Semaglutide(link:https://www.bloomtechz.com/synthetic-chemical/peptide/semaglutide-powder-cas-910463-68-2.html) yog cov tshuaj uas muaj nyob rau hauv chav kawm ntawm insulin-zoo li peptide -1 receptor agonists (GLP-1 RA).
1. Molecular qauv:
Cov qauv molecular ntawm Semaglutide yog hluavtaws polypeptide nrog 38 amino acid residues. Nws yog tau los ntawm kev hloov kho cov qauv ntawm ntuj insulin-zoo li peptide-1 (GLP-1). Tus qauv, Semaglutide muaj qhov zoo sib xws rau C-terminus ntawm GLP-1, thiab muaj ntau yam amino acid residue hloov kho.
2. Molecular mis thiab molecular hnyav:
Semaglutide muaj cov tshuaj formula C187H291N45O59 thiab qhov hnyav molecular ntawm kwv yees li 4113.6 g / mol.
3. Lub cev muaj zog:
Nws yog me ntsis soluble hauv dej thiab soluble hauv qee cov organic solvents xws li methanol thiab acetonitrile. Solubility ntawm semaglutide hloov nrog pH.
4. Pharmacological zog:
Semaglutide yog ib qho tshuaj insulin zoo li peptide-1 receptor agonist uas nws lub luag haujlwm tseem ceeb ntawm kev ua tshuaj yog ua raws li kev ua ntawm GLP-1 tsim tawm hauv lub cev. Nws khi rau GLP-1 receptor los txhawb kev tso tawm ntawm insulin thiab inhibit qhov tso tawm ntawm glucagon. Tsis tas li ntawd, semaglutide kuj tseem tuaj yeem ua rau txo qis qis ntawm lub plab zom mov thiab txo qhov nqus ntawm cov zaub mov, yog li txo cov ntshav qab zib. Nws kuj suppresses qab los noj mov, nce satiety, thiab pab tswj qhov hnyav.
5. Pharmacokinetic zog:
Lub pharmacokinetic zog ntawm semaglutide muaj xws li nqus, faib, metabolism thiab excretion. Nws yog absorbed sai sai tom qab txhaj tshuaj subcutaneous, thiab lub sijhawm kom ncav cuag qhov siab tshaj plaws plasma concentration yog li 5 hnub. Vim yog qhov ua haujlwm ntev ntawm semaglutide, nws muab cov nyhuv tshuaj tiv thaiv. Nws yog feem ntau metabolized los ntawm insulinase thiab lwm txoj hauv kev metabolic, thiab tom qab ntawd tawm los ntawm ob lub raum thiab quav.
6. Lwm yam nta:
Semaglutide muaj kev ruaj ntseg siab thiab tuaj yeem khaws cia hauv qhov chaw cia li qub. Thaum siv, nws qhov kev ruaj ntseg tsis cuam tshuam los ntawm kev hloov pauv kub me ntsis, yog li tsis tas yuav tsum muaj tub yees.
Semaglutide (lub npe lag luam: Ozempic) yog insulin-zoo li peptide -1 receptor agonist (GLP-1 RA) qhia rau kev kho mob ntshav qab zib hom 2. Cov txheej txheem hluavtaws ntawm semaglutide tuaj yeem muab faib ua ntau theem, feem ntau suav nrog cov khoom siv-theem synthesis, kua-theem synthesis thiab purification cov kauj ruam. Cov hauv qab no yog cov txheej txheem tseem ceeb ntawm Semaglutide:
1. Khoom theem synthesis:
- Lub synthesis ntawm semaglutide feem ntau pib nrog cov khoom theem synthesis.
- Ua ntej, thawj cov amino acid residue yog immobilized ntawm cov khoom txhawb nqa los ntawm cov khoom sib txuas ua ke.
- Tom qab ntawd, tiv thaiv nrog pab pawg tiv thaiv Fmoc ua ntej ntxiv cov amino acid residue tom ntej.
- Tom qab txhua qhov sib ntxiv ntawm cov amino acid residues, siv cov kuab tshuaj hydrophilic xws li carbon disulfide rau elution thiab ntxuav.
2. Ua kua theem synthesis:
- Kev tso tawm ntawm cov saw hlau polypeptide los ntawm cov khoom txhawb nqa mus rau hauv cov kua theem tom qab ua tiav cov txheej txheem synthesis tiav.
- Siv cov kua qaub (xws li trifluoroacetic acid) los yog lub hauv paus (xws li n-butylamine) kom tshem tawm cov saw hlau polypeptide los ntawm cov khoom txhawb nqa.
- Nyob rau hauv cov xwm txheej tsim nyog, cov saw hlau polypeptide raug xa mus rau theem ua kua rau cov kev tshwm sim tom ntej.
3. Kev sib txuas ntawm cov amino acid residues:
- Tshem tawm ntawm pawg tiv thaiv sib raug, nthuav tawm cov pab pawg nquag ntawm cov amino acid residue.
- Txuas cov amino acid residues ib los ntawm ib qho uas siv cov activator xws li bis-(1-hydrazino)-1,3-diisopropylcarboimide.
4. Thioether daim ntawv cog lus:
- Taw qhia ntawm cysteine residues hauv cov saw hlau polypeptide.
- Siv cov tshuaj tiv thaiv tsim nyog thiab txo cov neeg ua haujlwm (xws li triethylamine-trimercaptopropane) los txhawb kev tsim cov disulfide bonds ntawm cysteine thiab lwm yam amino acids.
5. Tiv thaiv pab pawg tshem tawm:
- Tom qab cov saw hlau polypeptide tau sib sau ua ke, cov pab pawg tiv thaiv ntawm cov amino acid residues yuav tsum raug tshem tawm.
- Cov pab pawg tiv thaiv Fmoc tuaj yeem raug tshem tawm siv cov kua qaub lossis cov kab mob yooj yim, thiab lwm pab pawg tiv thaiv tuaj yeem raug tshem tawm.
6. Purification thiab qauv kev pom zoo:
- Kev lim dej thiab cov qauv kev pom zoo ntawm Semaglutide tom qab ua tiav ntawm kev sib txuas.
- Kev ua kom huv thiab siv tau siv cov txheej txheem chromatographic xws li kev ua haujlwm siab ua kua chromatography thiab cov txheej txheem loj spectrometry xws li huab hwm coj spectrometry.
Nws yuav tsum raug sau tseg tias cov kauj ruam uas tau hais los saum toj no yog cov kauj ruam tseem ceeb hauv kev sib txuas ntawm Semaglutide, thiab qhov kev sib txuas tiag tiag yuav koom nrog ntau theem nrab thiab kev hloov kho. Vim muaj kev tiv thaiv patent, cov ncauj lus kom ntxaws txog cov txheej txheem hluavtaws thiab cov xwm txheej yuav tsis raug nthuav tawm. Tsis tas li ntawd, kev lag luam tsim khoom ntawm semaglutide feem ntau yog ua raws li kev tswj hwm nruj.
Semaglutide yog cov tshuaj insulin zoo li peptide-1 receptor agonist (GLP-1 RA) tsim los ntawm Danish kws tshuaj lub tuam txhab Novo Nordisk rau kev kho mob ntshav qab zib hom 2. Nws muaj cov txiaj ntsig zoo xws li txo cov ntshav qab zib, txo qhov hnyav, thiab txhim kho insulin tsis kam. Kev tshawb pom keeb kwm ntawm Semaglutide tuaj yeem taug qab rov qab mus rau xyoo 1990, uas yuav qhia meej hauv qab no:
Thaum ntxov xyoo 1990, Novo Nordisk pab pawg tshawb fawb tau pib tshawb xyuas qhov ua tau ntawm kev kho mob ntshav qab zib los ntawm kev ua cov tshuaj insulin zoo li peptide-1 (GLP-1). GLP-1 yog ib yam tshuaj uas tso tawm los ntawm cov hnyuv me uas txhawb nqa cov tshuaj insulin, inhibits glucagon tso tawm, thiab ua rau lub plab zom mov qeeb. Txawm li cas los xij, vim tias GLP-1 nws tus kheej tau yooj yim degraded hauv vivo, nws luv luv ib nrab-lub neej txwv nws daim ntawv thov ua tshuaj kho mob ntshav qab zib.
Txhawm rau kov yeej lub neej luv luv ntawm GLP-1 thiab txhim kho kev ruaj ntseg, cov kws tshawb fawb ntawm Novo Nordisk tau siv cov txheej txheem kev tsim kho caj ces los hloov kho cov amino acid ib ntu ntawm GLP-1 los tsim kom muaj kev ruaj khov thiab kav ntev. analogue, insulin zoo li Peptide-1 receptor agonist (GLP-1 RA). Qhov kev tshawb fawb tshiab no tau tshaj tawm thawj zaug hauv xyoo 1996.
Ob peb xyoos tom ntej no, pab neeg tshawb fawb tau ua kom zoo dua thiab ua kom zoo dua cov GLP-1 RAs. Lawv tau sim ntau txoj hauv kev, suav nrog kev hloov kho cov amino acid ib ntus, qhia cov piam thaj thiab fatty acid residues, thiab lwm yam, txhawm rau txhim kho kev ua haujlwm thiab kev ruaj ntseg ntawm cov tshuaj.
Hauv xyoo 2005, Novo Nordisk cov kws tshawb nrhiav thawj zaug tau tsim cov semaglutide thiab lees paub tias nws yog GLP muaj zog -1 RA. Semaglutide muaj kev sib raug zoo siab rau GLP-1 receptor, tuaj yeem ua raws li cov txiaj ntsig ntawm GLP-1, thiab muaj qhov ua haujlwm ntev thiab tuaj yeem siv los ntawm kev txhaj tshuaj subcutaneous.
Tom qab ntawd, kev sim tshuaj tau pib ntsuas qhov ua tau zoo thiab kev nyab xeeb ntawm semaglutide hauv kev kho cov neeg mob ntshav qab zib hom 2. Cov kev sim no suav nrog cov neeg mob sib txawv thiab ntau npaum li cas thiab muab piv rau lwm cov tshuaj ntshav qab zib.
Xyoo 2017, Novo Nordisk tau tshaj tawm cov txiaj ntsig ntawm qhov kev sim tshuaj tseem ceeb, hais tias Semaglutide tau ua tiav cov txiaj ntsig zoo kawg nkaus hauv kev kho mob ntshav qab zib hom 2. Kev sim, hu ua SUSTAIN (Semaglutide Unabated Sustainability hauv Kev Kho Mob Ntshav Qab Zib Hom 2)-6, koom nrog 3,000 cov neeg mob thiab piv semaglutide, nrog rau lwm yam GLP-1 RAs, nrog rau cov tshuaj placebo. Cov txiaj ntsig tau pom tias cov neeg mob kho nrog semaglutide tau pom cov txiaj ntsig tseem ceeb hauv kev txo cov ntshav qab zib, txo lub cev hnyav thiab txhim kho insulin tsis kam.
Raws li cov txiaj ntsig ntawm cov kev sim tshuaj no, Novo Nordisk tau xa daim ntawv thov tshuaj tshiab rau Semaglutide rau US Food and Drug Administration (FDA) hauv 2017 thiab tau pom zoo rau kev lag luam thaum kawg ntawm 2017. Tom qab ntawd, Semaglutide kuj tau pom zoo los ntawm lwm tus. lub teb chaws thiab cheeb tsam, thiab yog siv los ua thawj kab tshuaj rau kev kho mob ntshav qab zib hom 2.
Semaglutide tau txij li thaum pom cov lus cog tseg hauv lwm qhov chaw thiab. Piv txwv li, cov kev tshawb fawb tsis ntev los no tau pom tias cov koob tshuaj semaglutide qis kuj tseem muaj txiaj ntsig zoo rau kev tswj qhov hnyav thiab kev kho mob rog, ua rau semaglutide yog ib qho tshuaj tiv thaiv kev rog.
Feem ntau, kev tshawb pom keeb kwm ntawm semaglutide tuaj yeem taug qab mus rau thaum ntxov 1990s. Los ntawm kev hloov kho thiab kev ua kom zoo ntawm GLP-1, Novo Nordisk tau ua tiav qhov kev ua haujlwm ntev thiab ruaj khov GLP-1 RA, thiab tau lees paub nws qhov ua tau zoo thiab kev nyab xeeb raws li cov tshuaj rau kev kho mob ntshav qab zib hom 2. Tom qab xyoo ntawm kev tshawb fawb thiab kev sim tshuaj, Semaglutide tau dhau los ua ib qho tshuaj tseem ceeb rau kev kho mob ntshav qab zib thiab rog.