AT402503B - Gereinigte polypeptide mit einem molekulargewicht von mindestens 35.000 und verfahren zu ihrer herstellung - Google Patents
Gereinigte polypeptide mit einem molekulargewicht von mindestens 35.000 und verfahren zu ihrer herstellung Download PDFInfo
- Publication number
- AT402503B AT402503B AT0151591A AT151591A AT402503B AT 402503 B AT402503 B AT 402503B AT 0151591 A AT0151591 A AT 0151591A AT 151591 A AT151591 A AT 151591A AT 402503 B AT402503 B AT 402503B
- Authority
- AT
- Austria
- Prior art keywords
- polylactide
- microparticles
- glycolide
- solution
- purified
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 24
- 238000004519 manufacturing process Methods 0.000 title description 5
- 108090000765 processed proteins & peptides Proteins 0.000 title description 3
- 229920001184 polypeptide Polymers 0.000 title 1
- 102000004196 processed proteins & peptides Human genes 0.000 title 1
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 59
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 45
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 26
- 229920000642 polymer Polymers 0.000 claims description 25
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical group O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 19
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 17
- 239000000243 solution Substances 0.000 claims description 17
- 239000011859 microparticle Substances 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 238000004140 cleaning Methods 0.000 claims description 11
- 239000000047 product Substances 0.000 claims description 11
- 239000012088 reference solution Substances 0.000 claims description 10
- 239000000178 monomer Substances 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 239000008103 glucose Substances 0.000 claims description 8
- 239000011159 matrix material Substances 0.000 claims description 8
- 150000001768 cations Chemical group 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 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 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- SHZIWNPUGXLXDT-UHFFFAOYSA-N caproic acid ethyl ester Natural products CCCCCC(=O)OCC SHZIWNPUGXLXDT-UHFFFAOYSA-N 0.000 claims description 6
- 229910052751 metal Inorganic materials 0.000 claims description 6
- 239000002184 metal Substances 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- -1 ethylhexanoate anion Chemical class 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229920005862 polyol Polymers 0.000 claims description 5
- 150000003077 polyols Chemical class 0.000 claims description 5
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 claims description 4
- 108010016076 Octreotide Proteins 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 229960002700 octreotide Drugs 0.000 claims description 4
- 238000000108 ultra-filtration Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 claims description 3
- 229960002802 bromocriptine Drugs 0.000 claims description 3
- 150000005846 sugar alcohols Chemical class 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 2
- 239000013078 crystal Substances 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 150000002739 metals Chemical class 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims 3
- 239000000725 suspension Substances 0.000 claims 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- 241000283973 Oryctolagus cuniculus Species 0.000 claims 2
- 206010036832 Prolactinoma Diseases 0.000 claims 2
- 241000700159 Rattus Species 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 238000003127 radioimmunoassay Methods 0.000 claims 2
- 241000700112 Chinchilla Species 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 239000008351 acetate buffer Substances 0.000 claims 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims 1
- 235000019445 benzyl alcohol Nutrition 0.000 claims 1
- 239000008280 blood Substances 0.000 claims 1
- 210000004369 blood Anatomy 0.000 claims 1
- 230000037396 body weight Effects 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 1
- 229910000397 disodium phosphate Inorganic materials 0.000 claims 1
- 235000019800 disodium phosphate Nutrition 0.000 claims 1
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 claims 1
- 239000011521 glass Substances 0.000 claims 1
- 208000031424 hyperprolactinemia Diseases 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 229940098779 methanesulfonic acid Drugs 0.000 claims 1
- 230000036470 plasma concentration Effects 0.000 claims 1
- 229920001993 poloxamer 188 Polymers 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 230000005855 radiation Effects 0.000 claims 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- 239000011780 sodium chloride Substances 0.000 claims 1
- 239000001488 sodium phosphate Substances 0.000 claims 1
- 238000003756 stirring Methods 0.000 claims 1
- 230000009885 systemic effect Effects 0.000 claims 1
- 239000008215 water for injection Substances 0.000 claims 1
- 239000003054 catalyst Substances 0.000 description 27
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 14
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 14
- 239000004310 lactic acid Substances 0.000 description 7
- 235000014655 lactic acid Nutrition 0.000 description 7
- 229910052718 tin Inorganic materials 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000007858 starting material Substances 0.000 description 6
- 229960001031 glucose Drugs 0.000 description 5
- 239000002245 particle Substances 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000002378 acidificating effect Effects 0.000 description 4
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 4
- 239000007943 implant Substances 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- OBETXYAYXDNJHR-SSDOTTSWSA-M (2r)-2-ethylhexanoate Chemical compound CCCC[C@@H](CC)C([O-])=O OBETXYAYXDNJHR-SSDOTTSWSA-M 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000008186 active pharmaceutical agent Substances 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- XZZXKVYTWCYOQX-UHFFFAOYSA-J octanoate;tin(4+) Chemical compound [Sn+4].CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O.CCCCCCCC([O-])=O XZZXKVYTWCYOQX-UHFFFAOYSA-J 0.000 description 3
- 229920000570 polyether Polymers 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000004721 Polyphenylene oxide Substances 0.000 description 2
- 125000002947 alkylene group Chemical group 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000002149 energy-dispersive X-ray emission spectroscopy Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000005227 gel permeation chromatography Methods 0.000 description 2
- 239000011964 heteropoly acid Substances 0.000 description 2
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 2
- 239000000391 magnesium silicate Substances 0.000 description 2
- 229910052919 magnesium silicate Inorganic materials 0.000 description 2
- 235000019792 magnesium silicate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- 229920001281 polyalkylene Polymers 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 2
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 244000248349 Citrus limon Species 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 108010069514 Cyclic Peptides Proteins 0.000 description 1
- 102000001189 Cyclic Peptides Human genes 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 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 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- 102000005157 Somatostatin Human genes 0.000 description 1
- 108010056088 Somatostatin Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- GZCGUPFRVQAUEE-SLPGGIOYSA-N aldehydo-D-glucose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O GZCGUPFRVQAUEE-SLPGGIOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 150000004292 cyclic ethers Chemical class 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960003133 ergot alkaloid Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 238000000673 graphite furnace atomic absorption spectrometry Methods 0.000 description 1
- 230000005283 ground state Effects 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 150000004679 hydroxides Chemical class 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229910052745 lead Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 description 1
- 229960000553 somatostatin Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IUTCEZPPWBHGIX-UHFFFAOYSA-N tin(2+) Chemical class [Sn+2] IUTCEZPPWBHGIX-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 238000004454 trace mineral analysis Methods 0.000 description 1
- 229910052721 tungsten Inorganic materials 0.000 description 1
- 239000010937 tungsten Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/88—Post-polymerisation treatment
- C08G63/90—Purification; Drying
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Polyesters Or Polycarbonates (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB909016882A GB9016882D0 (en) | 1990-08-01 | 1990-08-01 | Improvements in or relating to organic compounds |
| GB909016840A GB9016840D0 (en) | 1990-08-01 | 1990-08-01 | Improvements in or relating to organic compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ATA151591A ATA151591A (de) | 1996-10-15 |
| AT402503B true AT402503B (de) | 1997-06-25 |
Family
ID=26297417
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT0151591A AT402503B (de) | 1990-08-01 | 1991-07-30 | Gereinigte polypeptide mit einem molekulargewicht von mindestens 35.000 und verfahren zu ihrer herstellung |
Country Status (27)
| Country | Link |
|---|---|
| EP (2) | EP0816413B1 (en:Method) |
| JP (1) | JP3137368B2 (en:Method) |
| KR (1) | KR100255904B1 (en:Method) |
| AT (1) | AT402503B (en:Method) |
| AU (1) | AU650277B2 (en:Method) |
| CA (1) | CA2048200C (en:Method) |
| CH (1) | CH683772A5 (en:Method) |
| CY (1) | CY1986A (en:Method) |
| DE (1) | DE4124468B4 (en:Method) |
| DK (2) | DK0469520T3 (en:Method) |
| ES (2) | ES2243966T3 (en:Method) |
| FI (2) | FI108040B (en:Method) |
| FR (1) | FR2665453B1 (en:Method) |
| GB (1) | GB2246573B (en:Method) |
| GR (1) | GR3026322T3 (en:Method) |
| HK (1) | HK11797A (en:Method) |
| HU (1) | HUT59837A (en:Method) |
| IE (1) | IE66185B1 (en:Method) |
| IL (1) | IL99007A (en:Method) |
| IT (1) | IT1252944B (en:Method) |
| LU (1) | LU87985A1 (en:Method) |
| MY (1) | MY108621A (en:Method) |
| NO (1) | NO912960D0 (en:Method) |
| NZ (1) | NZ239184A (en:Method) |
| PH (1) | PH31047A (en:Method) |
| PT (1) | PT98491B (en:Method) |
| TW (2) | TW282477B (en:Method) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5560929A (en) * | 1986-08-18 | 1996-10-01 | The Dow Chemical Company | Structured copolymers and their use as absorbents, gels and carriers of metal ions |
| US5527524A (en) * | 1986-08-18 | 1996-06-18 | The Dow Chemical Company | Dense star polymer conjugates |
| US5225521A (en) * | 1991-12-31 | 1993-07-06 | E. I. Du Pont De Nemours And Company | Star-shaped hydroxyacid polymers |
| US6200558B1 (en) | 1993-09-14 | 2001-03-13 | The United States Of America As Represented By The Department Of Health And Human Services | Biopolymer-bound nitric oxide-releasing compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
| US5405919A (en) * | 1992-08-24 | 1995-04-11 | The United States Of America As Represented By The Secretary Of Health And Human Services | Polymer-bound nitric oxide/nucleophile adduct compositions, pharmaceutical compositions and methods of treating biological disorders |
| US5525357A (en) * | 1992-08-24 | 1996-06-11 | The United States Of America As Represented By The Department Of Health And Human Services | Polymer-bound nitric oxide/nucleophile adduct compositions, pharmaceutical compositions incorporating same and methods of treating biological disorders using same |
| JPH06116381A (ja) * | 1992-10-09 | 1994-04-26 | Mitsui Toatsu Chem Inc | ポリヒドロキシカルボン酸の精製方法 |
| DE4412317A1 (de) * | 1993-04-21 | 1994-10-27 | Basf Ag | Polylactid mit verbreiterter Molmassenverteilung |
| US5359026A (en) * | 1993-07-30 | 1994-10-25 | Cargill, Incorporated | Poly(lactide) copolymer and process for manufacture thereof |
| US5496923A (en) * | 1993-09-20 | 1996-03-05 | Mitsui Toatsu Chemicals, Inc. | Purification process of aliphatic polyester |
| NZ276088A (en) | 1993-11-19 | 1999-07-29 | Janssen Pharmaceutica Nv | [(1,2-benzisoxazol-3-yl)-1-piperidinyl-alkyl-6,7,8,9-tetrahydro-4h- pyrido[1,2-a]-pyrimidin-4-one derivatives (ie risperidone) |
| IL128774A (en) * | 1994-03-07 | 2001-05-20 | Dow Chemical Co | Composition comprising a dendritic poymer in complex with at least one unit of biological response modifier and a process for the preparation thereof |
| AU5862199A (en) | 1998-09-11 | 2000-04-03 | Michael Raschke | Biologically active implants |
| US6362308B1 (en) * | 2000-08-10 | 2002-03-26 | Alkermes Controlled Therapeutics Inc. Ii | Acid end group poly(d,l-lactide-co-glycolide) copolymers high glycolide content |
| WO2003006525A1 (en) * | 2001-07-10 | 2003-01-23 | Kureha Chemical Industry Company, Limited | Polyhydroxycarboxylic acid and its production process |
| AU2002358831B2 (en) | 2001-10-10 | 2007-09-06 | Pierre Fabre Medicament | Prolonged release biodegradable microspheres and method for preparing same |
| FR2830448B1 (fr) * | 2001-10-10 | 2004-03-19 | Pf Medicament | Microspheres biodegradables a liberation prolongee et leur procede de preparation |
| GB0226993D0 (en) * | 2002-11-19 | 2002-12-24 | Novartis Ag | Organic compounds |
| AU2013204972B2 (en) * | 2002-11-19 | 2016-04-21 | Novartis Ag | Pharmaceutical composition comprising octreotide microparticles |
| US20040097419A1 (en) * | 2002-11-19 | 2004-05-20 | Holger Petersen | Organic compounds |
| ES2383303T3 (es) | 2005-11-10 | 2012-06-20 | Chemi S.P.A. | Formulaciones de inhibidores de la liberación prolongada de la hormona del crecimiento análogos de la somatostatina |
| CN101193531B (zh) | 2006-11-29 | 2010-12-01 | 富准精密工业(深圳)有限公司 | 散热装置 |
| WO2009091150A2 (en) * | 2007-12-31 | 2009-07-23 | Samyang Corporation | Highly pure amphiphilic copolymer comprising hydrophobic block from alpha-hydroxy acid and process for the preparation thereof |
| CA2756388C (en) * | 2009-03-23 | 2015-10-27 | Micell Technologies, Inc. | Biodegradable polymers with low acidic impurity |
| JP5594996B2 (ja) | 2009-09-14 | 2014-09-24 | 三菱重工業株式会社 | 航空機の操縦システム |
| US8722845B2 (en) | 2010-06-21 | 2014-05-13 | Lg Chem, Ltd. | Polylactide resin having excellent heat resistance and preparation method thereof |
| EP2455414A1 (de) * | 2010-11-17 | 2012-05-23 | Evonik Röhm GmbH | Verfahren zur Herstellung von hochmolekularen, resorbierbaren Polyestern, die mit dem Verfahren herstellbaren hochmolekularen resorbierbaren Polyester und deren Verwendung |
| EP2455415A1 (de) * | 2010-11-17 | 2012-05-23 | Evonik Röhm GmbH | Verfahren zur Herstellung von niedermolekularen, resorbierbaren Polyestern, die mit dem Verfahren herstellbaren niedermolekularen resorbierbaren Polyester und deren Verwendung |
| CN105820332B (zh) * | 2015-01-09 | 2018-06-29 | 北京化工大学 | 一种星形聚氨基酸和星形聚氨基酸载药纳米胶束及制备方法 |
| EP3408305B1 (en) | 2016-01-29 | 2024-03-06 | Tolmar Inc. | Purification and decolorization of polymers |
| CA3073842A1 (en) * | 2017-08-31 | 2019-03-07 | Evonik Corporation | Improved resorbable polymer purification process |
| GR1009392B (el) * | 2017-09-19 | 2018-10-25 | Φαρματεν Αβεε | Φαρμακευτικο σκευασμα που περιλαμβανει ενα πεπτιδικο φαρμακο και μεθοδος για την παρασκευη αυτου |
| GB2568526A (en) * | 2017-11-20 | 2019-05-22 | Rebio Tech Oy | Composition |
| CN112940234B (zh) * | 2021-01-28 | 2022-05-03 | 广东粤港澳大湾区黄埔材料研究院 | 一种高纯度聚乙丙交酯的制备方法 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0026599A1 (en) * | 1979-09-12 | 1981-04-08 | Eli Lilly And Company | Copolymer from lactic acid and glycolic acid and process for making same |
| EP0172636A1 (en) * | 1984-07-06 | 1986-02-26 | Wako Pure Chemical Industries, Ltd. | Method for producing a polymer or copolymer of lactic acid and/or glycolic acid |
| DE3641692A1 (de) * | 1986-12-06 | 1988-06-09 | Boehringer Ingelheim Kg | Katalysatorfreie resorbierbare homopolymere und copolymere |
| DE3708916A1 (de) * | 1987-03-19 | 1988-09-29 | Boehringer Ingelheim Kg | Verfahren zur reinigung resorbierbarer polyester |
| EP0202065B1 (en) * | 1985-05-07 | 1993-04-07 | Takeda Chemical Industries, Ltd. | Polymer, production and use thereof |
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| GB1467970A (en) * | 1975-05-02 | 1977-03-23 | Ici Ltd | Purification of polyethers |
| CH656884A5 (de) * | 1983-08-26 | 1986-07-31 | Sandoz Ag | Polyolester, deren herstellung und verwendung. |
| US4677231A (en) * | 1984-11-13 | 1987-06-30 | Asahi Kasei Kogyo Kabushiki Kaisha | Process for purification of polyether |
| JPH0610252B2 (ja) * | 1985-08-21 | 1994-02-09 | 和光純薬工業株式会社 | 重合体の製造法 |
| JP2714454B2 (ja) * | 1988-11-07 | 1998-02-16 | 三井東圧化学株式会社 | 生体吸収性ポリエステルの製造方法 |
| CA2040141C (en) * | 1990-04-13 | 2002-05-14 | Minoru Yamada | Biodegradable high-molecular polymers, production and use therof |
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1991
- 1991-07-17 MY MYPI91001289A patent/MY108621A/en unknown
- 1991-07-22 HU HU912452A patent/HUT59837A/hu unknown
- 1991-07-23 IT ITRM910553A patent/IT1252944B/it active IP Right Grant
- 1991-07-24 DE DE4124468A patent/DE4124468B4/de not_active Expired - Fee Related
- 1991-07-29 ES ES97202586T patent/ES2243966T3/es not_active Expired - Lifetime
- 1991-07-29 CH CH2264/91A patent/CH683772A5/de not_active IP Right Cessation
- 1991-07-29 DK DK91112725T patent/DK0469520T3/da active
- 1991-07-29 EP EP97202586A patent/EP0816413B1/en not_active Expired - Lifetime
- 1991-07-29 DK DK97202586T patent/DK0816413T3/da active
- 1991-07-29 EP EP91112725A patent/EP0469520B1/en not_active Expired - Lifetime
- 1991-07-29 ES ES91112725T patent/ES2112259T3/es not_active Expired - Lifetime
- 1991-07-30 FI FI913641A patent/FI108040B/fi active
- 1991-07-30 AU AU81430/91A patent/AU650277B2/en not_active Ceased
- 1991-07-30 PH PH42864A patent/PH31047A/en unknown
- 1991-07-30 FR FR9109673A patent/FR2665453B1/fr not_active Expired - Fee Related
- 1991-07-30 AT AT0151591A patent/AT402503B/de not_active IP Right Cessation
- 1991-07-30 NO NO912960A patent/NO912960D0/no unknown
- 1991-07-30 PT PT98491A patent/PT98491B/pt not_active IP Right Cessation
- 1991-07-30 LU LU87985A patent/LU87985A1/fr unknown
- 1991-07-30 NZ NZ239184A patent/NZ239184A/en not_active IP Right Cessation
- 1991-07-30 IL IL9900791A patent/IL99007A/en not_active IP Right Cessation
- 1991-07-30 GB GB9116396A patent/GB2246573B/en not_active Expired - Fee Related
- 1991-07-31 KR KR1019910013171A patent/KR100255904B1/ko not_active Expired - Fee Related
- 1991-07-31 CA CA002048200A patent/CA2048200C/en not_active Expired - Lifetime
- 1991-07-31 JP JP03191781A patent/JP3137368B2/ja not_active Expired - Fee Related
- 1991-07-31 IE IE269791A patent/IE66185B1/en not_active IP Right Cessation
- 1991-08-02 TW TW082100731A patent/TW282477B/zh not_active IP Right Cessation
- 1991-08-02 TW TW080106046A patent/TW218025B/zh not_active IP Right Cessation
-
1997
- 1997-02-05 HK HK11797A patent/HK11797A/xx not_active IP Right Cessation
- 1997-09-05 CY CY198697A patent/CY1986A/en unknown
-
1998
- 1998-03-11 GR GR980400513T patent/GR3026322T3/el unknown
-
2001
- 2001-06-05 FI FI20011189A patent/FI111268B/fi active
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| EP0026599A1 (en) * | 1979-09-12 | 1981-04-08 | Eli Lilly And Company | Copolymer from lactic acid and glycolic acid and process for making same |
| EP0172636A1 (en) * | 1984-07-06 | 1986-02-26 | Wako Pure Chemical Industries, Ltd. | Method for producing a polymer or copolymer of lactic acid and/or glycolic acid |
| US4677191A (en) * | 1984-07-06 | 1987-06-30 | Wada Pure Chemical Ind., Ltd. | Copolymer and method for producing the same |
| EP0202065B1 (en) * | 1985-05-07 | 1993-04-07 | Takeda Chemical Industries, Ltd. | Polymer, production and use thereof |
| DE3641692A1 (de) * | 1986-12-06 | 1988-06-09 | Boehringer Ingelheim Kg | Katalysatorfreie resorbierbare homopolymere und copolymere |
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| DE3708916A1 (de) * | 1987-03-19 | 1988-09-29 | Boehringer Ingelheim Kg | Verfahren zur reinigung resorbierbarer polyester |
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| ELJ | Ceased due to non-payment of the annual fee |