CN102161665B - Preparation method of azlocillin sodium and azlocillin sodium used for injection - Google Patents
Preparation method of azlocillin sodium and azlocillin sodium used for injection Download PDFInfo
- Publication number
- CN102161665B CN102161665B CN 201110114418 CN201110114418A CN102161665B CN 102161665 B CN102161665 B CN 102161665B CN 201110114418 CN201110114418 CN 201110114418 CN 201110114418 A CN201110114418 A CN 201110114418A CN 102161665 B CN102161665 B CN 102161665B
- Authority
- CN
- China
- Prior art keywords
- azlocillin
- acid
- water
- crystal
- drying
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Abstract
The invention provides a preparation method of azlocillin sodium and azlocillin sodium used for injection, and the azlocillin sodium and the azlocillin sodium used for injection which can be prepared by the method. The method comprises the steps of: in a new solution system, leading ampicillin trihydrate to have a reaction with 1- chloroformyl-2-imidazolone under the optimized temperature condition, and producing high-quality azlocillin acid with higher reaction efficiency and yield; and directly salifying, sterilizing and freeze-drying the prepared azlocillin acid, and obtaining the azlocillin sodium product used for injection.
Description
Technical field
The invention belongs to the synthetic field of medicine, particularly, relate to the preparation method of azlocillin sodium and azlocillin sodium for injection, and the azlocillin sodium and the azlocillin sodium for injection product that make through this method.
Background technology
Azlocillin sodium is a kind of semisynthetic penicillin, and its chemical being called (2S, 5R, 6R)-3,3-dimethyl--6-[(R)-2-(2-oxo-1-imidazolidine formamido group-2-phenylacetylamino)-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-formic acid sodium salt.Chemical formula is by shown in the following formula I:
。
Azlocillin sodium is not destroyed by the penicillinase that streptococcus aureus produces; Streptococcus aureus to producing enzyme is effective; Be mainly used in infecting of penicillin-fast streptococcus aureus and staphylococcus epidermidis on every side, comprise the infection at positions such as internal organ, skin and soft tissue.With amikacin, qingfengmeisu qiong, can produce synergy when netilmicin share.
The method that begins to prepare azlocillin sodium from the Ampicillin Trihydrate mainly contains following several kinds.
At Koealg, HansBodo; Metzer, KqrlG eorg; Offe, Hansert; Schroeck, wllrried:Azlocilln, A new penicillin the acylureldo serles, Synthesls and chemical puopers, Eur. J. Med, Chem-Chim.Ther, 1982; 17 (1): in the method for 59-63, at first Ampicillin Trihydrate-trihydrate is adjusted to pH=7.5 with 2N NaOH in water, adds 1-chloroformyl-2-imidazolidone, makes pH remain on 7-7.5 simultaneously; This solution is used ethyl acetate extraction, transfer pH=2.0 with ice/water and hydrochloric acid; Extract, on rotary evaporator, dried 1 hour down at 30 ℃; Make the azlocillin.Then, the azlocillin is in water and alcoholic acid mixture, and NaOH is water-soluble under the room temperature transfers pH7.5-8.0 with alcoholic acid solution; Successively add ethanol and ETHYLE ACETATE, up to beginning to occur muddiness.Extract, kept 1 hour on the rotary evaporator, so that make it roughly eliminate residual ETHYLE ACETATE.Then in the vacuum moisture trap, put an evening and, make azlocillin sodium the oven dry of paraffin sheet.This method is reacted at aqueous phase, and crystallization makes the azlocillin in ETHYLE ACETATE, and the residual quantity of ETHYLE ACETATE is high in this product, can not directly add the freeze-drying of water salify and form specification product (the acetate residual quantity is higher), and yield is low, produces loaded down with trivial details, the cost height.
In U.S. Pat 4; In 016,282, in the suspension of Ampicillin Trihydrate and 80% aqueous THF; Drip triethylamine at 20 ℃ and make that the pH value is 7.5～8.2; Cool to 0 ℃ then, drip N-chloroformyl-imidazoles-2-ketone/tetrahydrofuran solution, the pH value that keeps feed liquid is between 7.5～8.0.Stirred 30 minutes at 0 ℃, then in stirring at room until the pH of feed liquid value 7.5.Add water and stir, a large amount of THFs is removed in distillation.Use ether extraction, add ETHYLE ACETATE, transfer pH 1.5～2.0, separate organic phase with hydrochloric acid, this product slightly soluble in ETHYLE ACETATE, insoluble in water, filter, with washing, under the vacuum of 1 mmHg, use P
2O
5Dry.Yield: 71%, beta-lactam content: 93%.For this product (azlocillin) of 0.45 times, change into the form of sodium salt, can add the diethyl ether solution that contains methyl alcohol that contains 1mol 2 ethyl hexanoic acid sodium of 2 times of amounts after, separate to obtain with ethyl acetate extraction.This method can not directly add the freeze-drying of water salify because the ethyl acetate content of product is higher and make specification product.
A kind of method for preparing azlocillin sodium is provided among the Chinese patent CN1683375A, has comprised step (1), in the aqueous solution of Ampicillin Trihydrate, slowly added triethylamine, be stirred to the reaction solution clarification in 0-4 ℃; (2) in 0-4 ℃, in solution, add 2-imidazolidone acyl chlorides, drip Na simultaneously
2CO
3Or NaHCO
3The aqueous solution, control pH value is carried out condensation reaction at 7.5-8.5; (3), in reaction mixture, add ETHYLE ACETATE, and regulate the pH value to 1.7-1.9 in 0-5 ℃; (4) separate, get organic phase, behind thermal source and impurity, get crystallization stoste; (5) ethyl acetate solution of Sodium isooctanoate is added above-mentioned crystallization stoste, crystallization appears and after, get rid of material, drying, make the white powder azlocillin sodium.This method utilizes ETHYLE ACETATE to carry out crystallization equally, exists the residual too high problem of ETHYLE ACETATE.
A kind of Preparation of Azlocillin sodium method is disclosed among the Chinese patent CN1704418A; Ampicillin Trihydrate and ium chloride react in water; Crystallization makes the azlocillin in systems such as acetone, ethanol/water or acetone/water then; With the direct salify of sodium hydroxide, promptly get azlocillin sodium after the freeze-drying again.This method does not use ETHYLE ACETATE to carry out crystallization, thereby has avoided the higher and direct freeze dried problem of salify of ethyl acetate content.But this method is reacted in pure water, and reaction efficiency is not high.
The invention provides the preparation method of a kind of improved azlocillin sodium and azlocillin sodium for injection; This method makes Ampicillin Trihydrate three water acid react with 1-chloroformyl-2-imidazolidone under the temperature condition of optimization in a kind of new solution system; Thereby produce high-quality azlocillin acid with higher reaction efficiency and productive rate, and directly salify, degerming freeze-drying obtain the azlocillin sodium for injection product can to make the azlocillin acid that makes.
Summary of the invention
The technical process of production azlocillin sodium of the present invention is shown in accompanying drawing 1.
Particularly, the invention provides a kind of method for preparing azlocillin acid, comprise step:
(a) in reaction vessel, drop into acetone, water, the acid of Ampicillin Trihydrate three water, stir;
Drip triethylamine when (b) feed liquid in the reactor vessel cooled, temperature are reduced to below 15 ℃, stirring is clarified solution fully;
(c) the control feed temperature is 6 ~ 9 ℃, slowly at the uniform velocity adds 1-chloroformyl-2-imidazolidone, feeds intake to finish back stirring 1 hour, mends 6 ~ 9 ℃ of water;
(d) keep between 6 ~ 9 ℃ of the temperature stirring reaction 2 ~ 3 hours;
(e) concentration of reaction solution;
(f) in spissated reaction solution, add hydrochloric acid, carry out the crystallization of azlocillin acid;
(g) crystal is filtered, the water wash crystal with below 10 ℃ filters once more;
(h) crystal is taken out, with acetone crystal is broken into pulpous state and filter again, use acetone drip washing crystal again, filter;
(i) dry said crystal obtains azlocillin acid finished product.
Further, prepare in the sour method in azlocillin above-mentioned, the weight ratio of acetone, water and the acid of Ampicillin Trihydrate three water is 50 ~ 55:240:30 in the step (a).
Further, prepare in the sour method in azlocillin above-mentioned, step (a) is carried out under about 25 ℃.
Further, prepare in the sour method in azlocillin above-mentioned, the sour weight ratio of Ampicillin Trihydrate three water that adds in 1-chloroformyl-2-imidazolidone that adds in the step (c) and the step (a) is 10.92:30.
Further, prepare in the sour method in azlocillin above-mentioned, the described drying of step (i) is vacuum-drying.
The present invention further provides a kind of method for preparing azlocillin sodium, and except above-mentioned steps (a) arrived (i), it also comprised step:
(j) the azlocillin acid that makes is joined in the water for injection, the liquid material is cooled to 0 ~ 5 ℃;
(k) drip 2M NaOH and transfer pH to 7.0 ~ 7.5;
(l) add needle-use activated carbon, stir press filtration after 20 minutes, take off charcoal through plate filter;
(m) take off filtrating behind the charcoal through 0.45 μ m and 0.22 μ m strainer, Sterile Filtration;
(n) freeze-drying filtrating makes the azlocillin sodium pulvis.
Further, the weight ratio of azlocillin acid and water for injection is 1:3.0 ~ 3.5 in the step (j).
Further, the add-on of needle-use activated carbon is 2.0 ~ 4.0% of an azlocillin acid weight in the step (l).
Further, the freeze-drying of filtrating may further comprise the steps in the step (n):
(i) filtrating after the Sterile Filtration is filled in the freeze-drying dish about 10 mm of every dish dress liquid thickness;
When (ii) the flaggy temperature is reduced to below-30 ℃ the freeze-drying dish is put into freeze drying box;
(iii) continue cooling, open vacuum system after product temperature reaches-40 ℃, vacuum tightness reaches about 50Pa and begins sublimation drying when following in the case;
(iv) under the condition that keeps the following vacuum tightness of 50Pa, slowly heat up;
(v) shelf temperature rises to the highest design temperature (between 45 ~ 50 ℃) below 50 ℃, when products temperature is higher than 40 ℃, is incubated 4 ~ 6 hours, and whole freeze-drying time is 25 ~ 28 hours.
Further, said azlocillin sodium is an azlocillin sodium for injection.
The present invention has utilized the reaction soln system of water, acetone and triethylamine; And the temperature of reaction of system is controlled at 6 ~ 9 ℃; Thereby make Ampicillin Trihydrate three water acid be easier to dissolving; Ampicillin Trihydrate three water acid can be carried out rapidly with the condensation reaction of 1-chloroformyl-2-imidazolidone fully, has improved reaction efficiency, has improved the productive rate of product simultaneously.In addition, do not use in the production process of the present invention to be easy to cause residual ETHYLE ACETATE, make the azlocillin acid of preparation can be directly and sodium hydroxide react salify, prepare high-quality azlocillin sodium for injection.
Description of drawings
Accompanying drawing 1 is the process flow sheet of production azlocillin sodium of the present invention.
Accompanying drawing 2 is freeze-drying curves of azlocillin sodium.
Embodiment
Embodiment 1---the preparation of azlocillin acid.
1. prescription feeds intake:
Ampicillin Trihydrate three water acid 30 Kg
Triethylamine 7.5 Kg
1-chloroformyl-2-imidazolidone 10.92Kg
Purified water 240 Kg.
2. technological process:
By the above-mentioned good raw material of prescription weighing that feeds intake, about 25 ℃, in synthesis tank, drop into acetone, purified water, the acid of Ampicillin Trihydrate three water, stir.Feed liquid in the cooling synthesis tank.Drip triethylamine in the time of below the temperature to 15 ℃, stir solution is clarified fully.The control feed temperature slowly at the uniform velocity adds 1-chloroformyl-2-imidazolidone for 6 ~ 9 ℃, in 25 ~ 30 minutes, adds, and feeds intake to finish back stirring 1 hour, mends 6 ~ 9 ℃ of purified water 150L (150 Kg).Between 6 ~ 9 ℃ of the maintenance temperature, stirring reaction 2 ~ 3 hours.Concentration of reaction solution adds hydrochloric acid in spissated reaction solution, carry out the crystallization of azlocillin acid.After crystallization is accomplished, crystal is filtered, with 10 ℃ of following purified water drip washing crystal.Filter again.Crystal is removed, evenly put into 6 and wash brilliant bucket, with 120 ~ 140Kg acetone crystal is broken into pulpous state and filter again.Use 20Kg acetone drip washing crystal again, filter.Crystal after filtering, sabot place the vacuum drying oven inner drying.Control the temperature inside the box is at 30 ℃ ~ 36 ℃, and vacuum-0.09Mpa got final product to such an extent that the azlocillin is sour in dry 14 ~ 18 hours.Crossing the pulverizing of 40 mesh sieves behind dry the end granulates.In the method for present embodiment, the reaction times of Ampicillin Trihydrate and 1-chloroformyl-2-imidazolidone only needs 3 ~ 4 hours, and the productive rate of azlocillin acid is 96.13%.
1. prescription feeds intake:
Azlocillin acid: water for injection 1:3.0 ~ 3.5
Needle-use activated carbon: 2.0 ~ 4.0% of azlocillin acid weight.
2. technological process:
To join in the water for injection according to the azlocillin acid that embodiment 1 makes, feed liquid is cooled to 0 ~ 5 ℃.Drip 2M NaOH and transfer pH to 7.0 ~ 7.5.Add needle-use activated carbon, stir press filtration after 20 minutes, take off charcoal through plate filter.Take off filtrating behind the charcoal through 0.45 μ m, 0.22 μ m strainer, Sterile Filtration to ten thousand grade clean area under hundred grades of laminar flows sabot to freeze drying box.Every dish dress liquid thickness is about 10mm.Product sabot inlet when the flaggy temperature is reduced to below-30 ℃.Continue cooling, (need 1.5 ~ 2h) open vacuum systems approximately, vacuum tightness reached about 50Pa and begins sublimation drying when following in the case, for the fs drying (approximately need 11 ~ 13h) after product temperature reached-40 ℃.Subordinate phase is dry, under the condition that keeps the following vacuum tightness of 50Pa, slowly heats up, and begins adsorption stripping and dry in the time of more than the product temperature to 0 ℃.Shelf temperature to the highest design temperature (between 45 ~ 50 ℃) below 50 ℃ when products temperature is higher than 40 ℃, is incubated 4 ~ 6 hours, and the whole time is 25 ~ 28 hours.The freeze-drying curve of product is shown in accompanying drawing 2.Lyophilized powder is packed in the special-purpose stainless steel cask after sterilizing of finished product in will coil after freeze-drying finishes.Pouring Grindingandgranulatemachine into sieves through 40 orders.Make the azlocillin sodium powder ampoule agent for injection.Through the preparation method of embodiment 2, we prepare uniform particles, highly purified azlocillin sodium for injection powder injection, and it has, and foreign matter content is low, stability is high and dissolve characteristics rapidly.
Claims (10)
1. one kind prepares the sour method in azlocillin, comprises step:
(a) in reaction vessel, drop into acetone, water, the acid of Ampicillin Trihydrate three water, stir;
Drip triethylamine when (b) feed liquid in the reactor vessel cooled, temperature are reduced to below 15 ℃, stirring is clarified solution fully;
(c) the control feed temperature is 6 ~ 9 ℃, slowly at the uniform velocity adds 1-chloroformyl-2-imidazolidone, feeds intake to finish back stirring 1 hour, mends 6 ~ 9 ℃ of water;
(d) keep between 6 ~ 9 ℃ of the temperature stirring reaction 2 ~ 3 hours;
(e) concentration of reaction solution;
(f) in spissated reaction solution, add hydrochloric acid, carry out the crystallization of azlocillin acid;
(g) crystal is filtered, the water wash crystal with below 10 ℃ filters once more;
(h) crystal is taken out, with acetone crystal is broken into pulpous state and filter again, use acetone drip washing crystal again, filter;
(i) dry said crystal obtains azlocillin acid finished product.
2. according to the method for preparing azlocillin acid of claim 1, wherein, the weight ratio of acetone, water and the acid of Ampicillin Trihydrate three water is 50 ~ 55:240:30 in the step (a).
3. according to the method for preparing azlocillin acid of claim 1, wherein, step (a) is carried out under about 25 ℃.
4. according to the method for preparing azlocillin acid of claim 1, wherein, the weight ratio of the Ampicillin Trihydrate three water acid that adds in 1-chloroformyl-2-imidazolidone that adds in the step (c) and the step (a) is 10.92:30.
5. according to the method for preparing azlocillin acid of claim 1, wherein, the described drying of step (i) is vacuum-drying.
6. a method for preparing azlocillin sodium arrives (i) except comprising the described step of claim 1 (a), and it also comprises step:
(j) the azlocillin acid that makes is joined in the water for injection, the liquid material is cooled to 0 ~ 5 ℃;
(k) drip 2M NaOH and transfer pH to 7.0 ~ 7.5;
(l) add needle-use activated carbon, stir press filtration after 20 minutes, take off charcoal through plate filter;
(m) take off filtrating behind the charcoal through 0.45 μ m and 0.22 μ m strainer, Sterile Filtration;
(n) freeze-drying filtrating makes the azlocillin sodium pulvis.
7. according to the method for preparing azlocillin sodium of claim 6, wherein, azlocillin acid is 1:3.0 ~ 3.5 with the weight ratio of water for injection in the step (j).
8. according to the method for preparing azlocillin sodium of claim 6, wherein, the add-on of needle-use activated carbon is 2.0 ~ 4.0% of an azlocillin acid weight in the step (l).
9. according to the method for preparing azlocillin sodium of claim 6, wherein, the freeze-drying of filtrating may further comprise the steps in the step (n):
(i) filtrating after the Sterile Filtration is filled in the freeze-drying dish about 10 mm of every dish dress liquid thickness;
When (ii) the flaggy temperature is reduced to below-30 ℃ the freeze-drying dish is put into freeze drying box;
(iii) continue cooling, open vacuum system after product temperature reaches-40 ℃, vacuum tightness reaches about 50Pa and begins sublimation drying when following in the case;
(iv) under the condition that keeps the following vacuum tightness of 50Pa, slowly heat up;
(v) shelf temperature rises to the highest design temperature below 50 ℃, when products temperature is higher than 40 ℃, is incubated 4 ~ 6 hours, and whole freeze-drying time is 25 ~ 28 hours.
10. method for preparing azlocillin sodium for injection comprises step:
(a) in reaction vessel, drop into acetone, water, the acid of Ampicillin Trihydrate three water, stir;
Drip triethylamine when (b) feed liquid in the reactor vessel cooled, temperature are reduced to below 15 ℃, stirring is clarified solution fully;
(c) the control feed temperature is 6 ~ 9 ℃, slowly at the uniform velocity adds 1-chloroformyl-2-imidazolidone, feeds intake to finish back stirring 1 hour, mends 6 ~ 9 ℃ of water;
(d) keep between 6 ~ 9 ℃ of the temperature stirring reaction 2 ~ 3 hours;
(e) concentration of reaction solution;
(f) in spissated reaction solution, add hydrochloric acid, carry out the crystallization of azlocillin acid;
(g) crystal is filtered, the water wash crystal with below 10 ℃ filters once more;
(h) crystal is taken out, with acetone crystal is broken into pulpous state and filter again, use acetone drip washing crystal again, filter;
(i) dry said crystal obtains azlocillin acid finished product;
(j) the azlocillin acid that makes is joined in the water for injection, the liquid material is cooled to 0 ~ 5 ℃;
(k) drip 2M NaOH and transfer pH to 7.0 ~ 7.5;
(l) add needle-use activated carbon, stir press filtration after 20 minutes, take off charcoal through plate filter;
(m) take off filtrating behind the charcoal through 0.45 μ m and 0.22 μ m strainer, Sterile Filtration;
(n) freeze-drying filtrating makes the azlocillin sodium pulvis.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110114418 CN102161665B (en) | 2011-05-05 | 2011-05-05 | Preparation method of azlocillin sodium and azlocillin sodium used for injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201110114418 CN102161665B (en) | 2011-05-05 | 2011-05-05 | Preparation method of azlocillin sodium and azlocillin sodium used for injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102161665A CN102161665A (en) | 2011-08-24 |
| CN102161665B true CN102161665B (en) | 2012-11-14 |
Family
ID=44463153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201110114418 Active CN102161665B (en) | 2011-05-05 | 2011-05-05 | Preparation method of azlocillin sodium and azlocillin sodium used for injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102161665B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102311450B (en) * | 2011-09-23 | 2012-12-26 | 江苏汉斯通药业有限公司 | Preparation method for Azlocillin sodium |
| CN104478899B (en) * | 2014-11-06 | 2017-11-10 | 海南通用康力制药有限公司 | The preparation method of azlocillin sodium and azlocillin sodium for injection freeze-dried powder |
| CN104761569A (en) * | 2015-04-27 | 2015-07-08 | 四川制药制剂有限公司 | Method for preparing azlocillin sodium for injection and facilitating rejection of non-confirming products |
| CN105777778A (en) * | 2016-03-29 | 2016-07-20 | 南京正亮医药科技有限公司 | Preparation method of Azlocillin sodium freeze-dried powder injection |
| CN105753886A (en) * | 2016-03-29 | 2016-07-13 | 南京正亮医药科技有限公司 | Preparation method of azlocillin and preparation method of azlocillin sodium freeze-dried powder for injection |
| CN107383061A (en) * | 2017-08-03 | 2017-11-24 | 江苏汉斯通药业有限公司 | The synthetic method of azlocillin sodium |
| CN111362969A (en) * | 2020-04-22 | 2020-07-03 | 苏州二叶制药有限公司 | Preparation process of azlocillin sodium |
| CN111978334A (en) * | 2020-08-26 | 2020-11-24 | 山东鲁抗医药股份有限公司 | Preparation method of penicillin salt for injection |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4016282A (en) * | 1970-05-25 | 1977-04-05 | Bayer Aktiengesellschaft | Ureidoacetamido-penicillins |
| CN1683375A (en) * | 2005-03-03 | 2005-10-19 | 黄春荣 | Process for preparing sodium azlocillin |
| CN1704418A (en) * | 2004-06-02 | 2005-12-07 | 浙江金华康恩贝生物制药有限公司 | Process for preparing azlocillin sodium |
-
2011
- 2011-05-05 CN CN 201110114418 patent/CN102161665B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4016282A (en) * | 1970-05-25 | 1977-04-05 | Bayer Aktiengesellschaft | Ureidoacetamido-penicillins |
| CN1704418A (en) * | 2004-06-02 | 2005-12-07 | 浙江金华康恩贝生物制药有限公司 | Process for preparing azlocillin sodium |
| CN1683375A (en) * | 2005-03-03 | 2005-10-19 | 黄春荣 | Process for preparing sodium azlocillin |
Non-Patent Citations (1)
| Title |
|---|
| 张延峰.阿洛西林钠的制备.《齐鲁药事》.2005,第24卷(第4期),236-237. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102161665A (en) | 2011-08-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102161665B (en) | Preparation method of azlocillin sodium and azlocillin sodium used for injection | |
| CN100465171C (en) | Preparation method of potassium sodium dehydroandroan drographolide succinate, potassium sodium dehydroandroan drographolide succinate preparation and preparation method thereof | |
| CN101439022B (en) | Method for preparing clindamycin phosphate powder injection raw medicine | |
| CN102161666B (en) | Preparation method of mezlocillin sodium and mezlocillin sodium for injection | |
| CN102977168B (en) | Extraction and preparation method of abamectin B2a | |
| CN101972479A (en) | Preparation process of intravenous injection human immunoglobulin | |
| CN103755723B (en) | A kind of preparation method of rifampicin I crystal form | |
| CN101362786B (en) | Method for preparing ivermectin | |
| CN100427489C (en) | Process for preparing azlocillin sodium | |
| CN102391259B (en) | Nifuratel compound and preparation method thereof | |
| CN101759729B (en) | Method for producing isomaltulose alcohol crystals | |
| CN106749332B (en) | The production technology of ampicillin sodium crystal | |
| CN102321143A (en) | Method for preparing high-purity betulin | |
| CN103772413B (en) | A kind of preparation method of Rifampin II crystal formation | |
| JPS59132894A (en) | Production of rosmarine | |
| CN107879979A (en) | A kind of preparation method of Dexmedetomidine | |
| CN108774247B (en) | Preparation method of cefotetan acid | |
| CN109400491B (en) | Crystallization preparation method of L-p-hydroxyphenylglycine methyl ester | |
| CN110894521A (en) | Method for producing tetracycline | |
| CN101585844B (en) | Preparation process of Azlocillin | |
| CN104072362A (en) | Synthesis process for antiviral chemical compound protocatechuic acid | |
| CN106967128A (en) | A kind of extracting method of raffinose | |
| CN113667032B (en) | Selenized amomum villosum polysaccharide and preparation method and application thereof | |
| CN103127058A (en) | Moxidectin preparation and preparing method thereof | |
| CN102584812A (en) | Preparation method of tebipenem pivoxil impurities |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |