CN1583756A - Preparing method for amoxicillin by solvent crystallization - Google Patents
Preparing method for amoxicillin by solvent crystallization Download PDFInfo
- Publication number
- CN1583756A CN1583756A CN 200410043624 CN200410043624A CN1583756A CN 1583756 A CN1583756 A CN 1583756A CN 200410043624 CN200410043624 CN 200410043624 CN 200410043624 A CN200410043624 A CN 200410043624A CN 1583756 A CN1583756 A CN 1583756A
- Authority
- CN
- China
- Prior art keywords
- sodium
- dehydrated alcohol
- solution
- washing
- add
- 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.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention refers to preparation of medicine, eg, Sodium Amoxcillin by menstruum crystallization. At first, sodium isooctanoic acid water-free alcohol is prepared by: adding isooctanoic acid into water-free alcohold to dissolve it completely, keeping at (15-20)deg.C, adding active carbon, filtering to remove carbon and bacteria, washing the pipe passage which the reaction liquid passes through while filtering water-free alcohol, mixing filtration liquid with washing liquid with weight ratio of sodium isooctanate 0.38-0.49 parts, and water-free alcohol 1.96-2.48 parts. Then, Amoxcillin solution is prepared by: adding Amoxcillin into water-free alcohol, adding diisoproylamine, keeping at (10-15)deg.C to dissolve Amoxcillin completely, adding active carbon, filtering to remove carbon and bacteria, washing the pipe passage which reaction liquid passes through while filtering water-free alcohol, mixing filtration liquid with the washing liquid with weight ratio if Amoxcillin 1 part, water-free alcohold 2.3 -3.5 parts, and diisopropylamine 0.68-5.4 parts. Finally, amoxcillin solution reacts with sodium isooctanoic acid to crystallize at (15-20)deg.C, stirring at 50-80 rpm, and reactiing 100-150 minutes in total.
Description
(1) technical field: the present invention relates to the preparation method of Western medicine, be specially the solvent crystal preparation method of Amoxicillin Sodium.
(2) background technology: Amoxicillin Sodium is the wider penbritin class microbiotic of known clinical application, and Gram-negative bacteria and positive bacteria are all had killing action by force and rapidly, and Leptospira is also had killing action.This product sterilization mechanism uniqueness can suppress the synthetic of cell walls, makes cell become spheroplast and the dissolving of breaking rapidly, and effect is fast, and does not have the possibility that bacterium breeds again.Germicidal action is strong and rapidly than penbritin etc.Be mainly used in the infection of urinary system due to the sensitive organism, respiratory system, biliary tract etc. clinically.Especially Amoxicillin Sodium and Clavulanic Potassium share, and anti-microbial effect will increase by 130 times.The production method of Amoxicillin Sodium mainly contains three kinds at present, and a kind of is freeze-drying, and a kind of is spray-drying process, and also having a kind of is solvent crystallization.Preceding two kinds of methods exist very big deficiency on quality product, product content is lower, and related substances content is higher, easily produce anaphylaxis when clinical application, because crystallization is rapid, crystal formation is tiny simultaneously, degraded descends its curative effect rapidly in storage process easily.Go out two pieces of patent documentations through State Patent Office's update search, one piece be authorized, one piece with open.The patent No. 0010057.0 " a kind of preparation method of Amoxicillin Sodium " and solvent crystallization, the patent No. 02100123.5 " a kind of preparation method of Amoxicillin Sodium ".The patent No. 0010057.0 is made of three kinds of materials, and the patent No. 02100123.5 is made of five kinds of materials, cost height, complex process.Solvent crystallization has then remedied the deficiency of preceding two kinds of methods, has advantages such as content height, good stability.At present, show that according to pertinent data the method that solvent crystallization prepares Amoxicillin Sodium mainly contains following two kinds: will be dissolved with Sodium isooctanoate (ritalin and dehydrated alcohol) solution and amoxycilline Trihydrate bp (triethylamine, dehydrated alcohol, ritalin and Virahol) solution reaction crystalline method.To be dissolved with Sodium isooctanoate (vinyl acetic monomer and dehydrated alcohol) solution and amoxycilline Trihydrate bp (Diisopropylamine, dehydrated alcohol and Virahol) solution reaction crystalline method.Though these two kinds of methods have had very big leap than freeze-drying and spray-drying process on quality product, also exist the solvent system complex simultaneously, the cost height, toxic side effect is stronger, is unfavorable for deficiencies such as labour protection.
(3) summary of the invention: the purpose of this invention is to provide a kind of quality product height, cost is low, technology is simple, toxic side effect is little, the solvent crystal method of solvent system simplification, preparation Amoxicillin Sodium that cost is low.The object of the present invention is to provide a kind of amoxycilline Trihydrate bp in the presence of dehydrated alcohol, with Diisopropylamine reaction, reaction solution again with the ethanol solution reaction and the crystallization of Sodium isooctanoate, obtain the Amoxicillin Sodium finished product after crystallization filtration, washing, the drying.The object of the present invention is achieved like this: the preparation of (1) Sodium isooctanoate ethanol solution, in dehydrated alcohol, add Sodium isooctanoate, make it to dissolve fully, keep 15------20 ℃, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: Sodium isooctanoate 0.38----0.49 part, dehydrated alcohol 1.96----2.48 part; (2) preparation of amoxycilline Trihydrate bp solution, in dehydrated alcohol, add the amoxycilline Trihydrate bp, add Diisopropylamine again, keep 10----15 ℃, the amoxycilline Trihydrate bp is dissolved fully, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 1 part of amoxycilline Trihydrate bp, dehydrated alcohol 2.3----3.5 part, Diisopropylamine 0.68----5.4 part; (3) amoxycilline Trihydrate bp solution and the crystallization of Sodium isooctanoate solution reaction, Tc is 15----20 ℃, stirs to be 50---80 rev/min, the reaction whole process is 100----150 minute.The invention has the advantages that: the quality product height, cost is low, technology is simple, toxic side effect is little of meeting national regulation fully, and it is low to help labour protection, solvent system simplification, cost.Only used dehydrated alcohol, two kinds of solvents of Diisopropylamine among the present invention, and wherein dehydrated alcohol reclaims, the rate of recovery is 80%, and this greatly reduces production cost.Be beneficial to industrial hygiene: the solvent system is simple among the present invention, and dehydrated alcohol, belongs to industrial three class solvents, and less to the human body murder by poisoning, environmental pollution is also less.Quality product height, good stability: adopt the Amoxicillin Sodium quality product of the present invention's preparation better, it is carried out quality test: carry out the quality contrast with the additive method product:
A. supply test agent: our factory's trial product, lot number is: A20040301, A20040302, A20040303
B. control sample 1: certain factory's product (spray dry), lot number: 20040108
Control sample 2: certain factory's product (solvent method), lot number: the patent No. 0010057.0
According to the every requirement under 2000 editions Amoxicillin Sodium items of Pharmacopoeia of People's Republic of China, trial-product and reference substance are tested, the result is as follows:
By with the contrast of improving quality, can draw to draw a conclusion: products made thereby of the present invention is at aspects such as content, related substances, and quality obviously is better than reference substance.
Stability test is investigated:
Carry out the stability test investigation, the investigation condition to above for three batches of examination amoxycilline Trihydrate bp sodium samples: 60 ℃, 10 days, it was as follows to investigate the result:
| Lot number | Time (my god) | Proterties | Content (%) | Related substance | Moisture % | PH value | ||||
| ??A20040301 | ????0 | White crystals | ????92.1 | Meet | ????0.77 | ????9.0 | ||||
| ????5 | White crystals | ????90.1 | Meet | ????0.75 | ????9.0 | |||||
| ????10 | White crystals | ????89.8 | Meet | ????0.70 | ????9.0 | |||||
| ??A20040302 | ????0 | White crystals | ????91.1 | Meet | ????0.93 | ????8.9 | ||||
| ????5 | White crystals | ????90.5 | Meet | ????0.90 | ????8.9 | |||||
| ????10 | White crystals | ????89.4 | Meet | ????0.89 | ????8.9 | |||||
| ??A20040303 | ????0 | White crystals | ????91.1 | Meet | ????0.88 | ????8.9 | ||||
| ????5 | White crystals | ????89.8 | Meet | ????0.88 | ????8.9 | |||||
| ????10 | White crystals | ????89.0 | Meet | ????0.85 | ????8.9 | |||||
| 2000 editions standards of pharmacopoeia | White or off-white color crystallization or crystallization | ????≥80.0 | Should be up to specification | ????≤4.0 | ????8.0-10.0 | |||||
Aforementioned stable investigation result shows, the product of the present invention's preparation with this understanding, quality index such as content, related substance all do not have obvious change, stability is very good.
(4) preparation of embodiment (1) Sodium isooctanoate ethanol solution, in dehydrated alcohol, add Sodium isooctanoate, make it to dissolve fully, keep 15------20 ℃, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: Sodium isooctanoate 0.38----0.49 part, dehydrated alcohol 1.96----2.48 part; (2) preparation of amoxycilline Trihydrate bp solution, in dehydrated alcohol, add the amoxycilline Trihydrate bp, add Diisopropylamine again, keep 10----15 ℃, the amoxycilline Trihydrate bp is dissolved fully, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 1 part of amoxycilline Trihydrate bp, dehydrated alcohol 2.3----3.5 part, Diisopropylamine 0.68----5.4 part; (3) amoxycilline Trihydrate bp solution and the crystallization of Sodium isooctanoate solution reaction, Tc is 15----20 ℃, stirs to be 50---80 rev/min, the reaction whole process is 100----150 minute.Reaction is filtered after finishing, crystallization absolute ethanol washing 3 times.Promptly get the Amoxicillin Sodium finished product after the drying.Below for embodiment, implementation process of the present invention is described: the preparation of example 1, Sodium isooctanoate ethanol solution, in dehydrated alcohol, add Sodium isooctanoate, make it to dissolve fully, keep 15 ℃, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 0.38 part of Sodium isooctanoate, 1.96 parts of dehydrated alcohols; (2) preparation of amoxycilline Trihydrate bp solution, in dehydrated alcohol, add the amoxycilline Trihydrate bp, add Diisopropylamine again, keep 10 ℃, the amoxycilline Trihydrate bp is dissolved fully, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 1 part of amoxycilline Trihydrate bp, 2.3 parts of dehydrated alcohols, 0.68 part of Diisopropylamine; (3) amoxycilline Trihydrate bp solution and the crystallization of Sodium isooctanoate solution reaction, Tc is 15 ℃, and stirring is 50 rev/mins, and the reaction whole process is 100 minutes.Reaction is filtered after finishing, crystallization absolute ethanol washing 3 times.Promptly get the Amoxicillin Sodium finished product after the drying.
The preparation of example 2, Sodium isooctanoate ethanol solution, in dehydrated alcohol, add Sodium isooctanoate, make it to dissolve fully, keep 20 ℃, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 0.49 part of Sodium isooctanoate, 2.48 parts of dehydrated alcohols; (2) preparation of amoxycilline Trihydrate bp solution, in dehydrated alcohol, add the amoxycilline Trihydrate bp, add Diisopropylamine again, keep 15 ℃, the amoxycilline Trihydrate bp is dissolved fully, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 1 part of amoxycilline Trihydrate bp, 3.5 parts of dehydrated alcohols, 5.4 parts of Diisopropylamines; (3) amoxycilline Trihydrate bp solution and the crystallization of Sodium isooctanoate solution reaction, Tc is 20 ℃, and stirring is 80 rev/mins, and the reaction whole process is 150 minutes.Reaction is filtered after finishing, crystallization absolute ethanol washing 3 times.Promptly get the Amoxicillin Sodium finished product after the drying.
The preparation of example 3, Sodium isooctanoate ethanol solution, in dehydrated alcohol, add Sodium isooctanoate, make it to dissolve fully, keep 18 ℃, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 0.45 part of Sodium isooctanoate, 2.25 parts of dehydrated alcohols; (2) preparation of amoxycilline Trihydrate bp solution, in dehydrated alcohol, add the amoxycilline Trihydrate bp, add Diisopropylamine again, keep 13 ℃, the amoxycilline Trihydrate bp is dissolved fully, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 1 part of amoxycilline Trihydrate bp, 2.9 parts of dehydrated alcohols, 3.4 parts of Diisopropylamines; (3) amoxycilline Trihydrate bp solution and the crystallization of Sodium isooctanoate solution reaction, Tc is 18 ℃, and stirring is 70 rev/mins, and the reaction whole process is 120 minutes.Reaction is filtered after finishing, crystallization absolute ethanol washing 3 times.Promptly get the Amoxicillin Sodium finished product after the drying.
Claims (1)
1, a kind of solvent crystal preparation method of Amoxicillin Sodium, it is characterized in that: the preparation of (1) Sodium isooctanoate ethanol solution, in dehydrated alcohol, add Sodium isooctanoate, make it to dissolve fully, keep 15------20 ℃, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: Sodium isooctanoate 0.38----0.49 part, dehydrated alcohol 1.96----2.48 part; (2) preparation of amoxycilline Trihydrate bp solution, in dehydrated alcohol, add the amoxycilline Trihydrate bp, add Diisopropylamine again, keep 10----15 ℃, the amoxycilline Trihydrate bp is dissolved fully, add gac, through carbon removal filtration and Sterile Filtration, and the pipeline of reaction solution process during with the dehydrated alcohol washing and filtering, merging filtrate and washing lotion, concrete parts by weight proportioning is: 1 part of amoxycilline Trihydrate bp, dehydrated alcohol 2.3----3.5 part, Diisopropylamine 0.68----5.4 part; (3) amoxycilline Trihydrate bp solution and the crystallization of Sodium isooctanoate solution reaction, Tc is 15----20 ℃, stirs to be 50---80 rev/min, the reaction whole process is 100----150 minute.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410043624 CN1583756A (en) | 2004-06-14 | 2004-06-14 | Preparing method for amoxicillin by solvent crystallization |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200410043624 CN1583756A (en) | 2004-06-14 | 2004-06-14 | Preparing method for amoxicillin by solvent crystallization |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1583756A true CN1583756A (en) | 2005-02-23 |
Family
ID=34601723
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200410043624 Pending CN1583756A (en) | 2004-06-14 | 2004-06-14 | Preparing method for amoxicillin by solvent crystallization |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1583756A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102268016A (en) * | 2011-03-28 | 2011-12-07 | 哈药集团制药总厂 | Method for preparing amoxicillin sodium |
| CN101633663B (en) * | 2009-08-28 | 2011-12-21 | 沈阳顺旺动物药业有限公司 | Method for synthesizing penicillin sodium salt and potassium salt |
| CN104910180A (en) * | 2015-05-28 | 2015-09-16 | 浙江长典医药有限公司 | Children amoxicillin sodium compound entity and drug preparation thereof |
| CN105476988A (en) * | 2015-11-19 | 2016-04-13 | 杭州长典医药科技有限公司 | Amoxicillin sodium-clavulanate potassium special superfine-powder preparation and preparing method thereof |
| CN111205306A (en) * | 2020-03-06 | 2020-05-29 | 山东二叶制药有限公司 | Preparation process of amoxicillin sodium |
-
2004
- 2004-06-14 CN CN 200410043624 patent/CN1583756A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101633663B (en) * | 2009-08-28 | 2011-12-21 | 沈阳顺旺动物药业有限公司 | Method for synthesizing penicillin sodium salt and potassium salt |
| CN102268016A (en) * | 2011-03-28 | 2011-12-07 | 哈药集团制药总厂 | Method for preparing amoxicillin sodium |
| CN104910180A (en) * | 2015-05-28 | 2015-09-16 | 浙江长典医药有限公司 | Children amoxicillin sodium compound entity and drug preparation thereof |
| CN105476988A (en) * | 2015-11-19 | 2016-04-13 | 杭州长典医药科技有限公司 | Amoxicillin sodium-clavulanate potassium special superfine-powder preparation and preparing method thereof |
| CN111205306A (en) * | 2020-03-06 | 2020-05-29 | 山东二叶制药有限公司 | Preparation process of amoxicillin sodium |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102432629B (en) | Method for refining ceftriaxone sodium crude product | |
| CN104644640A (en) | Preparation method of cefoperazone sodium and sulbactam sodium powder injection for injection | |
| CN104031067B (en) | The process for purification of a kind of crude product of ceftriaxone sodium | |
| CN101550199A (en) | Method for preparing sodium hyaluronate from hyaluronic acid zymotic fluid | |
| CN104745566A (en) | Lactic acid bacterium immobilized capsules and preparation method and application thereof | |
| CN107344971A (en) | Poly-lysine modified chitosan and preparation method thereof | |
| CN106995502A (en) | Bifunctional group modified chitosan derivative and preparation method thereof | |
| CN103638551B (en) | Preparation method for chitosan 6-OH immobilized cyclodextrin included tea tree oil thermo-sensitive hydrogel | |
| CN103989630B (en) | Moxifloxacin hydrochloride injection and preparation method thereof | |
| CN1583756A (en) | Preparing method for amoxicillin by solvent crystallization | |
| CN109778350B (en) | Preparation method and application of alginate fiber containing chlorhexidine antibacterial drugs | |
| CN104302183A (en) | Use of delphinidin against staphylococcus aureus | |
| CN103113390B (en) | Sulbactam sodium compound and medical composition of sulbactam sodium compound and mezlocillin sodium | |
| CN104650115A (en) | Cefoperazone sodium, special superfine compound powder preparation thereof and preparation method of special superfine compound powder preparation | |
| CN104622695A (en) | Cefoxitin sodium powder preparation for injection | |
| CN104530082A (en) | Cefathiamidine compound | |
| CN105902499B (en) | Enrofloxacin soluble powder and preparation method thereof | |
| CN114702607A (en) | Water-soluble hydroxymethyl propyl chitosan and preparation method thereof | |
| CN108772096B (en) | Advanced oxidation method for treating levofloxacin hydrochloride in heterogeneous reaction system | |
| CN103936886B (en) | O-thiazolidine methyl esters-N-trimethyl chitin quaternary ammonium salt and method for making and application | |
| CN111154010A (en) | Medical cationic polymer biopolymer material, preparation method and application | |
| CN103193795B (en) | Pharmaceutical composition of amoxicillin sodium and sulbactam sodium | |
| CN110590878B (en) | 6-oxadiazole/thiadiazole chitosan oligosaccharide derivative and preparation and application thereof | |
| CN112168740B (en) | Functional facial mask containing medical components and preparation method thereof | |
| CN102634074B (en) | Chitin pulp and production method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |