CN106380500B - A kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality - Google Patents
A kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality Download PDFInfo
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Abstract
The present invention relates to a kind of leach extraction methods for improving Avermectin B1a fine powder production capacity and inherent quality, after being extracted in the methanol solvate that avermectin mycelia is added to 40~45 DEG C of temperature by it, mass concentration is 95~97%, then it is cooled to 0 DEG C or less, heat preservation 2~4 hours, filtrate is concentrated, is crystallized after purification, is recrystallized to give Avermectin B1a crystal.The leaching liquor that avermectin mycelia of the present invention obtains through 40~45 DEG C of temperature, the methanol that mass concentration is 95~97%, after low temperature, higher fatty acids grease with temperature reduction, solubility in methyl alcohol can be reduced rapidly and is largely precipitated, after filtering, it can make there is no grease residual to improve content in fine powder by subsequent crystallization and recrystallization, to improve the inherent quality of fine powder.
Description
Technical field:
The present invention relates to a kind of preparation method of biological pesticide, especially a kind of raising Avermectin B1a fine powder production capacity and
The leach extraction method of inherent quality belongs to preparation technique of pesticide field.
Background technique:
Avermectin is in ten similar hexa-atomic big rings of one group of structure being obtained by tunning separation and Extraction in streptomycete
Esters antibiotic, 8 homologues similar in one group of structure form, and B1 and B2 are two big components in the homologue.Avermectin
Plain B class component has high Biocidal activity to nematode, insect, mite class.
For avermectin as maximally efficient one of insecticide in the world at present, domestic year usage amount is about 4100 tons of left sides
The right side becomes the main product in agricultural chemical insecticide.Avermectin is a kind of most wide spectrum, efficient, safe and stable insecticidal materials,
Acarid, insect and the activity of helminth are killed off with very strong, can be used for people, animal and crops, and it is to people and the food in one's mouth
Newborn animal it is highly-safe, be a kind of good biological pesticide.
Currently, the production process of avermectin extracting is as follows: by fermentation liquid through plate compression, abandoning filtrate, obtain bacterium
Filament filter cake obtains avermectin drying mycelia after drying, then uses methanol soak extraction, and extracting technology is normal using 8 times
Warm methanol soak extraction, the leaching liquor potency that this method is extracted is low, and methanol usage amount is big, therefore, existing avermectin extracting
There are low output, energy consumption is high, the process time is long, high production cost disadvantage.
Higher fatty acids grease was extracted as the inevitable product in abamectin fermenting process in avermectin
It will be also extracted in leaching liquor together as impurity with avermectin in journey, and in the subsequent dedoping step of avermectin,
Although multiple recrystallization can be taken away using mother liquor wherein most, but still shadow among some fat residue to 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 there are unit consumption height for petroleum ether, and petroleum ether flash-point is lower, there are very big security risks.
Summary of the invention:
Extract that potency is low, methanol usage amount is big for existing avermectin extracting technique；Grease leads to AVM hereinafter more in fine powder
The technical problem that rhzomorph B1a content is low, inherent quality is poor, a kind of raising Avermectin B1a fine powder production capacity of the present invention 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, comprises the following steps that
(1) by avermectin mycelia be added to 40~45 DEG C of temperature, mass concentration be 95~97% methanol solvate in, Ah
Tie up the mass volume ratio of rhzomorph mycelia and methanol solvate are as follows: 1: (3~5), unit g/mL, insulated and stirred 20~30 minutes, filtering
Obtain avermectin extracting liquid；
(2) by avermectin extracting liquid be cooled to 0 DEG C hereinafter, heat preservation 2~4 hours, filtrate is then collected by filtration；
(3) filtrate of step (2) is warming up to 60~70 DEG C, is concentrated under vacuum condition, obtain the thick material of ointment, it is thick to ointment
75~85 DEG C of hot water is added in material, stirs 20~30 minutes, is then allowed to stand layering, removes upper water, it is thick to obtain ointment after purification
Material；
(4) the thick material of ointment adds in methanol solvate after purification, is warming up to 65~75 DEG C of dissolutions, adjusts mixing speed, slowly drops
Temperature is crystallized to 20~30 DEG C, is kept the temperature 1~2 hour progress growing the grain, is filtered to obtain B1a crude product,
(5) methanol rising temperature for dissolving is added in B1a crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is complete to B1a crude product
After fully dissolved, 30 minutes being kept the temperature, is filtered, recycling filtrate normal pressure is concentrated into 2~4 times of B1a crude product weight and is recrystallized,
Filtering, obtains Avermectin B1a crystal.
Currently preferred, method of the invention further includes step (6), by the Avermectin B1a crystal of step (5) according to
The method repetitive operation of step (5) 1~3 time, is then filtered, is dried, and Avermectin B1a fine powder is obtained.
Currently preferred, step (1), when extraction, methanol solvate temperature used was 40 DEG C, and the quality of methanol solvate is dense
Degree is 95%, the mass volume ratio of avermectin mycelia and methanol solvate are as follows: 1: 5, unit g/mL.
Currently preferred, step (2), avermectin extracting liquid is cooled to 0 DEG C, and soaking time is 4 hours.
Currently preferred, step (3), the vacuum degree of vacuum concentration is -0.05~-0.07Mpa, the additional amount 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, and mixing time is 30 minutes.
Currently preferred, step (3), the stratification time is 10-18min.
Currently preferred, the volume ratio of the thick material of ointment and methanol solvate is (8~12): (6~8) to step (4) after purification,
Preferably, the volume ratio of the thick material of ointment and methanol solvate is 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 rate is 3~5 DEG C per small
When, slow cooling is crystallized to 25 DEG C.Obtained B1a crude product is through methanol dissolution freezing without floccule.
Currently preferred, step (5), the mass volume ratio of B1a crude product and methanol: 1:(10~20), unit g/mL is excellent
Choosing, the mass volume ratio of B1a crude product and methanol: 1:15, unit g/mL, the mass concentration of methanol are 99%.
Currently preferred, step (5), activated carbon dosage is the 1% of B1a crude product quality.
The solubility of avermectin in methyl alcohol is the raising with methanol concentration and increases, higher fatty acids grease conduct
Inevitable product in abamectin fermenting process, after being leached into leaching liquor, though in later crystallization and recrystallization process
Right mother liquor can take away a part but take away not exclusively and stay in fine powder, present inventors have unexpectedly found that, avermectin mycelia is through temperature
40~45 DEG C, the obtained leaching liquor of methanol that mass concentration is 95~97%, after low temperature, higher fatty acids grease is with temperature
Reduction, solubility in methyl alcohol can be reduced rapidly and is largely precipitated, after filtering, by it is subsequent crystallization and recrystallization can make
There is no grease to remain and improve content in fine powder, to improve the inherent quality of fine powder.
The technological progress achieved by the present invention:
1, method of the invention impregnates avermectin using 40~45 DEG C of temperature, the methanol that mass concentration is 95~97%
Mycelia, methanol usage amount have 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/ml or more, yield increases 30%, thus overcome the prior art extraction yield it is low, energy consumption is high, the process time
Long, high production cost disadvantage.
2, method of the invention removes grease therein using leaching liquor low temperature, and production of high purity fine powder of making a living provides must
Ensure and it is subsequent reduce recrystallization number guarantee；Fine work quality is significantly improved, after drying no longer occurs in product
Yellowing phenomenon does downstream product and also no longer occurs that situation cannot be used due to avermectin oil content is excessively high, and Avermectin B1a contains
Amount can be increased to 94.5% or more by original 93%.
Detailed description of the invention:
Fig. 1 a is that the leaching liquor that 1 step of the embodiment of the present invention (1) obtains is cooled to -20 DEG C, leaching liquor photo figure；
Fig. 1 b is that the leaching liquor that 1 step of comparative example (1) obtains is cooled to -20 DEG C, leaching liquor photo figure；
Fig. 2 a is that B1a fine powder made from the embodiment of the present invention 1 is dissolved with 50 times of methanol, and fine work lysate is made, will obtain
Fine work lysate be cooled to -20 DEG C, lysate photo figure；
Fig. 2 b is that B1a fine powder made from comparative example 1 is dissolved with 50 times of methanol, and fine work lysate, the fine work that will be obtained is made
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
Rhzomorph drying mycelia is to be prepared in accordance with the following steps:
Abamectin fermented dry mycelium: it is aerobic by 280~300 hours that avermectin produces strain A Foman streptomycete
Fermentation after fermentation liquid potency reaches certain standard, stops fermentation, by the abamectin fermented liquid after plate and frame filter press filters
70% or so fermentation liquid filter cake of moisture content and useless fermentation aqueous solution are obtained, it is then again that 70% or so fermentation liquid filter cake is dry by flash distillation
It is dry to be used to 8~10% fermentation dry bacterium filament of moisture content as the raw material of the embodiment of the present invention.
Equipment used in embodiment is conventional existing equipment.
Embodiment 1:
A kind of leach extraction method improving Avermectin B1a fine powder production capacity and inherent quality, comprises the following steps that
(1) avermectin drying mycelia 2000g (mycelia potency is 10230 μ/g) is taken, 40 DEG C of 10000mL temperature, matter is added
It is stirred 30 minutes in the methanol that amount concentration is 95%, avermectin extracting liquid 9900ml is obtained by filtration, gained is extracted with HPLC
Liquid is detected, leaching liquor potency: 20842 μ/ml.
(2) leaching liquor 5L is taken, is freezed 4 hours under conditions of 0 DEG C, after floccule is precipitated, suction filtration obtains filtrate, and filtrate is put
It is kept the temperature under conditions of being placed in 0 DEG C, no floccule is precipitated.
(3) filtrate of step (2) is warming up to 65 DEG C, is concentrated under vacuum condition, obtain the thick material of ointment, into the thick material of ointment
80 DEG C of hot water is added, the additional amount of hot water and the volume ratio of the thick material of ointment are 1:2, stir 30 minutes, are then allowed to stand 15min points
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 volume ratio of the thick material of ointment and methanol solvate is 10:8 after purification,
The mass concentration of methanol solvate is 95%.70 DEG C of dissolutions are warming up to, adjustment mixing speed is 10~20r/min, per hour with 5 DEG C
Rate of temperature fall slow cooling crystallized to 25 DEG C, keep the temperature 2 hours progress growing the grains, B1a crude product 226g filtered to obtain, with HPLC pairs
The B1a content of crude product, mother liquor obtained by this step carries out detection content in crude product: 68.87%；Crude product obtained by this step is cold after methanol dissolves
Freeze observation without floccule.
(5) by 99% methanol rising temperature for dissolving of above-mentioned crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is complete to crude product
After fully dissolved, heat preservation 30 minutes is filtered, recycling filtrate to crystallizing tank, then 3 times of normal pressure concentration filtrate to crude product weight
Filtering, obtains Avermectin B1a crystal.Wherein, methanol solvate used: crude product=15ml:1g is recrystallized；Activated carbon dosage is
The 1% of coarse crystallization quality；
(6) by the Avermectin B1a crystal 76g of step (5), according to method repetitive operation 3 times of step (5), then into
Row filters, is dry, and detected with HPLC to B1a fine powder content obtained by this step: B1a content 95.03%, fine work is dissolved through methanol
Freezing is without floccule, qualified product.
Comparative example 1:
A kind of preparation method improving Avermectin B1a fine powder yield and content, steps are as follows:
(1) avermectin drying mycelia 2000g (mycelia potency is 10230 μ/g) is taken, 25 DEG C of 10000mL temperature, matter is added
It is stirred 30 minutes in the methanol that amount concentration is 92%, avermectin extracting liquid 9900ml is obtained by filtration, gained is extracted with HPLC
Liquid is detected, leaching liquor potency: 12561 μ/ml.
(2) leaching liquor is warming up to 70 DEG C and is evaporated in vacuo 2 hours, and solution is condensed into paste, obtains the thick material of ointment, when concentration
Vacuum degree is -0.07Mpa.80 DEG C of hot water is added into the thick material of ointment, the additional amount of hot water and the volume ratio of the thick material of ointment are
1:2 is stirred 30 minutes, is then allowed to stand 15min layering, is removed upper water, obtain the thick material of ointment after purification；
(3) the thick material of ointment adds in methanol solvate after purification, and the volume ratio of the thick material of ointment and methanol solvate is 10:8 after purification,
The mass concentration of methanol solvate is 95%.70 DEG C of dissolutions are warming up to, adjustment mixing speed is 10~20r/min, per hour with 5 DEG C
Rate of temperature fall slow cooling crystallized to 25 DEG C, keep the temperature 2 hours progress growing the grains, filter to obtain B1a crude product crude product 233g, use
HPLC carries out detection content in crude product to the B1a content of crude product, mother liquor obtained by this step: 64.11%；Crude product obtained by this step is molten through methanol
Floccule is obvious after solution.
(4) by 99% methanol rising temperature for dissolving of above-mentioned crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is complete to crude product
After fully dissolved, heat preservation 30 minutes is filtered, recycling filtrate to crystallizing tank, then 3 times of normal pressure concentration filtrate to crude product weight
Filtering, obtains Avermectin B1a crystal.Wherein, methanol solvate used: crude product=15ml:1g is recrystallized；Activated carbon dosage is
The 1% of coarse crystallization quality；
(5) by the Avermectin B1a crystal 76g of step (4), according to method repetitive operation 3 times of step (4), then into
Row filters, is dry, and detected with HPLC to B1a fine powder content obtained by this step: B1a content 93.02%, fine work is through 50 times of methanol
Dissolution cooling freezing, floccule are obvious.
The process of the embodiment of the present invention 1 and comparative example 1 is to leaching liquor potency, influence such as the following table 1 of fine powder b1a content
It is 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, comprises the following steps that
(1) avermectin drying mycelia 2000g (mycelia potency is 10230 μ/g) is taken, 42 DEG C of 10000mL temperature, matter is added
It is stirred 30 minutes in the methanol that amount concentration is 96%, avermectin extracting liquid 9900ml is obtained by filtration, gained is extracted with HPLC
Liquid is detected, leaching liquor potency: 20143 μ/ml.
(2) leaching liquor 5L is taken, is freezed 3 hours under conditions of 0 DEG C, after floccule is precipitated, suction filtration obtains filtrate, and filtrate is put
It is kept the temperature under conditions of being placed in 0 DEG C, no floccule is precipitated.
(3) filtrate of step (2) is warming up to 70 DEG C, is concentrated under vacuum condition, obtain the thick material of ointment, into the thick material of ointment
78 DEG C of hot water is added, the additional amount of hot water and the volume ratio of the thick material of ointment are 1:3, stir 30 minutes, are then allowed to stand 15min points
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 volume ratio of the thick material of ointment and methanol solvate is 10:7 after purification,
The mass concentration of methanol solvate is 95%.72 DEG C of dissolutions are warming up to, adjustment mixing speed is 10~20r/min, per hour with 5 DEG C
Rate of temperature fall slow cooling crystallized to 25 DEG C, keep the temperature 2 hours progress growing the grains, filter to obtain B1a crude product 223.05g, use
HPLC carries out detection content in crude product to the B1a content of crude product, mother liquor obtained by this step: 64.32%；Crude product obtained by this step is molten through methanol
Freezing observation is without floccule after solution.
(5) by 99% methanol rising temperature for dissolving of above-mentioned crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is complete to crude product
After fully dissolved, heat preservation 30 minutes is filtered, recycling filtrate to crystallizing tank, then 3 times of normal pressure concentration filtrate to crude product weight
Filtering, obtains Avermectin B1a crystal.Wherein, methanol solvate used: crude product=15ml:1g is recrystallized；Activated carbon dosage is
The 1% of coarse crystallization quality；
(6) by the Avermectin B1a crystal 76g of step (5), according to method repetitive operation 3 times of step (5), then into
Row filters, is dry, and detected with HPLC to B1a fine powder content obtained by this step: B1a content 94.89%, fine work is dissolved through methanol
Freezing is without floccule, qualified product.
Comparative example 2:
A kind of preparation method improving Avermectin B1a fine powder yield and content, steps are as follows:
(1) avermectin drying mycelia 2000g (mycelia potency is 10230 μ/g) is taken, 25 DEG C of 10000mL temperature, matter is added
It is stirred 30 minutes in the methanol that amount concentration is 92%, avermectin extracting liquid 9900ml is obtained by filtration, gained is extracted with HPLC
Liquid is detected, leaching liquor potency: 12338 μ/ml.
(2) leaching liquor is warming up to 70 DEG C and is evaporated in vacuo 2 hours, and solution is condensed into paste, obtains the thick material of ointment, when concentration
Vacuum degree is -0.07Mpa.80 DEG C of hot water is added into the thick material of ointment, the additional amount of hot water and the volume ratio of the thick material of ointment are
1:2 is stirred 30 minutes, is then allowed to stand 15min layering, is removed upper water, obtain the thick material of ointment after purification；
(3) the thick material of ointment adds in methanol solvate after purification, and the volume ratio of the thick material of ointment and methanol solvate is 10:8 after purification,
The mass concentration of methanol solvate is 95%.70 DEG C of dissolutions are warming up to, adjustment mixing speed is 10~20r/min, per hour with 5 DEG C
Rate of temperature fall slow cooling crystallized to 25 DEG C, keep the temperature 2 hours progress growing the grains, filter to obtain B1a crude product crude product 223.05g,
Detection content in crude product is carried out with B1a content of the HPLC to crude product, mother liquor obtained by this step: 65.33%, mother liquor potency: 16576 μ/
ml；Crude product obtained by this step cools to 0 DEG C through methanol dissolution, and floccule is obvious.
(4) by 99% methanol rising temperature for dissolving of above-mentioned crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is complete to crude product
After fully dissolved, heat preservation 30 minutes is filtered, recycling filtrate to crystallizing tank, then 3 times of normal pressure concentration filtrate to crude product weight
Filtering, obtains Avermectin B1a crystal.Wherein, methanol solvate used: crude product=15ml:1g is recrystallized；Activated carbon dosage is
The 1% of coarse crystallization quality；
(5) by the Avermectin B1a crystal 76g of step (4), according to method repetitive operation 3 times of step (4), then into
Row filters, is dry, and detected with HPLC to B1a fine powder content obtained by this step: B1a content 92.87%, fine work is dissolved through methanol
Cooling freezing, floccule are obvious.
The process of the embodiment of the present invention 2 and comparative example 2 is to leaching liquor potency, influence such as the following table 1 of fine powder b1a content
It is 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, comprises the following steps that
(1) avermectin drying mycelia 2000g (mycelia potency is 10230 μ/g) is taken, 10000mL temperature 45 C, matter is added
It is stirred 30 minutes in the methanol that amount concentration is 96%, avermectin extracting liquid 9900ml is obtained by filtration, gained is extracted with HPLC
Liquid is detected, leaching liquor potency: 20617 μ/ml.
(2) leaching liquor 5L is taken, is freezed 2 hours under conditions of -1 DEG C, after floccule is precipitated, suction filtration obtains filtrate, filtrate
It is kept the temperature under conditions of being placed in 0 DEG C, no floccule is precipitated.
(3) filtrate of step (2) is warming up to 68 DEG C, is concentrated under vacuum condition, obtain the thick material of ointment, into the thick material of ointment
82 DEG C of hot water is added, the additional amount of hot water and the volume ratio of the thick material of ointment are 1:2.5, stir 30 minutes, are then allowed to 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 volume ratio of the thick material of ointment and methanol solvate is 11:8 after purification,
The mass concentration of methanol solvate is 95%.68 DEG C of dissolutions are warming up to, adjustment mixing speed is 10~20r/min, per hour with 5 DEG C
Rate of temperature fall slow cooling crystallized to 25 DEG C, keep the temperature 2 hours progress growing the grains, B1a crude product 230g filtered to obtain, with HPLC pairs
The B1a content of crude product, mother liquor obtained by this step carries out detection content in crude product: 64.33%, mother liquor potency: 16576 μ/ml；This step institute
It obtains crude product and freezes observation after methanol dissolves without floccule.
(5) by 99% methanol rising temperature for dissolving of above-mentioned crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is complete to crude product
After fully dissolved, heat preservation 30 minutes is filtered, recycling filtrate to crystallizing tank, then 3 times of normal pressure concentration filtrate to crude product weight
Filtering, obtains Avermectin B1a crystal.Wherein, methanol solvate used: crude product=16ml:1g is recrystallized；Activated carbon dosage is
The 1% of coarse crystallization quality；
(6) by the Avermectin B1a crystal 76g of step (5), according to method repetitive operation 3 times of step (5), then into
Row filters, is dry, and detected with HPLC to B1a fine powder content obtained by this step: B1a content 94.81%, fine work is dissolved through methanol
Freezing is without floccule, qualified product.
Comparative example 3:
A kind of preparation method improving Avermectin B1a fine powder yield and content, steps are as follows:
(1) avermectin drying mycelia 2000g (mycelia potency is 10230 μ/g) is taken, 25 DEG C of 10000mL temperature, matter is added
It is stirred 30 minutes in the methanol that amount concentration is 92%, avermectin extracting liquid 9900ml is obtained by filtration, gained is extracted with HPLC
Liquid is detected, leaching liquor potency: 12831 μ/ml.
(2) leaching liquor is warming up to 70 DEG C and is evaporated in vacuo 2 hours, and solution is condensed into paste, obtains the thick material of ointment, when concentration
Vacuum degree is -0.07Mpa.80 DEG C of hot water is added into the thick material of ointment, the additional amount of hot water and the volume ratio of the thick material of ointment are
1:2 is stirred 30 minutes, is then allowed to stand 15min layering, is removed upper water, obtain the thick material of ointment after purification；
(3) the thick material of ointment adds in methanol solvate after purification, and the volume ratio of the thick material of ointment and methanol solvate is 10:8 after purification,
The mass concentration of methanol solvate is 95%.70 DEG C of dissolutions are warming up to, adjustment mixing speed is 10~20r/min, per hour with 5 DEG C
Rate of temperature fall slow cooling crystallized to 25 DEG C, keep the temperature 2 hours progress growing the grains, filter to obtain B1a crude product crude product 227g, use
HPLC carries out detection content in crude product to the B1a content of crude product, mother liquor obtained by this step: 67.87%；Crude product obtained by this step is molten through methanol
Solution cooling freezing, floccule are obvious.
(4) by 99% methanol rising temperature for dissolving of above-mentioned crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is complete to crude product
After fully dissolved, heat preservation 30 minutes is filtered, recycling filtrate to crystallizing tank, then 3 times of normal pressure concentration filtrate to crude product weight
Filtering, obtains Avermectin B1a crystal.Wherein, methanol solvate used: crude product=15ml:1g is recrystallized；Activated carbon dosage is
The 1% of coarse crystallization quality；
(5) by the Avermectin B1a crystal 76g of step (4), according to method repetitive operation 3 times of step (4), then into
Row filters, is dry, and detected with HPLC to B1a fine powder content obtained by this step: B1a content 93.14%, fine work is dissolved through methanol
Cooling freezing, floccule are obvious.
The process of the embodiment of the present invention 3 and comparative example 3 is to leaching liquor potency, influence such as the following table 1 of fine powder b1a content
It is 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
1, the leaching liquor that 1 step of the embodiment of the present invention (1) obtains and the leaching liquor that 1 step of comparative example (1) obtains are cooled down
To -20 DEG C, rate of temperature fall is identical, observes floccule in leaching liquor, and comparison diagram is as shown in Figure 1 a, 1 b, can by picture comparison
To find out, method of the invention, using 40 DEG C, 95% methanol of concentration impregnates nothing after the leaching liquor freezing that avermectin mycelia obtains
Floccule, and floccule is obvious after being freezed using the leaching liquor that the prior art extracts, under cryogenic in leaching liquor
Grease will be precipitated in the form of floccule, and existing floccule, and the grease illustrated in leaching liquor is more, to subsequent purification
It is unfavorable, it is not easy to remove in subsequent crystallization and recrystallization process.
2,50 times of water of B1a fine powder made from the embodiment of the present invention 1, comparative example 1 are dissolved respectively, fine work dissolution is made
Obtained fine work lysate is cooled to -20 DEG C by liquid, and rate of temperature fall is identical, observes floccule in lysate, comparison diagram is as schemed
Shown in 2a, Fig. 2 b, by picture comparison as can be seen that without floccule after the fine work lysate freezing that method of the invention obtains,
And floccule is obvious after being freezed using the fine work lysate that the prior art extracts, under cryogenic in fine powder lysate
Grease will be precipitated in the form of floccule, and existing floccule illustrates that fine powder quality is poorer, and content is lower, and product will appear
Yellowing phenomenon after drying, situation cannot be used because avermectin amount containing grease is excessively high by doing downstream product also and will appear.
Claims (10)
1. a kind of leach extraction method for improving Avermectin B1a fine powder production capacity and inherent quality, comprises the following steps that
(1) by avermectin mycelia be added to 40 ~ 45 DEG C of temperature, mass concentration be 95 ~ 97% methanol solvate in, avermectin
The mass volume ratio of mycelia and methanol solvate are as follows: 1: insulated and stirred 20 ~ 30 minutes, AVM hereinafter was obtained by filtration in (3 ~ 5), unit g/mL
Rhzomorph leaching liquor；
(2) by avermectin extracting liquid be cooled to 0 DEG C hereinafter, heat preservation 2 ~ 4 hours, filtrate is then collected by filtration；
(3) filtrate of step (2) is warming up to 60~70 DEG C, is concentrated under vacuum condition, obtain the thick material of ointment, into the thick material of ointment
75~85 DEG C of hot water is added, stirs 20 ~ 30 minutes, is then allowed to stand layering, removes 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 dissolutions, adjusts mixing speed, slow cooling is extremely
20 ~ 30 DEG C are crystallized, and are kept the temperature 1~2 hour progress growing the grain, are filtered to obtain B1a crude product,
(5) methanol rising temperature for dissolving is added in B1a crude product, active carbon stirring is added and is warming up to 65~70 DEG C, it is completely molten to B1a crude product
Xie Hou keeps the temperature 30 minutes, is filtered, and recycling filtrate normal pressure 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 according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
In further including step (6), by the Avermectin B1a crystal of step (5) according to method repetitive operation 1~3 time of step (5), so
After filtered, dried, obtain Avermectin B1a fine powder.
3. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
Methanol solvate temperature used is 40 DEG C when, step (1), extraction, and the mass concentration of methanol solvate is 95%, avermectin bacterium
The mass volume ratio of silk and methanol solvate are as follows: 1: 5, unit g/mL.
4. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
In step (2), avermectin extracting liquid is cooled to 0 DEG C, and soaking time is 4 hours.
5. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
In the vacuum degree of step (3), vacuum concentration is -0.05 ~ -0.07Mpa, and the additional amount of hot water and the volume ratio of the thick material of ointment are
1:(1~4), the temperature of hot water is 80 DEG C, and mixing time is 30 minutes.
6. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
In step (3), the stratification time is 10-18min.
7. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
In the volume ratio of the thick material of ointment and methanol solvate is (8~12): (6~8), the mass concentration of methanol solvate to step (4) after purification
It is 95 ~ 97%.
8. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
In, step (4), mixing speed is 10~20r/min, slow cooling rate be 3~5 DEG C per hour, slow cooling to 25 DEG C into
Row crystallization, obtained B1a crude product is through methanol dissolution freezing without floccule.
9. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, feature exist
In step (5), the mass volume ratio of B1a crude product and methanol: 1:(10 ~ 20), unit g/mL, the mass concentration of methanol is 99%.
10. the leach extraction method according to claim 1 for improving Avermectin B1a fine powder production capacity and inherent quality, 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 |
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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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