CN100345858C - Method for preparing vancomycin of norhydrochloric acid - Google Patents
Method for preparing vancomycin of norhydrochloric acid Download PDFInfo
- Publication number
- CN100345858C CN100345858C CNB2003101096889A CN200310109688A CN100345858C CN 100345858 C CN100345858 C CN 100345858C CN B2003101096889 A CNB2003101096889 A CN B2003101096889A CN 200310109688 A CN200310109688 A CN 200310109688A CN 100345858 C CN100345858 C CN 100345858C
- Authority
- CN
- China
- Prior art keywords
- hydrochloric acid
- demethyl vancomycin
- preparation
- acid demethyl
- vancomycin preparation
- 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.)
- Expired - Fee Related
Links
- 239000002253 acid Substances 0.000 title claims description 3
- 238000000034 method Methods 0.000 title abstract description 9
- 108010059993 Vancomycin Proteins 0.000 title 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 title 1
- 229960003165 vancomycin Drugs 0.000 title 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 title 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 79
- 239000011347 resin Substances 0.000 claims abstract description 27
- 229920005989 resin Polymers 0.000 claims abstract description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 18
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims abstract description 11
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 239000010451 perlite Substances 0.000 claims abstract description 6
- 235000019362 perlite Nutrition 0.000 claims abstract description 6
- 238000003795 desorption Methods 0.000 claims abstract description 5
- NUAQIRUAZSJTAI-TYIWBIPUSA-N chembl2374194 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@H](N)CC(C)C)[C@H]1C[C@](C)(N)C(O)[C@H](C)O1 NUAQIRUAZSJTAI-TYIWBIPUSA-N 0.000 claims description 29
- 108700023456 demethylvancomycin Proteins 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 19
- 239000000243 solution Substances 0.000 claims description 19
- 238000001914 filtration Methods 0.000 claims description 14
- BYGOPQKDHGXNCD-UHFFFAOYSA-N tripotassium;iron(3+);hexacyanide Chemical compound [K+].[K+].[K+].[Fe+3].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] BYGOPQKDHGXNCD-UHFFFAOYSA-N 0.000 claims description 10
- 229960001763 zinc sulfate Drugs 0.000 claims description 10
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 7
- 230000008025 crystallization Effects 0.000 claims description 7
- 239000012065 filter cake Substances 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 238000003756 stirring Methods 0.000 claims description 6
- 229910019142 PO4 Inorganic materials 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 239000010452 phosphate Substances 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 1
- 239000002594 sorbent Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 238000000855 fermentation Methods 0.000 abstract description 2
- 230000004151 fermentation Effects 0.000 abstract description 2
- 238000004042 decolorization Methods 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- -1 potassium ferricyanide Chemical compound 0.000 abstract 1
- 230000001105 regulatory effect Effects 0.000 abstract 1
- 238000001179 sorption measurement Methods 0.000 abstract 1
- 235000009529 zinc sulphate Nutrition 0.000 abstract 1
- 239000011686 zinc sulphate Substances 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000000047 product Substances 0.000 description 17
- LLWFHCJFZGXUAT-UMXPSMRGSA-N (1S,2R,18R,19R,22S,25R,28R,40S)-48-[(2S,3R,4S,5S,6R)-3-[(2S,4S,5S,6S)-4-amino-5-hydroxy-4,6-dimethyloxan-2-yl]oxy-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-19-[[(2R)-2-amino-4-methylpentanoyl]amino]-22-(2-amino-2-oxoethyl)-5,15-dichloro-2,18,32,35,37-pentahydroxy-20,23,26,42,44-pentaoxo-7,13-dioxa-21,24,27,41,43-pentazaoctacyclo[26.14.2.23,6.214,17.18,12.129,33.010,25.034,39]pentaconta-3,5,8(48),9,11,14,16,29(45),30,32,34(39),35,37,46,49-pentadecaene-40-carboxylic acid hydrochloride Chemical compound Cl.CC(C)C[C@@H](N)C(=O)N[C@@H]1[C@H](O)c2ccc(Oc3cc4cc(Oc5ccc(cc5Cl)[C@@H](O)[C@@H]5NC(=O)[C@H](NC(=O)[C@@H]4NC(=O)[C@H](CC(N)=O)NC1=O)c1ccc(O)c(c1)-c1c(O)cc(O)cc1[C@H](NC5=O)C(O)=O)c3O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1)c(Cl)c2 LLWFHCJFZGXUAT-UMXPSMRGSA-N 0.000 description 10
- 239000000843 powder Substances 0.000 description 7
- 229920005654 Sephadex Polymers 0.000 description 6
- 239000012507 Sephadex™ Substances 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229930182555 Penicillin Natural products 0.000 description 3
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 3
- 241000191940 Staphylococcus Species 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 206010014665 endocarditis Diseases 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 229940049954 penicillin Drugs 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- WFIYPADYPQQLNN-UHFFFAOYSA-N 2-[2-(4-bromopyrazol-1-yl)ethyl]isoindole-1,3-dione Chemical compound C1=C(Br)C=NN1CCN1C(=O)C2=CC=CC=C2C1=O WFIYPADYPQQLNN-UHFFFAOYSA-N 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NUAQIRUAZSJTAI-YRPZDAAMSA-N O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@H](N)CC(C)C)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@H](N)CC(C)C)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 NUAQIRUAZSJTAI-YRPZDAAMSA-N 0.000 description 2
- 206010034133 Pathogen resistance Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000003929 acidic solution Substances 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000036783 anaphylactic response Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 239000003637 basic solution Substances 0.000 description 2
- 238000010612 desalination reaction Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000003311 flocculating effect Effects 0.000 description 2
- 108700014375 norvancomycin Proteins 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- 206010009657 Clostridium difficile colitis Diseases 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- 206010031252 Osteomyelitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 208000003100 Pseudomembranous Enterocolitis Diseases 0.000 description 1
- 206010037128 Pseudomembranous colitis Diseases 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 206010062255 Soft tissue infection Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000010981 drying operation Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 208000010227 enterocolitis Diseases 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to a method for preparing norvoncomycin hydrochloride, which comprises the following steps: a, perlite is added to the fermentation liquid of norvoncomycin according to the proportion of 1 to 5%(w/v), potassium ferricyanide is added according to the proportion of 2 to 13%(w/v), zinc sulphate is added according to the proportion of 2 to 10%(w/v), and then the mixture is stirred and filtered; b, the filtered solution is decolorized with a macropore decolourization resin; c, the destainer which uses dextrane gel as a sorption agent is desorbed by an acidity desorption system; d, the desorption liquid with ph value of 6.0 to 7.8 regulated with base is filtered; e, the press cake is dissolved with aqueous hydrochloric acid, crystallized with acetone and dried. Because of adopting the steps, the quality of the norvoncomycin hydrochloride is enhanced effectively, the production period is shortened, the production cost is reduced effectively, and the yield loss of the norvoncomycin hydrochloride is reduced.
Description
Technical field
The present invention relates to the preparation method of pharmaceutical raw material, specifically belong to hydrochloric acid demethyl vancomycin preparation method.
Background technology
Hydrochloric acid demethyl vancomycin is a glycopeptide antibiotics, and structural formula is as follows:
This product appearance is a light brown powder, odorless, and bitter, soluble in water, slightly soluble in methyl alcohol, insoluble in acetone, butanols or ether, can be in solution by the various heavy precipitation of salts.
In recent years pharmacology and clinical study prove, the intravenous drip of hydrochloric acid demethyl vancomycin is applicable to endocarditis due to the Staphylococcus (comprising methicillin resistance bacterial strain and multiple antibiotic resistant strain), osteomyelitis, pneumonia, septicemia or soft tissue infection etc.Also be used for the faecalis endocarditis to penicillin anaphylaxis person, the drug of first choice of corynebacterium (diphtheroid genus) endocarditis treatment.The treatment that the artery and vein shunting is infected due to the Staphylococcus is taken place in penicillin anaphylaxis and penicillin hemodialysis person not hypersensitive.The oral treatment that is applicable to microbiotic dependency pseudomembranous colitis or multidrug-resistant staphylococcus enterocolitis.(seeing 688 pages of two clinical application notices of Pharmacopoeia of the People's Republic of China version in 2000)
The hydrochloric acid demethyl vancomycin preparation method of normal employing includes fermentation, filtration, decolouring, resin absorption, parsing, desalination, decolouring, spraying drying operation, be about to gained demethyl vancomycin fermented liquid and add diatomite, stir, filtration obtains filtrate, and filtrate is again through activated carbon decolorizing, and destainer concentrates after the DK-80 resin absorption, sodium hydroxide solution is resolved, desorbed solution is through the resin desalination, activated carbon decolorizing, and the destainer spraying drying obtains hydrochloric acid demethyl vancomycin powder.
There are many weak points in this method, and for example: filtration time is long, and it is low to filter yield; Adopt alkalescence to resolve agent and easily cause the mould through the ages degraded of first, transient temperature too high (transient temperature reaches more than 100 ℃) is partly degraded hydrochloric acid demethyl vancomycin during spraying drying, and product purity is low, and exterior quality is poor.See accompanying drawing 1.
Summary of the invention
The purpose of this invention is to provide a kind of novel method for preparing hydrochloric acid demethyl vancomycin, this method can effectively improve the quality of hydrochloric acid demethyl vancomycin, shorten the production cycle, also can effectively reduce production costs, reduce the yield losses of hydrochloric acid demethyl vancomycin.
The object of the present invention is achieved like this: will add perlite in the demethyl vancomycin fermented liquid, stir, filter, and decolouring, resin absorption, acidolysis are analysed, and alkali is heavy, crystallization, drying obtains hydrochloric acid demethyl vancomycin powder.
This method may further comprise the steps:
A. demethyl vancomycin fermented liquid is added perlite in the ratio of 1～5% (w/v), the ratio that adds the Tripotassium iron hexacyanide and 2～10% (w/v) by the ratio of 2～13% (w/v) adds zinc sulfate, stirs filtration; Perlitic additional proportion is preferred 2.5～4%, and the additional proportion of the Tripotassium iron hexacyanide is preferred 5～9%, and zinc sulfate is preferred 4～7%, to remove foreign protein and the metal ion in the fermented liquid effectively, guarantees filtering velocity, and obtains clear filtrate.
B. filtrate is used the decolouring of macropore decolorizing resin;
The macropore decolorizing resin can select D941, also can select XAD-III or X-5, preferably selects D941 for use, to reach best decolorizing effect.
C. destainer is concentrated to 20000～30000ug/ml, uses the dextrane gel separation and purification, and acidic solution is that moving phase is carried out desorb; Dextrane gel can be selected G-10 for use, also can select G-15 or G-25.But preferably select G-15 for use, to obtain the high product of content.Acidic solution can be a phosphate aqueous solution, also can be aqueous hydrochloric acid, but preferably selects phosphate aqueous solution for use.
D. desorbed solution filters with basic solution adjust pH 6.0～7.8;
Basic solution is the aqueous sodium hydroxide solution of 0.5mol/L.
E. filter cake concentration is to add acetone after the dissolving of 1% (W/V) aqueous hydrochloric acid to carry out crystallization, filtration, washing, drying.
The present invention uses perlite to replace diatomite to make flocculating aids, makes scavenging agent with the zinc sulfate and the Tripotassium iron hexacyanide, makes filtration time shorten 2/3, filters yield and brings up to more than 90% by 60%, has shortened the production cycle greatly, has improved product yield.Filter the yield tabulation and see Table 1:
Table 1: the filtration yield of three batches of products
| Numbering | Put jar total hundred million | Filtrate total hundred million | Filter yield (%) |
| 1 | 0.21 | 0.191 | 91.0 |
| 2 | 0.19 | 0.179 | 90.5 |
| 3 | 0.187 | 0.172 | 92.3 |
The present invention uses the macropore decolorizing resin to replace gac, has effectively improved the exterior quality of product, and product appearance is an off-white color by brown stain.Dextrane gel replaces the DK-80 resin, replaces alkaline desorption system with acid desorption system, has obviously improved the product separation effect, has reduced the destruction to hydrochloric acid demethyl vancomycin, and the content of product is brought up to more than 90% by 85%.
Beneficial effect of the present invention is also to adopt that alkali is heavy, solvent crystal and vacuum drying method, has avoided the instantaneous high temperature that suffers of product to destroy.See accompanying drawing 2.
Description of drawings:
A is a hydrochloric acid demethyl vancomycin in the accompanying drawing, and D is assorted component:
The HPLC figure of the norvancomycin hydrochloride of accompanying drawing 1 former method gained
The HPLC figure of the norvancomycin hydrochloride of accompanying drawing 2 novel method gained
Embodiment
Further describe the present invention below in conjunction with embodiment, but they are not to understand any restriction that becomes the scope of the invention.
In addition, used analytical procedure is all carried out for 553 pages by the Pharmacopoeia of the People's Republic of China 2000 editions (two ones) among the present invention.
Embodiment 1
The preparation of norvancomycin hydrochloride
The Norvancomycin fermented liquid adds 1～5% perlite (the Central-South flocculating aids in Henan company limited), 2～13% the Tripotassium iron hexacyanide (being the commercially available prod) and 2～10% zinc sulfate (for the commercially available prod), stir, Plate Filtration, filtrate is passed through macropore decolorizing resin X-5 (resin processing plant of Nankai University) post with 1～2BV/ hour flow velocity, the unit of destainer is 3000～5000ug/ml, it is concentrated into 20000～30000ug/ml, concentrated solution passes through sephadex G-10 resin (resin processing plant of Nankai University) post with 1～1.5BV/ hour flow velocity, saturated sephadex G-10 resin 0.1mol/L phosphate aqueous solution wash-out, elution speed is 0.5～1BV/ hour, HPLC detects when having hydrochloric acid demethyl vancomycin to flow out and begins to collect, in desorbed solution, slowly add 0.5mol/L sodium hydroxide (the being the commercially available prod) aqueous solution, transfer pH6.0～7.8, the limit edged stirred 30 minutes, stop to stir, left standstill 24 hours, Plate Filtration, filter cake dissolves with 1% hydrochloric acid (weight percent) (the being the commercially available prod) aqueous solution, add excessive 1% hydrochloric acid (W/V) aqueous solution and make the complete salify of Norvancomycin, industrial acetone to the crystallization that under agitation slowly adds 5～10 times of volumes is separated out, left standstill 24 hours, filter press, filter cake washing with acetone 2～3 times, vacuum-drying obtains the smart powder of norvancomycin hydrochloride.Product content reaches more than 90%.
Embodiment 2
The preparation of norvancomycin hydrochloride
With embodiment 1, be perlitic add-on be 3%, 7% the Tripotassium iron hexacyanide and 5% zinc sulfate, the macropore decolorizing resin is D941 (resin processing plant of Nankai University), the unit of destainer is 3672ug/ml, it is concentrated into 23500ug/ml, concentrated solution passes through sephadex G-15 resin column with 1BV/ hour flow velocity, saturated sephadex G-15 resin 0.1mol/L phosphate aqueous solution wash-out, and resolution speed is 0.5BV/ hour, desorbed solution is transferred pH7.0～7.4 with the 0.5mol/L aqueous sodium hydroxide solution, left standstill 24 hours, Plate Filtration, filter cake dissolves with 1% aqueous hydrochloric acid, industrial acetone to crystallization with 5 times of volumes is separated out, left standstill filter press, washing 24 hours., vacuum-drying obtains the smart powder of norvancomycin hydrochloride.Product content reaches 96.4%, and product appearance is an off-white color.
Embodiment 3
The preparation of norvancomycin hydrochloride
With embodiment 1, be perlitic add-on be 5%, 13% the Tripotassium iron hexacyanide and 2% zinc sulfate, use XAD-III macropore decolorizing resin (resin processing plant of Nankai University) decolouring, the unit of destainer is 4120ug/ml, it is concentrated into 27800ug/ml, concentrated solution passes through sephadex G-25 resin column with 1BV/ hour flow velocity, and saturated sephadex G-25 resin is resolved with the 0.1mol/L aqueous hydrochloric acid, and resolution speed is 0.5BV/ hour, desorbed solution is transferred pH7.8 with the 0.5mol/L aqueous sodium hydroxide solution, left standstill 24 hours, Plate Filtration, filter cake dissolves with 1% aqueous hydrochloric acid, industrial acetone to crystallization with 10 times of volumes is separated out, left standstill filter press, washing 24 hours, vacuum-drying obtains the smart powder of norvancomycin hydrochloride.Product content reaches 91.2%, and product appearance is an off-white color.
Embodiment 4
The preparation of norvancomycin hydrochloride
With embodiment 1, be perlitic add-on be 1%, the Tripotassium iron hexacyanide 2% and zinc sulfate 10%, the unit of destainer is 4300ug/ml, and it is concentrated into 25700ug/ml, and concentrated solution passes through sephadex G-15 resin column with 1BV/ hour flow velocity, saturated sephadex G-15 resin is resolved with the 0.1mol/L aqueous hydrochloric acid, resolution speed is 0.5BV/ hour, and desorbed solution is transferred pH6.0 with the 0.5mol/L aqueous sodium hydroxide solution, leaves standstill 24 hours, Plate Filtration, filter cake dissolves with 1% aqueous hydrochloric acid, separates out with industrial acetone to the crystallization of 5 times of volumes, leaves standstill 24 hours, filter press, washing., vacuum-drying obtains the smart powder of norvancomycin hydrochloride.Product content reaches 92.5%, and product appearance is an off-white color.
Claims (11)
1, a kind of hydrochloric acid demethyl vancomycin preparation method may further comprise the steps:
A. with hydrochloric acid demethyl vancomycin fermented liquid by weight the ratio of volume ratio 1～5% add perlite, by weight the ratio of volume ratio 2～13% add the Tripotassium iron hexacyanide and by weight the ratio of volume ratio 2～10% add zinc sulfate, stir filtration;
B. filtrate is used the decolouring of macropore decolorizing resin;
C. destainer uses dextrane gel to be sorbent material, and acid desorption system carries out desorb;
D. desorbed solution filters with adjusting PH with base value 6.0～7.8;
E. filter cake is with aqueous hydrochloric acid dissolving, acetone crystallization, drying.
2, hydrochloric acid demethyl vancomycin preparation method according to claim 1, wherein perlitic consumption is 3% in a step.
3, hydrochloric acid demethyl vancomycin preparation method according to claim 1, wherein the consumption of the Tripotassium iron hexacyanide is 5～9% in a step, the consumption of zinc sulfate is 4～7%.
4, hydrochloric acid demethyl vancomycin preparation method according to claim 3, wherein the consumption of the Tripotassium iron hexacyanide is 7% in a step, the consumption of zinc sulfate is 5%.
5, hydrochloric acid demethyl vancomycin preparation method according to claim 1, wherein the macropore decolorizing resin is D941, XAD-III or X-5 in the b step.
6, hydrochloric acid demethyl vancomycin preparation method according to claim 5, wherein the macropore decolorizing resin is D941 in the b step.
7, hydrochloric acid demethyl vancomycin preparation method according to claim 1, wherein dextrane gel is G-10, G-15 or G-25 in the c step.
8, hydrochloric acid demethyl vancomycin preparation method according to claim 1, wherein dextrane gel is G-15 in the c step.
9, hydrochloric acid demethyl vancomycin preparation method according to claim 1, wherein the desorbed solution that uses in the c step is phosphoric acid or aqueous hydrochloric acid, concentration is 0.1mol/L.
10, hydrochloric acid demethyl vancomycin preparation method according to claim 9, wherein the desorbed solution that uses in the c step is phosphate aqueous solution, concentration is 0.1mol/L.
11, hydrochloric acid demethyl vancomycin preparation method according to claim 1, wherein pH is controlled to be 7.0～7.4 in the d step.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101096889A CN100345858C (en) | 2003-12-09 | 2003-12-09 | Method for preparing vancomycin of norhydrochloric acid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101096889A CN100345858C (en) | 2003-12-09 | 2003-12-09 | Method for preparing vancomycin of norhydrochloric acid |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1626542A CN1626542A (en) | 2005-06-15 |
| CN100345858C true CN100345858C (en) | 2007-10-31 |
Family
ID=34758971
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2003101096889A Expired - Fee Related CN100345858C (en) | 2003-12-09 | 2003-12-09 | Method for preparing vancomycin of norhydrochloric acid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100345858C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101440127B (en) * | 2007-11-19 | 2012-10-17 | 浙江医药股份有限公司新昌制药厂 | Preparation of high-purity vancomycin hydrochloride |
| CN101613396B (en) * | 2008-06-26 | 2016-08-17 | 浙江医药股份有限公司新昌制药厂 | Non-crystalline form Lyphocin (Fujisawa) and its production and use and its pharmaceutical composition |
| CN103641895B (en) * | 2013-11-18 | 2015-06-17 | 宁夏泰瑞制药股份有限公司 | Method for producing vancomycin hydrochloride by utilizing vancomycin fermentation broth |
| CN105524146B (en) * | 2016-01-23 | 2018-10-09 | 雅赛利(台州)制药有限公司 | A kind of vancomycin crystallization processes |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1415758A (en) * | 2001-10-30 | 2003-05-07 | 上海医药工业研究院 | Technique for producing raw material of vancomycin hydrochloride |
-
2003
- 2003-12-09 CN CNB2003101096889A patent/CN100345858C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1415758A (en) * | 2001-10-30 | 2003-05-07 | 上海医药工业研究院 | Technique for producing raw material of vancomycin hydrochloride |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1626542A (en) | 2005-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101925695B1 (en) | Separation and Purification Method for Vancomycin Hydrochloride of High Purity | |
| CN109232717B (en) | Gram-negative bacterium targeted antibacterial peptide, and preparation method and application thereof | |
| CN105294910B (en) | A kind of preparation method of adsorbent applied to Pristinamycin separation | |
| CN101696210B (en) | High-purity antibiotic medicinal compound | |
| EP1612216B1 (en) | Process of purifying vancomycin hydrochloride | |
| WO2009046618A1 (en) | Deshydroxy vancomycin, the preparation, pharmaceutical composition and the use | |
| CN111533789A (en) | Tryptophan and lysine chain-crossing interaction beta-hairpin antibacterial peptide and preparation method thereof | |
| CN100345858C (en) | Method for preparing vancomycin of norhydrochloric acid | |
| CN1415758A (en) | Technique for producing raw material of vancomycin hydrochloride | |
| WO2013068538A1 (en) | Process of purification of teicoplanin | |
| CA2210990C (en) | New combined process for the purification of vancomycin hydrochloride | |
| CN106083952A (en) | A kind of method extracting gentamycin sulfate from gentamicin fermentation broth | |
| CN1240665C (en) | Process for preparing chicoric acid from echinacea purpurea | |
| CN101348494A (en) | High-purity cefmenoxime hydrochloride and preparation thereof | |
| CN104610282A (en) | Method for purifying cefazolin acid | |
| CN112409426B (en) | Preparation method of sisomicin sulfate | |
| CN110117310B (en) | Purification method of daptomycin | |
| CN108203723B (en) | Method for producing high-content polymyxin B1 through fermentation | |
| CN1974585A (en) | Membrane separating and purifying process for aminoglycoside antibiotics | |
| CN102690333B (en) | Preparation method of high-purity teicoplanin | |
| CN110606844B (en) | Mupirocin purification method | |
| CN101067132A (en) | Thrombin extracting and separating process | |
| CN1666990A (en) | Process for preparing ampicillin sodium | |
| CN112390806A (en) | Method for improving extraction yield of spectinomycin | |
| CN107936073B (en) | Method for improving water solubility of acetylisovaleryltylosin tartrate |
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 | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: NORTH CHINA PHARMACEUTICAL NEW DRUG R&D Co.,Ltd. Assignor: NORTH CHINA PHARMACEUTICAL Group Corp. Contract fulfillment period: 2008.10.7 to 2013.10.7 Contract record no.: 2008130000018 Denomination of invention: Method for preparing vancomycin of norhydrochloric acid Granted publication date: 20071031 License type: Exclusive license Record date: 20081022 |
|
| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: NORTH CHINA PHARMACEUTICAL NEW DRUG R&D Co.,Ltd. Assignor: NORTH CHINA PHARMACEUTICAL Group Corp. Contract fulfillment period: 2008.10.7 to 2013.10.7 Contract record no.: 2008130000018 Denomination of invention: Method for preparing vancomycin of norhydrochloric acid Granted publication date: 20071031 License type: Exclusive license Record date: 20081022 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.10.7 TO 2013.10.7; CHANGE OF CONTRACT Name of requester: NORTH CHINA PHARMACUETICAL GROUP NEW DRUG RESEARCH Effective date: 20081022 |
|
| ASS | Succession or assignment of patent right |
Owner name: NORTH CHINA PHARMACEUTICAL HUASHENG CO., LTD. Free format text: FORMER OWNER: HUABEI PHARMACEUTICAL GROUP CO., LTD. Effective date: 20140915 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 050015 SHIJIAZHUANG, HEBEI PROVINCE TO: 052160 SHIJIAZHUANG, HEBEI PROVINCE |
|
| TR01 | Transfer of patent right |
Effective date of registration: 20140915 Address after: 052160 No. 8, Yangzi Road, Shijiazhuang economic and Technological Development Zone, Hebei Patentee after: NORTH CHINA PHARMACEUTICAL HUASHENG Co.,Ltd. Address before: 050015 Heping East Road, Hebei, Shijiazhuang, No. 388 Patentee before: NORTH CHINA PHARMACEUTICAL Group Corp. |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20071031 |