CN101302247A - Method for extracting nosipeptide crude product - Google Patents
Method for extracting nosipeptide crude product Download PDFInfo
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- CN101302247A CN101302247A CNA2008100626128A CN200810062612A CN101302247A CN 101302247 A CN101302247 A CN 101302247A CN A2008100626128 A CNA2008100626128 A CN A2008100626128A CN 200810062612 A CN200810062612 A CN 200810062612A CN 101302247 A CN101302247 A CN 101302247A
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- nosiheptide
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Abstract
A method for extracting nosiheptide crude product comprises the following steps that: nosiheptide mycelium is taken as a raw material and is dipped in organic solvent of 2 to 6 times of bulking value with the temperature controlled between 30 and 50 DEG C; meanwhile, the mixture is stirred at a constant speed of between 30 and 150 revolution/minute for 0.5 to 4 hours; solid-liquid separation of the stirred mixture is completed, and the infused liquid is distilled on an evaporograph; organic solvent is reclaimed; condensed extract is placed inside a drying box and is dried at a temperature of between 25 and 85 DEG C for 8 to 30 hours; and nosiheptide crude product is obtained after the dried extract is crushed up. The organic solvent adopts anhydrous ethanol or methanol, or a chloroform-ethanol mixed solution with the volume ratio of between 1:1 and 1:5, or chloroform-methanol mixed solution with the volume ratio of between 1:1 and 1:5. The nosiheptide crude product extracted by the method can be used to make nosiheptide pre-mix agents or top-quality nosiheptide of various content specifications.
Description
Technical field
The invention belongs to chemical pharmacy field, relate to a kind of preparation method of bulk drug of veterinary drug fodder additives, be specifically related to a kind of method for preparing sulfur-bearing polypeptide antibiotics nosipeptide crude product.
Background technology
Nosiheptide is that French scientist in 1961 is found in Streptomyces actuosus 40037 fermented liquids, animal feeding test is carried out by Rhone-Poulenc's trial production and in a plurality of countries and regions such as Belgium, France, the U.S. in the back, finds that it is a kind of growth promoter of works very well.But because it yields poorly, cost is too high and fail large-scale promotion, MIT had carried out a large amount of seed selection research to nosiheptide generation bacterium afterwards, and animal feeding test, safety testing, acute and chronic toxicity test etc. have been carried out, be developed to product innovation at last, and be legal fodder additives the end of the year 1987 by Japan's approval, its commodity are called Primofax, in February, 1988 listing, sales volume then is 1,000,000,000 yen.Because nosiheptide belongs to macromolecular substance, do not absorb in vivo, therefore do not have residual, widely-used by states such as the European Community, North America, Japan at present.
Nosiheptide is the new veterinary drug of national three classes in approval in 1998, and calendar year 2001 is classified as by the Ministry of Agriculture and can add the feed medicated premix that uses for a long time in feed.Nosiheptide has following characteristics as fodder additives: 1. tangible promotion growth of animals or poultry is arranged and improve the effect of efficiency of feed utilization.2. low (2.5mg/kg～20mg/kg), use range wide (livestock and poultry and aquatic products) of consumption.3. animal specific microbiotic.4. have only bacteriostatic action and do not have germicidal action.5. effective to gram-positive microorganism.6. do not produce by R
-The caused resistance of plasmid does not have cross resistance with other microbiotic.7. do not absorbed the noresidue problem by digestive tube.8. safe in utilization, without any side effects to the animal and human.9. little to environmental influence, belong to environment-friendly feed additive.
The domestic and international at present preparation to the nosiheptide raw material has following several method: the one, the cyclic ethers kind solvent is mixed with the nosiheptide mycelium as extraction agent, and regulate the pH value, discard the solid kind material, the middle mutually organic salt that adds of remaining organic solvent, precipitation nosiheptide.The 2nd, the nosiheptide mycelium is mixed with organic solvent (acetone or alcohol etc.), regulate the pH value, solid-liquid separation, liquid portion adds and contains aqueous acid precipitation nosiheptide.The 3rd, adopt the solvent method that the nosiheptide in the nosiheptide mycelium fermentation broth is directly extracted, adopt and add equal-volume alcohol, homogenate then, centrifugal, collect supernatant, concentrate, with n-butanol extraction, concentrate evaporate to dryness, add the dioxane dissolving, add the water precipitation nosiheptide again, sedimentary nosiheptide washes with water again, oven dry is CN1899599A " a kind of method for preparing Nosiheptide premixed agent " as patent publication No..First method adopts the nosiheptide in the cyclic ethers kind solvent extraction mycelium, cyclic ethers kind solvent price is higher relatively, if the scale operation cost can increase greatly, leaching process also needs to regulate the pH value, and added organic salt during nosiheptide in precipitation, this is equivalent to add other impurity again in the nosiheptide of purifying, and is not easy to be removed.Second method also will be carried out the adjusting of system pH in whole process, increased certain workload, and with after the acidic aqueous solution precipitation nosiheptide, employed organic reagent just has no idea to utilize again, and the depleted reagent solution can bring the problem of environmental protection aspect.Therefore the third method has limited the use range of this method owing to be directly to utilize the broth extraction nosiheptide, and whole leaching process complex steps, and the production cycle is long, is not suitable for carrying out industrial production.
Summary of the invention
The purpose of this invention is to provide a kind of method of from the nosiheptide mycelium, extracting nosipeptide crude product.Advantages such as the present invention has that production technique is simple, easy to operate, production efficiency is high, economy and environmental protection can also be prepared into the Nosiheptide premixed agent of different content specification with the nosiheptide of extracting as required, or further be refined into the nosiheptide elaboration.
Nosipeptide crude product preparation technology of the present invention extracts the nosiheptide in the mycelium with organic solvent, then organic solvent is removed, and remaining solid is nosipeptide crude product.
The preparation method of nosipeptide crude product of the present invention is following steps:
(1) be raw material with the nosiheptide mycelium, soak with 2～6 bulking values organic solvent doubly that temperature is controlled at 30～50 ℃, at the uniform velocity stirs simultaneously, the speed of stirring is 30～150 rev/mins, and churning time is 0.5～4 hour;
(2) the organic solvent soak solution that will stir in the material of back separates with solid residue, and soak solution is distilled on evaporimeter, and temperature is 40～65 ℃, reclaims organic solvent, obtains concentrated extract;
(3) concentrated extract that will remove organic solvent places loft drier, and temperature is under 25～85 ℃ of conditions dry 8～30 hours, dry extract is pulverized obtained nosipeptide crude product.
The described organic solvent of step (1) is dehydrated alcohol or methyl alcohol one.
The described organic solvent of step (1) can also be the chloroform-methanol mixed solution one that 1: 1～1: 5 chloroform-alcohol mixeding liquid or volume ratio are 1: 1～1: 5 for volume ratio.
With the described solid residue of step (2) is raw material, further extracts residual nosiheptide by the step of claim 1.
Can be applied to prepare the Nosiheptide premixed agent or the nosiheptide elaboration of various content specifications by the nosipeptide crude product of the inventive method extraction.
The preparation method of nosipeptide crude product of the present invention is further described below:
Take by weighing a certain amount of nosiheptide mycelium, select to add a kind of of following organic solvent by 2～6 volumes amount doubly: dehydrated alcohol, methyl alcohol, chloroform and alcohol mixeding liquid (volume ratio is 1: 1～1: 5), chloroform and methyl alcohol mixed liquor (volume ratio is 1: 1～1: 5), at the uniform velocity stir with stirring rake, the speed that stirs is 30～150 rev/mins, churning time is 0.5～4 hour, and the temperature of whole system is controlled at 30～50 ℃; Then the organic solvent soak solution is separated with solid residue, it is to distill on 40～65 ℃ the evaporimeter that soak solution is placed temperature, removes organic solvent, simultaneously organic solvent is recycled; The concentrated extract of removing organic solvent was placed loft drier dry 8～30 hours, and temperature is 25～85 ℃, and dry extract obtains nosipeptide crude product after crushed.The above isolating solid residue is after quality examination, if nosiheptide is still contained in the inside, solid residue can be recycled, and repeats above operation.
Nosipeptide crude product of the present invention can be made into the Nosiheptide premixed agent of various content specifications or further is refined into the nosiheptide elaboration.
The invention has the advantages that: the present invention prepares the technology of nosipeptide crude product, be directly to extract nosiheptide in the mycelium with organic solvent, technology is simple, easy to operate, production efficiency is high, and nosiheptide mycelium and organic solvent can reuse, be economy environmental protection again like this, the nosipeptide crude product of preparing can also be made the pre-mixture of various content specifications as required, also it further can be purified and make the nosiheptide elaboration.Therefore the present invention is a kind of preparation method of comparatively ideal nosiheptide.
Embodiment
Embodiment 1:
Weighing nosiheptide mycelium 1000g adds 2000ml ethanol, is that 30 rev/mins stirring rake at the uniform velocity stirs with speed, and churning time 2 hours, the temperature of whole system are controlled at 40 ℃; Soak solution in the system is placed Rotary Evaporators, in 55 ℃ of water-baths, ethanol is removed, and utilize solvent recovery unit to reclaim ethanol.Concentrated extract is transferred in the loft drier dry 14 hours (50 ℃), takes out, and pulverizes, and obtains content and be nosiheptide 50～100g of about 30～70%.The nosipeptide crude product of the present invention preparation can be made into the pre-mixture of various content specifications or purifies further that to make content be elaboration nosiheptide more than 90%.
Embodiment 2:
Weighing nosiheptide mycelium 1000g, (chloroform: ethanol=1: 3), be that 100 rev/mins stirring rake at the uniform velocity stirs with speed, churning time 3 hours, the temperature of whole system are controlled at 35 ℃ to add 4000ml chloroform and alcohol mixeding liquid; To distill with the isolating organic solvent soak solution of solid residue, temperature is 50 ℃, with chloroform and alcohol mixeding liquid evaporate to dryness, reclaim organic solvent simultaneously, the concentrated extract of removing organic solvent is transferred to dry 10 hours (55 ℃) in the loft drier, take out, pulverize, obtain content and be nosiheptide 50～100g of about 30～70%.Nosipeptide crude product of the present invention can be made into the pre-mixture of various content specifications or further purifies that to make content be nosiheptide elaboration more than 90%.
Embodiment 3:
Weighing nosiheptide mycelium 1000g, (methyl alcohol: chloroform=1: 1), be that 150 rev/mins stirring rake at the uniform velocity stirs with speed, churning time 4 hours, the temperature of whole system are controlled at 45 ℃ to add 6000ml chloroform and methyl alcohol mixed liquor; To distill with the isolating organic solvent soak solution of solid residue, temperature is 60 ℃, with chloroform and methyl alcohol mixed liquor evaporate to dryness, reclaim organic solvent simultaneously, the concentrated extract of removing organic solvent is transferred to dry 18 hours (45 ℃) in the loft drier, take out, pulverize, obtain content and be nosiheptide 50～100g of about 30～70%.Nosipeptide crude product of the present invention can be made into the pre-mixture of various content specifications or further purifies that to make content be nosiheptide elaboration more than 90%.
Embodiment 4:
Solid residue in above-mentioned 3 examples after quality examination as still contains nosiheptide, then collect residue 1000g, add 6000ml chloroform and methyl alcohol mixed liquor (chloroform: methyl alcohol=1: 5), with speed is that 100 rev/mins stirring rake at the uniform velocity stirs, churning time 2 hours, the temperature of whole system are controlled at 45 ℃; To distill with the isolating organic solvent soak solution of solid residue, temperature is 60 ℃, with chloroform and methyl alcohol mixed liquor evaporate to dryness, reclaim organic solvent simultaneously, the concentrated extract of removing organic solvent is transferred to dry 12 hours (50 ℃) in the loft drier, take out, pulverize, obtain content and be nosiheptide 50～100g of about 30～70%.Nosipeptide crude product of the present invention can be made into the pre-mixture of various content specifications or further purifies that to make content be nosiheptide elaboration more than 90%.
Claims (5)
1, a kind of method of extracting nosipeptide crude product is characterized in that following steps:
(1) be raw material with the nosiheptide mycelium, soak with 2～6 bulking values organic solvent doubly that temperature is controlled at 30～50 ℃, at the uniform velocity stirs simultaneously, the speed of stirring is 30～150 rev/mins, and churning time is 0.5～4 hour;
(2) the organic solvent soak solution that will stir in the material of back separates with solid residue, and soak solution is distilled on evaporimeter, and temperature is 40～65 ℃, reclaims organic solvent, obtains concentrated extract;
(3) concentrated extract that will remove organic solvent places loft drier, and temperature is under 25～85 ℃ of conditions dry 8～30 hours, dry extract is pulverized obtained nosipeptide crude product.
2, a kind of according to claim 1 method of extracting nosipeptide crude product is characterized in that: the described organic solvent of step (1) is dehydrated alcohol or methyl alcohol one.
3, a kind of according to claim 1 method of extracting nosipeptide crude product is characterized in that: the described organic solvent of step (1) is that volume ratio is the chloroform-methanol mixed solution one that 1: 1～1: 5 chloroform-alcohol mixeding liquid or volume ratio are 1: 1～1: 5.
4, a kind of according to claim 1 method of extracting nosipeptide crude product is characterized in that: with the described solid residue of step (2) is raw material, further extracts residual nosiheptide by the step of claim 1.
5, a kind of according to claim 1 method of extracting nosipeptide crude product is characterized in that: the Nosiheptide premixed agent or the nosiheptide elaboration that are applied to prepare various content specifications by the nosipeptide crude product of this method extraction.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008100626128A CN101302247A (en) | 2008-06-24 | 2008-06-24 | Method for extracting nosipeptide crude product |
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| CNA2008100626128A CN101302247A (en) | 2008-06-24 | 2008-06-24 | Method for extracting nosipeptide crude product |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101869188A (en) * | 2010-06-11 | 2010-10-27 | 濮阳泓天威药业有限公司 | Preparation method of nosiheptide premix |
| CN102210630A (en) * | 2011-06-02 | 2011-10-12 | 浙江汇能动物药品有限公司 | System and method for preparing nosiheptide premix particles |
| CN101624418B (en) * | 2009-08-03 | 2012-04-18 | 安徽省皖北药业股份有限公司 | Method for preparing nosiheptide powder |
| CN104231044A (en) * | 2014-08-13 | 2014-12-24 | 浙江汇能动物药品有限公司 | Process for purifying nosiheptide by passing through column |
| CN104719634A (en) * | 2015-02-10 | 2015-06-24 | 河北圣雪大成制药有限责任公司 | Method for preparing nosiheptide pre-mixing agent |
| CN105420319A (en) * | 2015-12-24 | 2016-03-23 | 山东胜利生物工程有限公司 | Preparation method of pure nosiheptide |
| CN106083995A (en) * | 2016-08-26 | 2016-11-09 | 宁夏泰益欣生物科技有限公司 | A kind of extracting method of nosiheptide |
| CN106119157A (en) * | 2016-06-24 | 2016-11-16 | 中国科学院南海海洋研究所 | A kind of marine streptomyces and the application in preparing nosiheptide thereof |
| CN106317173A (en) * | 2016-08-23 | 2017-01-11 | 宁夏泰瑞制药股份有限公司 | Method for preparing coarse nosiheptide product by utilizing nosiheptide fermentation liquor |
| CN107619429A (en) * | 2016-07-15 | 2018-01-23 | 牡丹江佰佳信生物科技有限公司 | A kind of Nosiheptide method of purification |
-
2008
- 2008-06-24 CN CNA2008100626128A patent/CN101302247A/en active Pending
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101624418B (en) * | 2009-08-03 | 2012-04-18 | 安徽省皖北药业股份有限公司 | Method for preparing nosiheptide powder |
| CN101869188A (en) * | 2010-06-11 | 2010-10-27 | 濮阳泓天威药业有限公司 | Preparation method of nosiheptide premix |
| CN102210630A (en) * | 2011-06-02 | 2011-10-12 | 浙江汇能动物药品有限公司 | System and method for preparing nosiheptide premix particles |
| CN102210630B (en) * | 2011-06-02 | 2014-01-15 | 浙江汇能动物药品有限公司 | System and method for preparing nosiheptide premix particles |
| CN104231044A (en) * | 2014-08-13 | 2014-12-24 | 浙江汇能动物药品有限公司 | Process for purifying nosiheptide by passing through column |
| CN104719634B (en) * | 2015-02-10 | 2018-08-24 | 河北圣雪大成制药有限责任公司 | A method of preparing Nosiheptide premixed agent |
| CN104719634A (en) * | 2015-02-10 | 2015-06-24 | 河北圣雪大成制药有限责任公司 | Method for preparing nosiheptide pre-mixing agent |
| CN105420319A (en) * | 2015-12-24 | 2016-03-23 | 山东胜利生物工程有限公司 | Preparation method of pure nosiheptide |
| CN106119157A (en) * | 2016-06-24 | 2016-11-16 | 中国科学院南海海洋研究所 | A kind of marine streptomyces and the application in preparing nosiheptide thereof |
| CN106119157B (en) * | 2016-06-24 | 2019-08-13 | 中国科学院南海海洋研究所 | A kind of marine streptomyces and its preparing the application in Nosiheptide |
| CN107619429A (en) * | 2016-07-15 | 2018-01-23 | 牡丹江佰佳信生物科技有限公司 | A kind of Nosiheptide method of purification |
| CN106317173A (en) * | 2016-08-23 | 2017-01-11 | 宁夏泰瑞制药股份有限公司 | Method for preparing coarse nosiheptide product by utilizing nosiheptide fermentation liquor |
| CN106083995A (en) * | 2016-08-26 | 2016-11-09 | 宁夏泰益欣生物科技有限公司 | A kind of extracting method of nosiheptide |
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Open date: 20081112 |