FI110609B - Menetelmä kasvuhormonikiteiden valmistamiseksi - Google Patents
Menetelmä kasvuhormonikiteiden valmistamiseksi Download PDFInfo
- Publication number
- FI110609B FI110609B FI952021A FI952021A FI110609B FI 110609 B FI110609 B FI 110609B FI 952021 A FI952021 A FI 952021A FI 952021 A FI952021 A FI 952021A FI 110609 B FI110609 B FI 110609B
- Authority
- FI
- Finland
- Prior art keywords
- crystals
- growth hormone
- hgh
- buffer
- phenyl
- Prior art date
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 94
- 102000018997 Growth Hormone Human genes 0.000 title claims abstract description 59
- 108010051696 Growth Hormone Proteins 0.000 title claims abstract description 59
- 239000000122 growth hormone Substances 0.000 title claims abstract description 59
- 238000000034 method Methods 0.000 title claims abstract description 32
- 238000002360 preparation method Methods 0.000 title description 12
- 239000000872 buffer Substances 0.000 claims abstract description 18
- 150000001875 compounds Chemical class 0.000 claims abstract description 11
- 125000001624 naphthyl group Chemical class 0.000 claims abstract description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 6
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 5
- 239000007864 aqueous solution Substances 0.000 claims abstract description 4
- 238000002156 mixing Methods 0.000 claims abstract description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 36
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 12
- XPNGNIFUDRPBFJ-UHFFFAOYSA-N (2-methylphenyl)methanol Chemical compound CC1=CC=CC=C1CO XPNGNIFUDRPBFJ-UHFFFAOYSA-N 0.000 claims description 6
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 6
- VAJVDSVGBWFCLW-UHFFFAOYSA-N 3-Phenyl-1-propanol Chemical compound OCCCC1=CC=CC=C1 VAJVDSVGBWFCLW-UHFFFAOYSA-N 0.000 claims description 6
- CDRQOYRPWJULJN-UHFFFAOYSA-N 1-naphthalen-1-ylethanol Chemical compound C1=CC=C2C(C(O)C)=CC=CC2=C1 CDRQOYRPWJULJN-UHFFFAOYSA-N 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- BDCFWIDZNLCTMF-UHFFFAOYSA-N 2-phenylpropan-2-ol Chemical compound CC(C)(O)C1=CC=CC=C1 BDCFWIDZNLCTMF-UHFFFAOYSA-N 0.000 claims description 3
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 2
- 101001075374 Homo sapiens Gamma-glutamyl hydrolase Proteins 0.000 claims 2
- 101000664737 Homo sapiens Somatotropin Proteins 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 abstract description 3
- 108010000521 Human Growth Hormone Proteins 0.000 description 38
- 102000002265 Human Growth Hormone Human genes 0.000 description 38
- 239000000854 Human Growth Hormone Substances 0.000 description 38
- 239000000203 mixture Substances 0.000 description 23
- 239000000243 solution Substances 0.000 description 17
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 16
- 238000009472 formulation Methods 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 108090000623 proteins and genes Proteins 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 238000003860 storage Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 9
- 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 9
- 229930195725 Mannitol Natural products 0.000 description 9
- 239000000594 mannitol Substances 0.000 description 9
- 235000010355 mannitol Nutrition 0.000 description 9
- 102000004169 proteins and genes Human genes 0.000 description 9
- 239000004471 Glycine Substances 0.000 description 8
- 150000001768 cations Chemical class 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 5
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000004472 Lysine Substances 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 108010006025 bovine growth hormone Proteins 0.000 description 4
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- 238000007689 inspection Methods 0.000 description 4
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- 230000000007 visual effect Effects 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000002965 ELISA Methods 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- DYUQAZSOFZSPHD-UHFFFAOYSA-N Phenylpropanol Chemical compound CCC(O)C1=CC=CC=C1 DYUQAZSOFZSPHD-UHFFFAOYSA-N 0.000 description 3
- 150000001413 amino acids Chemical class 0.000 description 3
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- 239000008363 phosphate buffer Substances 0.000 description 3
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- 239000007790 solid phase Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- -1 1% acetic acid Chemical class 0.000 description 2
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 2
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 description 2
- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- 206010062767 Hypophysitis Diseases 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000007979 citrate buffer Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
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- 238000004128 high performance liquid chromatography Methods 0.000 description 2
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- 125000001360 methionine group Chemical group N[C@@H](CCSC)C(=O)* 0.000 description 2
- 238000000386 microscopy Methods 0.000 description 2
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- SQYNKIJPMDEDEG-UHFFFAOYSA-N paraldehyde Chemical compound CC1OC(C)OC(C)O1 SQYNKIJPMDEDEG-UHFFFAOYSA-N 0.000 description 2
- 229960003868 paraldehyde Drugs 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000001817 pituitary effect Effects 0.000 description 2
- 210000003635 pituitary gland Anatomy 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 230000004584 weight gain Effects 0.000 description 2
- 235000019786 weight gain Nutrition 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- HQRWWHIETAKIMO-JTQLQIEISA-N (1s)-1-phenylbutan-1-ol Chemical compound CCC[C@H](O)C1=CC=CC=C1 HQRWWHIETAKIMO-JTQLQIEISA-N 0.000 description 1
- BWRBVBFLFQKBPT-UHFFFAOYSA-N (2-nitrophenyl)methanol Chemical compound OCC1=CC=CC=C1[N+]([O-])=O BWRBVBFLFQKBPT-UHFFFAOYSA-N 0.000 description 1
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 1
- IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 1
- KOVQGYQQVNCUBR-UHFFFAOYSA-N (3-methyl-4-nitrophenyl)methanol Chemical compound CC1=CC(CO)=CC=C1[N+]([O-])=O KOVQGYQQVNCUBR-UHFFFAOYSA-N 0.000 description 1
- WAPNOHKVXSQRPX-UHFFFAOYSA-N 1-phenylethanol Chemical compound CC(O)C1=CC=CC=C1 WAPNOHKVXSQRPX-UHFFFAOYSA-N 0.000 description 1
- 101150055869 25 gene Proteins 0.000 description 1
- JKTYGPATCNUWKN-UHFFFAOYSA-N 4-nitrobenzyl alcohol Chemical compound OCC1=CC=C([N+]([O-])=O)C=C1 JKTYGPATCNUWKN-UHFFFAOYSA-N 0.000 description 1
- 101100335894 Caenorhabditis elegans gly-8 gene Proteins 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 206010021067 Hypopituitarism Diseases 0.000 description 1
- 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 1
- 101100285000 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) his-3 gene Proteins 0.000 description 1
- 108091005461 Nucleic proteins Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 102000006877 Pituitary Hormones Human genes 0.000 description 1
- 108010047386 Pituitary Hormones Proteins 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 101710128967 Somatotropin-1 Proteins 0.000 description 1
- 239000012505 Superdex™ Substances 0.000 description 1
- 101150006914 TRP1 gene Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- LVTKHGUGBGNBPL-UHFFFAOYSA-N Trp-P-1 Chemical compound N1C2=CC=CC=C2C2=C1C(C)=C(N)N=C2C LVTKHGUGBGNBPL-UHFFFAOYSA-N 0.000 description 1
- 208000026928 Turner syndrome Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 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
- 238000013459 approach Methods 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229950011260 betanaphthol Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000012928 buffer substance Substances 0.000 description 1
- 229940075397 calomel Drugs 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- ZOMNIUBKTOKEHS-UHFFFAOYSA-L dimercury dichloride Chemical compound Cl[Hg][Hg]Cl ZOMNIUBKTOKEHS-UHFFFAOYSA-L 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
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- 239000000428 dust Substances 0.000 description 1
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- 238000002474 experimental method Methods 0.000 description 1
- 239000013020 final formulation Substances 0.000 description 1
- 235000013312 flour Nutrition 0.000 description 1
- 238000001641 gel filtration chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000000960 hypophysis hormone Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000012931 lyophilized formulation Substances 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000002953 phosphate buffered saline Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 238000000197 pyrolysis Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 229960004532 somatropin Drugs 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical class [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000007794 visualization technique Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/575—Hormones
- C07K14/61—Growth hormone [GH], i.e. somatotropin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Gastroenterology & Hepatology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Toxicology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
- Crystals, And After-Treatments Of Crystals (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9203175A SE9203175D0 (sv) | 1992-10-28 | 1992-10-28 | Growth hormone |
| SE9203175 | 1992-10-28 | ||
| SE9302278 | 1993-07-02 | ||
| SE19939302278A SE9302278D0 (sv) | 1992-10-28 | 1993-07-02 | Growth hormone |
| SE9300885 | 1993-10-27 | ||
| PCT/SE1993/000885 WO1994010192A1 (en) | 1992-10-28 | 1993-10-27 | Process for manufacturing crystals of growth hormone and crystals thereby obtained |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| FI952021A0 FI952021A0 (fi) | 1995-04-27 |
| FI952021L FI952021L (fi) | 1995-04-27 |
| FI110609B true FI110609B (fi) | 2003-02-28 |
Family
ID=26661557
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI952021A FI110609B (fi) | 1992-10-28 | 1995-04-27 | Menetelmä kasvuhormonikiteiden valmistamiseksi |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US5734026A (da) |
| EP (1) | EP0669934B1 (da) |
| JP (1) | JP3470135B2 (da) |
| AT (1) | ATE174602T1 (da) |
| AU (1) | AU679012B2 (da) |
| CA (1) | CA2147482C (da) |
| DE (1) | DE69322654T2 (da) |
| DK (1) | DK0669934T3 (da) |
| ES (1) | ES2126660T3 (da) |
| FI (1) | FI110609B (da) |
| NO (1) | NO320171B1 (da) |
| SE (1) | SE9302278D0 (da) |
| WO (1) | WO1994010192A1 (da) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9302278D0 (sv) * | 1992-10-28 | 1993-07-02 | Kabi Pharmacia Ab | Growth hormone |
| DE69839563D1 (de) * | 1997-09-05 | 2008-07-10 | Altus Pharmaceuticals Inc | Kohlenhydrat-vernetzte glykoproteinkristalle |
| US6500933B1 (en) | 1997-09-05 | 2002-12-31 | Altus Biologics Inc. | Methods of preparing carbohydrate crosslinked glycoprotein crystals |
| US6380357B2 (en) | 1997-12-16 | 2002-04-30 | Eli Lilly And Company | Glucagon-like peptide-1 crystals |
| US6541606B2 (en) * | 1997-12-31 | 2003-04-01 | Altus Biologics Inc. | Stabilized protein crystals formulations containing them and methods of making them |
| PL209734B1 (pl) * | 2002-02-20 | 2011-10-31 | Emisphere Tech Inc | Preparat farmaceutyczny zawierający związek GLP-1 i czynnik dostarczający oraz jego zastosowanie |
| SE0202719D0 (sv) * | 2002-09-13 | 2002-09-13 | Pharmacia Ab | Process for mfg crystals of growth hormone |
| RU2357750C2 (ru) | 2002-12-31 | 2009-06-10 | Элтус Фармасьютикалз Инк. | Кристаллы человеческого гормона роста и способы их получения |
| US20060286129A1 (en) * | 2003-12-19 | 2006-12-21 | Emisphere Technologies, Inc. | Oral GLP-1 formulations |
| US7444197B2 (en) | 2004-05-06 | 2008-10-28 | Smp Logic Systems Llc | Methods, systems, and software program for validation and monitoring of pharmaceutical manufacturing processes |
| US7799273B2 (en) | 2004-05-06 | 2010-09-21 | Smp Logic Systems Llc | Manufacturing execution system for validation, quality and risk assessment and monitoring of pharmaceutical manufacturing processes |
| US20090023629A1 (en) * | 2005-12-23 | 2009-01-22 | Altus Pharmaceuticals Inc. | Compositions comprising polycation-complexed protein crystals and methods of treatment using them |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2098358T3 (es) * | 1990-06-04 | 1997-05-01 | Schering Corp | Metodo para preparar cristales de interferon alfa-2. |
| ES2093103T3 (es) * | 1990-06-15 | 1996-12-16 | Schering Corp | Interleuquina-4 cristalina. |
| DK168790D0 (da) * | 1990-07-13 | 1990-07-13 | Novo Nordisk As | |
| US5015627A (en) * | 1990-07-20 | 1991-05-14 | Smithkline Beecham Corporation | Stabilized somatotropin for parenteral administration |
| SE9302278D0 (sv) * | 1992-10-28 | 1993-07-02 | Kabi Pharmacia Ab | Growth hormone |
-
1993
- 1993-07-02 SE SE19939302278A patent/SE9302278D0/xx unknown
- 1993-10-27 WO PCT/SE1993/000885 patent/WO1994010192A1/en not_active Ceased
- 1993-10-27 AU AU54011/94A patent/AU679012B2/en not_active Ceased
- 1993-10-27 ES ES93924266T patent/ES2126660T3/es not_active Expired - Lifetime
- 1993-10-27 CA CA002147482A patent/CA2147482C/en not_active Expired - Fee Related
- 1993-10-27 DE DE69322654T patent/DE69322654T2/de not_active Expired - Fee Related
- 1993-10-27 DK DK93924266T patent/DK0669934T3/da active
- 1993-10-27 US US08/424,450 patent/US5734026A/en not_active Expired - Fee Related
- 1993-10-27 JP JP51096494A patent/JP3470135B2/ja not_active Expired - Fee Related
- 1993-10-27 EP EP93924266A patent/EP0669934B1/en not_active Expired - Lifetime
- 1993-10-27 AT AT93924266T patent/ATE174602T1/de not_active IP Right Cessation
-
1995
- 1995-04-24 NO NO19951547A patent/NO320171B1/no unknown
- 1995-04-27 FI FI952021A patent/FI110609B/fi active
Also Published As
| Publication number | Publication date |
|---|---|
| ATE174602T1 (de) | 1999-01-15 |
| NO951547D0 (no) | 1995-04-24 |
| FI952021A0 (fi) | 1995-04-27 |
| AU679012B2 (en) | 1997-06-19 |
| NO951547L (no) | 1995-04-24 |
| AU5401194A (en) | 1994-05-24 |
| NO320171B1 (no) | 2005-11-07 |
| HK1013299A1 (en) | 1999-08-20 |
| DK0669934T3 (da) | 1999-08-23 |
| DE69322654D1 (de) | 1999-01-28 |
| EP0669934B1 (en) | 1998-12-16 |
| ES2126660T3 (es) | 1999-04-01 |
| FI952021L (fi) | 1995-04-27 |
| DE69322654T2 (de) | 1999-06-17 |
| US5734026A (en) | 1998-03-31 |
| JP3470135B2 (ja) | 2003-11-25 |
| WO1994010192A1 (en) | 1994-05-11 |
| CA2147482A1 (en) | 1994-05-11 |
| JPH08505127A (ja) | 1996-06-04 |
| EP0669934A1 (en) | 1995-09-06 |
| SE9302278D0 (sv) | 1993-07-02 |
| CA2147482C (en) | 2003-09-23 |
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