Terlipressin API CAS 1884420-36-3

Terlipressin API|Terlipressin acetate cGMP ntau lawm|Lub siab thiab lub raum ua haujlwm txhim kho API|Kev tshawb fawb-Peptide

Terlipressin API CAS 1884420-36-3 - Peptide API rau Hepatorenal Syndrome(HRS-AKI) kho.Science-Peptide muab cGMP raws Terlipressin Acetate nrog cov txheej txheem paub tab, ntshiab impurity profile, kev txhawb nqa rau Tuam Tshoj, Tebchaws USA thiab Europe tshaj tawm, thiab tau dhau qhov cuam tshuam DMF ua ntaub ntawv ntawm FDA. Txais tos tiv tauj peb.

Terlipressin, hluavtaws vasopressin analog, yog dav siv thoob ntiaj teb rau kev kho mob hepatorenal syndrome- mob raum raug mob (HRS-AKI).The 2016 American College of Gastroenterology Guidelines thiab raug pom zoo los ntawm FDA hauv 2021 tau tsim nws ua lub hauv paus rau kev kho mob ntawm HRS{5}AKI.

 

Nws cov txheej txheem ntawm kev ua yog tshwj xeeb: los ntawm kev ua ntawm V1a receptor ntawm visceral ncig, nws xaiv constricts lub dilated splanchnic thiab visceral hlab ntsha, txo cov visceral ntshav txaus, thiab ua rau kom cov hlab ntsha zoo npaum li cas thiab txhais tau tias arterial siab, thiaj li ua rau kom lub raum perfusion thiab txhim kho lub raum ua haujlwm. Cov ntaub ntawv kho mob qhia tau tias tom qab terlipressin ua ke nrog kev kho mob albumin, kwv yees li 40% -45% ntawm cov neeg mob lub raum ua haujlwm tau zoo dua qub.

 

Kev tshawb fawb-Peptide tau sau ntau tshaj 20 xyoo ntawm kev paub hauv peptide APIs. Terlipressin yog ib hom tsiaj uas peb tau ua tiav cov txheej txheem kev tsim kho thiab ua lag luam ua ntej. Peb tau txais kev paub txog cov khoom ua kom paub tab-theem synthesis thiab fragment condensation txoj kev, nrog cov txheej txheem ruaj khov thiab meej impurity profile. Peb tau dhau los ntawm DMF cov ntaub ntawv cuam tshuam nrog FDA, thiab muaj peev xwm txhawb nqa peb cov neeg siv khoom hauv kev sau npe ntawm kev npaj hauv kev lag luam loj xws li Tuam Tshoj, Tebchaws Meskas, Tebchaws Europe, thiab lwm yam.

Terlipressin (Terlipressin Acetate) yog cyclic peptide uas muaj 12 amino acids uas tsim cov qauv cyclized los ntawm disulfide daim ntawv cog lus ntawm 1- txoj hauj lwm thiab 6-txoj hauj lwm cysteine. Nws thawj peb glycines yog enzymatically cleaved nyob rau hauv vivo kom maj mam tso cov active metabolite, lysopressin, uas ua rau ib tug ntev-ntev nyhuv.

Kev kho mob tseem ceeb ntawm terlipressin suav nrog:

Hepatorenal Syndrome-Kev mob raum mob hnyav (HRS-AKI):Tam sim no qhov no yog thawj qhov qhia. Los ntawm constricting dilated visceral cov hlab ntsha thiab txhim kho lub zoo circulating ntshav ntim, ua hauj lwm raum raug mob yuav thim rov qab.
Los ntshav los ntawm esophageal varices:raws li ib tug vasoactive tshuaj, siv nyob rau hauv ua ke nrog endoscopic ligation los tswj mob los ntshav.
Lwm yam kev siv:Refractory ascites, kis kab mob, thiab lwm yam (siv dhau cov lus qhia).
Los ntawm kev pom kev lag luam, terlipressin yog cov tshuaj classic. Nrog rau kev qhib hauv Teb Chaws Asmeskas kev lag luam tom qab FDA pom zoo thiab qhov kev thov tsis tu ncua rau kev kho mob cirrhosis- cuam tshuam rau lub raum raug mob thoob ntiaj teb, qhov kev thov rau nws API tau ruaj khov.

1. Cov kev paub dhau los hauv cov txheej txheem routing thiab scale - nce

Cov teeb meem nyob rau hauv lub synthesis ntawm terlipressin dag nyob rau hauv lub meej tsim ntawm disulfide bonds thiab efficiency ntawm cyclization. Peb txais yuav ib lub tswv yim ua ke ntawm "fragment condensation + kua theem cyclization":

• Qhov tag nrho -ntev ib ntus tau muab faib ua 2-3 ntu ua ke sib cais hauv cov theem khoom
• Cyclization ntawm disulfide bonds nyob rau hauv cov kua theem nyob rau hauv me me tej yam kev mob thiab nrog ob peb sab tshwm sim
• fragment sib dhos ua raws los ntawm ntau- kauj ruam npaj HPLC purification

Peb tau khiav cov txheej txheem no rau ntau tshaj kaum xyoo, los ntawm kev sim mus rau kev lag luam ntau lawm ntawm 100 kilograms. Cov txiaj ntsig peptide crude yog qhov ruaj khov, kev ua haujlwm cyclization tuaj yeem ncav cuag ntau dua 95%, thiab purity ntawm cov khoom kawg yog ruaj khov ntawm ntau dua 99%. Peb cov txheej txheem validation batch cov ntaub ntawv qhia tau hais tias cov impurity profiles yog heev reproducible nyob rau hauv successive batch.

2. Kev tswj xyuas nruj, raws li cov qauv cGMP

Peb tsim Terlipressin API CAS 1884420-36-3 raws li cGMP cov cai, txhua pawg raug kuaj nruj me ntsis:

• Kev sim tso tawm: cov ntsiab lus (97.0%-102.0% los ntawm cov dej tsis muaj dej thiab cov kuab tshuaj tsis muaj zog), purity (HPLC, Ntau dua lossis sib npaug li 99.0%), lwm yam tshuaj (singletons Tsawg dua lossis sib npaug li 0.15%), noo noo, cov kuab tshuaj seem, cov kab mob endotoxins, microbial txwv
• Impurity profile tswj: kev txheeb xyuas cov txheej txheem impurities thiab degradation khoom. Cov impurities tseem ceeb xws li disulfide daim ntawv cog lus mismatch isomers, oxidized impurities, peptides uas ploj lawm, thiab lwm yam tau tswj tsis pub dhau qhov kev txwv.
• Cov kev tshawb fawb txog kev ruaj ntseg: ntev- lub sij hawm, ceev cov ntaub ntawv ruaj ntseg los txhawb 24-36 lub hlis rov qab xeem, raws li ICH Q1
• Method validation: Txhua txoj kev tshuaj ntsuam xyuas tau raug lees paub raws li ICH Q2.

3. Ua kom tiav cov ntaub ntawv thiab kev sau npe txhawb nqa

Cov ntaub ntawv dav dav rau terlipressin muaj cov ntaub ntawv API meej. Peb tuaj yeem muab:

• Cov txheej txheem kev txhim kho daim ntawv tshaj tawm (nrog rau cov txheej txheem ntawm kev txiav txim siab cov txheej txheem tseem ceeb)
• Cov txheej txheem validation program thiab tshaj tawm (nrog validation batch data) analytical method validation reports
• Cov ntaub ntawv kawm ruaj khov (ntev-lub sijhawm, nrawm, cuam tshuam)
• Heterogeneous mass spectrometry report (nrog kev pom zoo)
• Cov ntaub ntawv pov thawj ntawm cov qauv (NMR, MS, IR, thiab lwm yam)
• Batch ntau lawm cov ntaub ntawv (ua tiav thiab traceable)
• Kev koom tes nrog cov neeg siv khoom nyob rau hauv - kev tshuaj xyuas qhov chaw los ntawm cov chaw muag tshuaj

Peb Terlipressin API tau ua tiav FDA DMF cov ntaub ntawv, thiab tuaj yeem tso cai rau cov neeg siv khoom siv hauv Suav teb, Tebchaws Asmeskas thiab Europe tshaj tawm.

4. Txhim khu kev ruaj ntseg cov saw hlau

• Dual -Kev yuav khoom: ob lossis ntau tus neeg muag khoom tsim nyog rau cov ntaub ntawv tseem ceeb (amino acids, resins)
• Strategic stockpiling: tsim kom muaj kev ruaj ntseg cov khoom ntawm cov khoom siv sij hawm ntev
• Kev tsim khoom tas mus li: ntau cov kab ntau lawm tuaj yeem ua rau tib lub sijhawm kom ntseeg tau ntawm - lub sijhawm xa khoom xaj
• Batch Consistency: Pov thawj los ua hauv cov khoom sib law liag, nrog cov khoom tsim tawm zoo nkauj thiab tsis huv.

5. Cov hom kev sib koom tes yooj yim

• API Muag: Muab cGMP- ua raws Terlipressin APIs thiab txhawb kev tsim cov formulations
• Kev tso cai DMF: muab cov ntawv tso cai DMF, txhawb cov neeg siv khoom kom tshaj tawm cov tshuaj generic
• Kev hloov pauv tshuab: Cov txheej txheem tuaj yeem hloov mus rau cov neeg siv khoom- cov chaw tsim khoom tshwj xeeb
• Customized ntim: raws li qhov xav tau ntawm kev npaj, muab cov khoom sib txawv ntawm kev ntim khoom

• cGMP chaw tsim khoom (10 acres)
• Ua raws li US FDA, Europe EMA, Tuam Tshoj NMPA cGMP cov cai
• ISO 9001: 2015 tau ntawv pov thawj
• Automated khoom theem synthesis cog (100 kg peev)
• Preparative HPLC purification system (ntau pawg)
• Txias-rhiav kom qhuav (ntau tshaj 30 square meters)
• Qhov chaw huv (ISO chav kawm 7/8)
• Ua tiav QC kuaj: HPLC, UPLC, LC-MS, GC, thiab lwm yam

Qhov system zoo

• Kev tswj xyuas nruj, kev tswj kev sib txawv, CAPA system
• Cov neeg muab khoom kuaj xyuas thiab tag nrho traceability ntawm cov ntaub ntawv
• Kev tshuaj xyuas zoo txhua xyoo, kev txhim kho tas mus li
• Peb tau muaj ntau yam kev paub dhau los hauv kev koom tes nrog cov neeg siv khoom thiab cov neeg tswj hwm hauv -kev tshuaj xyuas qhov chaw

1. Kev siv tshuab paub tab, ntshiab impurity profile

Peb tau sau ntau tshaj kaum xyoo ntawm kev tsim khoom nyob rau hauv Terlipressin API, thiab cov txheej txheem yog tas li optimized, thiab cov impurity profile yog zoo ib yam nrog cov thawj kev tshawb fawb. Cov impurities tseem ceeb xws li disulfide daim ntawv cog lus mismatch, oxidation khoom, peptides ploj, thiab lwm yam. muaj kev paub tab thiab tswj cov tswv yim.

2. Kev ua raws cai, uas tuaj yeem tiv taus kev tshuaj xyuas

Peb cov chaw cGMP thiab cov ntaub ntawv kaw lus tuaj yeem tiv thaiv kev tshuaj xyuas ntawm cov chaw tswj xyuas tshuaj hauv tsev thiab txawv teb chaws. Terlipressin tau ua tiav FDA DMF cov ntaub ntawv, thiab qee cov neeg siv khoom tau ua tiav kev soj ntsuam kev sib raug zoo hauv tsev thiab ANDA ua ntaub ntawv siv peb API.

3. Kev ruaj ntseg ntawm kev xa khoom thiab tsis yog - txiav tawm ntawm cov khoom lag luam

Peb tau tsim kom muaj kev tswj xyuas cov khoom lag luam zoo tshaj plaws, ob qho - kev yuav khoom ntawm cov ntaub ntawv tseem ceeb thiab cov tswv yim txaus. Peb muaj cov chaw muag khoom seem rau cov ntaub ntawv tseem ceeb xws li amino acid raw cov ntaub ntawv thiab cov resin ntawm Terlipressin, thiab kev tsim khoom yuav tsis raug tso tseg vim muaj cov khoom tsis txaus.

4. Tshaj tawm kev txhawb nqa, txuag kev siv zog

Peb tsis tsuas yog muab APIs nkaus xwb, tab sis kuj tseem muaj cov ntaub ntawv tiav thiab cov ntaub ntawv los txhawb kev sau npe, DMF cov qauv ntaub ntawv yog qhov tseeb, ua tiav cov ntaub ntawv, thiab tsawg dua kev tshuaj xyuas thiab kho.

Lub tuam txhab kws tshuaj hauv tsev xav tau Terlipressin API rau kev ntsuam xyuas qhov sib xws. Peb muab cov txheej txheem ua tiav cov ntaub ntawv pov thawj thiab cov ntaub ntawv ruaj khov, thiab koom tes nrog nws kom ua tiav cov lus tshaj tawm. Ntau yam tam sim no tau dhau qhov kev ntsuas qhov sib xws, thiab peb tau dhau los ua nws cov khoom siv sijhawm ntev -.
European generic tuam txhab: Peb tau npaj ua ntaub ntawv ANDA hauv Tebchaws Europe, thiab xav tau terlipressin API nrog qhov zoo ib yam li cov kev tshawb fawb thawj zaug. Peb muab DMF daim ntawv tso cai thiab koom tes nrog lawv kom tau txais kev tshuaj xyuas, thiab thaum kawg cov khoom tau txais kev pom zoo tiav.

Terlipressin yog cov tshuaj tseem ceeb hauv kev kho mob hepatorenal syndrome, nrog kev lag luam paub tab thiab kev xav tau ruaj khov. Peb tau ua haujlwm ntawm Terlipressin API rau ntau tshaj 10 xyoo, nrog cov txheej txheem paub tab, ruaj khov zoo, ua tiav cov ntaub ntawv, thiab tau ua tiav FDA DMF cov ntaub ntawv. Yog tias koj tab tom tsim Terlipressin formulations thiab xav tau ib tug raws, ruaj khov thiab traceable API tus neeg muag khoom, txais tos tham nrog peb.