is incubated 30 minutes, carries out suction filtration, reclaim filtrate to crystallizing tank, then normal pressure concentrates filtrate to 3 times of crude product weight
Filter, obtain Avermectin B1a crystal.Wherein, recrystallize methanol solvate used：Crude product=15ml：1g；Activated carbon dosage is
The 1% of coarse crystallization quality；
(6) by the Avermectin B1a crystal 76g of step (5), the method according to step (5) repeats 3 times, Ran Houjin
Row suction filtration, drying, are detected to this step gained B1a fine powder content with HPLC：B1a content 94.89%, fine work dissolves through methyl alcohol
Freezing no floccule, qualified product.
Comparative example 2：
A kind of preparation method improving Avermectin B1a fine powder yield and content, step is as follows：
(1) take AVM to dry mycelia 2000g (mycelia potency is 10230 μ/g), add 25 DEG C of 10000mL temperature, matter
Measure in the methyl alcohol that concentration is 92% and stir 30 minutes, be filtrated to get avermectin extracting liquid 9900ml, with HPLC, gained is extracted
Liquid is detected, leaching liquor potency：12338μ/ml.
(2) leaching liquor is warming up to 70 DEG C of vacuum distillations 2 hours, and solution is condensed into paste, obtains the thick material of ointment, during concentration
Vacuum is -0.07Mpa.Add 80 DEG C of hot water in the thick material of ointment, the addition of hot water with the volume ratio of the thick material of ointment is
1：2, stir 30 minutes, then standing 15min layering, removes upper water, obtain the thick material of ointment after purification；
(3) the thick material of ointment adds in methanol solvate after purification, and the thick material of ointment and the volume ratio of methanol solvate are 10 after purification：8,
The mass concentration of methanol solvate is 95%.It is warming up to 70 DEG C of dissolvings, adjustment mixing speed is 10～20r/min, with 5 DEG C per hour
Rate of temperature fall slow cooling crystallized to 25 DEG C, insulation carry out growing the grain within 2 hours, suction filtration obtains B1a crude product crude product 223.05g,
With HPLC, the B1a content of this step gained crude product, mother liquor is carried out detecting content in crude product：65.33%, mother liquor potency：16576μ/
ml；This step gained crude product cools to 0 DEG C through methyl alcohol dissolving, and floccule is obvious.
(4) by above-mentioned crude product with 99% methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that crude product is complete
After CL, it is incubated 30 minutes, carries out suction filtration, reclaim filtrate to crystallizing tank, then normal pressure concentrates filtrate to 3 times of crude product weight
Filter, obtain Avermectin B1a crystal.Wherein, recrystallize methanol solvate used：Crude product=15ml：1g；Activated carbon dosage is
The 1% of coarse crystallization quality；
(5) by the Avermectin B1a crystal 76g of step (4), the method according to step (4) repeats 3 times, Ran Houjin
Row suction filtration, drying, are detected to this step gained B1a fine powder content with HPLC：B1a content 92.87%, fine work dissolves through methyl alcohol
Cooling freezing, floccule is obvious.
The impact such as table 1 below to leaching liquor potency, fine powder b1a content for the process of the embodiment of the present invention 2 and comparative example 2
Shown.
Table 2
| Methanol usage | Leaching liquor potency μ/ml | Fine powder b1a content | |
| The embodiment of the present invention 1 | 5 times | 20143 | 94.89% |
| Comparative example 1 | 8 times | 12338 | 92.87% |
Embodiment 3：
A kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality, as follows including step：
(1) take AVM to dry mycelia 2000g (mycelia potency is 10230 μ/g), add 10000mL temperature 45 C, matter
Measure in the methyl alcohol that concentration is 96% and stir 30 minutes, be filtrated to get avermectin extracting liquid 9900ml, with HPLC, gained is extracted
Liquid is detected, leaching liquor potency：20617μ/ml.
(2) take leaching liquor 5L, freeze 2 hours under conditions of -1 DEG C, after separating out floccule, suction filtration obtains filtrate, filtrate
It is incubated under conditions of being positioned over 0 DEG C, no floccule separates out.
(3) filtrate of step (2) is warming up to 68 DEG C, concentrates under vacuum condition, obtain the thick material of ointment, in the thick material of ointment
Add 82 DEG C of hot water, the addition of hot water is 1 with the volume ratio of the thick material of ointment：2.5, stir 30 minutes, then stand 15min
Layering, removes upper water, obtains the thick material of ointment after purification；
(4) the thick material of ointment adds in methanol solvate after purification, and the thick material of ointment and the volume ratio of methanol solvate are 11 after purification：8,
The mass concentration of methanol solvate is 95%.It is warming up to 68 DEG C of dissolvings, adjustment mixing speed is 10～20r/min, with 5 DEG C per hour
Rate of temperature fall slow cooling crystallized to 25 DEG C, insulation carry out growing the grain within 2 hours, suction filtration obtains B1a crude product 230g, with HPLC pair
This step gained crude product, the B1a content of mother liquor carry out detecting content in crude product：64.33%, mother liquor potency：16576μ/ml；This step institute
Obtain crude product freezing after methyl alcohol dissolving and observe no floccule.
(5) by above-mentioned crude product with 99% methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that crude product is complete
After CL, it is incubated 30 minutes, carries out suction filtration, reclaim filtrate to crystallizing tank, then normal pressure concentrates filtrate to 3 times of crude product weight
Filter, obtain Avermectin B1a crystal.Wherein, recrystallize methanol solvate used：Crude product=16ml：1g；Activated carbon dosage is
The 1% of coarse crystallization quality；
(6) by the Avermectin B1a crystal 76g of step (5), the method according to step (5) repeats 3 times, Ran Houjin
Row suction filtration, drying, are detected to this step gained B1a fine powder content with HPLC：B1a content 94.81%, fine work dissolves through methyl alcohol
Freezing no floccule, qualified product.
Comparative example 3：
A kind of preparation method improving Avermectin B1a fine powder yield and content, step is as follows：
(1) take AVM to dry mycelia 2000g (mycelia potency is 10230 μ/g), add 25 DEG C of 10000mL temperature, matter
Measure in the methyl alcohol that concentration is 92% and stir 30 minutes, be filtrated to get avermectin extracting liquid 9900ml, with HPLC, gained is extracted
Liquid is detected, leaching liquor potency：12831μ/ml.
(2) leaching liquor is warming up to 70 DEG C of vacuum distillations 2 hours, and solution is condensed into paste, obtains the thick material of ointment, during concentration
Vacuum is -0.07Mpa.Add 80 DEG C of hot water in the thick material of ointment, the addition of hot water with the volume ratio of the thick material of ointment is
1：2, stir 30 minutes, then standing 15min layering, removes upper water, obtain the thick material of ointment after purification；
(3) the thick material of ointment adds in methanol solvate after purification, and the thick material of ointment and the volume ratio of methanol solvate are 10 after purification：8,
The mass concentration of methanol solvate is 95%.It is warming up to 70 DEG C of dissolvings, adjustment mixing speed is 10～20r/min, with 5 DEG C per hour
Rate of temperature fall slow cooling crystallized to 25 DEG C, insulation carry out growing the grain within 2 hours, suction filtration obtains B1a crude product crude product 227g, use
HPLC carries out to the B1a content of this step gained crude product, mother liquor detecting content in crude product：67.87%；This step gained crude product is molten through methyl alcohol
Solution cooling freezing, floccule is obvious.
(4) by above-mentioned crude product with 99% methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that crude product is complete
After CL, it is incubated 30 minutes, carries out suction filtration, reclaim filtrate to crystallizing tank, then normal pressure concentrates filtrate to 3 times of crude product weight
Filter, obtain Avermectin B1a crystal.Wherein, recrystallize methanol solvate used：Crude product=15ml：1g；Activated carbon dosage is
The 1% of coarse crystallization quality；
(5) by the Avermectin B1a crystal 76g of step (4), the method according to step (4) repeats 3 times, Ran Houjin
Row suction filtration, drying, are detected to this step gained B1a fine powder content with HPLC：B1a content 93.14%, fine work dissolves through methyl alcohol
Cooling freezing, floccule is obvious.
The impact such as table 1 below to leaching liquor potency, fine powder b1a content for the process of the embodiment of the present invention 3 and comparative example 3
Shown.
Table 3
| Methanol usage | Leaching liquor potency μ/ml | Fine powder b1a content | |
| The embodiment of the present invention 1 | 5 times | 20617 | 94.81% |
| Comparative example 1 | 8 times | 12831 | 93.14% |
Experimental example
1st, the leaching liquor cooling that the leaching liquor obtaining the embodiment of the present invention 1 step (1) and comparative example 1 step (1) obtain
To -20 DEG C, rate of temperature fall is identical, observes floccule in leaching liquor, and comparison diagram as shown in Figure 1 a, 1 b, can by picture contrast
To find out, the method for the present invention, using 40 DEG C, concentration 95% methyl alcohol soaks nothing after the leaching liquor freezing that AVM mycelia obtains
Floccule, and after the leaching liquor freezing being obtained using prior art extraction, floccule is obvious, under cryogenic in leaching liquor
Grease will be separated out in the form of floccule, and the grease in the floccule existing more explanations leaching liquor is more, to follow-up purification
Unfavorable, it is difficult in follow-up crystallization and recrystallization process to remove.
2nd, B1a fine powder 50 times of water dissolves, the prepared fine work the dissolving respectively embodiment of the present invention 1, comparative example 1 being obtained
Liquid, the fine work obtaining lysate is cooled to -20 DEG C, rate of temperature fall is identical, observes floccule in lysate, and comparison diagram is as schemed
Shown in 2a, Fig. 2 b, by picture contrast as can be seen that no floccule after the fine work lysate freezing that obtains of the method for the present invention,
And floccule is obvious after the fine work lysate freezing being obtained using prior art extraction, under cryogenic in fine powder lysate
Grease will be separated out in the form of floccule, and the floccule existing more explanations fine powder quality is poorer, and content is lower, and product occurs
Yellowing phenomenon after drying, does downstream product and also occurs because AVM amount containing grease is too high and can not use situation.
Claims (10)
1. a kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality, as follows including step：
(1) AVM mycelia is added to 40～45 DEG C of temperature, mass concentration is Avermectin in 95～97% methanol solvate
Plain mycelia with the mass volume ratio of methanol solvate is：1: (3～5), unit g/mL, insulated and stirred 20～30 minutes, it is filtrated to get
Avermectin extracting liquid；
(2) avermectin extracting liquid is cooled to less than 0 DEG C, is incubated 2～4 hours, filtrate is then collected by filtration；
(3) filtrate of step (2) is warming up to 60～70 DEG C, concentrates under vacuum condition, obtain the thick material of ointment, in the thick material of ointment
Add 75～85 DEG C of hot water, stir 20～30 minutes, then stratification, remove upper water, obtain the thick material of ointment after purification；
(4) the thick material of ointment adds in methanol solvate after purification, is warming up to 65～75 DEG C of dissolvings, adjusts mixing speed, slow cooling is extremely
20～30 DEG C are crystallized, and insulation carries out growing the grain in 1～2 hour, and suction filtration obtains B1a crude product,
(5) B1a crude product is added methyl alcohol rising temperature for dissolving, add activated carbon stirring to be warming up to 65～70 DEG C, treat that B1a crude product is completely molten
Xie Hou, is incubated 30 minutes, carries out suction filtration, reclaims filtrate normal pressure and is concentrated into 2～4 times of B1a crude product weight and is recrystallized, mistake
Filter, obtains Avermectin B1a crystal.
2. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In also including step (6), the Avermectin B1a crystal of step (5) repeated 1～3 time according to the method for step (5), so
After carry out suction filtration, drying, obtain Avermectin B1a fine powder.
3. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In, step (1), methanol solvate temperature used during extraction is 40 DEG C, and the mass concentration of methanol solvate is 95%, AVM bacterium
Silk and the mass volume ratio of methanol solvate are：1: 5, unit g/mL.
4. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In, step (2), avermectin extracting liquid is cooled to 0 DEG C, and temperature retention time is 4 hours.
5. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In, step (3), vacuum concentrated in vacuo is -0.05～-0.07Mpa, and the addition of hot water with the volume ratio of the thick material of ointment is
1：(1～4), it is preferred that the temperature of hot water is 80 DEG C, mixing time is 30 minutes.
6. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In, step (3), the stratification time is 10-18min.
7. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In, step (4), the thick material of ointment and the volume ratio of methanol solvate are (8～12) after purification: (6～8) are it is preferred that ointment after purification
The volume ratio of thick material and methanol solvate is 10: 8, and the mass concentration of methanol solvate is 95～97% it is preferred that the matter of methanol solvate
Amount concentration is 95%.
8. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In, step (4), mixing speed is 10～20r/min, and for 3～5 DEG C per hour, slow cooling enters slow cooling speed to 25 DEG C
Row crystallization；The B1a crude product obtaining is through methyl alcohol dissolving freezing no floccule.
9. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature exists
In, step (5), the mass volume ratio of B1a crude product and methyl alcohol：1: (10～20), unit g/mL is it is preferred that B1a crude product and methyl alcohol
Mass volume ratio：1: 15, unit g/mL, the mass concentration of methyl alcohol is 99%.
10. the leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality according to claim 1, its feature
It is, step (5), activated carbon dosage is the 1% of B1a crude product quality.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4427663A (en) * | 1982-03-16 | 1984-01-24 | Merck & Co., Inc. | 4"-Keto-and 4"-amino-4"-deoxy avermectin compounds and substituted amino derivatives thereof |
| CN103030675A (en) * | 2012-11-19 | 2013-04-10 | 河北威远生物化工股份有限公司 | Process of extracting abamectin components B1 and B2 step by step by utilizing crystallization method |
| CN104876991A (en) * | 2015-06-12 | 2015-09-02 | 齐鲁制药（内蒙古）有限公司 | Method preparing abamectin Bla fine powder by secondary crystallization in abamectin Bla |
-
2016
- 2016-08-30 CN CN201610773417.0A patent/CN106380500B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4427663A (en) * | 1982-03-16 | 1984-01-24 | Merck & Co., Inc. | 4"-Keto-and 4"-amino-4"-deoxy avermectin compounds and substituted amino derivatives thereof |
| CN103030675A (en) * | 2012-11-19 | 2013-04-10 | 河北威远生物化工股份有限公司 | Process of extracting abamectin components B1 and B2 step by step by utilizing crystallization method |
| CN104876991A (en) * | 2015-06-12 | 2015-09-02 | 齐鲁制药（内蒙古）有限公司 | Method preparing abamectin Bla fine powder by secondary crystallization in abamectin Bla |
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