Ganirelix API CAS 129311-55-3

Ganirelix API CAS 129311-55-3|Ganirelix acetate cGMP ntau lawm|GnRH antagonist API|Science-Peptide

Ganirelix API CAS 129311-55-3- GnRH antagonist rau kev pabcuam kev tsim cov tshuaj tiv thaiv zes qe menyuam.Science-Peptide muab Ganirelix Acetate raws li tus qauv cGMP, nrog cov txheej txheem mature, clear impurity profiles, txhawb rau Tuam Tshoj, Tebchaws USA thiab Europe tshaj tawm, thiab tuaj yeem tso cai DMF.W.

Ganirelix tau siv ntau ntxiv hauv thaj chaw ntawm kev pab tu me nyuam. Cov neeg mob uas tau IVF yuav tsum tau tswj lub zes qe menyuam kom tiv thaiv kom tsis txhob ntxov ntxov follicular. Ganirelix yog "precision hloov" - nrawm- ua yeeb yam, tsis muaj "flare effect" - thiab nyob hauv tib chav kawm xws li cetrorelix, lwm tus GnRH antagonist. Cetrorelix, lwm tus GnRH antagonist.

 

Nws yog tsim raws li ib tug decapeptide nrog ntau yam unnatural amino acids nyob rau hauv lub sequence: D-Lys, D-Asn, D-Ala, D-Arg, L-Har (high arginine). Cov kev hloov kho no ua rau nws muaj kev sib raug zoo rau GnRH receptor, ib nrab ib nrab ntawm - lub neej, thiab nws tuaj yeem txhaj tshuaj subcutaneously ib hnub. Daim ntawv ntau npaum li cas feem ntau yog tus cwj mem txhaj tshuaj ua ntej, uas tus neeg mob tuaj yeem tswj hwm hauv tsev.

 

Kev tshawb fawb-Peptide tau ua haujlwm ntawm peptide APIs tau ntau dua 20 xyoo, thiab peb tau ua haujlwm ntawm Ganirelix tau ob peb xyoos. Cov teeb meem hauv kev sib txuas ntawm peptide no dag hauv kev qhia ntau yam D-hom amino acids thiab L-Har, nrog rau kev sib cais ntawm impurities thaum lub sij hawm purification. Tam sim no, peb muaj cov khoom ruaj khov ntawm Ganirelix Acetate API los ntawm gram mus rau kilogram, FDA DMF tau raug foob, thiab peb txhawb Tuam Tshoj, Asmeskas thiab Europe tshaj tawm. Nyob rau hauv lub impurity spectrum, muaj cov paub tab tswj schemes rau txawv isomerism (D / L interchange), uas ploj lawm peptides thiab oxidized impurities.

Puas yog Ganirelix yog cyclic decapeptide? Qhov tseeb, nws yog linear decapeptide yam tsis muaj disulfide daim ntawv cog lus, nrog cov qauv tshwj xeeb: thawj ob peb yog D-hom amino acids, thiab ob lub lysine sab chains nyob rau hauv nruab nrab nqa ntau pawg acylation (adamantanecarbonyl thiab isonicotinoyl).

Cov ntawv thov kev kho mob tseem ceeb:

• Tswj Ovarian Stimulation (COS): Siv nyob rau hauv IVF cycles txhawm rau txhawm rau pib ntxov LH peaks thiab tiv thaiv ntxov follicular ovulation. Pib hnub 5 lossis 6 ntawm lub voj voog stimulation kom txog thaum ovulation tshwm sim.
• Kev sib xyaw nrog FSH: Hauv cov txheej txheem ovulation, Ganirelix antagonizes endogenous GnRH, tso cai rau kev tswj hwm FSH ntau dua.
• Tsis ntev -kev kho mob: luv ib nrab-lub neej, haum rau luv- siv sijhawm nkaus xwb.
• Los ntawm API qhov kev xav, qhov impurity profile ntawm Ganirelix yog qhov tshwj xeeb heev: vim muaj ntau yam D-hom amino acids, txawv isomerism (xws li, D- hom hloov rov qab rau L- hom) yog qhov tseem ceeb impurity; Tsis tas li ntawd, ob sab -chain acylation sites, yog tias qhov acylation tsis tiav lossis tsis raug acylated, cov khoom muaj feem cuam tshuam yuav raug tsim tawm. Peb tau siv zog ntau hauv cov cheeb tsam no.

1. Cov txheej txheem yog mature, nrog D-amino acids thiab diacylation ntawm cov tub ntxhais
Cov teeb meem hauv kev sib txuas ntawm Ganirelix yog qhov tseeb tias ntau D-hom amino acids tsis ua ke zoo li L- hom, thiab ob lub lysine sab chains yuav tsum tau txuas mus rau ntau pawg acylation (adamantanecarboxylic acid thiab isonicotinic acid), feem. Peb siv cov tswv yim nram no:

• Khoom-theem synthesis: Fmoc lub tswv yim, D- hom amino acid coupling rau ncua sij hawm ntawm lub sij hawm, ob coupling yog tsim nyog.
• Kev tiv thaiv Orthogonal: Ob lub lysines tau deprotected nrog cov pab pawg tiv thaiv sib txawv (xws li, Mtt thiab Dde), thiab ob pawg acyl tau sib txuas ua ke tom qab deprotection kom tsis txhob hla - tawm tsam.
• Kev Ua kom huv: Ntau-qib kev npaj HPLC tau ua kom huv si cais cov isomers, tsis muaj peptides, thiab cov khoom siv monoacylated (tsuas yog ib pawg acyl txuas nrog).
• Process validation data: the purity was stable above 99.0%, the proportion of diacylated product was >99.5%, thiab qhov sib txawv isomerization yog<0.10% in several successive batches.

2. Kev tswj kom zoo, nrog rau qhov tseem ceeb ntawm qhov sib txawv isomers thiab monoacylated impurities
Txhua pawg raug tso tawm rau kev sim raws li cGMP, suav nrog USP / EP cov cai, thaum peb them tshwj xeeb rau:

• Purity: HPLC Ntau dua lossis sib npaug rau 99.0%, qhov tseeb batch 99.2% -99.5%.
• Differential isomerism: D-hom amino acids yuav racemize rau L-type. Peb sib cais lawv ntawm ib tus tswv chiral kem nrog kev tswj ntawm<0.10%.
• Monoacylated impurities: intermediates nrog tsuas yog adamantanecarbonyl lossis tsuas yog isonicotinoyl txuas. Tswj rau<0.15%.
• Peptides ploj lawm: qhov chaw uas ploj lawm uas muaj kev tswj hwm, tag nrho cov peptides ploj lawm<0.5%.
• Oxidizing impurities: tyrosine, tryptophan ua ntu zus? Tsis muaj tryptophan hauv Ganirelix, tab sis tyrosine yuav raug oxidized, tswj<0.10%.
• Endotoxin:<0.25 EU/mg, in accordance with the standard for injection.
• Kev ruaj ntseg yog ua tiav ob lub sijhawm ntev thiab nrawm, txhawb nqa 24-36 lub hlis rov kuaj dua. Cov txheej txheem raug lees paub.

3. Ua tiav cov ntaub ntawv thiab DMF ua ntaub ntawv

• Kev tshaj tawm cov ntaub ntawv tuaj yeem siv ncaj qha: daim ntawv tshaj tawm kev txhim kho (nrog rau qhov tseem ceeb ntawm cov kauj ruam diacylation), cov txheej txheem validation program thiab daim ntawv qhia, analytical method validation, stability data, impurity profileing (differential isomers, monoacylated impurities, etc.), structural confirmation (NMR, MS, IR), thiab batch production records. Koom tes nrog rau ntawm - kev tshuaj xyuas qhov chaw.

DMF tau raug xa mus rau US FDA thiab tuaj yeem tso cai siv hauv Suav teb, Asmeskas thiab Europe.

4. Cov saw hlau, cov khoom siv tshwj xeeb

• Ganirelix siv ntau cov amino acids tshwj xeeb: Fmoc-D-Nal(2)-OH, Fmoc-D-Phe(4Cl)-OH, Fmoc-D-Pal(3)-OH, Fmoc-D-Lys(Mtt)-OH, Fmoc-Lys(Dde)-OH, as well as two acylation reagents. Muaj ob peb tus neeg muag khoom ntawm cov ntaub ntawv no, yog li peb tau ua cov khoom ruaj ntseg ua ntej thiab yuav los ntawm ob qhov chaw.

• Chaw tsim khoom 10 daim av, cGMP tus qauv, FDA / EMA / NMPA ua raws, ISO 9001: 2015.
• Synthesis cog: automated khoom theem synthesis, 100 kg peev
• Purification Rhiav: ntau yam kev npaj HPLC
• Txias-rhiav tshuab ziab khaub ncaws: 30 square meters +, industrial khov- tshuab ziab khaub ncaws
• Qhov chaw huv: ISO 7/8
• QC Lab: HPLC, UPLC, LC-MS, GC, Chiral Columns
• Kev Tswjhwm Zoo: Kev Hloov Kho, Kev Tswj Xyuas Kev Sib Dev, CAPA, Kev Tshawb Fawb Txog Kev Lag Luam, Kev Ntsuam Xyuas Txhua Xyoo. Koom tes nrog FDA, EMA, NMPA ntawm -kev tshuaj xyuas qhov chaw.

Lub tuam txhab tshuaj hauv tsev, Ganirelix kev tshuaj ntsuam xyuas qhov sib xws: cov ntaub ntawv raw siv yav dhau los muaj qhov hloov pauv loj hauv kev sib txawv isomerization. Peb muab peb qhov kev siv tau zoo, thiab qhov sib txawv isomerization tau ruaj khov ntawm tsawg dua 0.06%, thiab peb kuj tau muab cov kev tswj xyuas thiab cov qauv kev pom zoo. Lawv dhau qhov kev ntsuam xyuas tiav, thiab tam sim no tab tom yuav khoom tsis tu ncua txhua lub hlis.

European generic kws tuam txhab: xav tau Ganirelix API rau ANDA ntaub ntawv. Peb tau tso cai DMF thiab koom tes nrog EMA tshawb xyuas. Tus kws tshuaj xyuas tau tsom mus rau kev tswj hwm ntawm monoacylated impurities - peb tau nthuav tawm cov tswv yim kev tiv thaiv orthogonal thiab kev tshem tawm cov ntaub ntawv pov thawj purification. Kev tshuaj xyuas tau dhau los thiab API tau muab los ntawm peb nkaus xwb.

US tuam txhab tshuaj: tsim Ganirelix prefilled txhaj cwj mem, xav tau siab purity, tsawg endotoxin API. Peb muab plaub pawg ua ke nrog purity ntawm 99.3% -99.5% thiab endotoxin<0.05 EU/mg (stricter than the standard). They were directly used in the production of preparations and passed the FDA's on-site inspection.

Ganirelix yog ib qho tshuaj tseem ceeb hauv kev pabcuam kev yug me nyuam, nrog cov qauv kev ua haujlwm thiab kev tswj xyuas siab impurity. Peb tau sau ntau xyoo ntawm kev paub hauv cov tsiaj no, cov txheej txheem ruaj khov thiab ua tiav cov ntaub ntawv. Yog tias koj tab tom tsim Ganirelix npaj thiab xav tau APIs, thov hu rau peb.