JPH0378847B2 - - Google Patents
Info
- Publication number
- JPH0378847B2 JPH0378847B2 JP60013226A JP1322685A JPH0378847B2 JP H0378847 B2 JPH0378847 B2 JP H0378847B2 JP 60013226 A JP60013226 A JP 60013226A JP 1322685 A JP1322685 A JP 1322685A JP H0378847 B2 JPH0378847 B2 JP H0378847B2
- Authority
- JP
- Japan
- Prior art keywords
- composition
- aqueous solution
- leu
- solution
- freeze
- 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.)
- Expired - Lifetime
Links
- 239000000203 mixture Substances 0.000 claims description 33
- -1 aliphatic amino acid Chemical class 0.000 claims description 5
- 102000008100 Human Serum Albumin Human genes 0.000 claims description 3
- 108091006905 Human Serum Albumin Proteins 0.000 claims description 3
- 102000015696 Interleukins Human genes 0.000 claims 1
- 108010063738 Interleukins Proteins 0.000 claims 1
- 108010002350 Interleukin-2 Proteins 0.000 description 57
- 102000000588 Interleukin-2 Human genes 0.000 description 57
- 239000007864 aqueous solution Substances 0.000 description 30
- 239000000047 product Substances 0.000 description 19
- 239000000243 solution Substances 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 230000000694 effects Effects 0.000 description 13
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 235000002639 sodium chloride Nutrition 0.000 description 12
- 101001002657 Homo sapiens Interleukin-2 Proteins 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 235000001014 amino acid Nutrition 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 150000001413 amino acids Chemical class 0.000 description 8
- 238000004108 freeze drying Methods 0.000 description 8
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 150000002772 monosaccharides Chemical class 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 239000004471 Glycine Substances 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
- 238000010790 dilution Methods 0.000 description 6
- 239000012895 dilution Substances 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 150000005846 sugar alcohols Chemical class 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 239000012980 RPMI-1640 medium Substances 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 239000006228 supernatant Substances 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- IQFYYKKMVGJFEH-OFKYTIFKSA-N 1-[(2r,4s,5r)-4-hydroxy-5-(tritiooxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione Chemical compound C1[C@H](O)[C@@H](CO[3H])O[C@H]1N1C(=O)NC(=O)C(C)=C1 IQFYYKKMVGJFEH-OFKYTIFKSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 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 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 238000013329 compounding Methods 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 239000012156 elution solvent Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 102000055277 human IL2 Human genes 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 230000006798 recombination Effects 0.000 description 3
- 238000005215 recombination Methods 0.000 description 3
- 239000011550 stock solution Substances 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- 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 2
- 241001452028 Escherichia coli DH1 Species 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- 206010061598 Immunodeficiency Diseases 0.000 description 2
- 208000029462 Immunodeficiency disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 238000005194 fractionation Methods 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 230000007813 immunodeficiency Effects 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 108010054155 lysyllysine Proteins 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000012460 protein solution Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- VZZUJVDCIBINIT-YDALLXLXSA-N (2s)-2-acetamido-3-(1h-indol-3-yl)propanoic acid;sodium Chemical compound [Na].C1=CC=C2C(C[C@H](NC(=O)C)C(O)=O)=CNC2=C1 VZZUJVDCIBINIT-YDALLXLXSA-N 0.000 description 1
- FXEDIXLHKQINFP-UHFFFAOYSA-N 12-O-tetradecanoylphorbol-13-acetate Natural products CCCCCCCCCCCCCC(=O)OC1CC2(O)C(C=C(CO)CC3(O)C2C=C(C)C3=O)C4C(C)(C)C14OC(=O)C FXEDIXLHKQINFP-UHFFFAOYSA-N 0.000 description 1
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- WDIYWDJLXOCGRW-ACZMJKKPSA-N Ala-Asp-Glu Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(O)=O WDIYWDJLXOCGRW-ACZMJKKPSA-N 0.000 description 1
- MVBWLRJESQOQTM-ACZMJKKPSA-N Ala-Gln-Ser Chemical compound [H]N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(O)=O MVBWLRJESQOQTM-ACZMJKKPSA-N 0.000 description 1
- WKPXXXUSUHAXDE-SRVKXCTJSA-N Arg-Pro-Arg Chemical compound NC(N)=NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CCCN=C(N)N)C(O)=O WKPXXXUSUHAXDE-SRVKXCTJSA-N 0.000 description 1
- AWXDRZJQCVHCIT-DCAQKATOSA-N Asn-Pro-Lys Chemical compound NCCCC[C@@H](C(O)=O)NC(=O)[C@@H]1CCCN1C(=O)[C@@H](N)CC(N)=O AWXDRZJQCVHCIT-DCAQKATOSA-N 0.000 description 1
- QNNBHTFDFFFHGC-KKUMJFAQSA-N Asn-Tyr-Lys Chemical compound C1=CC(=CC=C1C[C@@H](C(=O)N[C@@H](CCCCN)C(=O)O)NC(=O)[C@H](CC(=O)N)N)O QNNBHTFDFFFHGC-KKUMJFAQSA-N 0.000 description 1
- JNCRAQVYJZGIOW-QSFUFRPTSA-N Asn-Val-Ile Chemical compound [H]N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O JNCRAQVYJZGIOW-QSFUFRPTSA-N 0.000 description 1
- RQHLMGCXCZUOGT-ZPFDUUQYSA-N Asp-Leu-Ile Chemical compound [H]N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(O)=O RQHLMGCXCZUOGT-ZPFDUUQYSA-N 0.000 description 1
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 1
- 108010062580 Concanavalin A Proteins 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
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- 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 1
- 208000006558 Dental Calculus Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MUSGDMDGNGXULI-DCAQKATOSA-N Glu-Glu-Leu Chemical compound CC(C)C[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O MUSGDMDGNGXULI-DCAQKATOSA-N 0.000 description 1
- QJCKNLPMTPXXEM-AUTRQRHGSA-N Glu-Glu-Val Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CCC(O)=O QJCKNLPMTPXXEM-AUTRQRHGSA-N 0.000 description 1
- DVLZZEPUNFEUBW-AVGNSLFASA-N Glu-His-Leu Chemical compound CC(C)C[C@@H](C(=O)O)NC(=O)[C@H](CC1=CN=CN1)NC(=O)[C@H](CCC(=O)O)N DVLZZEPUNFEUBW-AVGNSLFASA-N 0.000 description 1
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- LYERIXUFCYVFFX-GVXVVHGQSA-N Val-Leu-Glu Chemical compound CC(C)C[C@@H](C(=O)N[C@@H](CCC(=O)O)C(=O)O)NC(=O)[C@H](C(C)C)N LYERIXUFCYVFFX-GVXVVHGQSA-N 0.000 description 1
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- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 108010092114 histidylphenylalanine Proteins 0.000 description 1
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
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Landscapes
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
Priority Applications (17)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP60013226A JPS60222424A (ja) | 1985-01-25 | 1985-01-25 | インタ−ロイキン−2組成物 |
DE8585302176T DE3583880D1 (de) | 1984-04-09 | 1985-03-28 | Stabile interleukin-2-zusammensetzung. |
AT85302176T ATE66612T1 (de) | 1984-04-09 | 1985-03-28 | Stabile interleukin-2-zusammensetzung. |
EP19850302176 EP0158487B1 (en) | 1984-04-09 | 1985-03-28 | Stable composition of interleukin-2 |
PH32069A PH22897A (en) | 1984-04-09 | 1985-03-29 | Stable composition of interleukin-2 |
CN85101301A CN1019453B (zh) | 1985-01-25 | 1985-04-01 | 白细胞介素-2的稳定组合物的制备方法 |
DK148885A DK148885A (da) | 1984-04-09 | 1985-04-02 | Stabilt praeparat af interleukin-2 |
IL74823A IL74823A (en) | 1984-04-09 | 1985-04-04 | Stable composition of interleukin-2 |
NZ211702A NZ211702A (en) | 1984-04-09 | 1985-04-04 | Interleukin composition |
CA000478351A CA1285478C (en) | 1984-04-09 | 1985-04-04 | Stable composition of interleukin-2 |
AU40839/85A AU579359B2 (en) | 1984-04-09 | 1985-04-04 | Stable composition of interleukin-2 |
US06/720,754 US4645830A (en) | 1984-04-09 | 1985-04-08 | Stable composition of interleukin-2 and albumin |
KR1019850002345A KR920005048B1 (ko) | 1984-04-09 | 1985-04-08 | 인터로이킨-2의 안정화 조성물 제조방법 |
PT80247A PT80247B (pt) | 1984-04-09 | 1985-04-08 | Processo para a preparacao de uma composicao de interleucina-2 estavel |
ES542028A ES542028A0 (es) | 1984-04-09 | 1985-04-08 | Un metodo de producir una composicion de interleuquina-2 |
IE90285A IE58161B1 (en) | 1984-04-09 | 1985-04-10 | Stable composition of interleukin-2 |
US06/931,704 US4812557A (en) | 1984-04-09 | 1986-11-17 | Stable composition of interleukin-2 and human serum albumin |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP60013226A JPS60222424A (ja) | 1985-01-25 | 1985-01-25 | インタ−ロイキン−2組成物 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP59071568A Division JPS60215631A (ja) | 1984-04-09 | 1984-04-09 | インタ−ロイキン−2組成物 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS60222424A JPS60222424A (ja) | 1985-11-07 |
JPH0378847B2 true JPH0378847B2 (pt) | 1991-12-17 |
Family
ID=11827263
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP60013226A Granted JPS60222424A (ja) | 1984-04-09 | 1985-01-25 | インタ−ロイキン−2組成物 |
Country Status (1)
Country | Link |
---|---|
JP (1) | JPS60222424A (pt) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH0645551B2 (ja) * | 1986-01-07 | 1994-06-15 | 塩野義製薬株式会社 | インタ−ロイキン−2組成物 |
DE3621828A1 (de) * | 1986-06-28 | 1988-01-14 | Biotest Pharma Gmbh | Stabilisierung eines fuer therapeutische zwecke, insbesondere beim menschen, bestimmten interleukin-2-praeparates sowie dieses praeparat enthaltende stabilisierte waessrige loesung oder feststoff |
JP2629000B2 (ja) * | 1986-07-18 | 1997-07-09 | 中外製薬株式会社 | 安定な顆粒球コロニー刺激因子含有製剤 |
EP0274219A3 (en) * | 1986-12-04 | 1988-08-03 | Takeda Chemical Industries, Ltd. | Interleukin-2-containing liposome composition and method for the production thereof |
-
1985
- 1985-01-25 JP JP60013226A patent/JPS60222424A/ja active Granted
Also Published As
Publication number | Publication date |
---|---|
JPS60222424A (ja) | 1985-11-07 |
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