CN103910783A - Preparation method of high-purity echinocandin B mother nuclide - Google Patents
Preparation method of high-purity echinocandin B mother nuclide Download PDFInfo
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- CN103910783A CN103910783A CN201410164318.3A CN201410164318A CN103910783A CN 103910783 A CN103910783 A CN 103910783A CN 201410164318 A CN201410164318 A CN 201410164318A CN 103910783 A CN103910783 A CN 103910783A
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Abstract
The invention discloses a preparation method of a high-purity echinocandin B mother nuclide. The method comprises the following steps: regulating different pH values of an echinocandin B mother nuclide conversion solution, filtering, decolorizing with a decolorizing resin, adsorbing with a macroporous adsorbent resin, desorbing, concentrating, separating the concentrated solution through a polystyrene or divinylbenzene chromatographic resin, and freeze-drying the desorbed solution to obtain the high-purity echinocandin B mother nuclide product, of which the content is greater than 96% and the total yield is greater than 70%. The method is simple and easy to implement and suitable for industrial production, uses fewer organic solvents in the whole preparation process, and thus, is environment-friendly.
Description
Technical field
The invention belongs to industrial microbial technology field, be specifically related to a kind of preparation method of high purity echinocandin B parent nucleus.
Background technology
In recent years, because organ transfer operation causes a large amount of uses of immunosuppressor, chemotherapy and the many reasons such as application that has more invasive therapy cause immunocompromised patient to increase, fungi infestation sickness rate significantly raises, especially the sickness rate of deep fungal infection and case fatality rate increase year by year, and therefore novel antifungal drugs becomes study hotspot.Echinocandin class antifungal drug is taking fungal cell wall as action target spot, and noncompetitive inhibition cell walls β (1,3)-D-dextran is synthetic, makes cell cycle arrest, and cell walls thoroughness is destroyed, and causes cytolysis death.And the acellular wall of Mammals lacks this synthetic enzyme, therefore echinocandin class medicine has higher specificity to fungal cell, less on human normal cell's impact.
Echinocandin B(Echinocandin B) under deacylase effect; acyl side-chain is cut away; generate echinocandin B parent nucleus (Echinocandin B Nucleus; be called for short ECB Nucleus); connect again active ester side chain and generate anidulafungin; in U.S.'s listing, market potential was huge in 2006 for this medicine.
Echinocandin B parent nucleus is buff powder, easily molten in water, dimethyl sulfoxide (DMSO), and slightly soluble in methyl alcohol, ethanol is atomic molten in chloroform, insoluble in acetone.Echinocandin B mother nucleus structure complexity, is difficult to chemosynthesis, and main dependence microorganism fermentation at present transforms and obtains.
About the report of echinocandin B parent nucleus separation and purification fewer.Document (Boeck LD, Fukuda DS, Abbott BJ. Deacylation of echinocandin B by Actinoplanes utahensis[J]. J Antibiot, 1989,42 (3): 382-388.) separation-extraction technology of introducing: the conversion fluid of echinocandin B parent nucleus uses HP-20 resin absorption to separate, and rear use preparative chromatography is isolated highly purified echinocandin B parent nucleus, and this legal system is higher for purity, but treatment capacity is little, cannot realize suitability for industrialized production.
The separation purification method of some echinocandin B parent nucleus is also disclosed in domestic patent documentation.Patent documentation CN102336817, by the conversion fluid of echinocandin B parent nucleus, first uses nonpolar macroporous adsorption resin roughing out, re-uses the secondary separation of macroporous acrylic resin and obtains the echinocandin B parent nucleus that purity is higher.Although this method is applicable to fairly large production, has used a large amount of solvents in leaching process, has not only increased production cost, also easy contaminate environment.
Therefore how from fermentation conversion fluid, to prepare high purity echinocandin B parent nucleus, and cost is low, environmental friendliness, is applicable to large-scale industrial production, becomes the difficult point of research.
Summary of the invention
The object of the present invention is to provide the novel process of a kind of high purity, low cost, environment friendly and pollution-free, the echinocandin B parent nucleus that is suitable for suitability for industrialized production.The echinocandin B parent nucleus product preparing, content is greater than 96%, and total recovery is greater than 70%.
Below the present invention is specifically described:
Method of the present invention comprises the steps: first in the conversion fluid of echinocandin B parent nucleus, to add acid to be adjusted to acidity, add polyacrylamide flocculant precipitation foreign protein, add flocculating aids, stir, after filtration, obtain just filtrate, just filtrate is filtered removal impurity after being adjusted to nearly neutrality again, obtain whole filtrate, the upper decolorizing resin post of whole filtrate, macroporous adsorptive resins on destainer, acid solution is resolved, after desorbed solution is concentrated, regulate pH value, upper polystyrene or Vinylstyrene class chromatographic resin post, containing the aqueous acid wash-out of ethanol, elutriant freeze-drying obtains high purity echinocandin B parent nucleus fine powder.
Particularly, the present invention relates to a kind of preparation method of high purity echinocandin B parent nucleus, comprise the following steps:
1) the conversion fluid acid for adjusting pH value of echinocandin B parent nucleus is 4.0-4.5, adds polyacrylamide flocculant precipitated impurities, adds flocculating aids dispersed with stirring even, and solid-liquid separation obtains just filtrate of echinocandin B parent nucleus;
2) the first filtrate of echinocandin B parent nucleus is 6.0-6.5 by alkaline solution adjusting pH value, adds flocculating aids dispersed with stirring even, and solid-liquid separation, obtains the whole filtrate of echinocandin B parent nucleus;
3) whole echinocandin B parent nucleus filtrate is decoloured by macropore decolorizing resin, obtained destainer;
4) destainer is imported to absorption with macroporous adsorbent resin, adsorb completely, use aqueous acid to resolve, HPLC detects, and collects desorbed solution, concentrated, obtains concentrated solution;
5) concentrated solution is regulated pH value for 6.0-6.5, upper polystyrene or Vinylstyrene class chromatographic resin post, resolve with the aqueous acid containing ethanol, and HPLC detects, and collects chromatographic solution, and freeze-drying makes echinocandin B parent nucleus fine powder.
Wherein in step 1), regulating the acid used of pH value is any one in hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid or glacial acetic acid, be preferably glacial acetic acid, conversion fluid acid adjustment, being conducive on the one hand conversion fluid filters, be conducive on the other hand flocculation sediment impurity, the polyacrylamide flocculant molecular weight adding is 2000-15000 KDa, and final concentration is 50 ppm.
Step 1) or 2) in flocculating aids used be perlite or diatomite, be preferably perlite, consumption is in every liter of conversion fluid, to add flocculating aids 0.03-0.05 kilogram.
Step 2) in to regulate pH alkaline solution used be any one in sodium hydroxide solution, dipotassium hydrogen phosphate solution, ammonium dibasic phosphate solution, preferably phosphoric acid hydrogen dipotassium or ammonium dibasic phosphate solution, add phosphoric acid salt to form buffer system, keep filtrate pH stable, pH is larger on upper prop impact, be that 6 left and right adsorption effects are better at pH, when pH < 5, adsorption effect is poor, when pH > 7, can damage.
In step 3), decolorizing resin used is any one in LX-700, D290, XDA-7, D301 or HZ801 resin, is preferably HZ801 resin, and resin demand is that the whole filtrate of the conversion fluid of every liter of echinocandin B parent nucleus is used resin 0.05-0.1 liter.
In step 4), polymeric adsorbent used is any one in D312, HZ813, HZ816, HZ818 or 700F resin, is preferably 700F resin, and resin demand is the whole filtrate of the conversion fluid of every liter of echinocandin B parent nucleus, uses resin 0.1-0.2 liter.
Aqueous acid in step 4) is acetic acid aqueous solution, and concentration is 0.5%.
In step 5), regulating pH value solution used is sodium hydroxide solution, and concentration is 0.1mol/L, and chromatography media is any one in UniPS 30-300 or UniPS 40-300, and upper column flow rate is 10% BV/min, resolves flow velocity 10% BV/min.
In step 5), after upper prop completes, first use the impurity on 0.08% acetic acid water washing chromatographic resin post, after again with resolving containing the aqueous acid of ethanol, be that volume ratio is acetic acid containing the aqueous acid of ethanol: the solution of ethanol: water=0.08:3:96.92.
Macroporous adsorbent resin in macropore decolorizing resin or step 4) in step 3) is first removed impurity with ethanol prewashing before use.
Gained echinocandin B parent nucleus of the present invention, the important intermediate that can be used as synthetic anidulafungin compound is used.The echinocandin B parent nucleus content that the present invention makes is more than 96%, and sample yield is greater than 70%.
The present invention has the following advantages: 1, in solid-liquid separation process, regulate at twice pH, add flocculating aids, improved filtration velocity, shortened process cycle, effectively stop product to decompose and destroy; Give up pigment, protein and other impurity through solid-liquid separation simultaneously, improved the quality of filtrate.2, the application of macropore decolorizing resin, has removed most of pigment in extracting solution, effectively reduces pigment ratio, has improved clarity and the quality of destainer.3, chromatography process adopts most of pigment and the strong polar impurity that first can remove resin absorption with acetic acid water rinse resin post, adds ethanol chromatographic separation in rear elutriant, and main peak is separated with impurity, has effectively removed the close impurity of molecular weight.4, technique is simple, and product yield is high, and omnidistance total recovery reaches more than 70%, and extraction cost is low, is applicable to suitability for industrialized production.5, whole preparation process is seldom used organic solvent, and environmental friendliness is pollution-free.6, quality controllable, for the other raw material of production pharmaceutical grade provides quality assurance.
Embodiment
Following embodiment only realizes method of the present invention for setting forth, and should not be construed as limitation of the present invention.Unless stated otherwise, in the present invention, all per-cent is volume percent.The conversion fluid of echinocandin B parent nucleus can adopt any prior art to make; the conversion fluid of echinocandin B parent nucleus used in the present invention is North China Pharmacuetical Group New Drug Research & Development Co., Ltd echinocandin B is transformed and made through deacylase, and equipment used and reagent are commercially available prod.
Echinocandin B parent nucleus HPLC condition:
Chromatographic column: octadecylsilane chemically bonded silica post is (long: 250mm, internal diameter: 4.6mm, packing material size: 5 μ m)
Moving phase: acetonitrile: 0.2 ‰ trifluoroacetic acid aqueous solutions=4:96
Detector: UV detector
Detect wavelength: 210nm
Column temperature: 40 DEG C
Flow velocity: 0.8ml/min
Embodiment 1
Get the conversion fluid 2L of echinocandin B parent nucleus, the 1186 μ g/mL of conversion fluid unit, it is 4.5 that glacial acetic acid regulates pH value, adding molecular weight is that 2000KDa polyacrylamide flocculant 0.1g is to final concentration 50ppm, flocculation 30min, add diatomite 100g, stir, filter to obtain first filtrate, it is 6.5 that just filtrate use 1mol/L dipotassium hydrogen phosphate solution regulates pH value, leave standstill 2h, add 100g diatomite, stir, filter, obtain whole filtrate 1.83L, whole filtrate is decoloured by the decolorizing resin post LX-700 of blade diameter length ratio 1:6, resin loading amount 100mL, flow velocity is 200mL/h, destainer imports the adsorption resin column 700F absorption of blade diameter length ratio 1:6, resin loading amount 200mL, upper column flow rate is 200mL/h, upper prop is complete, first with the impurity on purified water washing adsorption resin column, then analyse adsorption resin column with 0.5% acetolysis, resolve flow velocity 100mL/h, HPLC detects, merge desorbed solution, be evaporated to 10mL, regulating concentrated solution pH value with 0.1mol/L sodium hydroxide solution is 6.5, by the chromatographic resin post UniPS 40-300 chromatographic separation of blade diameter length ratio 1:4, resin loading amount 100mL, after upper prop, first use impurity on 0.08% acetic acid water washing chromatography column, it is acetic acid by volume ratio afterwards: the eluant solution of ethanol: water=0.08:3:96.92, flow velocity is 10mL/min, HPLC detects, collect target elutriant, elutriant freeze-drying, obtain 1.76 grams of fine powders, purity is 97%, total recovery 72%.
Embodiment 2
Get the conversion fluid 2L of echinocandin B parent nucleus, the 1244 μ g/mL of conversion fluid unit, grass acid for adjusting pH value is 4.0, adding molecular weight is that 15000KDa polyacrylamide flocculant 0.1g is to final concentration 50ppm, 30 min flocculate, add perlite 60g, stir, first filtrate is filtered to obtain in filtration, it is 6.0 that just filtrate use 2mol/L ammonium dibasic phosphate solution regulates pH value, leave standstill 2h, add 60g perlite, stir, filter, obtain whole filtrate 1.90L, whole filtrate is decoloured by the decolorizing resin post D290 of blade diameter length ratio 1:6, resin loading amount 150mL, flow velocity is 300mL/h, destainer imports the adsorption resin column HZ818 absorption of blade diameter length ratio 1:6, resin loading amount 300mL, upper column flow rate is 300mL/h, upper prop is complete, first with the impurity on purified water washing adsorption resin column, analyse adsorption resin column with 0.5% acetolysis afterwards, parsing flow velocity is 150mL/h, HPLC detects, merge desorbed solution, be evaporated to 13mL, regulating concentrated solution pH value with 0.1mol/L sodium hydroxide solution is 6.0, by the chromatographic resin post UniPS 30-300 chromatographic separation of blade diameter length ratio 1:4, resin loading amount 130mL, after upper prop, first use the impurity on 0.08% acetic acid water washing chromatography column, it is acetic acid by volume ratio afterwards: the eluant solution of ethanol: water=0.08:3:96.92, flow velocity is 13mL/min, HPLC detects, collect target elutriant, elutriant freeze-drying, obtain 1.84 grams of fine powders, purity is 98.5%, total recovery 72.6%.
Embodiment 3
Get the conversion fluid 2L of echinocandin B parent nucleus, the 1256 μ g/mL of conversion fluid unit, with 1mol/L phosphorus acid for adjusting pH value be 4.3, adding molecular weight is that 10000 KDa polyacrylamide flocculant 0.1g are to final concentration 50ppm, 30 min flocculate, add perlite 80g, stir, filter to obtain first filtrate, it is 6.3 that just filtrate use 0.1mol/L sodium hydroxide solution regulates pH value, leave standstill 2h, add 80g perlite, stir, filter, obtain whole filtrate 1.85L, whole filtrate is decoloured by the decolorizing resin post XDA-7 of blade diameter length ratio 1:6, resin loading amount 170mL, flow velocity is 340mL/h, destainer imports the adsorption resin column HZ816 absorption of blade diameter length ratio 1:6, resin loading amount 340mL, upper column flow rate is 340mL/h, upper prop is complete, first with the impurity on purified water washing adsorption resin column, analyse adsorption resin column with 0.5% acetolysis again, resolve flow velocity 170mL/h, HPLC detects, merge desorbed solution, be evaporated to 15mL, adjusting concentrated solution pH value with 0.1mol/L sodium hydroxide is 6.3, by the chromatographic resin post UniPS 40-300 chromatographic separation of blade diameter length ratio 1:4, resin loading amount 150mL, after upper prop, first use the impurity on 0.08% acetic acid water washing chromatography column, it is acetic acid by volume ratio afterwards: the eluant solution of ethanol: water=0.08:3:96.92, flow velocity is 15mL/min, HPLC detects, collect target elutriant, elutriant freeze-drying, obtain 1.83 grams of fine powders, purity is 98.1%, total recovery 71.5%.
Embodiment 4
Get the conversion fluid 2L of echinocandin B parent nucleus, the 1218 μ g/mL of conversion fluid unit, with 0.5mol/L sulphur acid for adjusting pH value be 4.2, adding molecular weight is that the polyacrylamide flocculant 0.1g of 8000 KDa is to final concentration 50ppm, 30 min flocculate, add perlite 80g, stir, filter to obtain first filtrate, it is 6.2 that just filtrate use 1mol/L dipotassium hydrogen phosphate solution regulates pH value, leave standstill 2h, add 80g perlite, stir, filter, obtain whole filtrate 1.80L, whole filtrate is decoloured by the decolorizing resin post D301 of blade diameter length ratio 1:6, resin loading amount 180mL, flow velocity is 360mL/h, destainer imports the adsorption resin column HZ813 absorption of blade diameter length ratio 1:6, resin loading amount 360mL, upper column flow rate is 360mL/h, upper prop is complete, first with the impurity on purified water washing adsorption resin column, analyse adsorption resin column with 0.5% acetolysis again, resolve flow velocity 180mL/h, HPLC detects, merge desorbed solution, be evaporated to 12mL, regulating concentrated solution pH value with 0.1mol/L sodium hydroxide solution is 6.2, by the chromatographic resin post UniPS 40-300 chromatographic separation of blade diameter length ratio 1:4, resin loading amount 120mL, after upper prop, first use the impurity on 0.08% acetic acid water washing chromatography column, it is acetic acid by volume ratio afterwards: the eluant solution of ethanol: water=0.08:3:96.92, flow velocity is 12mL/min, HPLC detects, collect target elutriant, elutriant freeze-drying, obtain 1.76 grams of fine powders, purity is 98.5%, total recovery 71.1%.
Embodiment 5
Get the conversion fluid 2L of echinocandin B parent nucleus, the 1130 μ g/mL of conversion fluid unit, with 0.5mol/L salt acid for adjusting pH value be 4.1, adding molecular weight is that 12000 KDa polyacrylamide flocculant 0.1g are to final concentration 50ppm, 30 min flocculate, add perlite 80g, stir, filter to obtain first filtrate, it is 6.1 that just filtrate use 1mol/L dipotassium hydrogen phosphate solution regulates pH value, leave standstill 2h, add 80g perlite, stir, filter, obtain whole filtrate 1.90L, whole filtrate is decoloured by the decolorizing resin post HZ801 of blade diameter length ratio 1:6, resin loading amount 160mL, flow velocity is 320mL/h, destainer is imported to the adsorption resin column D312 absorption of blade diameter length ratio 1:6, resin loading amount 320mL, upper column flow rate is 320mL/h, upper prop is complete, first with the impurity on purified water washing adsorption resin column, use again 0.5% acetic acid Dissociative adsorption resin column, resolve flow velocity 160mL/h, HPLC detects, merge desorbed solution, be evaporated to 10mL, regulating concentrated solution pH value with 0.1mol/L sodium hydroxide solution is 6.1, by the chromatographic resin post UniPS 30-300 chromatographic separation of blade diameter length ratio 1:4, resin loading amount 100mL, after upper prop, first use the impurity on 0.08% acetic acid water washing chromatography column, it is acetic acid by volume ratio afterwards: the eluant solution of ethanol: water=0.08:3:96.92, flow velocity is 10mL/min, HPLC detects, collect target elutriant, elutriant freeze-drying, obtain 1.69 grams of fine powders, purity is 96.6%, total recovery 72.2%.
Embodiment 6
Get the conversion fluid 2L of echinocandin B parent nucleus, the 1124 μ g/mL of conversion fluid unit, regulating pH value with glacial acetic acid is 4.5, adding molecular weight is that 5000 KDa polyacrylamide flocculant 0.1g are to final concentration 50ppm, 30 min flocculate, add diatomite 80g, stir, filter to obtain first filtrate, it is 6.0 that just filtrate use 1mol/L dipotassium hydrogen phosphate solution regulates pH value, leave standstill 2h, add 80g diatomite, stir, filter, obtain whole filtrate 1.87L, whole filtrate is decoloured by the decolorizing resin post D290 of blade diameter length ratio 1:6, resin loading amount 100mL, flow velocity is 200mL/h, destainer imports the adsorption resin column HZ816 absorption of blade diameter length ratio 1:6, resin loading amount 150mL, upper column flow rate is 150mL/h, adsorb complete, first with the impurity on purified water washing adsorption resin column, use again 0.5% acetic acid Dissociative adsorption resin column, parsing flow velocity is 75mL/h, HPLC detects, merge desorbed solution, be evaporated to 13mL, adjusting concentrated solution pH value with 0.1mol/L sodium hydroxide is 6.0, by the chromatographic resin post UniPS 30-300 chromatographic separation of blade diameter length ratio 1:4, resin loading amount 130mL, after upper prop, first use the impurity on 0.08% acetic acid water washing chromatography column, it is acetic acid by volume ratio afterwards: the eluant solution of ethanol: water=0.08:3:96.92, flow velocity is 13mL/min, HPLC detects, collect target elutriant, elutriant freeze-drying, obtain 1.67 grams of fine powders, purity is 97.5%, total recovery 72.4%.
Embodiment 7
Get the conversion fluid 2L of echinocandin B parent nucleus, the 1172 μ g/mL of conversion fluid unit, it is 4.2 that glacial acetic acid regulates pH value, adding molecular weight is that 12000 KDa polyacrylamide flocculant 0.1g are to final concentration 50ppm, 30 min flocculate, add perlite 80g, stir, filter to obtain first filtrate, just filtrate is used 1mol/L dipotassium hydrogen phosphate solution to regulate pH6.4, leave standstill 2h, add 80g perlite, stir, filter, obtain whole filtrate 1.82L, whole filtrate is decoloured by the decolorizing resin post HZ801 of blade diameter length ratio 1:6, resin loading amount 180mL, flow velocity is 360mL/h, destainer imports the adsorption resin column 700F absorption of blade diameter length ratio 1:6, resin loading amount 360mL, flow velocity is 360mL/h, adsorb complete, first with the impurity on purified water washing adsorption resin column, use again 0.5% acetic acid Dissociative adsorption resin column, parsing flow velocity is 180mL/h, HPLC detects, merge desorbed solution, be evaporated to 15mL, adjusting concentrated solution pH value with 0.1mol/L sodium hydroxide is 6.3, by the chromatographic resin post UniPS 30-300 chromatographic separation of blade diameter length ratio 1:4, resin loading amount 150mL, after upper prop, first use the impurity on 0.08% acetic acid water washing chromatography column, it is acetic acid by volume ratio afterwards: the eluant solution of ethanol: water=0.08:3:96.92, flow velocity is 15mL/min, HPLC detects, collect target elutriant, elutriant freeze-drying, obtain 1.76 grams of fine powders, purity is 98.1%, total recovery 73.4%.
Claims (9)
1. a preparation method for high purity echinocandin B parent nucleus, is characterized in that the method comprises the following steps:
1) the conversion fluid acid for adjusting pH value of echinocandin B parent nucleus is 4.0-4.5, adds polyacrylamide flocculant precipitated impurities, adds flocculating aids dispersed with stirring even, and solid-liquid separation obtains just filtrate of echinocandin B parent nucleus;
2) the first filtrate of echinocandin B parent nucleus is 6.0-6.5 by alkaline solution adjusting pH value, adds flocculating aids dispersed with stirring even, and solid-liquid separation, obtains the whole filtrate of echinocandin B parent nucleus;
3) whole echinocandin B parent nucleus filtrate is decoloured by macropore decolorizing resin, obtained destainer;
4) destainer is imported to absorption with macroporous adsorbent resin, adsorb completely, use aqueous acid to resolve, HPLC detects, and collects desorbed solution, concentrated, obtains concentrated solution;
5) concentrated solution is regulated pH value for 6.0-6.5, upper polystyrene or Vinylstyrene class chromatographic resin post, resolve with the aqueous acid containing ethanol, and HPLC detects, and collects chromatographic solution, and freeze-drying makes echinocandin B parent nucleus fine powder.
2. method according to claim 1, wherein regulates pH acid used in step 1), be any one in hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, oxalic acid or glacial acetic acid.
3. method according to claim 1, wherein step 1) or 2) in flocculating aids used be perlite or diatomite, consumption is that every liter of conversion fluid adds flocculating aids 0.03-0.05 kilogram.
4. method according to claim 1, wherein step 2) in to regulate pH alkaline solution used be any one in sodium hydroxide solution, dipotassium hydrogen phosphate solution, ammonium dibasic phosphate solution.
5. method according to claim 1, wherein in step 3), decolorizing resin used is any one in LX-700, D290, XDA-7, D301 or HZ801 resin.
6. method according to claim 1, wherein in step 4), polymeric adsorbent used is any one in D312, HZ813, HZ816, HZ818 or 700F resin.
7. method according to claim 1, wherein the aqueous acid in step 4) is acetic acid aqueous solution, concentration is 0.5%.
8. method according to claim 1, wherein in step 5), chromatography media is any one in UniPS 30-300 or UniPS 40-300.
9. method according to claim 1, wherein the aqueous acid containing ethanol in step 5) is that volume ratio is acetic acid: the solution of ethanol: water=0.08:3:96.92.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107759668A (en) * | 2017-05-25 | 2018-03-06 | 博瑞生物医药（苏州）股份有限公司 | A kind of high purity echinocandin B parent nucleus or its salt purification process |
| CN113087774A (en) * | 2020-01-09 | 2021-07-09 | 鲁南制药集团股份有限公司 | Method for removing echinocandin B mother nucleus degradation impurities |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6506726B1 (en) * | 1998-12-09 | 2003-01-14 | Eli Lilly And Company | Purification of Echinocandin cyclopeptide compounds |
| US7785826B2 (en) * | 2004-12-15 | 2010-08-31 | Sanofi-Aventis Deutschland Gmbh | Method for the deacylation of lipopeptides |
| CN102336817A (en) * | 2010-07-16 | 2012-02-01 | 浙江震元制药有限公司 | Separation method of echinocandin B mother nucleus |
| CN103387606A (en) * | 2012-05-11 | 2013-11-13 | 浙江震元制药有限公司 | Method for preparing echinocandin B parent nucleus |
-
2014
- 2014-04-23 CN CN201410164318.3A patent/CN103910783B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6506726B1 (en) * | 1998-12-09 | 2003-01-14 | Eli Lilly And Company | Purification of Echinocandin cyclopeptide compounds |
| US7785826B2 (en) * | 2004-12-15 | 2010-08-31 | Sanofi-Aventis Deutschland Gmbh | Method for the deacylation of lipopeptides |
| CN102336817A (en) * | 2010-07-16 | 2012-02-01 | 浙江震元制药有限公司 | Separation method of echinocandin B mother nucleus |
| CN103387606A (en) * | 2012-05-11 | 2013-11-13 | 浙江震元制药有限公司 | Method for preparing echinocandin B parent nucleus |
Non-Patent Citations (1)
| Title |
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| BOECK LD ET AL.,: "Deacylation of echinocandin B by Actinoplanes utahensis", 《J ANTIBIOT》, 31 March 1989 (1989-03-31) * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107759668A (en) * | 2017-05-25 | 2018-03-06 | 博瑞生物医药（苏州）股份有限公司 | A kind of high purity echinocandin B parent nucleus or its salt purification process |
| CN113087774A (en) * | 2020-01-09 | 2021-07-09 | 鲁南制药集团股份有限公司 | Method for removing echinocandin B mother nucleus degradation impurities |
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| CN103910783B (en) | 2016-07-06 |
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