DE1933301A1 - Verfahren zur Herstellung von hypoallergenischen Penicillinen - Google Patents
Verfahren zur Herstellung von hypoallergenischen PenicillinenInfo
- Publication number
- DE1933301A1 DE1933301A1 DE19691933301 DE1933301A DE1933301A1 DE 1933301 A1 DE1933301 A1 DE 1933301A1 DE 19691933301 DE19691933301 DE 19691933301 DE 1933301 A DE1933301 A DE 1933301A DE 1933301 A1 DE1933301 A1 DE 1933301A1
- Authority
- DE
- Germany
- Prior art keywords
- enzyme
- aqueous solution
- solution
- cell
- acylase
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 41
- 229930182555 Penicillin Natural products 0.000 title claims description 34
- 238000004519 manufacturing process Methods 0.000 title claims description 25
- 150000002960 penicillins Chemical class 0.000 title claims description 22
- 230000000774 hypoallergenic effect Effects 0.000 title claims description 7
- 239000000243 solution Substances 0.000 claims description 105
- 102000004190 Enzymes Human genes 0.000 claims description 78
- 108090000790 Enzymes Proteins 0.000 claims description 78
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 55
- 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 claims description 52
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 claims description 27
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 claims description 27
- 239000007864 aqueous solution Substances 0.000 claims description 27
- 239000000463 material Substances 0.000 claims description 24
- 229920001864 tannin Polymers 0.000 claims description 24
- 239000001648 tannin Substances 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 23
- 235000018553 tannin Nutrition 0.000 claims description 22
- 235000019371 penicillin G benzathine Nutrition 0.000 claims description 20
- 229940056360 penicillin g Drugs 0.000 claims description 20
- 108010073038 Penicillin Amidase Proteins 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 17
- 238000003756 stirring Methods 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 150000002500 ions Chemical class 0.000 claims description 14
- 239000002244 precipitate Substances 0.000 claims description 14
- 229940049954 penicillin Drugs 0.000 claims description 12
- -1 iron ions Chemical class 0.000 claims description 10
- 238000000746 purification Methods 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 239000005695 Ammonium acetate Substances 0.000 claims description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 8
- 229940043376 ammonium acetate Drugs 0.000 claims description 8
- 238000004108 freeze drying Methods 0.000 claims description 8
- 239000012535 impurity Substances 0.000 claims description 8
- 238000000502 dialysis Methods 0.000 claims description 7
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000005119 centrifugation Methods 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000002523 gelfiltration Methods 0.000 claims description 5
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 4
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 claims description 4
- 239000012531 culture fluid Substances 0.000 claims description 4
- 238000001704 evaporation Methods 0.000 claims description 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 3
- 239000007853 buffer solution Substances 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 claims description 3
- 229910001410 inorganic ion Inorganic materials 0.000 claims description 3
- 244000005700 microbiome Species 0.000 claims description 3
- 239000002861 polymer material Substances 0.000 claims description 3
- 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 claims description 2
- 229940072049 amyl acetate Drugs 0.000 claims description 2
- PGMYKACGEOXYJE-UHFFFAOYSA-N anhydrous amyl acetate Natural products CCCCCOC(C)=O PGMYKACGEOXYJE-UHFFFAOYSA-N 0.000 claims description 2
- 229960004328 azidocillin Drugs 0.000 claims description 2
- 239000002738 chelating agent Substances 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 238000005188 flotation Methods 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 claims description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N iron Substances [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 239000002243 precursor Substances 0.000 claims description 2
- 229960003672 propicillin Drugs 0.000 claims description 2
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 claims 1
- 230000009172 bursting Effects 0.000 claims 1
- KTUQUZJOVNIKNZ-UHFFFAOYSA-N butan-1-ol;hydrate Chemical compound O.CCCCO KTUQUZJOVNIKNZ-UHFFFAOYSA-N 0.000 claims 1
- 125000002091 cationic group Chemical group 0.000 claims 1
- DVSDDICSXBCMQJ-UHFFFAOYSA-N diethyl 2-acetylbutanedioate Chemical compound CCOC(=O)CC(C(C)=O)C(=O)OCC DVSDDICSXBCMQJ-UHFFFAOYSA-N 0.000 claims 1
- 238000007599 discharging Methods 0.000 claims 1
- 239000001963 growth medium Substances 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 229960004894 pheneticillin Drugs 0.000 claims 1
- 238000009738 saturating Methods 0.000 claims 1
- 150000004684 trihydrates Chemical class 0.000 claims 1
- 230000000694 effects Effects 0.000 description 78
- 229940088598 enzyme Drugs 0.000 description 62
- 108700023418 Amidases Proteins 0.000 description 53
- 102000005922 amidase Human genes 0.000 description 53
- 210000004027 cell Anatomy 0.000 description 35
- 241000588724 Escherichia coli Species 0.000 description 21
- 239000000047 product Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 14
- 239000007788 liquid Substances 0.000 description 13
- 230000001580 bacterial effect Effects 0.000 description 12
- 239000000872 buffer Substances 0.000 description 12
- 239000006228 supernatant Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 229920005654 Sephadex Polymers 0.000 description 9
- 239000012507 Sephadex™ Substances 0.000 description 9
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 7
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 7
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 7
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 235000019257 ammonium acetate Nutrition 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 description 6
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 6
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 6
- 229940079919 digestives enzyme preparation Drugs 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 5
- 229920000642 polymer Polymers 0.000 description 5
- JVIPLYCGEZUBIO-UHFFFAOYSA-N 2-(4-fluorophenyl)-1,3-dioxoisoindole-5-carboxylic acid Chemical compound O=C1C2=CC(C(=O)O)=CC=C2C(=O)N1C1=CC=C(F)C=C1 JVIPLYCGEZUBIO-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 229920001425 Diethylaminoethyl cellulose Polymers 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000008367 deionised water Substances 0.000 description 4
- 229910021641 deionized water Inorganic materials 0.000 description 4
- 230000002255 enzymatic effect Effects 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229960003424 phenylacetic acid Drugs 0.000 description 4
- 239000003279 phenylacetic acid Substances 0.000 description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 239000012064 sodium phosphate buffer Substances 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 229910021538 borax Inorganic materials 0.000 description 3
- 239000006285 cell suspension Substances 0.000 description 3
- 230000001413 cellular effect Effects 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000004140 cleaning Methods 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 238000005342 ion exchange Methods 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- 239000004328 sodium tetraborate Substances 0.000 description 3
- OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000005273 aeration Methods 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000000356 contaminant Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000010339 sodium tetraborate Nutrition 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 238000001694 spray drying Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- 102000004092 Amidohydrolases Human genes 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 229930195708 Penicillin V Natural products 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000002009 allergenic effect Effects 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000012870 ammonium sulfate precipitation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000000721 bacterilogical effect Effects 0.000 description 1
- 125000003460 beta-lactamyl group Chemical group 0.000 description 1
- 230000001851 biosynthetic effect Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
- 239000008395 clarifying agent Substances 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002054 inoculum Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000004255 ion exchange chromatography Methods 0.000 description 1
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 description 1
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 description 1
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 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
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 150000007530 organic bases Chemical group 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004816 paper chromatography Methods 0.000 description 1
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
- 239000008057 potassium phosphate buffer Substances 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
- C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
- C12N11/10—Enzymes or microbial cells immobilised on or in an organic carrier the carrier being a carbohydrate
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/78—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
- C12N9/80—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides (3.5.1)
- C12N9/84—Penicillin amidase (3.5.1.11)
-
- 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
- C12P37/00—Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin
- C12P37/04—Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin by acylation of the substituent in the 6 position
-
- 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
- C12P37/00—Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin
- C12P37/06—Preparation of compounds having a 4-thia-1-azabicyclo [3.2.0] heptane ring system, e.g. penicillin by desacylation of the substituent in the 6 position
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Biotechnology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Mycology (AREA)
- Medicinal Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Enzymes And Modification Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Solid-Sorbent Or Filter-Aiding Compositions (AREA)
- Handcart (AREA)
- Cleaning Implements For Floors, Carpets, Furniture, Walls, And The Like (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB754468 | 1968-02-15 | ||
| GB57373/68A GB1261711A (en) | 1968-02-15 | 1968-12-03 | Process for producing a penicillin acylose composition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1933301A1 true DE1933301A1 (de) | 1970-06-25 |
Family
ID=26241501
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1966428A Expired DE1966428C3 (de) | 1968-02-15 | 1969-02-14 | Verfahren zur Herstellung von wasserunlöslicher Penicillinacylase |
| DE19691933301 Pending DE1933301A1 (de) | 1968-02-15 | 1969-02-14 | Verfahren zur Herstellung von hypoallergenischen Penicillinen |
| DE19691907365 Pending DE1907365A1 (de) | 1968-02-15 | 1969-02-14 | Verfahren zur Herstellung einer zellfreien Penicillinacylase |
| DE1966427A Expired DE1966427C3 (de) | 1968-02-15 | 1969-02-14 | Verfahren zur Herstellung von 6-AminopenicUlansäure |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE1966428A Expired DE1966428C3 (de) | 1968-02-15 | 1969-02-14 | Verfahren zur Herstellung von wasserunlöslicher Penicillinacylase |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19691907365 Pending DE1907365A1 (de) | 1968-02-15 | 1969-02-14 | Verfahren zur Herstellung einer zellfreien Penicillinacylase |
| DE1966427A Expired DE1966427C3 (de) | 1968-02-15 | 1969-02-14 | Verfahren zur Herstellung von 6-AminopenicUlansäure |
Country Status (17)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2134530A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1971-04-28 | 1972-12-08 | Snam Progetti |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1357317A (en) * | 1970-08-27 | 1974-06-19 | Beecham Group Ltd | Enzymes |
| BE791748A (fr) * | 1971-11-23 | 1973-05-22 | Bayer Ag | Procede de production d'acide 6-aminopenicillanique par ruptureenzymatique de penicillines |
| JPS5420193A (en) * | 1977-07-12 | 1979-02-15 | Tanabe Seiyaku Co Ltd | Immobilized aminoacylase and its preparation |
| GB9718740D0 (en) | 1997-09-05 | 1997-11-12 | Advanced Phytonics Ltd | Improvements in or relating to the preparation of a compound |
| DE10123048A1 (de) * | 2001-05-11 | 2002-11-21 | Bermatingen Maschf | Messer für Kreiselmulchgeräte |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB877898A (en) * | 1956-12-06 | 1961-09-20 | Apv Co Ltd | A new or improved method of liberating enzymes |
| GB1118566A (en) * | 1964-11-25 | 1968-07-03 | Beecham Group Ltd | Production of 6-aminopenicillanic acid |
-
1969
- 1969-01-24 BE BE727506D patent/BE727506A/xx unknown
- 1969-02-01 IT IT34651/69A patent/IT1061759B/it active
- 1969-02-04 CA CA041,889A patent/CA941769A/en not_active Expired
- 1969-02-06 AT AT118469A patent/AT297218B/de not_active IP Right Cessation
- 1969-02-06 AT AT100971A patent/AT300198B/de not_active IP Right Cessation
- 1969-02-10 NL NL6902045.A patent/NL158547B/xx not_active IP Right Cessation
- 1969-02-11 SE SE01820/69A patent/SE352643B/xx unknown
- 1969-02-11 SE SE7111628A patent/SE382990B/xx unknown
- 1969-02-13 ES ES363592A patent/ES363592A1/es not_active Expired
- 1969-02-13 SU SU1309423A patent/SU404195A3/ru active
- 1969-02-14 DK DK80469AA patent/DK128421B/da unknown
- 1969-02-14 IE IE199/69A patent/IE32962B1/xx unknown
- 1969-02-14 NO NO610/69A patent/NO131388C/no unknown
- 1969-02-14 DE DE1966428A patent/DE1966428C3/de not_active Expired
- 1969-02-14 FI FI690482A patent/FI47109C/fi active
- 1969-02-14 DE DE19691933301 patent/DE1933301A1/de active Pending
- 1969-02-14 CH CH226769A patent/CH523320A/de not_active IP Right Cessation
- 1969-02-14 DE DE19691907365 patent/DE1907365A1/de active Pending
- 1969-02-14 CS CS176071*1A patent/CS155970B2/cs unknown
- 1969-02-14 DE DE1966427A patent/DE1966427C3/de not_active Expired
- 1969-02-14 FR FR6903732A patent/FR2001977A1/fr active Granted
- 1969-02-15 JP JP44010799A patent/JPS4833386B1/ja active Pending
- 1969-05-23 NO NO692139A patent/NO131387C/no unknown
-
1970
- 1970-09-26 ES ES384026A patent/ES384026A1/es not_active Expired
- 1970-09-26 ES ES384025A patent/ES384025A1/es not_active Expired
- 1970-12-16 FR FR7045429A patent/FR2081316B1/fr not_active Expired
- 1970-12-26 ES ES70384027A patent/ES384027A1/es not_active Expired
-
1971
- 1971-09-14 SE SE7111629A patent/SE400291B/xx unknown
-
1972
- 1972-02-14 CH CH79172A patent/CH538540A/de unknown
-
1973
- 1973-01-29 NO NO73361A patent/NO131386C/no unknown
-
1979
- 1979-03-13 JP JP2909779A patent/JPS5622278B1/ja active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2134530A1 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1971-04-28 | 1972-12-08 | Snam Progetti |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE202015009775U1 (de) | Abscheidung von 2'-FL aus einer Fermentationsbrühe | |
| DE2908241A1 (de) | Bakterienzellenextrakt, verfahren zu seiner herstellung, diesen bakterienzellenextrakt enthaltende antitumoraktive zubereitung und adjuvanspraeparat | |
| DE2457090C2 (de) | Verfahren zur Herstellung von Impfstoffen sowie Antibronchialimpfstoff | |
| DE2422737A1 (de) | Verfahren zur herstellung von l-carbamylaminosaeuren und der entsprechenden l-aminosaeuren | |
| DE2818922A1 (de) | Verbesserte impfstoffe mit gehalt an kapselpolysacchariden | |
| DE2731570A1 (de) | Verfahren zur gewinnung eines polysaccharids mit therapeutischer wirkung | |
| DE1933301A1 (de) | Verfahren zur Herstellung von hypoallergenischen Penicillinen | |
| DE2167325C2 (de) | Antibiotikum A-201B und Verfahren zu seiner Herstellung | |
| DE60002020T2 (de) | Verfahren zur Herstellen von hochreinem Xylitol | |
| DE3019895C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | ||
| DE19545303C1 (de) | Verfahren zur Herstellung einer organischen Säure | |
| DE3119453A1 (de) | Verfahren zum reinigen bzw. anreichern von biologisch aktiven proteinen und hierzu geeignetes mittel | |
| DE2808563A1 (de) | Derivate der 3-thio-6-(1-hydroxyaethyl)-7-oxo-1-aza-bicyclo eckige klammer auf 3.2.0 eckige klammer zu hept-2-en- 2-carbonsaeure, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| DE3329255C2 (de) | Verfahren zur Herstellung der Substanz TF-500 mit carcinostatischen und immunostimulierenden Eigenschaften | |
| DE10309281A1 (de) | Verfahren zur Herstellung eines beta-1,3-Glukans mit verbesserten Eigenschaften | |
| DD207219A5 (de) | Verfahren zur herstellung einer zellfreien aspartase-loesung | |
| DE869679C (de) | Verfahren zur Erzeugung und Gewinnung eines antibiotischen Stoffes | |
| CH498158A (de) | Verfahren zur Anreicherung von L-Asparaginase | |
| DE2157847A1 (de) | Verfahren zur Erzeugung von Citronensäure | |
| DE60313518T2 (de) | Verfahren zur Herstellung eines Amylaseinhibitors | |
| DE1940083C3 (de) | Verfahren zur Herstellung konzentrierter wäßriger Lösungen von Mirakulin | |
| DE966852C (de) | Verfahren zum Reinigen und Fraktionieren von Dextranen | |
| CH636127A5 (en) | Process for the preparation of the novel antibiotic MSD890A9 | |
| DE1617899A1 (de) | Lydimycin und Verfahren zu seiner Gewinnung | |
| DE1252365B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| SH | Request for examination between 03.10.1968 and 22.04.1971 |