JP5277167B2 - ムピロシンカルシウムの生成方法及び精製方法 - Google Patents
ムピロシンカルシウムの生成方法及び精製方法 Download PDFInfo
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- mupirocin
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- DDHVILIIHBIMQU-YJGQQKNPSA-L mupirocin calcium hydrate Chemical compound O.O.[Ca+2].C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1.C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC([O-])=O)OC1 DDHVILIIHBIMQU-YJGQQKNPSA-L 0.000 title claims abstract description 122
- 229960000313 mupirocin calcium Drugs 0.000 title claims abstract description 53
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- MINDHVHHQZYEEK-UHFFFAOYSA-N (E)-(2S,3R,4R,5S)-5-[(2S,3S,4S,5S)-2,3-epoxy-5-hydroxy-4-methylhexyl]tetrahydro-3,4-dihydroxy-(beta)-methyl-2H-pyran-2-crotonic acid ester with 9-hydroxynonanoic acid Natural products CC(O)C(C)C1OC1CC1C(O)C(O)C(CC(C)=CC(=O)OCCCCCCCCC(O)=O)OC1 MINDHVHHQZYEEK-UHFFFAOYSA-N 0.000 claims abstract description 72
- 229960003128 mupirocin Drugs 0.000 claims abstract description 68
- 229930187697 mupirocin Natural products 0.000 claims abstract description 64
- 238000000034 method Methods 0.000 claims abstract description 61
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims abstract description 24
- 239000011575 calcium Substances 0.000 claims abstract description 24
- 229910052791 calcium Inorganic materials 0.000 claims abstract description 24
- 239000003463 adsorbent Substances 0.000 claims abstract description 19
- 229920005989 resin Polymers 0.000 claims abstract description 18
- 239000011347 resin Substances 0.000 claims abstract description 18
- 230000008569 process Effects 0.000 claims abstract description 14
- 230000002209 hydrophobic effect Effects 0.000 claims abstract description 13
- 238000000746 purification Methods 0.000 claims abstract description 11
- 238000005406 washing Methods 0.000 claims abstract description 5
- 239000007787 solid Substances 0.000 claims description 37
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 35
- 238000001179 sorption measurement Methods 0.000 claims description 18
- 239000000463 material Substances 0.000 claims description 15
- 238000000855 fermentation Methods 0.000 claims description 11
- 230000004151 fermentation Effects 0.000 claims description 11
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 10
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical group N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 claims description 9
- 229910052921 ammonium sulfate Inorganic materials 0.000 claims description 9
- 235000011130 ammonium sulphate Nutrition 0.000 claims description 9
- 229920003053 polystyrene-divinylbenzene Polymers 0.000 claims description 9
- 150000003839 salts Chemical group 0.000 claims description 8
- VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 7
- 239000001639 calcium acetate Substances 0.000 claims description 7
- 235000011092 calcium acetate Nutrition 0.000 claims description 7
- 229960005147 calcium acetate Drugs 0.000 claims description 7
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 6
- ZCCIPPOKBCJFDN-UHFFFAOYSA-N calcium nitrate Chemical compound [Ca+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ZCCIPPOKBCJFDN-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 5
- 239000004793 Polystyrene Substances 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 229920002223 polystyrene Polymers 0.000 claims description 4
- BCZXFFBUYPCTSJ-UHFFFAOYSA-L Calcium propionate Chemical compound [Ca+2].CCC([O-])=O.CCC([O-])=O BCZXFFBUYPCTSJ-UHFFFAOYSA-L 0.000 claims description 3
- 239000001110 calcium chloride Substances 0.000 claims description 3
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 3
- 239000004330 calcium propionate Substances 0.000 claims description 3
- 235000010331 calcium propionate Nutrition 0.000 claims description 3
- 241000589540 Pseudomonas fluorescens Species 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000002244 precipitate Substances 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 239000004925 Acrylic resin Substances 0.000 claims 1
- 229920000178 Acrylic resin Polymers 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 6
- 238000002360 preparation method Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 23
- 239000000047 product Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000002253 acid Substances 0.000 description 12
- 238000010828 elution Methods 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 9
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 9
- MINDHVHHQZYEEK-HBBNESRFSA-N mupirocin Chemical compound C[C@H](O)[C@H](C)[C@@H]1O[C@H]1C[C@@H]1[C@@H](O)[C@@H](O)[C@H](C\C(C)=C\C(=O)OCCCCCCCCC(O)=O)OC1 MINDHVHHQZYEEK-HBBNESRFSA-N 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 230000003115 biocidal effect Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 229930194369 pseudomonic acid Natural products 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 159000000007 calcium salts Chemical class 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 241000191967 Staphylococcus aureus Species 0.000 description 2
- 241000193996 Streptococcus pyogenes Species 0.000 description 2
- UGUYQBMBIJFNRM-OQFOIZHKSA-N [(z)-but-2-en-2-yl]benzene Chemical compound C\C=C(\C)C1=CC=CC=C1 UGUYQBMBIJFNRM-OQFOIZHKSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229940088710 antibiotic agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 229910001424 calcium ion Inorganic materials 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000002178 crystalline material Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Chemical class CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 2
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical class CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 2
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Chemical class COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- -1 that is Chemical compound 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 229940100613 topical solution Drugs 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 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 description 1
- 101001055216 Homo sapiens Interleukin-9 Proteins 0.000 description 1
- 102100026871 Interleukin-9 Human genes 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- PILOURHZNVHRME-UHFFFAOYSA-N [Na].[Ba] Chemical compound [Na].[Ba] PILOURHZNVHRME-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000000274 adsorptive effect Effects 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 159000000009 barium salts Chemical class 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000000416 exudates and transudate Anatomy 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012263 liquid product Substances 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 125000005395 methacrylic acid group Chemical group 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N n-heptane Substances CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/16—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing two or more hetero rings
- C12P17/162—Heterorings having oxygen atoms as the only ring heteroatoms, e.g. Lasalocid
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- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Health & Medical Sciences (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Wood Science & Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Genetics & Genomics (AREA)
- General Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Description
ここで説明された方法を用いて精製されたムピロシンカルシウムは、当技術分野の標準的な技術を用い、哺乳類を治療する組成物として生成される。その組成物は従来の調剤方法に従って加工され、ヒト及び他の哺乳類を含む患者に投与する薬剤が製造される(すなわち、「医薬組成物」)。前記医薬組成物は、好ましくは所定量の精製ムピロシンを含む用量単位の形で、単独で又は別の活性物質と組合せて、主に薬学的に許容可能なキャリアとともに製造される。「薬学的に許容可能なキャリア」とは、医薬組成物としてのムピロシンの運搬を促進又は達成するのに適切な一つ以上の製剤材料を指す。前記医薬組成物はまた、殺菌等の従来の製薬工程に従ってもよく、かつ/又は、防腐剤、安定化剤、湿潤剤、乳化剤、緩衝剤等のような従来の補助剤を含んでもよい。
ムピロシン酸を含む発酵ブロスは、本来周知の態様、すなわち、前述の特許文献2の実施例1の工程と同じ態様によって、蛍光菌のムピロシン産生培養物の発酵によって得られた。実験用発酵器から得られた5リットルのムピロシン含有全培養発酵ブロスがpH=8.3に調製され(3M NaOHの添加により)、室温で144μmの金属スクリーンを通して濾過され、その後限外濾過された(ミリポアペリコン‐2バイオマックス‐5)。発酵ブロス中に存在する約70%のムピロシンが、最終浄化ブロス中に回収された。ムピロシンを含む透過液は、任意でNF(オスモニック デサル DKメンブレン)によって濃縮された。
A.実施例1で得られた濾過液(363ml、ムピロシン1.3g)に(NH4)2SO4(24g)が加えられた。pHが1M NaOHの添加によりpH7.5に調整された。アクリル系吸着剤XAD7HP(登録商標)(ローム・アンド・ハース社)がクロマトグラフィカラム(24ml)に充填され、生成されたムピロシン溶液が(シュードモネート溶液として)前記カラムに加えられた(1ml/分)。カラムは0.5M(NH4)2SO4を含むpH7.5の0.1Mトリス緩衝液(120ml)で洗浄された。その後、0.1M酢酸カルシウム溶液が前記カラムに加えられ(72ml)、続いて水(48ml)が加えられた。ムピロシンカルシウムは、80%メタノールによって前記カラムから溶出された。0.9gのムピロシンカルシウムが溶出プール中に回収された(60ml、収率70%)。
Claims (30)
- ムピロシンを疎水性の固体支持体に吸着して結合ムピロシンを形成する段階と、
前記結合ムピロシンを可溶性カルシウム含有物質に暴露し、ムピロシンカルシウムを形成する段階と、
形成された前記ムピロシンカルシウムを洗浄する段階と、
前記固体支持体から精製ムピロシンカルシウムを溶出する段階と
からなるムピロシンカルシウムの精製方法。 - 前記ムピロシンが、
蛍光菌(Pseudomonas fluorescens)のムピロシン産生培養物を発酵させる段階と、
前記発酵させる段階によって形成される発酵ブロスを得る段階と、
任意で濾過により前記ブロスを浄化する段階と
によって生成される請求項1に記載の方法。 - 前記固体支持体が疎水性吸着樹脂である請求項1又は2に記載の方法。
- 前記疎水性吸着樹脂が、変性シリカ、ポリスチレン、及びアクリル系材料からなる群より選択される請求項3に記載の方法。
- 前記ムピロシンカルシウムが、更に結晶化によって精製される請求項1〜4のいずれか1項に記載の方法。
- 前記ムピロシンカルシウムが、少なくとも50%に精製される請求項1〜5のいずれか1項に記載の方法。
- 前記ムピロシンカルシウムが、少なくとも65%に精製される請求項1〜5のいずれか1項に記載の方法。
- 前記ムピロシンカルシウムが、少なくとも90%に精製される請求項1〜5のいずれか1項に記載の方法。
- 塩基が前記ムピロシンに添加されて前記固体支持体への吸着を助ける請求項1〜8のいずれか1項に記載の方法。
- 前記塩基が硫酸アンモニウムである請求項9に記載の方法。
- 前記カルシウム含有物質が、酢酸カルシウム、塩化カルシウム、硝酸カルシウム、プロピオン酸カルシウムのいずれかである請求項1〜10のいずれか1項に記載の方法。
- 前記ムピロシンに硫酸アンモニウム溶液が添加されてムピロシンの前記固体支持体への吸着を助けるとともに、前記固体支持体がアクリル系吸着剤またはポリスチレンジビニルベンゼン系吸着剤であって、前記カルシウム含有物質が酢酸カルシウムであり、かつ、前記精製ムピロシンカルシウムがメタノールを用いて溶出される請求項1に記載の方法。
- 前記ムピロシンに硫酸アンモニウム溶液が添加されてムピロシンの前記固体支持体への吸着を助けるとともに、前記固体支持体がポリスチレンジビニルベンゼン系吸着剤であって、前記カルシウム含有物質が塩化カルシウムであり、かつ、前記精製ムピロシンカルシウムがメタノールを用いて溶出される請求項1に記載の方法。
- a.精製ムピロシンを疎水性の固体支持体に吸着させる段階と、
b.吸着させたムピロシンをカルシウム含有物質に暴露する段階と、
c.過剰カルシウム含有溶液を除去する段階と、
d.前記固体支持体からムピロシンカルシウムを溶出する段階と
からなるムピロシンカルシウムの生成方法。 - 前記カルシウム含有溶液が、塩化カルシウム溶液、酢酸カルシウム溶液、硝酸カルシウム溶液、及びプロピオン酸カルシウム溶液からなる群より選択される請求項14に記載の方法。
- 前記カルシウム含有溶液が酢酸カルシウム溶液である請求項15に記載の方法。
- 前記カルシウム含有溶液が塩化カルシウム溶液である請求項15に記載の方法。
- ムピロシンカルシウムが、有機溶媒を用いて前記固体支持体から溶出される請求項14〜17のいずれか1項に記載の方法。
- 前記有機溶媒がメタノールを含む請求項18に記載の方法。
- 前記固体支持体が疎水性吸着樹脂である請求項14〜19のいずれか1項に記載の方法。
- 前記疎水性吸着樹脂が、変性シリカ沈殿物、ポリスチレン、及びアクリル系材料からなる群より選択される請求項20に記載の方法。
- 前記疎水性吸着樹脂が、アクリル系樹脂及びポリスチレンジビニルベンゼン系樹脂からなる群より選択される請求項21に記載の方法。
- 前記ムピロシンカルシウムが、更に結晶化によって精製される請求項14〜22のいずれか1項に記載の方法。
- 前記ムピロシンカルシウムが、少なくとも50%に精製される請求項14〜22のいずれか1項に記載の方法。
- 前記ムピロシンカルシウムが、少なくとも65%に精製される請求項14〜22のいずれか1項に記載の方法。
- 前記ムピロシンカルシウムが、少なくとも90%に精製される請求項14〜22のいずれか1項に記載の方法。
- 前記精製ムピロシンに塩基が添加されて前記固体支持体への吸着を助ける請求項14〜26のいずれか1項に記載の方法。
- 前記塩基が硫酸アンモニウムである請求項27に記載の方法。
- 前記精製ムピロシンに硫酸アンモニウム溶液が添加されてムピロシンの前記固体支持体への吸着を助けるとともに、前記固体支持体がアクリル系吸着剤又はポリスチレンジビニルベンゼン系吸着剤であり、かつ、前記ムピロシンカルシウムがメタノールを用いて溶出される請求項14に記載の方法。
- 前記精製ムピロシンに硫酸アンモニウム溶液が添加されてムピロシンの前記固体支持体への吸着を助けるとともに、前記固体支持体がポリスチレンジビニルベンゼン系樹脂であって、前記カルシウム含有溶液が塩化カルシウム溶液であり、かつ、前記ムピロシンカルシウムがメタノールを用いて溶出される請求項14に記載の方法。
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GB0617069A GB2441328A (en) | 2006-08-30 | 2006-08-30 | A method for obtaining mupirocin calcium |
GB0617069.0 | 2006-08-30 | ||
PCT/EP2007/007547 WO2008025534A1 (en) | 2006-08-30 | 2007-08-29 | Preparation and purification of mupirocin calcium |
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CN101591333B (zh) * | 2009-07-02 | 2012-01-04 | 山东健威生物工程有限公司 | 一种提纯假单胞菌酸a的方法 |
CN104370896A (zh) * | 2013-11-29 | 2015-02-25 | 江苏汉邦科技有限公司 | 一种纯化假单孢菌素的方法 |
TW202214611A (zh) * | 2020-08-25 | 2022-04-16 | 大陸商杭州中美華東製藥有限公司 | 莫匹羅星的提取方法 |
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US4071536A (en) * | 1971-06-12 | 1978-01-31 | Beecham Group Limited | Antibiotics |
CA1103264A (en) * | 1977-09-30 | 1981-06-16 | Norman H. Rogers | Purification of pseudomonic acid |
CA1115699A (en) * | 1978-05-20 | 1982-01-05 | Alan D. Curzons | Lithium pseudomonate and its preparation |
GB8415579D0 (en) * | 1984-06-19 | 1984-07-25 | Beecham Group Plc | Compounds |
JPH01268682A (ja) * | 1988-04-21 | 1989-10-26 | Minofuaagen Seiyaku Honpo:Goushi | 腎機能改善剤及びリソスペルミン酸塩の製造方法 |
US5235037A (en) * | 1991-08-15 | 1993-08-10 | American Cyanamid Company | Vancomycin precipitation process |
HUP0105286A3 (en) * | 1999-02-03 | 2003-03-28 | Biogal Gyogyszergyar | Process for the isolation of pseudomonic acid a from pseudomonic acid complex-containing culture broth |
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NO20091293L (no) | 2009-03-27 |
TW200825070A (en) | 2008-06-16 |
US7868191B2 (en) | 2011-01-11 |
WO2008025534A1 (en) | 2008-03-06 |
PL2081926T3 (pl) | 2012-12-31 |
JP2010501608A (ja) | 2010-01-21 |
CN101511826B (zh) | 2011-06-22 |
CA2649758A1 (en) | 2008-03-06 |
US20090240071A1 (en) | 2009-09-24 |
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