CN103833804A - Synthetic method of etimicin sulfate - Google Patents
Synthetic method of etimicin sulfate Download PDFInfo
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- CN103833804A CN103833804A CN201410107616.9A CN201410107616A CN103833804A CN 103833804 A CN103833804 A CN 103833804A CN 201410107616 A CN201410107616 A CN 201410107616A CN 103833804 A CN103833804 A CN 103833804A
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Abstract
The invention discloses a synthetic method of etimicin sulfate. The synthetic method comprises the following steps: carrying out a reaction on gentamicin C1a, zinc acetate and acetic anhydride to obtain 3, 2', 6'-tri(N-acetyl) gentamicin C1a; after separating and purifying the 3, 2', 6-tri(N-acetyl) gentamicin C1a, carrying out a reaction with iodoethane to obtain 3, 2', 6'-tri(N-acetyl)-1-ethyl gentamicin C1a; hydrolyzing the 3, 2', 6'-tri(N-acetyl)-1-ethyl gentamicin C1a by sodium hydroxide to obtain an aqueous solution of etimicin sulfate; and carrying out HZD-2 macroporous resin adsorption, separation and purification, concentration, sulfate formation, decarburization and drying on the aqueous solution of etimicin sulfate to obtain an etimicin sulfate finished product. The method disclosed by the invention is high in yield which is 55%, and satisfies the requirements of Chinese pharmacopoeia (Edition 2010).
Description
Technical field
The present invention relates to the preparation method of Etimicin sulfate, relate in particular to the preparation method by the synthetic Etimicin sulfate of Gentamicin C1a, belong to the semi-synthetic technical field of aminoglycoside drug.
Background technology
Etimicin sulfate is a kind of new semi-synthetic water soluble amino glucosides class microbiotic, and its mechanism of action is to suppress the normal protein synthesis of sensitive organism.Etimicin sulfate is Broad spectrum antibiotics, most of gram-positive microorganism and negative bacterium are had to good anti-microbial effect, especially intestinal bacteria, the white pneumobacillus of Cray, Serratia, Salmonellas and staphylococcus etc. are all had to good anti-microbial activity, golden Portugal bacterium to part gentamicin, micronomicin and Kefzol resistance, intestinal bacteria, the white pneumobacillus of Cray all have anti-microbial activity, also have certain anti-microbial activity to producing the part staphylococcus of penicillinase and the staphylococcus of the low-level methicillin resistance of part.The features such as Etimicin sulfate has efficiently, low toxicity, antimicrobial agent, has a broad antifungal spectrum, has good anti-microbial effect to multiple pathogenic bacteria, and respiratory tract infection, kidney and urinary system infection, skin histology infection are all had to good curative effect.
The existing synthetic method of Etimicin sulfate is: Gentamicin C1a is reacted and obtains 3 with Cobaltous diacetate and aceticanhydride, 2 ', 6 '-tri-(N-acetyl) Gentamicin C1a (being called for short P1), to after P1 separation and purification, react and obtain 3 with acetaldehyde and sodium borohydride, 2 ', 6 '-tri-(N-acetyl)-1-ethyl Gentamicin C1as (being called for short P2), P2 obtains the Etimicin aqueous solution after sodium hydroxide hydrolysis, the Etimicin aqueous solution through macroporous resin adsorption, separation and purification, concentrated, become vitriol, de-, the dry Etimicin sulfate finished product that obtains of charcoal.This existing Etimicin sulfate synthetic method craft yield is 36%, and yield is low.
Summary of the invention
Technical problem to be solved by this invention is: the preparation method that the Etimicin sulfate that a kind of process recovery ratio is high is provided.
Technical solution of the present invention is: a kind of Etimicin synthetic method, comprises the following steps:
(1) Gentamicin C1a is added methyl alcohol stir 30 minutes, fully mix, obtain Gentamicin C1a methanol solution;
(2) solution step (1) being obtained adds zinc acetate, is warming up to 45 DEG C, reacts and within 3 hours, obtains reaction solution;
(3) reaction solution step (2) being obtained adds triethylamine, then adds aceticanhydride, is warming up to 55 DEG C, reacts 4 hours, then, by concentrated this reaction solution, evaporate to dryness, obtains yellow solid;
(4) yellow solid step (3) being obtained adds purified water, opens stirring, makes abundant dissolving;
(5) aqueous solution step (4) being obtained adds sodium sulphite, is warming up to 45 DEG C, reacts 1 hour, and solution produces and precipitates and form yellow turbid solution;
(6) solution filter step (5) being obtained, yellow solid discards after adding purified water washing, obtains faint yellow filtrate;
(7) faint yellow filtrate step (6) being obtained concentrates, evaporate to dryness obtains solid P1;
(8) solid P1 step (7) being obtained adds dimethyl formamide to dissolve;
(9) solution step (8) being obtained adds sodium bicarbonate, drips iodoethane, is warming up to 60 DEG C, reacts 4 hours, makes complete reaction;
(10) the concentrated evaporate to dryness of solution step (9) being obtained obtains solid P2;
(11) solid P2 step (10) being obtained adds purified water, opens stirring, makes abundant dissolving;
(12) it is 30% sodium hydroxide solution that solution step (11) being obtained adds concentration, is adjusted to PH11, is warming up to 100 DEG C, is hydrolyzed 6 hours, between the reaction period, maintains PH11 with the sodium hydroxide solution that concentration is 30%, makes to react completely, and obtains the Etimicin aqueous solution;
(13) it is that 10% sulfuric acid is adjusted to PH6.5 that Etimicin aqueous solution step (12) being obtained adds concentration;
(14) solution step (13) being obtained adds HZD-2 macroporous resin, adsorbs 4 hours;
(15) resin and the solution that step (14) are obtained, separate with 80 order stainless steel meshs, and liquid discards, and washs after resin is filled to post, resolves, the concentrated concentrated solution that obtains;
(16) it is 98% sulfuric acid that concentrated solution step (15) being obtained adds concentration, is adjusted to PH5.5, makes into vitriol, obtains Etimicin sulfate concentrated solution;
(17) Etimicin sulfate concentrated solution step (16) being obtained adds gac, filters the dry Etimicin sulfate finished product that obtains of spraying.
Above-mentioned steps (1) adds 20 milliliters of calculating of methyl alcohol by every 1 gram of Gentamicin C1a; Step (2) adds 4 grams of calculating of zinc acetate by every 3 grams of Gentamicin C1as; Step (3) adds 20 milliliters of triethylamines by every 3 grams of Gentamicin C1as, and every 3 grams of Gentamicin C1as add 2 milliliters of calculating of aceticanhydride; Step (4) adds 10 milliliters of purified water by every 1 gram of yellow solid and calculates; Step (5) adds 2 grams of sodium sulphite by every 1 gram of Gentamicin C1a and calculates; Step (6) adds 1 milliliter of purified water by every 1 gram of yellow solid and calculates; Step (8) by every 1 gram 3,2 ', 6 '-tri-(N-acetyl) Gentamicin C1a adds 5 milliliters of dimethyl formamides and calculates; Step (9) adds 1 gram of sodium bicarbonate by every 10 grams of Gentamicin C1as, and every 10 grams of Gentamicin C1as add 1.2 milliliters of iodoethane and calculate; Step (11) by every 1 gram 3,2 ', 6 '-tri-(N-acetyl)-1-ethyl Gentamicin C1as add 20 milliliters of purified water and calculate; Step (17) adds 100 grams of calculating of gac by every 1 liter of Etimicin sulfate concentrated solution.
Technique effect of the present invention is: the present invention reacts Gentamicin C1a to obtain 3 with zinc acetate and aceticanhydride, 2 ', 6 '-tri-(N-acetyl) Gentamicin C1a (being called for short P1), to after P1 separation and purification, react and obtain 3 with iodoethane, 2 ', 6 '-tri-(N-acetyl)-1-ethyl Gentamicin C1as (being called for short P2), P2 obtains the Etimicin aqueous solution after sodium hydroxide hydrolysis, the Etimicin aqueous solution through HZD-2 macroporous resin adsorption, separation and purification, concentrated, become vitriol, de-, the dry Etimicin sulfate finished product that obtains of charcoal.Process recovery ratio of the present invention is 55%, and yield is high, and quality meets the requirement of " Chinese Pharmacopoeia " (2010 editions).
The concrete difference of the present invention and existing technique:
(a) the present invention reacts and obtains P1 with Gentamicin C1a with zinc acetate, and existing technique is to react and obtain P1 with Gentamicin C1a with Cobaltous diacetate; This step can improve P1 yield 7.9%, because make to react more complete with zinc acetate.
(b) the present invention reacts and obtains P2 with P1 with iodoethane, and existing technique is to obtain P2 with acetaldehyde and sodium borohydride reaction, and this step can improve P2 yield 17.1%, because make to react more complete with iodoethane.
(c) the present invention is adsorbed Etimicin with HZD-2 macroporous resin, washing, and separation and purification is once altogether, existing technique is with adsorptive type macroporous resin, P2 and Etimicin to be adsorbed respectively, separation and purification secondary altogether, this step can improve Etimicin yield 2%, because reduced step.
Concrete data as shown in Table 1 and Table 2, three batches of product data of Etimicin sulfate that table 1 is existing explained hereafter, three batches of product data that table 2 is produced Etimicin sulfate for the present invention.
Process recovery ratio=(Etimicin sulfate weight/Gentamicin C1a weight) × 100%
Table 1
| ? | Criticize 1 | Criticize 2 | Criticize 3 | On average |
| Yield (%) | 34.6 | 37.2 | 35.7 | 35.8 |
| Quality | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) |
Table 2
| ? | Criticize 1 | Criticize 2 | Criticize 3 | On average |
| Yield (%) | 56.7 | 54.2 | 55.1 | 55.3 |
| Quality | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) | Meet the requirement of " Chinese Pharmacopoeia " (2010 editions) |
Process recovery ratio=(Etimicin sulfate weight/Gentamicin C1a weight) × 100%
The requirement of Etimicin sulfate " Chinese Pharmacopoeia " (2010 editions): this product is white or off-white powder, in water, very easily dissolve, almost insoluble in methyl alcohol, acetone and Glacial acetic acid, 115 ° of 100 °-﹢ of specific optical rotation: ﹢, pH value should be 4.0-6.5, and vitriol should be 31.5-35%, moisture≤10%, residue on ignition≤0.5%, single impurity≤2.5%, total impurities≤5.0%.
Embodiment
The present invention is by the preparation method of the synthetic Etimicin of Gentamicin C1a, specifically comprises the following steps:
1, get 1500 grams of Gentamicin C1as, adding volume is in the stainless steel reaction tank of the sandwich heating of 50 liters and agitating function, then in this retort, add 30 liters of methyl alcohol (adding 20 milliliters of calculating of methyl alcohol by 1 gram of Gentamicin C1a), stir 30 minutes, mixing speed 80 Zhuan ∕ minute, Gentamicin C1a is fully mixed in methyl alcohol, obtains Gentamicin C1a methanol solution.
Gentamicin C1a is one of gentamicin component, for white or off-white powder, soluble in water, is slightly soluble in methyl alcohol, acetone and other organic solvent, the chemical structural formula of Gentamicin C1a:
The molecular weight of Gentamicin C1a: 449
The molecular formula of Gentamicin C1a: C
19h
39n
5o
7
2, methanol solution step 1 being obtained adds 2000 grams of zinc acetates (to add 4 grams of calculating of zinc acetate by 3 grams of Gentamicin C1as
),whether be warming up to 45 DEG C with sandwich heating and the stainless steel reaction tank that stirs, react 3 hours, making to react completely obtains reaction solution, react completely with Liquid Detection reaction solution.
Step 2 Liquid Detection step is:
(2-1) extract reaction solution 1 milliliter, add 24 milliliters of purified water, mix, with filter paper filtering, obtain diluting soln,
(2-2) get the diluting soln of 1 milliliter of step (2-1), add 99 milliliters of purified water, mix, obtain secondary dilution solution,
(2-3) get the secondary dilution solution of 20 microlitre steps (2-2), injection liquid chromatography, records collection of illustrative plates,
(2-4), in the time that collection of illustrative plates shows that Gentamicin C1a content is less than 0.5%, can think that reaction finishes.3, reaction solution step 2 being obtained adds 10 liters of triethylamines, add again 1 liter of aceticanhydride (to add 20 milliliters of triethylamines by 3 grams of Gentamicin C1as, 3 grams of Gentamicin C1as add 2 milliliters of calculating of aceticanhydride), be warming up to 55 DEG C, react 4 hours, in the stainless steel reaction tank of sandwich heating and stirring, make raw material complete reaction, whether react completely by Liquid Detection, by concentrated reaction solution, evaporate to dryness, obtain yellow solid, yellow solid main component is: 3,2 ', 6 '-tri-(N-acetyl) Gentamicin C1as (P1), zinc acetate and a small amount of methyl alcohol and triethylamine.
4, yellow solid step 3 being obtained adds 35 liters of purified water, and (add 10 milliliters of purified water by 1 gram of yellow solid and add, open stirring with the stainless steel reaction tank of sandwich heating and stirring, mixing speed 80 Zhuan ∕ minute, make abundant dissolving.
5, aqueous solution step 4 being obtained adds 3000 grams, sodium sulphite (adding 2 grams of sodium sulphite by 1 gram of Gentamicin C1a adds), be warming up to 45 DEG C, react 1 hour, solution produces and precipitates and form yellow turbid solution, the composition of yellow turbid solution is: P1, zinc sulphide and water, the throw out being mixed in liquid is zinc sulphide.
6, solution step 5 being obtained filters by solid-liquid filter, add 1200 order filter clothes, yellow solid discards after adding 2 liters of purified water (adding 1 milliliter of purified water by 1 gram of yellow solid calculates) washing, obtain faint yellow filtrate, the composition of yellow solution is 3,2 ', 6 '-tri-(N-acetyl) Gentamicin C1a (P1) and water.Faint yellow filtrate comprises filters the liquid obtaining and washs the liquid sum that yellow solid obtains.
7, faint yellow filtrate step 6 being obtained concentrates, evaporate to dryness, obtains solid P1; Concentrated, evaporate to dryness is heated and opened stirring simultaneously by interlayer, and mixing speed 80 Zhuan ∕ minute, with the stainless steel reaction tank of sandwich heating and stirring.Reaction product is removed zinc sulphide after filtration, removes water through concentrated evaporate to dryness, residue P1
The title of P1: 3,2 ', 6 '-tri-(N-acetyl) Gentamicin C1a
The chemical structural formula of P1:
Molecular weight: 575
Molecular formula: C
25h
45n
5o
10
8, solid P1 step 7 being obtained adds dimethyl formamide (being called for short DMF) 10 liters (adding 5 milliliters of DMF by 1 gram of solid P1), opens stirring, and mixing speed 80 Zhuan ∕ minute, make abundant dissolving;
Whether the solution 9, step 8 being obtained adds 150 grams of sodium bicarbonates, drips 180 milliliters of iodoethane, is warming up to 60 DEG C, reacts 4 hours, makes complete reaction, react completely by Liquid Detection.
The present embodiment liquid phase detection method is:
(9-1) extract reaction solution 1 milliliter, add 24 milliliters of purified water, mix, with filter paper filtering,
(9-2) get the diluting soln of 1 milliliter of step (9-1), add 99 milliliters of purified water, mix,
(9-3) get the diluting soln of 20 microlitre steps (9-2), injection liquid chromatography, records collection of illustrative plates,
(9-4) collection of illustrative plates shows when P1 content is less than 0.5%, can finish reaction.
The present embodiment adds 1 gram of sodium bicarbonate by 10 grams of Gentamicin C1as, and 10 grams of Gentamicin C1as add 1.2 milliliters of iodoethane and calculate.
10, the concentrated evaporate to dryness of solution step 9 being obtained obtains solid P2; With the stainless steel reaction tank of sandwich heating and stirring; heat and open stirring simultaneously by interlayer, mixing speed 80 Zhuan ∕ minute, iodoethane reacts and obtains product P 2 with the upper not protected amino of P1; remove after dimethyl formamide and unnecessary iodoethane residue P2 by concentrated evaporate to dryness.
The title of P2: 3,2 ', 6 '-tri-(N-acetyl)-1-ethyl Gentamicin C1as
The chemical structural formula of P2:
The molecular weight of P2: 603
The molecular formula of P2: C
27h
49n
5o
10
11, solid P2 step 10 being obtained adds 35 liters of purified water, opens stirring, and mixing speed 80 Zhuan ∕ minute, make abundant dissolving, and add 20 milliliters of purified water by 1 gram of solid P2 and calculate, mixing speed 80 Zhuan ∕ minute, the time is 30 minutes.
12, it is 30% sodium hydroxide solution that solution step 11 being obtained adds concentration, be adjusted to PH11, be warming up to 100 DEG C with sandwich heating and the stainless steel reaction tank that stirs, be hydrolyzed 6 hours, between the reaction period, maintaining PH11(with the sodium hydroxide solution that concentration is 30% is that soda acid pH value reaches 11), make to react completely, whether react completely by Liquid Detection, obtain the Etimicin aqueous solution.
The chemical structural formula of Etimicin:
Molecular weight: 477
Molecular formula: C
21h
39n
5o
7
13, it is that 10% sulfuric acid is adjusted to PH6.5 that Etimicin aqueous solution step 12 being obtained adds concentration.
14, solution step 13 being obtained adds 12 liters of HZD-2 macroporous resins, and mixing speed 30 Zhuan ∕ minute adsorb 4 hours, makes absorption completely, inhales remaining liquid by Liquid Detection, judges whether that absorption completely;
Its main physical and chemical index of the present embodiment HZD-2 macroporous resin:
| Sequence number | Index name | Index |
| 1 | Skeleton | Acrylic acid series |
| 2 | Functional group | -COO- |
| 3 | Pattern | Na+ |
| 4 | Water content % | 47-58 |
| 5 | Quality complete exchange capacity (m mol/ml) | ≥9.5 |
| 6 | Wet volume density g/ml | 0.70-0.80 |
| 7 | Wet true density (20 DEG C) g/ml | 1.10 -1.25 |
| 8 | Size range mm | 0.315-1.25 |
| 5 | Granularity % | ≥ 90 |
Step 14 Liquid Detection is:
(14-1) get and inhale 10 milliliters of remaining liquid, with filter paper filtering,
(14-2) get filtrate 20 microlitres of step 1, injection liquid chromatography, records collection of illustrative plates,
(14-3) when collection of illustrative plates shows Etimicin content for trace (being less than 50ug/ml), i.e. absorption completely.
15, resin step 14 being obtained and solution, with 80 order stainless steel meshs separation, liquid discards, resin is filled after post to the 240 liters of washings of ammoniacal liquor that are 0.15% by concentration, 36 liters of parsings of the ammoniacal liquor that is 4.5% by concentration, desorbed solution is concentrated with thin film concentrator, be concentrated into 5 liters.
Resin of the present invention dress post, washing, parsing, concentrated concrete grammar:
(15-1) dress post: resin is packed in the line with rubber post that blade diameter length ratio is 1:20, and loading amount reaches 90%,
(15-2) washing: be that 0.15% ammoniacal liquor passes in resin column by concentration, flow velocity is amount of resin 1/3rd, flux is amount of resin 20 times,
(15-3) resolve: pass in resin column with the ammoniacal liquor that concentration is 4.5%, flow velocity is amount of resin 1/10th, flux is amount of resin 3 times,
(15-4) concentrated: concentrated with thin film concentrator, be concentrated into 1/20th of desorbed solution volume.
16, it is 98% sulfuric acid that concentrated solution step 15 being obtained adds concentration, is adjusted to PH5.5, becomes vitriol, obtains Etimicin sulfate finished fluid.
17, Etimicin sulfate finished fluid step 16 being obtained adds 500 grams of gacs (adding 100 grams of calculating of gac by 1 liter of Etimicin sulfate concentrated solution), be warming up to 55 DEG C, stir 4 hours, filter by solid-liquid filter, add 1200 order filter clothes, spray with spray tower dry, obtain 830 grams of Etimicin sulfate finished products.
Being dried concrete grammar with the spraying of spray tower is: Etimicin sulfate finished fluid is sprayed in tower by shower nozzle, and the hot blast in spray tower is dry by vaporific Etimicin sulfate finished fluid, forms pulverous finished powder.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, although the present invention is had been described in detail with reference to previous embodiment, for a person skilled in the art, its technical scheme that still can record aforementioned each embodiment is modified, or part technical characterictic is wherein equal to replacement.Within the spirit and principles in the present invention all, any amendment of doing, be equal to replacement, improvement etc., within all should being included in protection of the present invention.
Claims (2)
1. a synthetic method for Etimicin sulfate, is characterized in that, comprises the following steps:
(1) Gentamicin C1a is added methyl alcohol stir 30 minutes, fully mix, obtain Gentamicin C1a methanol solution;
(2) solution step (1) being obtained adds zinc acetate, is warming up to 45 DEG C, reacts and within 3 hours, obtains reaction solution;
(3) reaction solution step (2) being obtained adds triethylamine, then adds aceticanhydride, is warming up to 55 DEG C, reacts 4 hours, then, by concentrated this reaction solution, evaporate to dryness, obtains yellow solid;
(4) yellow solid step (3) being obtained adds purified water, opens stirring, makes abundant dissolving;
(5) aqueous solution step (4) being obtained adds sodium sulphite, is warming up to 45 DEG C, reacts 1 hour, and solution produces and precipitates and form yellow turbid solution;
(6) solution filter step (5) being obtained, yellow solid discards after adding purified water washing, obtains faint yellow filtrate;
(7) the faint yellow filtrate that step (6) obtained is concentrated, evaporate to dryness obtains 3,2 ', 6 '-tri-(N-acetyl) Gentamicin C1a;
(8) step (7) is obtained 3,2 ', 6 '-tri-(N-acetyl) Gentamicin C1a add dimethyl formamide dissolve;
(9) solution step (8) being obtained adds sodium bicarbonate, drips iodoethane, is warming up to 60 DEG C, reacts 4 hours, makes complete reaction;
(10) the concentrated evaporate to dryness of the solution that step (9) obtained obtains 3,2 ', 6 '-tri-(N-acetyl)-1-ethyl Gentamicin C1as;
(11) step (10) is obtained 3,2 ', 6 '-tri-(N-acetyl)-1-ethyl Gentamicin C1as add purified water, open stirring, make abundant dissolving;
(12) it is 30% sodium hydroxide solution that solution step (11) being obtained adds concentration, is adjusted to PH11, is warming up to 100 DEG C, is hydrolyzed 6 hours, between the reaction period, maintains PH11 with the sodium hydroxide solution that concentration is 30%, makes to react completely, and obtains the Etimicin aqueous solution;
(13) it is that 10% sulfuric acid is adjusted to PH6.5 that Etimicin aqueous solution step (12) being obtained adds concentration;
(14) solution step (13) being obtained adds HZD-2 macroporous resin, adsorbs 4 hours;
(15) resin and the solution that step (14) are obtained, separate with 80 order stainless steel meshs, and liquid discards, and washs after resin is filled to post, resolves, the concentrated concentrated solution that obtains;
(16) it is 98% sulfuric acid that concentrated solution step (15) being obtained adds concentration, is adjusted to PH5.5, makes into vitriol, obtains Etimicin sulfate concentrated solution;
(17) Etimicin sulfate concentrated solution step (16) being obtained adds gac, filters the dry Etimicin sulfate finished product that obtains of spraying.
2. a kind of synthetic method of Etimicin sulfate according to claim 1, is characterized in that: step (1) adds 20 milliliters of calculating of methyl alcohol by every 1 gram of Gentamicin C1a; Step (2) adds 4 grams of calculating of zinc acetate by every 3 grams of Gentamicin C1as; Step (3) adds 20 milliliters of triethylamines by every 3 grams of Gentamicin C1as, and every 3 grams of Gentamicin C1as add 2 milliliters of calculating of aceticanhydride; Step (4) adds 10 milliliters of purified water by every 1 gram of yellow solid and calculates; Step (5) adds 2 grams of sodium sulphite by every 1 gram of Gentamicin C1a and calculates; Step (6) adds 1 milliliter of purified water by every 1 gram of yellow solid and calculates; Step (8) by every 1 gram 3,2 ', 6 '-tri-(N-acetyl) Gentamicin C1a adds 5 milliliters of dimethyl formamides and calculates; Step (9) adds 1 gram of sodium bicarbonate by every 10 grams of Gentamicin C1as, and every 10 grams of Gentamicin C1as add 1.2 milliliters of iodoethane and calculate; Step (11) by every 1 gram 3,2 ', 6 '-tri-(N-acetyl)-1-ethyl Gentamicin C1as add 20 milliliters of purified water and calculate; Step (17) adds 100 grams of calculating of gac by every 1 liter of Etimicin sulfate concentrated solution.
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| CN111825732A (en) * | 2020-07-18 | 2020-10-27 | 无锡济煜山禾药业股份有限公司 | Method for preparing etimicin sulfate by ultrasonic wave |
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| CN105524129A (en) * | 2015-12-25 | 2016-04-27 | 无锡济民可信山禾药业股份有限公司 | Etimicin sulfate preparation method |
| CN105524129B (en) * | 2015-12-25 | 2018-06-26 | 无锡济民可信山禾药业股份有限公司 | A kind of preparation method of Etimicin Sulfate |
| CN111004291A (en) * | 2019-12-19 | 2020-04-14 | 卓和药业集团有限公司 | Etimicin derivative and synthetic method thereof |
| CN111825732A (en) * | 2020-07-18 | 2020-10-27 | 无锡济煜山禾药业股份有限公司 | Method for preparing etimicin sulfate by ultrasonic wave |
| CN113416118A (en) * | 2021-06-24 | 2021-09-21 | 无锡济煜山禾药业股份有限公司 | Method for recovering solvent methanol in production process of bulk drugs |
| CN114213471A (en) * | 2021-12-27 | 2022-03-22 | 无锡福祈制药有限公司 | Synthesis method of etimicin |
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