BG106578A - Фармацевтични състави на фибринолитичен агент - Google Patents

Фармацевтични състави на фибринолитичен агент Download PDF

Info

Publication number: BG106578A
Authority: BG; Bulgaria
Prior art keywords: pharmaceutical composition; nat; composition; metalloproteinase; zinc
Prior art date: 1999-10-01

Application number

BG106578A

Other languages

Bulgarian (bg)

English (en)

Inventor

Brent KENDRICK

Brian Peterson

Original Assignee

Amgen Inc.

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.)

1999-10-01

Filing date

2002-04-04

Publication date

2003-04-30

2002-04-04 Application filed by Amgen Inc. filed Critical Amgen Inc.

2003-04-30 Publication of BG106578A publication Critical patent/BG106578A/bg

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 29
239000000203 mixture Substances 0.000 claims abstract description 69
238000000034 method Methods 0.000 claims abstract description 26
108010006035 Metalloproteases Proteins 0.000 claims abstract description 22
102000005741 Metalloproteases Human genes 0.000 claims abstract description 22
239000003527 fibrinolytic agent Substances 0.000 claims abstract description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 49
108010090109 Fibrolase Proteins 0.000 claims description 39
239000000872 buffer Substances 0.000 claims description 28
238000004108 freeze drying Methods 0.000 claims description 21
239000000243 solution Substances 0.000 claims description 21
239000003381 stabilizer Substances 0.000 claims description 16
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 12
229930195725 Mannitol Natural products 0.000 claims description 12
239000000594 mannitol Substances 0.000 claims description 12
235000010355 mannitol Nutrition 0.000 claims description 12
239000007983 Tris buffer Substances 0.000 claims description 11
239000007788 liquid Substances 0.000 claims description 11
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 11
239000003795 chemical substances by application Substances 0.000 claims description 10
239000011701 zinc Substances 0.000 claims description 9
229910052725 zinc Inorganic materials 0.000 claims description 9
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 9
229960001763 zinc sulfate Drugs 0.000 claims description 9
229910000368 zinc sulfate Inorganic materials 0.000 claims description 9
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 8
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 8
229920000053 polysorbate 80 Polymers 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 7
150000003751 zinc Chemical class 0.000 claims description 7
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 claims description 6
229930006000 Sucrose Natural products 0.000 claims description 6
VSGNNIFQASZAOI-UHFFFAOYSA-L calcium acetate Chemical compound [Ca+2].CC([O-])=O.CC([O-])=O VSGNNIFQASZAOI-UHFFFAOYSA-L 0.000 claims description 6
239000001639 calcium acetate Substances 0.000 claims description 6
229960005147 calcium acetate Drugs 0.000 claims description 6
235000011092 calcium acetate Nutrition 0.000 claims description 6
239000005720 sucrose Substances 0.000 claims description 6
239000004094 surface-active agent Substances 0.000 claims description 6
ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 5
239000003146 anticoagulant agent Substances 0.000 claims description 5
239000007864 aqueous solution Substances 0.000 claims description 5
150000002016 disaccharides Chemical class 0.000 claims description 5
239000001509 sodium citrate Substances 0.000 claims description 5
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 claims description 5
230000002537 thrombolytic effect Effects 0.000 claims description 5
239000004246 zinc acetate Substances 0.000 claims description 5
208000007536 Thrombosis Diseases 0.000 claims description 4
159000000007 calcium salts Chemical class 0.000 claims description 4
OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
239000002904 solvent Substances 0.000 claims description 3
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 2
239000001110 calcium chloride Substances 0.000 claims description 2
229910001628 calcium chloride Inorganic materials 0.000 claims description 2
238000004090 dissolution Methods 0.000 claims description 2
239000011592 zinc chloride Substances 0.000 claims description 2
235000005074 zinc chloride Nutrition 0.000 claims description 2
229960000103 thrombolytic agent Drugs 0.000 claims 3
230000000087 stabilizing effect Effects 0.000 claims 2
125000003275 alpha amino acid group Chemical group 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 claims 1
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims 1
229920001184 polypeptide Polymers 0.000 description 17
108090000765 processed proteins & peptides Proteins 0.000 description 17
102000004196 processed proteins & peptides Human genes 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
239000000945 filler Substances 0.000 description 11
238000001035 drying Methods 0.000 description 10
238000007710 freezing Methods 0.000 description 9
230000008014 freezing Effects 0.000 description 9
238000009472 formulation Methods 0.000 description 8
108020004414 DNA Proteins 0.000 description 6
238000003860 storage Methods 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
230000000694 effects Effects 0.000 description 5
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
-1 PVP Chemical class 0.000 description 4
230000015556 catabolic process Effects 0.000 description 4
238000006731 degradation reaction Methods 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
239000002773 nucleotide Substances 0.000 description 4
125000003729 nucleotide group Chemical group 0.000 description 4
239000000523 sample Substances 0.000 description 4
235000000346 sugar Nutrition 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
102000053602 DNA Human genes 0.000 description 3
102000009123 Fibrin Human genes 0.000 description 3
108010073385 Fibrin Proteins 0.000 description 3
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 3
240000004808 Saccharomyces cerevisiae Species 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
241000700605 Viruses Species 0.000 description 3
238000002835 absorbance Methods 0.000 description 3
239000000654 additive Substances 0.000 description 3
238000004220 aggregation Methods 0.000 description 3
230000002776 aggregation Effects 0.000 description 3
235000001014 amino acid Nutrition 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
239000003814 drug Substances 0.000 description 3
229950003499 fibrin Drugs 0.000 description 3
230000007774 longterm Effects 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
150000008163 sugars Chemical class 0.000 description 3
102000008946 Fibrinogen Human genes 0.000 description 2
108010049003 Fibrinogen Proteins 0.000 description 2
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 2
239000004471 Glycine Substances 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
230000000996 additive effect Effects 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
239000012736 aqueous medium Substances 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
238000004166 bioassay Methods 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
239000006172 buffering agent Substances 0.000 description 2
230000003139 buffering effect Effects 0.000 description 2
239000000969 carrier Substances 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
238000002144 chemical decomposition reaction Methods 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
238000011161 development Methods 0.000 description 2
238000000502 dialysis Methods 0.000 description 2
229940012952 fibrinogen Drugs 0.000 description 2
230000003480 fibrinolytic effect Effects 0.000 description 2
239000008103 glucose Substances 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
238000004255 ion exchange chromatography Methods 0.000 description 2
238000004811 liquid chromatography Methods 0.000 description 2
239000012669 liquid formulation Substances 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
239000000825 pharmaceutical preparation Substances 0.000 description 2
229920000642 polymer Polymers 0.000 description 2
229920005862 polyol Polymers 0.000 description 2
150000003077 polyols Chemical class 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
238000012545 processing Methods 0.000 description 2
238000003259 recombinant expression Methods 0.000 description 2
238000011084 recovery Methods 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
238000004007 reversed phase HPLC Methods 0.000 description 2
239000008223 sterile water Substances 0.000 description 2
238000000108 ultra-filtration Methods 0.000 description 2
HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
101000774685 Agkistrodon contortrix contortrix Snake venom metalloproteinase fibrolase Proteins 0.000 description 1
208000035404 Autolysis Diseases 0.000 description 1
241000894006 Bacteria Species 0.000 description 1
101000851165 Bothrops pirajai Snake venom metalloproteinase BpirMP Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
206010057248 Cell death Diseases 0.000 description 1
206010053567 Coagulopathies Diseases 0.000 description 1
108091026890 Coding region Proteins 0.000 description 1
241000700626 Cowpox virus Species 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-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
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
241000238631 Hexapoda Species 0.000 description 1
241000235058 Komagataella pastoris Species 0.000 description 1
QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
102000013566 Plasminogen Human genes 0.000 description 1
108010051456 Plasminogen Proteins 0.000 description 1
229920001213 Polysorbate 20 Polymers 0.000 description 1
108010023197 Streptokinase Proteins 0.000 description 1
HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000002411 adverse Effects 0.000 description 1
235000004279 alanine Nutrition 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-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
239000003963 antioxidant agent Substances 0.000 description 1
239000011324 bead Substances 0.000 description 1
230000023555 blood coagulation Effects 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
239000004067 bulking agent Substances 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000035602 clotting Effects 0.000 description 1
239000000470 constituent Substances 0.000 description 1
239000013068 control sample Substances 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
230000006240 deamidation Effects 0.000 description 1
230000001627 detrimental effect Effects 0.000 description 1
229940079593 drug Drugs 0.000 description 1
238000009509 drug development Methods 0.000 description 1
238000005516 engineering process Methods 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
210000003527 eukaryotic cell Anatomy 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
230000037406 food intake Effects 0.000 description 1
239000012520 frozen sample Substances 0.000 description 1
238000007496 glass forming Methods 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
210000004962 mammalian cell Anatomy 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
244000005700 microbiome Species 0.000 description 1
150000002772 monosaccharides Chemical class 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000006174 pH buffer Substances 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
210000001236 prokaryotic cell Anatomy 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
230000001846 repelling effect Effects 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
239000012488 sample solution Substances 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000007789 sealing Methods 0.000 description 1
230000028043 self proteolysis Effects 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
229960005202 streptokinase Drugs 0.000 description 1
239000000758 substrate Substances 0.000 description 1
238000012360 testing method Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000013518 transcription Methods 0.000 description 1
230000035897 transcription Effects 0.000 description 1
230000009466 transformation Effects 0.000 description 1
238000013519 translation Methods 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
238000000870 ultraviolet spectroscopy Methods 0.000 description 1
241000701161 unidentified adenovirus Species 0.000 description 1
241001515965 unidentified phage Species 0.000 description 1
229960005356 urokinase Drugs 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- 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
- A61K9/08—Solutions
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/4886—Metalloendopeptidases (3.4.24), e.g. collagenase
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- 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
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Oil, Petroleum & Natural Gas (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Immunology (AREA)
Gastroenterology & Hepatology (AREA)
Inorganic Chemistry (AREA)
Biochemistry (AREA)
Molecular Biology (AREA)
Diabetes (AREA)
Organic Chemistry (AREA)
Hematology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Enzymes And Modification Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)

BG106578A 1999-10-01 2002-04-04 Фармацевтични състави на фибринолитичен агент BG106578A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US09/411,335 US6440414B1 (en)	1999-10-01	1999-10-01	Pharmaceutical compositions of fibrinolytic agent
PCT/US2000/027022 WO2001024817A2 (en)	1999-10-01	2000-09-29	Pharmaceutical compositions of fibrinolytic agent

Publications (1)

Publication Number	Publication Date
BG106578A true BG106578A (bg)	2003-04-30

Family

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BG106578A BG106578A (bg)	1999-10-01	2002-04-04	Фармацевтични състави на фибринолитичен агент

Country Status (28)

Country	Link
US (4)	US6440414B1 (de)
EP (2)	EP1438967A3 (de)
JP (1)	JP2003510369A (de)
KR (1)	KR100717435B1 (de)
CN (2)	CN100353999C (de)
AT (1)	ATE262923T1 (de)
AU (1)	AU769313B2 (de)
BG (1)	BG106578A (de)
BR (1)	BR0014420A (de)
CA (1)	CA2385966A1 (de)
CZ (1)	CZ20021033A3 (de)
DE (2)	DE60009529T2 (de)
DK (1)	DK1220685T3 (de)
EA (2)	EA004627B1 (de)
ES (2)	ES2224917T1 (de)
HK (1)	HK1049112B (de)
HU (1)	HUP0202654A3 (de)
IL (1)	IL148842A0 (de)
MX (1)	MXPA02003197A (de)
NO (1)	NO20021500L (de)
NZ (4)	NZ540967A (de)
PL (1)	PL355016A1 (de)
PT (1)	PT1220685E (de)
SG (1)	SG148823A1 (de)
SK (1)	SK4242002A3 (de)
WO (1)	WO2001024817A2 (de)
YU (1)	YU23302A (de)
ZA (1)	ZA200202400B (de)

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CN102000022A (zh) *	2010-11-23	2011-04-06	郑州大学	注射用重组双功能纤溶酶冻干制剂及其制备方法
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JP6000353B2 (ja)	2011-08-12	2016-09-28	スロンボジェニックス・ナムローゼ・フェンノートシャップＴｈｒｏｍｂｏＧｅｎｉｃｓＮＶ	プラスミノーゲンおよびプラスミンの変異体
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CN107250375A (zh) *	2014-11-06	2017-10-13	科罗拉多州立大学董事会	在血栓溶解剂存在下使用粘弹性分析鉴定新疾病状态
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1999
- 1999-10-01 US US09/411,335 patent/US6440414B1/en not_active Expired - Fee Related
2000
- 2000-09-28 NZ NZ540967A patent/NZ540967A/en unknown
- 2000-09-29 DE DE60009529T patent/DE60009529T2/de not_active Expired - Fee Related
- 2000-09-29 EP EP04007657A patent/EP1438967A3/de not_active Withdrawn
- 2000-09-29 MX MXPA02003197A patent/MXPA02003197A/es active IP Right Grant
- 2000-09-29 AT AT00967197T patent/ATE262923T1/de not_active IP Right Cessation
- 2000-09-29 DK DK00967197T patent/DK1220685T3/da active
- 2000-09-29 DE DE2004007657 patent/DE04007657T1/de active Pending
- 2000-09-29 BR BR0014420-7A patent/BR0014420A/pt not_active Application Discontinuation
- 2000-09-29 CN CNB008163790A patent/CN100353999C/zh not_active Expired - Fee Related
- 2000-09-29 NZ NZ518007A patent/NZ518007A/en unknown
- 2000-09-29 KR KR1020027004128A patent/KR100717435B1/ko not_active Expired - Fee Related
- 2000-09-29 WO PCT/US2000/027022 patent/WO2001024817A2/en not_active Ceased
- 2000-09-29 PL PL00355016A patent/PL355016A1/xx not_active Application Discontinuation
- 2000-09-29 SK SK424-2002A patent/SK4242002A3/sk unknown
- 2000-09-29 ES ES04007657T patent/ES2224917T1/es active Pending
- 2000-09-29 PT PT00967197T patent/PT1220685E/pt unknown
- 2000-09-29 NZ NZ550200A patent/NZ550200A/en unknown
- 2000-09-29 SG SG200400542-7A patent/SG148823A1/en unknown
- 2000-09-29 AU AU77430/00A patent/AU769313B2/en not_active Ceased
- 2000-09-29 JP JP2001527816A patent/JP2003510369A/ja not_active Withdrawn
- 2000-09-29 NZ NZ530959A patent/NZ530959A/en unknown
- 2000-09-29 IL IL14884200A patent/IL148842A0/xx unknown
- 2000-09-29 HK HK03100282.4A patent/HK1049112B/en not_active IP Right Cessation
- 2000-09-29 ES ES00967197T patent/ES2218228T3/es not_active Expired - Lifetime
- 2000-09-29 YU YU23302A patent/YU23302A/sh unknown
- 2000-09-29 EA EA200200396A patent/EA004627B1/ru not_active IP Right Cessation
- 2000-09-29 EA EA200400182A patent/EA006600B1/ru unknown
- 2000-09-29 CA CA002385966A patent/CA2385966A1/en not_active Abandoned
- 2000-09-29 HU HU0202654A patent/HUP0202654A3/hu unknown
- 2000-09-29 EP EP00967197A patent/EP1220685B1/de not_active Expired - Lifetime
- 2000-09-29 CZ CZ20021033A patent/CZ20021033A3/cs unknown
- 2000-09-29 CN CNA2007101529313A patent/CN101209347A/zh active Pending
2002
- 2002-03-26 NO NO20021500A patent/NO20021500L/no not_active Application Discontinuation
- 2002-03-26 ZA ZA200202400A patent/ZA200202400B/en unknown
- 2002-04-04 BG BG106578A patent/BG106578A/bg unknown
- 2002-08-23 US US10/226,408 patent/US7138114B2/en not_active Expired - Fee Related
2006
- 2006-06-29 US US11/479,214 patent/US7311908B2/en not_active Expired - Fee Related
- 2006-07-28 US US11/495,487 patent/US7244426B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
WO2001024817A2 (en)	2001-04-12
DE60009529T2 (de)	2005-04-14
WO2001024817A3 (en)	2001-10-18
CZ20021033A3 (cs)	2003-06-18
NZ518007A (en)	2004-03-26
NZ540967A (en)	2007-02-23
US6440414B1 (en)	2002-08-27
US20060246053A1 (en)	2006-11-02
IL148842A0 (en)	2002-09-12
MXPA02003197A (es)	2002-09-30
CN101209347A (zh)	2008-07-02
US7244426B2 (en)	2007-07-17
EP1220685A2 (de)	2002-07-10
HUP0202654A2 (hu)	2002-12-28
KR20020053065A (ko)	2002-07-04
NZ530959A (en)	2005-08-26
ES2218228T3 (es)	2004-11-16
ZA200202400B (en)	2003-05-28
EA004627B1 (ru)	2004-06-24
SK4242002A3 (en)	2003-08-05
HK1049112A1 (en)	2003-05-02
CA2385966A1 (en)	2001-04-12
EP1438967A3 (de)	2005-01-26
EA200400182A1 (ru)	2004-08-26
NO20021500L (no)	2002-05-27
ES2224917T1 (es)	2005-03-16
HK1049112B (en)	2005-01-21
NO20021500D0 (no)	2002-03-26
PL355016A1 (en)	2004-03-22
DE04007657T1 (de)	2005-01-13
DK1220685T3 (da)	2004-08-02
US7138114B2 (en)	2006-11-21
AU769313B2 (en)	2004-01-22
EA200200396A1 (ru)	2002-10-31
US20060263347A1 (en)	2006-11-23
EA006600B1 (ru)	2006-02-24
PT1220685E (pt)	2004-08-31
EP1220685B1 (de)	2004-03-31
EP1438967A2 (de)	2004-07-21
US20020192207A1 (en)	2002-12-19
HUP0202654A3 (en)	2003-11-28
SG148823A1 (en)	2009-01-29
DE60009529D1 (de)	2004-05-06
NZ550200A (en)	2008-04-30
KR100717435B1 (ko)	2007-05-14
BR0014420A (pt)	2002-06-11
CN100353999C (zh)	2007-12-12
YU23302A (sh)	2005-06-10
US7311908B2 (en)	2007-12-25
JP2003510369A (ja)	2003-03-18
AU7743000A (en)	2001-05-10
CN1402641A (zh)	2003-03-12
ATE262923T1 (de)	2004-04-15

Publication	Publication Date	Title
BG106578A (bg)	2003-04-30	Фармацевтични състави на фибринолитичен агент
KR100767473B1 (ko)	2007-10-17	간실질세포 증식인자 동결건조 제제
FI85335C (fi)	1992-04-10	Foerfarande foer framstaellning av lyofiliserad, farmaceutisk vaevnadsplasminogenaktivator(t-pa)-komposition.
KR20110086583A (ko)	2011-07-28	제8 인자 제형
AU659997B2 (en)	1995-06-08	Stable pharmaceutical compositions containing a fibroblast growth factor
AU2004201694B2 (en)	2006-03-02	Pharmaceutical compositions of fibrinolytic agent
AU2006200638B2 (en)	2007-11-01	Pharmaceutical compositions of fibrinolytic agent
HK1068500A (en)	2005-04-22	Pharmaceutical compositions of fibrinolytic agent
JP2971680B2 (ja)	1999-11-08	組織プラスミノーゲン活性化因子含有組成物
CN115998690A (zh)	2023-04-25	包含免疫球蛋白g降解酶的冻干制剂及其制备工艺