CA2089143C - Compositions de facteur de croissance, leur preparation et leur utilisation - Google Patents

Compositions de facteur de croissance, leur preparation et leur utilisation Download PDF

Info

Publication number: CA2089143C
Authority: CA; Canada
Prior art keywords: nicked; egf1; egf; hegf1; pure
Prior art date: 1990-08-02
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 - Fee Related

Application number

CA002089143A

Other languages

English (en)

Other versions

CA2089143A1 (fr

Inventor

Indu Parikh

Ronald Nardi

Tanchum Amarant

Antonio Guglietta

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Individual

Original Assignee

Individual

Priority date (The priority date 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 date listed.)

1990-08-02

Filing date

1991-07-30

Publication date

2002-01-15

1991-07-30 Application filed by Individual filed Critical Individual

1991-07-30 Priority claimed from PCT/US1991/005396 external-priority patent/WO1992002246A1/fr

1992-02-03 Publication of CA2089143A1 publication Critical patent/CA2089143A1/fr

2002-01-15 Application granted granted Critical

2002-01-15 Publication of CA2089143C publication Critical patent/CA2089143C/fr

2011-07-30 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title abstract description 20
239000003102 growth factor Substances 0.000 title abstract description 4
238000002360 preparation method Methods 0.000 title description 2
150000003839 salts Chemical class 0.000 claims abstract description 20
239000000039 congener Substances 0.000 claims abstract description 17
230000002496 gastric effect Effects 0.000 claims abstract description 11
239000002552 dosage form Substances 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
108090000765 processed proteins & peptides Proteins 0.000 claims description 28
102000004196 processed proteins & peptides Human genes 0.000 claims description 18
229920001184 polypeptide Polymers 0.000 claims description 16
238000011282 treatment Methods 0.000 claims description 14
201000010099 disease Diseases 0.000 claims description 10
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
230000003628 erosive effect Effects 0.000 claims description 8
230000002265 prevention Effects 0.000 claims description 4
210000004877 mucosa Anatomy 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 2
230000002757 inflammatory effect Effects 0.000 claims 1
101800003838 Epidermal growth factor Proteins 0.000 abstract description 69
VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 abstract description 69
229940116977 epidermal growth factor Drugs 0.000 abstract description 65
238000000034 method Methods 0.000 abstract description 20
230000003902 lesion Effects 0.000 abstract description 10
150000001875 compounds Chemical class 0.000 abstract description 6
230000001225 therapeutic effect Effects 0.000 abstract description 4
230000010261 cell growth Effects 0.000 abstract description 3
230000007515 enzymatic degradation Effects 0.000 abstract description 2
102000009024 Epidermal Growth Factor Human genes 0.000 abstract 1
230000002159 abnormal effect Effects 0.000 abstract 1
230000002183 duodenal effect Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 121
102400001368 Epidermal growth factor Human genes 0.000 description 67
GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 45
101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 44
238000000855 fermentation Methods 0.000 description 30
230000004151 fermentation Effects 0.000 description 30
210000004027 cell Anatomy 0.000 description 28
235000010633 broth Nutrition 0.000 description 27
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
230000014509 gene expression Effects 0.000 description 22
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 21
241000894007 species Species 0.000 description 19
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
238000004128 high performance liquid chromatography Methods 0.000 description 15
230000000694 effects Effects 0.000 description 14
238000004519 manufacturing process Methods 0.000 description 14
239000011347 resin Substances 0.000 description 14
229920005989 resin Polymers 0.000 description 14
108010025188 Alcohol oxidase Proteins 0.000 description 13
241000235058 Komagataella pastoris Species 0.000 description 13
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 13
239000001301 oxygen Substances 0.000 description 13
229910052760 oxygen Inorganic materials 0.000 description 13
239000002253 acid Substances 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
240000004808 Saccharomyces cerevisiae Species 0.000 description 9
150000001413 amino acids Chemical class 0.000 description 9
241000700159 Rattus Species 0.000 description 8
229960000583 acetic acid Drugs 0.000 description 8
230000001965 increasing effect Effects 0.000 description 8
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 8
102000004142 Trypsin Human genes 0.000 description 7
108090000631 Trypsin Proteins 0.000 description 7
235000011054 acetic acid Nutrition 0.000 description 7
230000002297 mitogenic effect Effects 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
238000012546 transfer Methods 0.000 description 7
239000012588 trypsin Substances 0.000 description 7
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
235000001014 amino acid Nutrition 0.000 description 6
230000015556 catabolic process Effects 0.000 description 6
238000006731 degradation reaction Methods 0.000 description 6
230000027119 gastric acid secretion Effects 0.000 description 6
230000012010 growth Effects 0.000 description 6
230000035876 healing Effects 0.000 description 6
230000006698 induction Effects 0.000 description 6
238000000746 purification Methods 0.000 description 6
238000011084 recovery Methods 0.000 description 6
238000013341 scale-up Methods 0.000 description 6
241001529936 Murinae Species 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
230000004071 biological effect Effects 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
210000004051 gastric juice Anatomy 0.000 description 5
239000001963 growth medium Substances 0.000 description 5
239000000047 product Substances 0.000 description 5
235000018102 proteins Nutrition 0.000 description 5
102000004169 proteins and genes Human genes 0.000 description 5
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
208000007107 Stomach Ulcer Diseases 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
208000025865 Ulcer Diseases 0.000 description 4
159000000021 acetate salts Chemical class 0.000 description 4
210000001035 gastrointestinal tract Anatomy 0.000 description 4
238000011534 incubation Methods 0.000 description 4
229960000905 indomethacin Drugs 0.000 description 4
230000004044 response Effects 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
230000000638 stimulation Effects 0.000 description 4
231100000397 ulcer Toxicity 0.000 description 4
239000013598 vector Substances 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
108020004414 DNA Proteins 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
206010062575 Muscle contracture Diseases 0.000 description 3
108091028043 Nucleic acid sequence Proteins 0.000 description 3
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
108700005078 Synthetic Genes Proteins 0.000 description 3
229910000147 aluminium phosphate Inorganic materials 0.000 description 3
239000003699 antiulcer agent Substances 0.000 description 3
238000003556 assay Methods 0.000 description 3
230000027455 binding Effects 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
238000005341 cation exchange Methods 0.000 description 3
239000003729 cation exchange resin Substances 0.000 description 3
238000005119 centrifugation Methods 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
229960001380 cimetidine Drugs 0.000 description 3
CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
208000006111 contracture Diseases 0.000 description 3
238000011161 development Methods 0.000 description 3
230000018109 developmental process Effects 0.000 description 3
208000000718 duodenal ulcer Diseases 0.000 description 3
238000010828 elution Methods 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
208000027866 inflammatory disease Diseases 0.000 description 3
238000002955 isolation Methods 0.000 description 3
230000004060 metabolic process Effects 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
238000011020 pilot scale process Methods 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
230000001105 regulatory effect Effects 0.000 description 3
238000004007 reversed phase HPLC Methods 0.000 description 3
230000002441 reversible effect Effects 0.000 description 3
238000000926 separation method Methods 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
238000001179 sorption measurement Methods 0.000 description 3
230000009466 transformation Effects 0.000 description 3
229910001868 water Inorganic materials 0.000 description 3
239000003643 water by type Substances 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
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
239000005695 Ammonium acetate Substances 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
208000004300 Atrophic Gastritis Diseases 0.000 description 2
241000193830 Bacillus <bacterium> Species 0.000 description 2
208000023514 Barrett esophagus Diseases 0.000 description 2
206010009900 Colitis ulcerative Diseases 0.000 description 2
RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
230000006820 DNA synthesis Effects 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
206010063655 Erosive oesophagitis Diseases 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
208000036495 Gastritis atrophic Diseases 0.000 description 2
101150069554 HIS4 gene Proteins 0.000 description 2
101100118545 Holotrichia diomphalia EGF-like gene Proteins 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
208000022559 Inflammatory bowel disease Diseases 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
102000015731 Peptide Hormones Human genes 0.000 description 2
108010038988 Peptide Hormones Proteins 0.000 description 2
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
201000006704 Ulcerative Colitis Diseases 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
235000019257 ammonium acetate Nutrition 0.000 description 2
229940043376 ammonium acetate Drugs 0.000 description 2
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
244000309466 calf Species 0.000 description 2
238000013375 chromatographic separation Methods 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
208000016644 chronic atrophic gastritis Diseases 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000013461 design Methods 0.000 description 2
238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 2
231100000673 dose–response relationship Toxicity 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000003814 drug Substances 0.000 description 2
206010013864 duodenitis Diseases 0.000 description 2
239000013604 expression vector Substances 0.000 description 2
239000000284 extract Substances 0.000 description 2
210000000744 eyelid Anatomy 0.000 description 2
210000002950 fibroblast Anatomy 0.000 description 2
239000012467 final product Substances 0.000 description 2
239000000834 fixative Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
239000012634 fragment Substances 0.000 description 2
231100001014 gastrointestinal tract lesion Toxicity 0.000 description 2
-1 hEGFl-48 Chemical class 0.000 description 2
239000003485 histamine H2 receptor antagonist Substances 0.000 description 2
230000006872 improvement Effects 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000011835 investigation Methods 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
210000002429 large intestine Anatomy 0.000 description 2
238000011068 loading method Methods 0.000 description 2
239000002609 medium Substances 0.000 description 2
230000000813 microbial effect Effects 0.000 description 2
230000008747 mitogenic response Effects 0.000 description 2
239000002773 nucleotide Substances 0.000 description 2
125000003729 nucleotide group Chemical group 0.000 description 2
239000006186 oral dosage form Substances 0.000 description 2
239000000813 peptide hormone Substances 0.000 description 2
238000002953 preparative HPLC Methods 0.000 description 2
230000008569 process Effects 0.000 description 2
238000003259 recombinant expression Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
210000003079 salivary gland Anatomy 0.000 description 2
239000000523 sample Substances 0.000 description 2
238000005549 size reduction Methods 0.000 description 2
210000000813 small intestine Anatomy 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000000243 solution Substances 0.000 description 2
238000002336 sorption--desorption measurement Methods 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
238000012799 strong cation exchange Methods 0.000 description 2
230000001629 suppression Effects 0.000 description 2
238000002560 therapeutic procedure Methods 0.000 description 2
230000005030 transcription termination Effects 0.000 description 2
230000001131 transforming effect Effects 0.000 description 2
LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
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 1
NUJPVNQBDUACNW-BYPYZUCNSA-N 2-[[(2s)-1,4-diamino-1,4-dioxobutan-2-yl]amino]ethanesulfonic acid Chemical compound NC(=O)C[C@@H](C(N)=O)NCCS(O)(=O)=O NUJPVNQBDUACNW-BYPYZUCNSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 1
MQLZLIYPFDIDMZ-HAFWLYHUSA-N Asn-Ile Chemical compound CC[C@H](C)[C@@H](C(O)=O)NC(=O)[C@@H](N)CC(N)=O MQLZLIYPFDIDMZ-HAFWLYHUSA-N 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
239000002028 Biomass Substances 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000282465 Canis Species 0.000 description 1
241000282472 Canis lupus familiaris Species 0.000 description 1
BQENDLAVTKRQMS-SBBGFIFASA-L Carbenoxolone sodium Chemical compound [Na+].[Na+].C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C([O-])=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](OC(=O)CCC([O-])=O)C1(C)C BQENDLAVTKRQMS-SBBGFIFASA-L 0.000 description 1
102000005367 Carboxypeptidases Human genes 0.000 description 1
108010006303 Carboxypeptidases Proteins 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 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
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
239000001263 FEMA 3042 Substances 0.000 description 1
241000287828 Gallus gallus Species 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
238000010268 HPLC based assay Methods 0.000 description 1
229940122957 Histamine H2 receptor antagonist Drugs 0.000 description 1
241000282412 Homo Species 0.000 description 1
101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
108700026244 Open Reading Frames Proteins 0.000 description 1
229920002230 Pectic acid Polymers 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
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 description 1
LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
108010020346 Polyglutamic Acid Proteins 0.000 description 1
102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
238000002105 Southern blotting Methods 0.000 description 1
238000000692 Student's t-test Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
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 1
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
JAQGKXUEKGKTKX-HOTGVXAUSA-N Tyr-Tyr Chemical compound C([C@H](N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(O)=O)C1=CC=C(O)C=C1 JAQGKXUEKGKTKX-HOTGVXAUSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
239000000362 adenosine triphosphatase inhibitor Substances 0.000 description 1
238000013019 agitation Methods 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229940043315 aluminum hydroxide / magnesium hydroxide Drugs 0.000 description 1
SXSTVPXRZQQBKQ-UHFFFAOYSA-M aluminum;magnesium;hydroxide;hydrate Chemical compound O.[OH-].[Mg].[Al] SXSTVPXRZQQBKQ-UHFFFAOYSA-M 0.000 description 1
229940069428 antacid Drugs 0.000 description 1
239000003159 antacid agent Substances 0.000 description 1
230000003466 anti-cipated effect Effects 0.000 description 1
230000000767 anti-ulcer Effects 0.000 description 1
239000002518 antifoaming agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229960005070 ascorbic acid Drugs 0.000 description 1
235000010323 ascorbic acid Nutrition 0.000 description 1
239000011668 ascorbic acid Substances 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 1
230000000975 bioactive effect Effects 0.000 description 1
238000012742 biochemical analysis Methods 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
235000020958 biotin Nutrition 0.000 description 1
239000011616 biotin Substances 0.000 description 1
229910052797 bismuth Inorganic materials 0.000 description 1
JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
239000004327 boric acid Substances 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
229910052793 cadmium Inorganic materials 0.000 description 1
BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000011575 calcium Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
229960000530 carbenoxolone Drugs 0.000 description 1
230000023852 carbohydrate metabolic process Effects 0.000 description 1
235000021256 carbohydrate metabolism Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000010307 cell transformation Effects 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
235000015218 chewing gum Nutrition 0.000 description 1
239000000812 cholinergic antagonist Substances 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
229910017052 cobalt Inorganic materials 0.000 description 1
239000010941 cobalt Substances 0.000 description 1
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
GVPFVAHMJGGAJG-UHFFFAOYSA-L cobalt dichloride Chemical compound [Cl-].[Cl-].[Co+2] GVPFVAHMJGGAJG-UHFFFAOYSA-L 0.000 description 1
239000002131 composite material Substances 0.000 description 1
238000007906 compression Methods 0.000 description 1
230000006835 compression Effects 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
238000010276 construction Methods 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
ARUVKPQLZAKDPS-UHFFFAOYSA-L copper(II) sulfate Chemical compound [Cu+2].[O-][S+2]([O-])([O-])[O-] ARUVKPQLZAKDPS-UHFFFAOYSA-L 0.000 description 1
229910000366 copper(II) sulfate Inorganic materials 0.000 description 1
UFULAYFCSOUIOV-UHFFFAOYSA-O cysteaminium Chemical compound [NH3+]CCS UFULAYFCSOUIOV-UHFFFAOYSA-O 0.000 description 1
125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 1
238000004042 decolorization Methods 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
238000010586 diagram Methods 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
230000003292 diminished effect Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
238000006911 enzymatic reaction Methods 0.000 description 1
VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000010195 expression analysis Methods 0.000 description 1
229960001596 famotidine Drugs 0.000 description 1
XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
238000010265 fast atom bombardment Methods 0.000 description 1
239000011790 ferrous sulphate Substances 0.000 description 1
235000003891 ferrous sulphate Nutrition 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000005187 foaming Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
235000011087 fumaric acid Nutrition 0.000 description 1
LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
201000005917 gastric ulcer Diseases 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000000174 gluconic acid Substances 0.000 description 1
235000012208 gluconic acid Nutrition 0.000 description 1
239000008103 glucose Substances 0.000 description 1
229940093915 gynecological organic acid Drugs 0.000 description 1
238000003306 harvesting Methods 0.000 description 1
229940116978 human epidermal growth factor Drugs 0.000 description 1
238000007654 immersion Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
210000004283 incisor Anatomy 0.000 description 1
230000001939 inductive effect Effects 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000000266 injurious effect Effects 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 1
229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
238000002647 laser therapy Methods 0.000 description 1
238000013532 laser treatment Methods 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
230000014759 maintenance of location Effects 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229940099596 manganese sulfate Drugs 0.000 description 1
239000011702 manganese sulphate Substances 0.000 description 1
235000007079 manganese sulphate Nutrition 0.000 description 1
SQQMAOCOWKFBNP-UHFFFAOYSA-L manganese(II) sulfate Chemical compound [Mn+2].[O-]S([O-])(=O)=O SQQMAOCOWKFBNP-UHFFFAOYSA-L 0.000 description 1
239000000463 material Substances 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
229960003151 mercaptamine Drugs 0.000 description 1
230000002503 metabolic effect Effects 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
229960005249 misoprostol Drugs 0.000 description 1
239000003226 mitogen Substances 0.000 description 1
230000011278 mitosis Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical class C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
235000015097 nutrients Nutrition 0.000 description 1
229960000381 omeprazole Drugs 0.000 description 1
239000008203 oral pharmaceutical composition Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002892 organic cations Chemical class 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
235000006408 oxalic acid Nutrition 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
229960004633 pirenzepine Drugs 0.000 description 1
RMHMFHUVIITRHF-UHFFFAOYSA-N pirenzepine Chemical compound C1CN(C)CCN1CC(=O)N1C2=NC=CC=C2NC(=O)C2=CC=CC=C21 RMHMFHUVIITRHF-UHFFFAOYSA-N 0.000 description 1
239000013600 plasmid vector Substances 0.000 description 1
239000010318 polygalacturonic acid Substances 0.000 description 1
229920002643 polyglutamic acid Polymers 0.000 description 1
230000034918 positive regulation of cell growth Effects 0.000 description 1
229910000160 potassium phosphate Inorganic materials 0.000 description 1
235000011009 potassium phosphates Nutrition 0.000 description 1
OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
229910052939 potassium sulfate Inorganic materials 0.000 description 1
235000011151 potassium sulphates Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
150000003138 primary alcohols Chemical class 0.000 description 1
238000004886 process control Methods 0.000 description 1
150000003166 prostaglandin E2 derivatives Chemical class 0.000 description 1
238000000734 protein sequencing Methods 0.000 description 1
238000001243 protein synthesis Methods 0.000 description 1
230000017854 proteolysis Effects 0.000 description 1
229940126409 proton pump inhibitor Drugs 0.000 description 1
239000000612 proton pump inhibitor Substances 0.000 description 1
238000005086 pumping Methods 0.000 description 1
239000012521 purified sample Substances 0.000 description 1
VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
229960000620 ranitidine Drugs 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
210000003370 receptor cell Anatomy 0.000 description 1
230000006798 recombination Effects 0.000 description 1
238000005215 recombination Methods 0.000 description 1
230000037309 reepithelialization Effects 0.000 description 1
230000008439 repair process Effects 0.000 description 1
230000010076 replication Effects 0.000 description 1
230000000754 repressing effect Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
230000007017 scission Effects 0.000 description 1
230000028327 secretion Effects 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
239000011684 sodium molybdate Substances 0.000 description 1
235000015393 sodium molybdate Nutrition 0.000 description 1
TVXXNOYZHKPKGW-UHFFFAOYSA-N sodium molybdate (anhydrous) Chemical compound [Na+].[Na+].[O-][Mo]([O-])(=O)=O TVXXNOYZHKPKGW-UHFFFAOYSA-N 0.000 description 1
238000010183 spectrum analysis Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000011550 stock solution Substances 0.000 description 1
210000002784 stomach Anatomy 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
239000012607 strong cation exchange resin Substances 0.000 description 1
238000005556 structure-activity relationship Methods 0.000 description 1
210000001913 submandibular gland Anatomy 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229960004291 sucralfate Drugs 0.000 description 1
MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
239000000725 suspension Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000012353 t test Methods 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000015523 tannic acid Nutrition 0.000 description 1
229920002258 tannic acid Polymers 0.000 description 1
229940033123 tannic acid Drugs 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000036346 tooth eruption Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000014616 translation Effects 0.000 description 1
230000001228 trophic effect Effects 0.000 description 1
108010003137 tyrosyltyrosine Proteins 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
210000005253 yeast cell Anatomy 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1
MJIBOYFUEIDNPI-HBNMXAOGSA-L zinc 5-[2,3-dihydroxy-5-[(2R,3R,4S,5R,6S)-4,5,6-tris[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxy]-2-[[3,4-dihydroxy-5-(3,4,5-trihydroxybenzoyl)oxybenzoyl]oxymethyl]oxan-3-yl]oxycarbonylphenoxy]carbonyl-3-hydroxybenzene-1,2-diolate Chemical class [Zn++].Oc1cc(cc(O)c1O)C(=O)Oc1cc(cc(O)c1O)C(=O)OC[C@H]1O[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H](OC(=O)c2cc(O)c(O)c(OC(=O)c3cc(O)c(O)c(O)c3)c2)[C@@H]1OC(=O)c1cc(O)c(O)c(OC(=O)c2cc(O)c([O-])c([O-])c2)c1 MJIBOYFUEIDNPI-HBNMXAOGSA-L 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1

Landscapes

Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

CA002089143A 1990-08-02 1991-07-30 Compositions de facteur de croissance, leur preparation et leur utilisation Expired - Fee Related CA2089143C (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US56152590A	1990-08-02	1990-08-02
US561,525		1990-08-02
US59139990A	1990-10-01	1990-10-01
US591,399		1990-10-01
PCT/US1991/005396 WO1992002246A1 (fr)	1990-08-02	1991-07-30	Compositions de facteur de croissance, preparation et emploi

Publications (2)

Publication Number	Publication Date
CA2089143A1 CA2089143A1 (fr)	1992-02-03
CA2089143C true CA2089143C (fr)	2002-01-15

Family

ID=27072671

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002089143A Expired - Fee Related CA2089143C (fr)	1990-08-02	1991-07-30	Compositions de facteur de croissance, leur preparation et leur utilisation

Country Status (1)

Country	Link
CA (1)	CA2089143C (fr)

1991
- 1991-07-30 CA CA002089143A patent/CA2089143C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2089143A1 (fr)	1992-02-03

Legal Events

Date	Code	Title	Description
1998-07-13	EEER	Examination request
2010-07-30	MKLA	Lapsed

Publication	Publication Date	Title
US4876242A (en)	1989-10-24	Human insulin-like growth factor analoges with reduced binding to serum carrier proteins and their production in yeast
US5874406A (en)	1999-02-23	Synthetic peptide analogs of lung surface protein SP-C
US5434135A (en)	1995-07-18	Growth factor compositions, preparation and use
KR940000756B1 (ko)	1994-01-29	인슈린 유사체의 제조방법
EP0235205B1 (fr)	1992-10-28	Analogues peptidiques du facteur de croissance 1 similaire a l'insuline chez les mammiferes
KR0139629B1 (ko)	1998-07-01	미니-프로인슐린, 이의 제조방법 및 용도
JPH0829097B2 (ja)	1996-03-27	線維芽細胞発育因子
US5547935A (en)	1996-08-20	Muteins of human epidermal growth factor exhibiting enhanced binding at low PH
US5158935A (en)	1992-10-27	Human epidermal growth factor having substitution at position 11
WO1988005788A1 (fr)	1988-08-11	FACTEUR TRANSFORMATEUR DE CROISSANCE DE TYPE beta
JP2823690B2 (ja)	1998-11-11	プロテアーゼ耐性ｐｄｇｆ及び使用法
RU2162857C2 (ru)	2001-02-10	Димер "клеверного" пептида
KR920001691B1 (ko)	1992-02-22	항생물질 l17392(데글루코테이코플라닌) 및 그 염을 제조하는 방법
US5599792A (en)	1997-02-04	Bone-stimulating, non-vasoactive parathyroid hormone variants
EP0541726B1 (fr)	2000-03-15	Compositions de facteur de croissance, preparation et emploi
KR20010052635A (ko)	2001-06-25	아연 결합이 향상된 신규한 인슐린 동족체
US5616476A (en)	1997-04-01	Synthetic isohirudins with improved stability
CA2089143C (fr)	2002-01-15	Compositions de facteur de croissance, leur preparation et leur utilisation
WO1992011286A1 (fr)	1992-07-09	Variantes d'hormone de parathyroide resistantes a l'oxydation
IE840999L (en)	1984-11-09	Polypeptides
HUP0202793A2 (hu)	2002-12-28	A humán inzulin monomer analógjai
US5359036A (en)	1994-10-25	Growth hormone-like glycoproteins
JPH07119237B2 (ja)	1995-12-20	ヒルジン変異体，その製造法及び抗凝血剤