CN102408462A - Preparation method of erythromycin thiocyanate - Google Patents
Preparation method of erythromycin thiocyanate Download PDFInfo
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- CN102408462A CN102408462A CN201110396176XA CN201110396176A CN102408462A CN 102408462 A CN102408462 A CN 102408462A CN 201110396176X A CN201110396176X A CN 201110396176XA CN 201110396176 A CN201110396176 A CN 201110396176A CN 102408462 A CN102408462 A CN 102408462A
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- China
- Prior art keywords
- erythromycin
- weight part
- matachrom
- oxacyclotetradecane
- preparation
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- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- PGNYNCTUBKSHHL-UHFFFAOYSA-N 2,3-diaminobutanedioic acid Chemical compound OC(=O)C(N)C(N)C(O)=O PGNYNCTUBKSHHL-UHFFFAOYSA-N 0.000 title claims abstract description 23
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims abstract description 182
- 229960003276 erythromycin Drugs 0.000 claims abstract description 91
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 60
- 238000000034 method Methods 0.000 claims abstract description 31
- 238000000855 fermentation Methods 0.000 claims abstract description 24
- 230000004151 fermentation Effects 0.000 claims abstract description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 62
- SKDGGFHGLZBNBC-YZPBMOCRSA-N (3r,4s,5s,6r,7r,9r,11r,12r,13s,14r)-6-[(2s,3r,4s,6r)-4-(dimethylamino)-3-hydroxy-6-methyloxan-2-yl]oxy-14-ethyl-7,12,13-trihydroxy-4-[(2r,4r,5s,6s)-5-hydroxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-3,5,7,9,11,13-hexamethyl-oxacyclotetradecane-2,10-dione;dodec Chemical compound CCCCCCCCCCCCOS(O)(=O)=O.O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 SKDGGFHGLZBNBC-YZPBMOCRSA-N 0.000 claims description 61
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 43
- 239000007788 liquid Substances 0.000 claims description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 40
- 239000012528 membrane Substances 0.000 claims description 26
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 claims description 25
- 238000002425 crystallisation Methods 0.000 claims description 24
- 230000008025 crystallization Effects 0.000 claims description 24
- 229960000583 acetic acid Drugs 0.000 claims description 21
- 229920002472 Starch Polymers 0.000 claims description 20
- 239000012362 glacial acetic acid Substances 0.000 claims description 20
- 239000011148 porous material Substances 0.000 claims description 20
- 235000019698 starch Nutrition 0.000 claims description 20
- 239000008107 starch Substances 0.000 claims description 20
- 239000008399 tap water Substances 0.000 claims description 20
- 235000020679 tap water Nutrition 0.000 claims description 20
- 239000008213 purified water Substances 0.000 claims description 18
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 16
- 230000001954 sterilising effect Effects 0.000 claims description 16
- 238000004659 sterilization and disinfection Methods 0.000 claims description 16
- 238000012258 culturing Methods 0.000 claims description 14
- 239000000919 ceramic Substances 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 12
- 244000068988 Glycine max Species 0.000 claims description 12
- 235000010469 Glycine max Nutrition 0.000 claims description 12
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 claims description 12
- HIVLDXAAFGCOFU-UHFFFAOYSA-N ammonium hydrosulfide Chemical compound [NH4+].[SH-] HIVLDXAAFGCOFU-UHFFFAOYSA-N 0.000 claims description 12
- 238000004458 analytical method Methods 0.000 claims description 12
- 239000012141 concentrate Substances 0.000 claims description 12
- 239000008103 glucose Substances 0.000 claims description 12
- 239000000843 powder Substances 0.000 claims description 12
- 235000008504 concentrate Nutrition 0.000 claims description 11
- 238000001953 recrystallisation Methods 0.000 claims description 11
- 238000009987 spinning Methods 0.000 claims description 11
- 239000002609 medium Substances 0.000 claims description 10
- 235000013311 vegetables Nutrition 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 9
- 235000014666 liquid concentrate Nutrition 0.000 claims description 9
- 239000006166 lysate Substances 0.000 claims description 9
- -1 polyoxypropylene glycerine Polymers 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- 229920001817 Agar Polymers 0.000 claims description 8
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 8
- 229920001353 Dextrin Polymers 0.000 claims description 8
- 239000004375 Dextrin Substances 0.000 claims description 8
- 239000008272 agar Substances 0.000 claims description 8
- 239000001110 calcium chloride Substances 0.000 claims description 8
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 8
- 235000019425 dextrin Nutrition 0.000 claims description 8
- 239000006260 foam Substances 0.000 claims description 8
- 238000011218 seed culture Methods 0.000 claims description 8
- 241000187747 Streptomyces Species 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000011534 incubation Methods 0.000 claims description 6
- 241000894006 Bacteria Species 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 239000001963 growth medium Substances 0.000 claims description 4
- 239000012452 mother liquor Substances 0.000 claims description 4
- 230000000050 nutritive effect Effects 0.000 claims description 4
- 239000004576 sand Substances 0.000 claims description 4
- 238000007710 freezing Methods 0.000 claims description 3
- 230000008014 freezing Effects 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 11
- 239000003960 organic solvent Substances 0.000 abstract description 5
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 238000001914 filtration Methods 0.000 abstract description 2
- 239000002699 waste material Substances 0.000 abstract description 2
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 52
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 13
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 10
- 238000000605 extraction Methods 0.000 description 8
- 238000005516 engineering process Methods 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 235000019484 Rapeseed oil Nutrition 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
- 229940043232 butyl acetate Drugs 0.000 description 4
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical group CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 3
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 3
- 229960001763 zinc sulfate Drugs 0.000 description 3
- 229910000368 zinc sulfate Inorganic materials 0.000 description 3
- 229930006677 Erythromycin A Natural products 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000004744 fabric Substances 0.000 description 2
- 238000005189 flocculation Methods 0.000 description 2
- 230000016615 flocculation Effects 0.000 description 2
- 229910017053 inorganic salt Inorganic materials 0.000 description 2
- 239000003350 kerosene Substances 0.000 description 2
- 238000001728 nano-filtration Methods 0.000 description 2
- 229920000570 polyether Polymers 0.000 description 2
- 230000000452 restraining effect Effects 0.000 description 2
- 239000002893 slag Substances 0.000 description 2
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 description 1
- BWDBEAQIHAEVLV-UHFFFAOYSA-N 6-methylheptan-1-ol Chemical compound CC(C)CCCCCO BWDBEAQIHAEVLV-UHFFFAOYSA-N 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000589562 Brucella Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 241000193403 Clostridium Species 0.000 description 1
- 241000186216 Corynebacterium Species 0.000 description 1
- 240000009138 Curcuma zedoaria Species 0.000 description 1
- 235000003405 Curcuma zedoaria Nutrition 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 241000194031 Enterococcus faecium Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000606768 Haemophilus influenzae Species 0.000 description 1
- 241000589989 Helicobacter Species 0.000 description 1
- 235000003935 Hippophae Nutrition 0.000 description 1
- 241000229143 Hippophae Species 0.000 description 1
- 241000589248 Legionella Species 0.000 description 1
- 208000007764 Legionnaires' Disease Diseases 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 241000588653 Neisseria Species 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 235000004347 Perilla Nutrition 0.000 description 1
- 244000124853 Perilla frutescens Species 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 241001312524 Streptococcus viridans Species 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000001812 curcuma zedoaria berg. rosc. Substances 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 235000008397 ginger Nutrition 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000001683 mentha spicata herb oil Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000582 semen Anatomy 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019721 spearmint oil Nutrition 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 235000020238 sunflower seed Nutrition 0.000 description 1
- 239000010681 turmeric oil Substances 0.000 description 1
- 235000019509 white turmeric Nutrition 0.000 description 1
- 239000001841 zingiber officinale Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/10—Process efficiency
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/59—Biological synthesis; Biological purification
Landscapes
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The invention relates to a preparation method of erythromycin thiocyanate, which comprises the following steps: and adding sodium hydroxide into the erythromycin fermentation liquor to adjust the pH value, filtering, concentrating and recrystallizing to obtain the erythromycin thiocyanate. The method greatly reduces the usage amount of the organic solvent, reduces the production cost, reduces the generation of waste residues, and is beneficial to environmental protection and production safety.
Description
Technical field
The present invention relates to a kind of THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method, particularly a kind of Matachrom aqueous crystallization and acetone recrystallization technology belong to the medical biotechnology field.
Background technology
Oxacyclotetradecane,erythromycin deriv is a kind of alkaline antibiotic of from the streptomyces erythreus nutrient solution, separating nineteen fifty-two; Oxacyclotetradecane,erythromycin deriv has broad-spectrum antibacterial action; To gram positive organism, stronger restraining effect is arranged like staphylococcus, micrococcus scarlatinae, viridans streptococci, streptococcus pneumoniae, streptococcus faecium, clostridium spp, diphtheria corynebacterium etc.To gram-negative bacteria, suitable restraining effect is also arranged like gonococcus, helicobacter, bordetella pertussis, Brucella, legionella and hemophilus influenzae, bacterioide.China is from the nineteen fifty-seven production of trial-produceing successfully and progressively have high input.
The process for extracting of Oxacyclotetradecane,erythromycin deriv mainly is a solvent extration at present, and used extraction solvent is a butylacetate, promptly under alkaline condition, from ferment filtrate, uses n-butyl acetate extraction, gets final crystalline product again through other processing.This technology main drawback is: solvent-oil ratio is big during n-butyl acetate extraction.Patent CN95105997.1 discloses " process for extracting macrolide antibiotics "; In this technology; Ferment filtrate adopts extraction agent---and eight carbon alcohol (n-Octanol, isooctyl alcohol or secondary octanol) and thinner (normal hexane, hexanaphthene, normal heptane, sulfonated kerosene or hydrogenation kerosene) extract, and extraction liquid is stripped with acetic acid and sodium-acetate buffer.There is complicated operation in this method, and directly extracts with ferment filtrate, and required organic solvent requirement is big, is unfavorable for environment protection and operational safety.
Summary of the invention
It is simple to an object of the present invention is to provide a kind of method, aqueous crystallization of the Matachrom that is easy to grasp and acetone recrystallization technology.
The present invention seeks to realize through following technical scheme:
THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of the present invention comprises the steps:
(1) fermented liquid concentrates: erythromycin fermentation liquid use concentration be 5～20% sodium hydroxide solution to transfer pH be 7.5～9.0, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator;
(2) crystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, and every BOU Oxacyclotetradecane,erythromycin deriv adds 5～20% sodium thiocyanate solutions of 0.15～0.2kg, and using 20～80% glacial acetic acid solution adjusting pH is 5.5～7.0; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 1～1: 8 ratio; Use concentration be 5%～20% sodium hydroxide solution to regulate pH be 9.5～10.5, Matachrom is changed into erythromycin, leave standstill; get acetone soln, every BOU Oxacyclotetradecane,erythromycin deriv adds 5～20% sodium thiocyanate solutions of 0.15～0.2kg, transfers pH to 5.5～7.5 with 20～80% glacial acetic acid solutions; extraordinarily go into 45～60 ℃ of purified water by 1～3 of lysate volume; 20～35 ℃ of crystallization control temperature, adopts variable-frequency motor slowly to stir 10 minutes, leave standstill again 0.5～2 hour entering whizzer of cooling separate the wet article of Matachrom; Matachrom wets and uses acetone, 45～60 ℃ of purified water drip washing respectively in the article whizzer; spinning is discharged up to mother liquor, and drying promptly gets the Matachrom finished product.
The preferred following steps of a kind of THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of the present invention:
(1) fermented liquid concentrates: erythromycin fermentation liquid use concentration be 10% sodium hydroxide solution to transfer pH be 8.0～8.4, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator.
(2) recrystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, and every BOU Oxacyclotetradecane,erythromycin deriv adds 10% the sodium thiocyanate solution of 0.18kg, and using 50% glacial acetic acid solution to regulate pH is 6.0～6.5; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 4 ratio; Use concentration be 8% sodium hydroxide solution to regulate pH be 9.8～10.0, Matachrom is changed into erythromycin, standing separation; Divide the sub-cloud mother liquor to get acetone soln, every BOU Oxacyclotetradecane,erythromycin deriv adds 10% the sodium thiocyanate solution of 0.18kg, with 50% glacial acetic acid solution accent pH to 6.5; Extraordinarily go into 50～55 ℃ of purified water by 1.5 of lysate volume; 25～30 ℃ of crystallization control temperature adopt variable-frequency motor slowly to stir 10 minutes; Leave standstill 1 hour entering whizzer of cooling separate the wet article of Matachrom; The wet article of Matachrom are used acetone, 50～55 ℃ of purified water drip washing in whizzer respectively, and drying promptly gets the Matachrom finished product.
The preferred following steps of a kind of THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of the present invention:
(1) fermented liquid concentrates: erythromycin fermentation liquid use concentration be 15% sodium hydroxide solution to transfer pH be 7.8～8.2, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator.
(2) recrystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, and every BOU Oxacyclotetradecane,erythromycin deriv adds 15% the sodium thiocyanate solution of 0.15kg, and using 40% glacial acetic acid solution to regulate pH is 6.0～6.5; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 3 ratio; Use concentration be 10% sodium hydroxide solution to regulate pH be 9.6～9.8, Matachrom is changed into erythromycin, leave standstill; get acetone soln, every BOU Oxacyclotetradecane,erythromycin deriv adds 15% the sodium thiocyanate solution of 0.15kg, transfers pH to 6.5 with 40% glacial acetic acid solution; extraordinarily go into 50～55 ℃ of purified water by 1.0 of lysate volume, 25～30 ℃ of crystallization control temperature adopt variable-frequency motor slowly to stir 10 minutes;, leave standstill 1 hour entering whizzer of cooling separate the wet article of Matachrom, the Matachrom article that wet are used acetone, 50～55 ℃ of purified water drip washing in whizzer respectively; drying promptly gets the Matachrom finished product.
Said erythromycin fermentation liquid prepares according to following method:
(1) the Oxacyclotetradecane,erythromycin deriv seed liquor is cultivated: 1. female slant pore preparation: (streptomyces erythareus that the present invention uses is the bacterial classification of Guangdong Province's commercial extensive sale in microbial strains preservation center to spore will freezingly to be kept at streptomyces erythareus (generation bacterium) in the sand pipe; GIM numbering: GIM4.14; Other numberings: AS4.198); Be inoculated on the slant medium of sterilization, under 32～34 ℃ of conditions of temperature, cultivated 7～9 days; 2. sub-slant pore preparation: with female slant pore, be inoculated on the slant medium of sterilization, under 32～34 ℃ of conditions of temperature, cultivated 7～9 days; 3. seed culture: with sub-slant pore, be inoculated in seed culture medium,, obtain the Oxacyclotetradecane,erythromycin deriv seed liquor through three grades of seed enlarged culturing through sterilization;
(2) ferment: the Oxacyclotetradecane,erythromycin deriv seed liquor is inoculated in the substratum of sterilization by 10～20% volume ratios, feeds sterile air and also stirred 15～30 hours, add nutritive substance,, get erythromycin fermentation liquid through cultivation in 7～10 days.
Above-mentioned female slant pore prepares substratum and is made up of following component: starch 0.1～1.0 weight part, steeping water 0.05～0.2 weight part, agar 0.1～1.0 weight part, glucose 0.1～1.0 weight part, sodium-chlor 0.5～2.0 weight part, calcium chloride 0.1～1.0 weight part, with the tap water constant volume to 100 parts by volume.
Above-mentioned sub-slant pore prepares slant medium and is made up of following component: starch 0.1～1.0 weight part, steeping water 0.05～0.2 weight part, agar 0.1～1.0 weight part, glucose 0.1～1.0 weight part, sodium-chlor 0.5～2.0 weight part, calcium chloride 0.1～1.0 weight part, with the tap water constant volume to 100 parts by volume.
Above-mentioned first order seed enlarged culturing condition is: (1) substratum is formed: analysis for soybean powder 2～4 weight parts, starch 1～2 weight part, CaCO
30.6～0.8. weight part, dextrin 1～2 weight part, sulphur ammonium 0.2～0.4 weight part, steeping water 1～4 weight part, vegetables oil 0.5～1 weight part, with the tap water constant volume to 100 parts by volume; (2) temperature is 32～34 ℃; (3) incubation time is 48～96 hours;
Above-mentioned two, three grades of seed enlarged culturing conditions are: (1) substratum is formed: analysis for soybean powder 2.0～4.5 weight parts, starch 2.5～4.0 weight parts, CaCO
30.5～0.7 weight part, sodium-chlor 0.4～0.6 weight part, dextrin 2.5～4.0 weight parts, sulphur ammonium 0.1～0.3 weight part, steeping water 1～2 weight part, vegetables oil 0.8～1.5 weight part, foam killer 0～0.02 weight part, with the tap water constant volume to 100 parts by volume; (2) temperature is 32～34 ℃; (3) incubation time is 24～48 hours.
Above-mentioned fermention medium consists of: analysis for soybean powder 3.5～5.5 weight parts, starch 2.0～4.0 weight parts, sulphur ammonium 0.08～0.15 weight part, CaCO
30.6～1.0 weight parts, vegetables oil 0.5～1.0 weight part, foam killer 0.005～0.02 weight part, with the tap water constant volume to 100 parts by volume.
Above-mentioned interpolation composition of nutritive substance is: liquid sugar 10～50 weight parts, vegetables oil 1～10 weight part, n-propyl alcohol solution 0.5～5 weight part.
Above-mentioned vegetables oil is: any in peanut oil, rapeseed oil, VT 18, Oleum Gossypii semen, sesame oil, sunflower seed oil, sweet oil, zedoary turmeric oil, Oleum Bulbus Allii, Oleum Hippophae, Radix Angelicae Sinensis oil, Oils, Zingiber officinale, Fructus Forsythiae oil, perilla oil, Oleum Citri Reticulatae, Viscotrol C, spearmint oil, the ucuhuba oil.
Described vegetables oil is preferably any in VT 18, the rapeseed oil.
Described liquid sugar is 20～70% glucose solutions.
Described n-propyl alcohol solution is 20～70% n-propyl alcohol solution.
Described foam killer is the polyethers foam killer.
Described polyethers foam killer is the compsn of any or two kinds in polyoxypropylene glycerine and the polyoxyethylene oxypropylene glycerine.
The inventive method is following with the progressive that existing Matachrom preparation method compares:
1, ceramic membrane filter does not add throw outs such as zinc sulfate, Poly aluminum Chloride (PAC), and the microorganism growth breeding can not receive metals ion and suppress, and the biochemical of gained filter residue greatly improves, and is easy to be developed to compoiste fertilizer and biogas, reduces waste residue and produces; Production cost is greatly reduced.
2, do not use sheet frame, the production scene need not to wash sheet frame and cleans filter cloth, and the anhydrous no slag in place is realized cleaner production.
3, behind the employing nf membrane concentration technology; The extraction of Oxacyclotetradecane,erythromycin deriv concentrates solvents such as not re-using butylacetate and Oxacyclotetradecane,erythromycin deriv is extracted concentrated; The use and the volume of the circular flow of organic solvent greatly reduce; Safety and production is more guaranteed, need not distill the recovery butylacetate to the factory effluent after extracting.
4, after the employing nanofiltration concentrated, the nf membrane wet water did not have other organism except that the inorganic salt that trace is arranged, can make the cover water and the unit bath water of ceramic membrane unit, economizes on resources.
5, behind the employing primary crystallization, purify with a spot of acetone recrystallization, the Erythromycin A component can be up to 90%, and the quality of Matachrom greatly improves, and the organic solvent usage quantity greatly reduces, and helps environmental protection and production safety.
Following embodiment will help those of ordinary skill in the art further to understand the present invention, but not limit the present invention in any form.
Experimental example 1 simultaneous test
Existing Matachrom preparation method:
Fermented liquid put jar the back use concentration be 10% sodium hydroxide solution to transfer pH be 8.0～8.4, add 4% zinc sulfate flocculation afterwards, solid substance is removed with Plate Filtration in the flocculation back; Filtrating is adjusted to pH6.0～6.5 with glacial acetic acid solution; With the extraction of double solvents such as butylacetate, solvent is added to Sodium Thiocyanate 99 and Glacial acetic acid min. 99.5, and Matachrom is crystallized out again; Crystal promptly gets Matachrom through washing, oven dry.
Matachrom preparation method of the present invention:
(1) fermented liquid concentrates: after the erythromycin fermentation liquid slagging-off, use concentration be 10% sodium hydroxide solution to transfer pH be 8.0～8.4, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator.
(2) recrystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, add 10% sodium thiocyanate solution (every BOU Oxacyclotetradecane,erythromycin deriv adds 10% sodium thiocyanate solution of 0.18kg), using 50% glacial acetic acid solution adjusting pH is 6.0～6.5; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 4 ratio; Use concentration be 10% sodium hydroxide solution to regulate pH be 9.8～10.0, Matachrom is changed into erythromycin, leave standstill; get acetone soln; add 10% sodium thiocyanate solution (every BOU Oxacyclotetradecane,erythromycin deriv adds 10% sodium thiocyanate solution of 0.18kg), transfer pH to 6.5, extraordinarily go into 50～55 ℃ of purified water by 1.5 of lysate volume; 25～30 ℃ of crystallization control temperature; stop stirring with 50% glacial acetic acid solution, leave standstill 1 hour entering whizzer separate the wet article of Matachrom, the Matachrom article that wet are used acetone, 50～55 ℃ of purified water drip washing respectively; drying promptly gets the Matachrom finished product.
Table one Matachrom preparing method's comparison
Can know through table one: the used ceramic membrane filter of the present invention does not add throw outs such as zinc sulfate, Poly aluminum Chloride (PAC), has reduced organic consumption, and production cost is greatly reduced; Do not use sheet frame, the production scene need not to wash sheet frame and cleans filter cloth, and the anhydrous no slag in place is realized cleaner production; After adopting the nf membrane concentration technology, the extraction of Oxacyclotetradecane,erythromycin deriv concentrates solvents such as not re-using N-BUTYL ACETATE and Oxacyclotetradecane,erythromycin deriv is extracted concentrated, and the use of organic solvent and volume of the circular flow greatly reduce; After adopting nanofiltration to concentrate, the nf membrane wet water does not have other organism except that the inorganic salt that trace is arranged, can make the cover water and the unit bath water of ceramic membrane unit, economizes on resources; After adopting primary crystallization, purify with a spot of acetone recrystallization, the Erythromycin A component can be up to 90%, and the quality of Matachrom greatly improves.
Following embodiment is used to further specify but is not limited to the present invention.
Embodiment 1: the preparation of erythromycin fermentation liquid
(1) fermented liquid concentrates: after the erythromycin fermentation liquid slagging-off, use concentration be 10% sodium hydroxide solution to transfer pH be 8.0～8.4, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator.
(2) recrystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, add 10% sodium thiocyanate solution (every BOU Oxacyclotetradecane,erythromycin deriv adds 10% sodium thiocyanate solution of 0.18kg), using 50% glacial acetic acid solution adjusting pH is 6.0～6.5; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 4 ratio; Use concentration be 10% sodium hydroxide solution to regulate pH be 9.8～10.0, Matachrom is changed into erythromycin, leave standstill; get acetone soln; add 10% sodium thiocyanate solution (every BOU Oxacyclotetradecane,erythromycin deriv adds 10% sodium thiocyanate solution of 0.18kg), transfer pH to 6.5, extraordinarily go into 50～55 ℃ of purified water by 1.5 of lysate volume; 25～30 ℃ of crystallization control temperature; stop stirring with 50% glacial acetic acid solution, leave standstill 1 hour entering whizzer separate the wet article of Matachrom, the Matachrom article that wet are used acetone, 50～55 ℃ of purified water drip washing respectively; drying promptly gets the Matachrom finished product.
The preparation of erythromycin fermentation liquid
(1) the Oxacyclotetradecane,erythromycin deriv seed liquor is cultivated: 1. female slant pore preparation: with freezing streptomyces erythareus (the producing bacterium) spore that is kept in the sand pipe, be inoculated on the slant medium of sterilization, substratum is formed: starch 0.2g; Steeping water 0.1g; Agar 0.2g, glucose 0.8g, sodium-chlor 1.5g; Calcium chloride 0.8g, with the tap water constant volume to 100ml; Under 34 ℃ of conditions of temperature, cultivated 8 days; 2. the preparation of sub-slant pore: with female slant pore, be inoculated on the slant medium of sterilization, substratum consists of: starch 0.2g, steeping water 0.15g, agar 0.6g, glucose 0.2g, sodium-chlor 0.8g, calcium chloride 0.8g, with the tap water constant volume to 100ml; Under 34 ℃ of conditions of temperature, cultivated 8 days; 3. seed culture: with sub-slant pore, be inoculated in seed culture medium,, obtain the Oxacyclotetradecane,erythromycin deriv seed liquor through three grades of seed enlarged culturing through sterilization;
(2) fermentation: the Oxacyclotetradecane,erythromycin deriv seed liquor is inoculated in the substratum of sterilization in 20% ratio, and substratum consists of: analysis for soybean powder 5.0g, starch 2.5g, sulphur ammonium 0.15g, CaCO
30.7g, rapeseed oil 0.9g, polyoxyethylene oxypropylene glycerine 0.005g, with the tap water constant volume to 100ml; The feeding sterile air also stirred, and added 60% glucose solution 40g at 15 hours, rapeseed oil 5g, and 30% n-propyl alcohol 1g through cultivation in 7 days, gets erythromycin fermentation liquid.
First order seed enlarged culturing base composition is preferably: analysis for soybean powder 2g, starch 2g, CaCO
30.75g, dextrin 1g, sulphur ammonium 0.4g, steeping water 3g, rapeseed oil 0.8g, with the tap water constant volume to 100ml.
Two, three grades of seed enlarged culturing bases are formed: (1) substratum is formed: analysis for soybean powder 4g, starch 3g, CaCO
30.5g, sodium-chlor 0.4g, dextrin 4g, sulphur ammonium 0.3g, steeping water 1g, rapeseed oil 0.8g, polyoxyethylene oxypropylene glycerine 0.01g, with the tap water constant volume to 100ml.
Embodiment 2: a kind of THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method
(1) fermented liquid concentrates: after the erythromycin fermentation liquid slagging-off, use concentration be 15% sodium hydroxide solution to transfer pH be 7.8～8.2, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator.
(2) recrystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, add 15% sodium thiocyanate solution (every BOU Oxacyclotetradecane,erythromycin deriv adds 15% sodium thiocyanate solution of 0.15kg), using 40% glacial acetic acid solution adjusting pH is 6.0～6.5; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 3 ratio; Use concentration be 15% sodium hydroxide solution to regulate pH be 9.6～9.8, Matachrom is changed into erythromycin, leave standstill; get acetone soln; add 15% sodium thiocyanate solution (every BOU Oxacyclotetradecane,erythromycin deriv adds 15% sodium thiocyanate solution of 0.15kg), transfer pH to 6.5, extraordinarily go into 50～55 ℃ of purified water by 1.0 of lysate volume; 25～30 ℃ of crystallization control temperature; stop stirring with 40% glacial acetic acid solution, leave standstill 2 hours entering whizzers separate the wet article of Matachrom, the Matachrom article that wet are used acetone, 50～55 ℃ of purified water drip washing respectively; drying promptly gets the Matachrom finished product.
The preparation of erythromycin fermentation liquid
(1) the Oxacyclotetradecane,erythromycin deriv seed liquor is cultivated: 1. female slant pore preparation: with freezing streptomyces erythareus (the producing bacterium) spore that is kept in the sand pipe, be inoculated on the slant medium of sterilization, substratum consists of: starch 0.5g, steeping water 0.1g, agar 0.5g.Glucose 0.5g, sodium-chlor 1g, calcium chloride 0.5g, with the tap water constant volume to 100ml; Under 34 ℃ of conditions of temperature, cultivated 9 days; 2. the preparation of sub-slant pore: with female slant pore, be inoculated on the slant medium of sterilization, substratum consists of: starch 0.4g, steeping water 0.2g, agar 0.4g, glucose 0.4g, sodium-chlor 1.5g, calcium chloride 1.0g, with the tap water constant volume to 100ml; Under 34 ℃ of conditions of temperature, cultivated 9 days; 3. seed culture: with sub-slant pore, be inoculated in seed culture medium,, obtain the Oxacyclotetradecane,erythromycin deriv seed liquor through three grades of seed enlarged culturing through sterilization;
(2) fermentation: the Oxacyclotetradecane,erythromycin deriv seed liquor is inoculated in the substratum of sterilization in 10% ratio, and substratum consists of: analysis for soybean powder 4.5g, starch 3.0g, sulphur ammonium 0.12g, CaCO
30.gg, VT 18 0.7g, polyoxypropylene glycerine 0.01g, with the tap water constant volume to 100ml; The feeding sterile air also stirred 20 hours, added 40% glucose solution 20g, VT 18 4g, and 60% n-propyl alcohol solution 2g through cultivation in 8 days, gets erythromycin fermentation liquid.
First order seed enlarged culturing condition is: (1) analysis for soybean powder 3g, starch 1.5g, CaCO
30.7g, dextrin 1.5g, sulphur ammonium 0.3g, steeping water 2g, VT 18 0.7g, with the tap water constant volume to 100ml; (2) temperature is 33 ℃; (3) incubation time is 70 hours;
Two, three grades of seed enlarged culturing conditions are: (1) substratum is formed: analysis for soybean powder 3.5g, starch 3.2g, CaCO
30.6g, sodium-chlor 0.5g, dextrin 3.2g, sulphur ammonium 0.2g, steeping water 1.5g, VT 18 1.1g, polyoxypropylene glycerine 0.005g, with the tap water constant volume to 100ml; (2) temperature is 32～34 ℃; (3) incubation time is 24～48 hours.
Claims (14)
1. a THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method is characterized in that this method comprises the steps:
(1) fermented liquid concentrates: erythromycin fermentation liquid concentration be 5～20% sodium hydroxide solution to transfer pH be 7.5～9.0, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator;
(2) crystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, and every BOU Oxacyclotetradecane,erythromycin deriv adds 5～20% sodium thiocyanate solutions of 0.15～0.2kg, and using 20～80% glacial acetic acid solution adjusting pH is 5.5～7.0; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 1～1: 8 ratio; Use concentration be 5%～20% sodium hydroxide solution to regulate pH be 9.5～10.5, Matachrom is changed into erythromycin, leave standstill; get acetone soln, every BOU Oxacyclotetradecane,erythromycin deriv adds 5～20% sodium thiocyanate solutions of 0.15～0.2kg, transfers pH to 5.5～7.5 with 20～80% glacial acetic acid solutions; extraordinarily go into 45～60 ℃ of purified water by 1～3 of lysate volume; 20～35 ℃ of crystallization control temperature, adopts variable-frequency motor slowly to stir 10 minutes, leave standstill again 0.5～2 hour entering whizzer of cooling separate the wet article of Matachrom; Matachrom wets and uses acetone, 45～60 ℃ of purified water drip washing respectively in the article whizzer; spinning is discharged up to mother liquor, and drying promptly gets the Matachrom finished product;
Erythromycin fermentation liquid prepares according to following steps:
(1) the Oxacyclotetradecane,erythromycin deriv seed liquor is cultivated: 1. female slant pore preparation: freezing streptomyces erythareus (the producing bacterium) spore inoculating that is kept in the sand pipe, was cultivated 7～9 days under 32～34 ℃ of conditions of temperature on the slant medium of sterilization; 2. sub-slant pore preparation: with female slant pore, be inoculated on the slant medium of sterilization, under 32～34 ℃ of conditions of temperature, cultivated 7～9 days; 3. seed culture: with sub-slant pore, be inoculated in seed culture medium,, obtain the Oxacyclotetradecane,erythromycin deriv seed liquor through three grades of seed enlarged culturing through sterilization;
(2) fermentation: the Oxacyclotetradecane,erythromycin deriv seed liquor is inoculated in the substratum of sterilization by 10～20% volume ratios, and the feeding sterile air is also opened and is stirred, and adds nutritive substance, through cultivation in 7～10 days, gets erythromycin fermentation liquid.
2. THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) fermented liquid concentrates: erythromycin fermentation liquid use concentration be 10% sodium hydroxide solution to transfer pH be 8.0～8.4, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator.
(2) recrystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, and every BOU Oxacyclotetradecane,erythromycin deriv adds 10% the sodium thiocyanate solution of 0.18kg, and using 50% glacial acetic acid solution to regulate pH is 6.0～6.5; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 4 ratio; Use concentration be 8% sodium hydroxide solution to regulate pH be 9.8～10.0, Matachrom is changed into erythromycin, standing separation; Divide the sub-cloud mother liquor to get acetone soln, every BOU Oxacyclotetradecane,erythromycin deriv adds 10% the sodium thiocyanate solution of 0.18kg, with 50% glacial acetic acid solution accent pH to 6.5; Extraordinarily go into 50～55 ℃ of purified water by 1.5 of lysate volume; 25～30 ℃ of crystallization control temperature adopt variable-frequency motor slowly to stir 10 minutes; Leave standstill 1 hour entering whizzer of cooling separate the wet article of Matachrom; The wet article of Matachrom are used acetone, 50～55 ℃ of purified water drip washing in whizzer respectively, and drying promptly gets the Matachrom finished product.
3. THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method as claimed in claim 1 is characterized in that this method comprises the steps:
(1) fermented liquid concentrates: erythromycin fermentation liquid use concentration be 15% sodium hydroxide solution to transfer pH be 7.8～8.2, adopt the ceramic membrane filter in 50nm～100nm aperture, filtered liq concentrates with the nf membrane of 200 molecular weight, obtains the Oxacyclotetradecane,erythromycin deriv liquid concentrator.
(2) recrystallization: the Oxacyclotetradecane,erythromycin deriv liquid concentrator is placed crystallizer, and every BOU Oxacyclotetradecane,erythromycin deriv adds 15% the sodium thiocyanate solution of 0.15kg, and using 40% glacial acetic acid solution to regulate pH is 6.0～6.5; Matachrom is separated out in crystallization, and solidliquid mixture gets the Matachrom bullion through spinning, and the Matachrom bullion adds acetone according to 1: 3 ratio; Use concentration be 10% sodium hydroxide solution to regulate pH be 9.6～9.8, Matachrom is changed into erythromycin, leave standstill; get acetone soln, every BOU Oxacyclotetradecane,erythromycin deriv adds 15% the sodium thiocyanate solution of 0.15kg, transfers pH to 6.5 with 40% glacial acetic acid solution; extraordinarily go into 50～55 ℃ of purified water by 1.0 of lysate volume, 25～30 ℃ of crystallization control temperature adopt variable-frequency motor slowly to stir 10 minutes;, leave standstill 1 hour entering whizzer of cooling separate the wet article of Matachrom, the Matachrom article that wet are used acetone, 50～55 ℃ of purified water drip washing in whizzer respectively; drying promptly gets the Matachrom finished product.
4. like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3, it is characterized in that
The female slant pore of said Oxacyclotetradecane,erythromycin deriv prepares substratum and is made up of following component: starch 0.1～1.0 weight part, steeping water 0.05～0.2 weight part, agar 0.1～1.0 weight part, glucose 0.1～1.0 weight part, sodium-chlor 0.5～2.0 weight part, calcium chloride 0.1～1.0 weight part, tap water preparation.
5. like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3, it is characterized in that the sub-slant pore of Oxacyclotetradecane,erythromycin deriv prepares substratum and is made up of following component: starch 0.1～1.0 weight part, steeping water 0.05～0.2 weight part, agar 0.1～1.0 weight part, glucose 0.1～1.0 weight part, sodium-chlor 0.5～2.0 weight part, calcium chloride 0.1～1.0 weight part, with the tap water constant volume to 100 parts by volume.
6. like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3, it is characterized in that Oxacyclotetradecane,erythromycin deriv first order seed enlarged culturing base composition: analysis for soybean powder 2～4 weight parts, starch 1～2 weight part, CaCO
30.6～0.8 weight part, dextrin 1～2 weight part, sulphur ammonium 0.2～0.4 weight part, steeping water 1～4 weight part, vegetables oil 0.5～1 weight part, with the tap water constant volume to 100 parts by volume.
7. like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3, it is characterized in that Oxacyclotetradecane,erythromycin deriv first order seed enlarged culturing temperature is 32～34 ℃, incubation time is 48～96 hours.
8. like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3, it is characterized in that two, three grades of seed enlarged culturing bases of Oxacyclotetradecane,erythromycin deriv consist of: analysis for soybean powder 2.0～4.5 weight parts, starch 2.5～4.0 weight parts, CaCO
30.5～0.7 weight part, sodium-chlor 0.4～0.6 weight part, dextrin 2.5～4.0 weight parts, sulphur ammonium 0.1～0.3 weight part, steeping water 1～2 weight part, vegetables oil 0.8～1.5 weight part, foam killer 0～0.02 weight part, with the tap water constant volume to 100 parts by volume.
9. like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3, it is characterized in that two, three grades of seed enlarged culturing temperature of Oxacyclotetradecane,erythromycin deriv are 32～34 ℃, incubation time is 24～48 hours.
10. like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3, it is characterized in that the abomacetin fermentation substratum consists of: analysis for soybean powder 3.5～5.5 weight parts, starch 2.0～4.0 weight parts, sulphur ammonium 0.08～0.15 weight part, CaCO
30.6～1.0 weight parts, vegetables oil 0.5～1.0 weight part, foam killer 0.005～0.02 weight part, with the tap water constant volume to 100 parts by volume.
11., it is characterized in that the composition of nutritive substance that adds in the abomacetin fermentation substratum is: liquid sugar 10～50 weight parts, vegetables oil 1～10 weight part, n-propyl alcohol solution 0.5～5 weight part like the arbitrary described THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method of claim 1～3.
12. THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method as claimed in claim 11 is characterized in that described liquid sugar is 20～70% glucose solutions.
13. THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method as claimed in claim 11 is characterized in that described n-propyl alcohol solution is 20～70% n-propyl alcohol solution.
14. THE PREPARATION OF ERYTHROMYCIN THIOCYANATE method as claimed in claim 8 is characterized in that described foam killer is the compsn of any or two kinds in polyoxypropylene glycerine and the polyoxyethylene oxypropylene glycerine.
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| CN105348340A (en) * | 2015-11-27 | 2016-02-24 | 宁夏启元药业有限公司 | Preparation method of erythromycin thiocyanate |
| CN105601687A (en) * | 2016-03-28 | 2016-05-25 | 伊犁川宁生物技术有限公司 | Refinement method of erythromycin thiocyanate |
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| CN109942655B (en) * | 2019-04-29 | 2020-05-12 | 宜昌东阳光药业股份有限公司 | Continuous crystallization method of erythromycin thiocyanate crude product |
| CN111848701A (en) * | 2019-04-29 | 2020-10-30 | 伊犁川宁生物技术有限公司 | Continuous crystallization method of crude erythromycin thiocyanate |
| CN112978993A (en) * | 2021-02-25 | 2021-06-18 | 宜昌东阳光生化制药有限公司 | Method for recovering thiocyanate ions from rectification waste liquid of erythromycin thiocyanate crystallization mother liquor and application |
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