SK73794A3 - Stabilized pharmaceutical formulation comprising growth hormone and aspargine - Google Patents
Stabilized pharmaceutical formulation comprising growth hormone and aspargine Download PDFInfo
- Publication number
- SK73794A3 SK73794A3 SK737-94A SK73794A SK73794A3 SK 73794 A3 SK73794 A3 SK 73794A3 SK 73794 A SK73794 A SK 73794A SK 73794 A3 SK73794 A3 SK 73794A3
- Authority
- SK
- Slovakia
- Prior art keywords
- growth hormone
- hgh
- asparagine
- formulation
- deamidation
- Prior art date
Links
- 239000000122 growth hormone Substances 0.000 title claims abstract description 25
- 102000018997 Growth Hormone Human genes 0.000 title claims abstract description 24
- 108010051696 Growth Hormone Proteins 0.000 title claims abstract description 24
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 title claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 9
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims abstract description 18
- 235000009582 asparagine Nutrition 0.000 claims abstract description 18
- 229960001230 asparagine Drugs 0.000 claims abstract description 18
- 238000002360 preparation method Methods 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 5
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 235000014633 carbohydrates Nutrition 0.000 claims description 3
- 239000000203 mixture Substances 0.000 abstract description 25
- 238000009472 formulation Methods 0.000 abstract description 22
- 230000006240 deamidation Effects 0.000 abstract description 16
- 230000003647 oxidation Effects 0.000 abstract description 6
- 238000007254 oxidation reaction Methods 0.000 abstract description 6
- 238000003776 cleavage reaction Methods 0.000 abstract description 4
- 230000007017 scission Effects 0.000 abstract description 4
- 206010056438 Growth hormone deficiency Diseases 0.000 abstract description 3
- 239000000654 additive Substances 0.000 abstract description 3
- 230000000996 additive effect Effects 0.000 abstract description 2
- 239000006172 buffering agent Substances 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 34
- 102000002265 Human Growth Hormone Human genes 0.000 description 34
- 239000000854 Human Growth Hormone Substances 0.000 description 34
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 15
- 239000000243 solution Substances 0.000 description 15
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 238000003860 storage Methods 0.000 description 6
- 235000019445 benzyl alcohol Nutrition 0.000 description 5
- 238000006731 degradation reaction Methods 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 241000282414 Homo sapiens Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-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
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 125000000539 amino acid group Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000010452 phosphate Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 108010013127 Met-human growth hormone Proteins 0.000 description 2
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 230000003139 buffering effect Effects 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Natural products OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 238000004255 ion exchange chromatography Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000012931 lyophilized formulation 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
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 150000003248 quinolines Chemical class 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000006641 stabilisation Effects 0.000 description 2
- 238000011105 stabilization Methods 0.000 description 2
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- FSJVVVCZSRCTBM-RXSVEWSESA-N (2S)-2-[(2R)-3,4-dihydroxy-5-oxo-2H-furan-2-yl]-2-hydroxyethanolate 2-hydroxyethyl(trimethyl)azanium Chemical compound C[N+](C)(C)CCO.O[C@@H](C[O-])[C@H]1OC(=O)C(O)=C1O FSJVVVCZSRCTBM-RXSVEWSESA-N 0.000 description 1
- WEZNMMBMSZOXAZ-UHFFFAOYSA-N 2-boronooxyethyl(trimethyl)azanium Chemical compound C[N+](C)(C)CCOB(O)O WEZNMMBMSZOXAZ-UHFFFAOYSA-N 0.000 description 1
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 1
- UJWRGESBUBDIIB-JJKGCWMISA-M 2-hydroxyethyl(trimethyl)azanium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate Chemical compound C[N+](C)(C)CCO.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O UJWRGESBUBDIIB-JJKGCWMISA-M 0.000 description 1
- RPERJPYDELTDMR-UHFFFAOYSA-K 2-hydroxyethyl(trimethyl)azanium;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound C[N+](C)(C)CCO.C[N+](C)(C)CCO.C[N+](C)(C)CCO.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O RPERJPYDELTDMR-UHFFFAOYSA-K 0.000 description 1
- SUJMSBLYCLWFHB-UHFFFAOYSA-L 2-hydroxyethyl(trimethyl)azanium;sulfate Chemical compound [O-]S([O-])(=O)=O.C[N+](C)(C)CCO.C[N+](C)(C)CCO SUJMSBLYCLWFHB-UHFFFAOYSA-L 0.000 description 1
- KZSXRDLXTFEHJM-UHFFFAOYSA-N 5-(trifluoromethyl)benzene-1,3-diamine Chemical compound NC1=CC(N)=CC(C(F)(F)F)=C1 KZSXRDLXTFEHJM-UHFFFAOYSA-N 0.000 description 1
- PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 description 1
- 241000972773 Aulopiformes Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 235000019743 Choline chloride Nutrition 0.000 description 1
- 239000004381 Choline salt Substances 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 229920001917 Ficoll Polymers 0.000 description 1
- 206010017788 Gastric haemorrhage Diseases 0.000 description 1
- 206010062767 Hypophysitis Diseases 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
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229920000805 Polyaspartic acid Polymers 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 208000002607 Pseudarthrosis Diseases 0.000 description 1
- 241000277331 Salmonidae Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 208000026928 Turner syndrome Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 235000015278 beef Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- QWJSAWXRUVVRLH-UHFFFAOYSA-M choline bitartrate Chemical compound C[N+](C)(C)CCO.OC(=O)C(O)C(O)C([O-])=O QWJSAWXRUVVRLH-UHFFFAOYSA-M 0.000 description 1
- 229960004874 choline bitartrate Drugs 0.000 description 1
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 1
- 229960003178 choline chloride Drugs 0.000 description 1
- 229950002847 choline gluconate Drugs 0.000 description 1
- 235000019417 choline salt Nutrition 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- UHMKISIRZFDJRU-UHFFFAOYSA-L diethyl-methyl-[2-(1,1,6-trimethylpiperidin-1-ium-2-carbonyl)oxyethyl]azanium;diiodide Chemical compound [I-].[I-].CC[N+](C)(CC)CCOC(=O)C1CCCC(C)[N+]1(C)C UHMKISIRZFDJRU-UHFFFAOYSA-L 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 108700003601 dimethylglycine Proteins 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- -1 hydrochloric acid Chemical class 0.000 description 1
- DQKGOGJIOHUEGK-UHFFFAOYSA-M hydron;2-hydroxyethyl(trimethyl)azanium;carbonate Chemical compound OC([O-])=O.C[N+](C)(C)CCO DQKGOGJIOHUEGK-UHFFFAOYSA-M 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 229940078490 n,n-dimethylglycine Drugs 0.000 description 1
- 210000004789 organ system Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- WXZMFSXDPGVJKK-UHFFFAOYSA-N pentaerythritol Chemical compound OCC(CO)(CO)CO WXZMFSXDPGVJKK-UHFFFAOYSA-N 0.000 description 1
- 229940112042 peripherally acting choline derivative muscle relaxants Drugs 0.000 description 1
- 229950004354 phosphorylcholine Drugs 0.000 description 1
- PYJNAPOPMIJKJZ-UHFFFAOYSA-N phosphorylcholine chloride Chemical compound [Cl-].C[N+](C)(C)CCOP(O)(O)=O PYJNAPOPMIJKJZ-UHFFFAOYSA-N 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 1
- 108010011110 polyarginine Proteins 0.000 description 1
- 108010064470 polyaspartate Proteins 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920002704 polyhistidine Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 235000019515 salmon Nutrition 0.000 description 1
- 210000002356 skeleton Anatomy 0.000 description 1
- 238000003307 slaughter Methods 0.000 description 1
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 239000001433 sodium tartrate Substances 0.000 description 1
- 229960002167 sodium tartrate Drugs 0.000 description 1
- 235000011004 sodium tartrates Nutrition 0.000 description 1
- 230000009576 somatic growth Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960002317 succinimide Drugs 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 230000029663 wound healing Effects 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/27—Growth hormone [GH], i.e. somatotropin
-
- 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
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Endocrinology (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK912047A DK204791D0 (da) | 1991-12-20 | 1991-12-20 | Hidtil ukendt farmaceutisk praeparat |
| PCT/DK1992/000378 WO1993012811A1 (en) | 1991-12-20 | 1992-12-16 | A stabilized pharmaceutical formulation comprising growth hormone and asparagine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK73794A3 true SK73794A3 (en) | 1995-03-08 |
Family
ID=8109696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK737-94A SK73794A3 (en) | 1991-12-20 | 1992-12-16 | Stabilized pharmaceutical formulation comprising growth hormone and aspargine |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US5977069A (fi) |
| EP (1) | EP0618806B1 (fi) |
| JP (1) | JP3662580B2 (fi) |
| KR (1) | KR100270726B1 (fi) |
| AT (1) | ATE177645T1 (fi) |
| AU (1) | AU664416B2 (fi) |
| BG (1) | BG98804A (fi) |
| CA (1) | CA2125856A1 (fi) |
| CZ (1) | CZ282826B6 (fi) |
| DE (1) | DE69228704T2 (fi) |
| DK (1) | DK204791D0 (fi) |
| FI (1) | FI942905A0 (fi) |
| HU (1) | HUT69682A (fi) |
| NO (1) | NO942299L (fi) |
| NZ (1) | NZ246555A (fi) |
| RO (1) | RO112086B1 (fi) |
| RU (1) | RU2098130C1 (fi) |
| SK (1) | SK73794A3 (fi) |
| WO (1) | WO1993012811A1 (fi) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5981485A (en) | 1997-07-14 | 1999-11-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
| US5763394A (en) * | 1988-04-15 | 1998-06-09 | Genentech, Inc. | Human growth hormone aqueous formulation |
| US5849700A (en) * | 1991-12-20 | 1998-12-15 | Novo Nordisk A/S | Pharmaceutical formulation |
| US5849704A (en) * | 1991-12-20 | 1998-12-15 | Novo Nordisk A/S | Pharmaceutical formulation |
| US6022858A (en) * | 1991-12-20 | 2000-02-08 | Novo Nordisk A/S | Pharmaceutical formulation of human-growth hormone pretreated with zinc salt |
| DK204791D0 (da) * | 1991-12-20 | 1991-12-20 | Novo Nordisk As | Hidtil ukendt farmaceutisk praeparat |
| SE9201073D0 (sv) * | 1992-04-03 | 1992-04-03 | Kabi Pharmacia Ab | Protein formulation |
| US5652216A (en) * | 1994-05-26 | 1997-07-29 | Novo Nordisk A/S | Pharmaceutical preparation |
| US5580856A (en) * | 1994-07-15 | 1996-12-03 | Prestrelski; Steven J. | Formulation of a reconstituted protein, and method and kit for the production thereof |
| US5654278A (en) * | 1994-10-13 | 1997-08-05 | Novo Nordisk A/S | Composition and method comprising growth hormone and leucine |
| US5547696A (en) * | 1994-10-13 | 1996-08-20 | Novo Nordisk A/S | Pharmaceutical formulation |
| US5631225A (en) * | 1994-10-13 | 1997-05-20 | Novo Nordisk A/S | Pharmaceutical formulation |
| ZA96122B (en) * | 1995-01-13 | 1996-07-24 | Novo Nordisk As | A pharmaceutical formulation |
| KR19980701351A (ko) * | 1995-01-13 | 1998-05-15 | 슈타르 피아 | 성장호르몬 및 Ｘ-Ｌｙｓ를 함유하는 안정화된 약제조제물(A STABILIZED PHARMACEUTICAL FORMULATION COMPRISING A GROWTH HORMONE AND X-Lys |
| US5705482A (en) * | 1995-01-13 | 1998-01-06 | Novo Nordisk A/S | Pharmaceutical formulation |
| US5552385A (en) * | 1995-06-05 | 1996-09-03 | Novo Nordisk A/S | Pharmaceutical formulation |
| ZA965367B (en) * | 1995-07-12 | 1997-01-23 | Novo Nordisk As | A pharmaceutical formulation |
| JP4060884B2 (ja) * | 1995-08-28 | 2008-03-12 | 昭和薬品化工株式会社 | 局所麻酔用組成物 |
| US20070179096A1 (en) | 1996-04-24 | 2007-08-02 | Novo Nordisk A/S | Pharmaceutical Formulation |
| US20020077461A1 (en) * | 1996-04-24 | 2002-06-20 | Soren Bjorn | Pharmaceutical formulation |
| IL126999A (en) | 1996-07-24 | 2002-03-10 | Warner Lambert Co | Pharmaceutical preparations containing isobutylgaba and its history for use in the treatment of pain |
| US6696063B1 (en) | 1998-12-30 | 2004-02-24 | Applied Research Systems Ars Holding N.V. | Treatment of HIV-associated dysmorphia/dysmetabolic syndrome (HADDS) with or without lipodystrophy |
| TWI283182B (en) * | 2000-08-07 | 2007-07-01 | Nektar Therapeutics | Inhalable spray dried 4-helix bundle protein powders having minimized aggregation |
| WO2002092619A2 (en) * | 2001-05-14 | 2002-11-21 | The Gouvernment Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Modified growth hormone |
| RU2234945C2 (ru) * | 2002-10-15 | 2004-08-27 | Вардосанидзе Ирина Викторовна | Стабилизатор водного раствора и водосодержащего сырья с самопроизвольно изменяющимися окислительно-восстановительными свойствами |
| DE10333317A1 (de) * | 2003-07-22 | 2005-02-17 | Biotecon Therapeutics Gmbh | Formulierung für Proteinarzneimittel ohne Zusatz von humanem Serumalbumin (HSA) |
| EP2099496A2 (en) * | 2006-12-08 | 2009-09-16 | Massachusetts Institute of Technology | Delivery of nanoparticles and/or agents to cells |
| US20160015789A1 (en) * | 2014-07-17 | 2016-01-21 | Teva Pharmaceutical Industries, Ltd. | FORMULATIONS OF AN ALBUMIN hGH FUSION PROTEIN |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816568A (en) * | 1986-05-16 | 1989-03-28 | International Minerals & Chemical Corp. | Stabilization of growth hormones |
| US4917685A (en) * | 1986-05-16 | 1990-04-17 | International Minerals & Chem. Corp. | Delivery device for the administration of stabilized growth promoting hormones |
| ES2044941T5 (es) * | 1987-08-21 | 1999-02-16 | Mallinckrodt Group Inc | Estabilizador de hormonas promotoras del crecimiento. |
| US5096885A (en) * | 1988-04-15 | 1992-03-17 | Genentech, Inc. | Human growth hormone formulation |
| US5122512A (en) * | 1988-09-12 | 1992-06-16 | Pitman-Moore, Inc. | Swine growth promoting composition |
| EP0374120A3 (en) * | 1988-12-13 | 1991-07-31 | Monsanto Company | Comosition for controlled release of polypeptides |
| DK204791D0 (da) * | 1991-12-20 | 1991-12-20 | Novo Nordisk As | Hidtil ukendt farmaceutisk praeparat |
| WO1993012812A1 (en) * | 1991-12-20 | 1993-07-08 | Novo Nordisk A/S | A stabilized pharmaceutical formulation comprising growth hormone and histidine |
| SE9201073D0 (sv) * | 1992-04-03 | 1992-04-03 | Kabi Pharmacia Ab | Protein formulation |
| ATE359824T1 (de) * | 1992-07-31 | 2007-05-15 | Genentech Inc | Wässrige formulierung enthaltend menschliches wachstumshormon |
| US5547696A (en) * | 1994-10-13 | 1996-08-20 | Novo Nordisk A/S | Pharmaceutical formulation |
| US5552385A (en) * | 1995-06-05 | 1996-09-03 | Novo Nordisk A/S | Pharmaceutical formulation |
-
1991
- 1991-12-20 DK DK912047A patent/DK204791D0/da not_active Application Discontinuation
-
1992
- 1992-01-28 US US07/827,178 patent/US5977069A/en not_active Expired - Fee Related
- 1992-12-16 SK SK737-94A patent/SK73794A3/sk unknown
- 1992-12-16 KR KR1019940702140A patent/KR100270726B1/ko not_active IP Right Cessation
- 1992-12-16 AU AU33445/93A patent/AU664416B2/en not_active Ceased
- 1992-12-16 NZ NZ246555A patent/NZ246555A/en unknown
- 1992-12-16 RU RU9494045921A patent/RU2098130C1/ru active
- 1992-12-16 CA CA002125856A patent/CA2125856A1/en not_active Abandoned
- 1992-12-16 RO RO94-01055A patent/RO112086B1/ro unknown
- 1992-12-16 DE DE69228704T patent/DE69228704T2/de not_active Expired - Fee Related
- 1992-12-16 JP JP51136093A patent/JP3662580B2/ja not_active Expired - Fee Related
- 1992-12-16 HU HU9401831A patent/HUT69682A/hu unknown
- 1992-12-16 AT AT93902088T patent/ATE177645T1/de not_active IP Right Cessation
- 1992-12-16 EP EP93902088A patent/EP0618806B1/en not_active Expired - Lifetime
- 1992-12-16 WO PCT/DK1992/000378 patent/WO1993012811A1/en active IP Right Grant
- 1992-12-16 CZ CZ941458A patent/CZ282826B6/cs unknown
-
1994
- 1994-05-30 BG BG98804A patent/BG98804A/bg unknown
- 1994-06-17 FI FI942905A patent/FI942905A0/fi not_active Application Discontinuation
- 1994-06-17 NO NO942299A patent/NO942299L/no unknown
-
1995
- 1995-06-06 US US08/469,283 patent/US5851992A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| RU94045921A (ru) | 1996-08-27 |
| HU9401831D0 (en) | 1994-09-28 |
| EP0618806A1 (en) | 1994-10-12 |
| NO942299D0 (no) | 1994-06-17 |
| HUT69682A (en) | 1995-09-28 |
| DK204791D0 (da) | 1991-12-20 |
| US5977069A (en) | 1999-11-02 |
| FI942905A (fi) | 1994-06-17 |
| JP3662580B2 (ja) | 2005-06-22 |
| NZ246555A (en) | 1996-03-26 |
| CZ145894A3 (en) | 1994-12-15 |
| AU664416B2 (en) | 1995-11-16 |
| CA2125856A1 (en) | 1993-07-08 |
| DE69228704T2 (de) | 1999-09-16 |
| US5851992A (en) | 1998-12-22 |
| ATE177645T1 (de) | 1999-04-15 |
| KR100270726B1 (ko) | 2000-11-01 |
| WO1993012811A1 (en) | 1993-07-08 |
| JPH07502515A (ja) | 1995-03-16 |
| AU3344593A (en) | 1993-07-28 |
| DE69228704D1 (de) | 1999-04-22 |
| EP0618806B1 (en) | 1999-03-17 |
| RU2098130C1 (ru) | 1997-12-10 |
| NO942299L (no) | 1994-06-17 |
| KR940703689A (ko) | 1994-12-12 |
| RO112086B1 (ro) | 1997-05-30 |
| FI942905A0 (fi) | 1994-06-17 |
| CZ282826B6 (cs) | 1997-10-15 |
| BG98804A (bg) | 1995-02-28 |
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