Teduglutideyog ib qho tshuaj peptide hluavtaws uas tsom mus rau txoj hnyuv nws tus kheej rau kev kho mob. Nws xyaum thiab txhim kho lub cev kev ua haujlwm ntawm tib neeg lub plab hnyuv glucagon-zoo li peptide-2 (GLP-2), uas sawv cev rau kev hloov pauv ntawm "kev txhawb nqa zaub mov tsis zoo" mus rau "kev ua haujlwm ua haujlwm rov qab" rau cov neeg mob plab hnyuv. Cov tshuaj no ua kom cov GLP-2 receptors rau ntawm plab hnyuv epithelial hlwb, txhawb kev loj hlob ntawm plab hnyuv mucosal villi, tob zuj zus ntawm cov crypts, thiab txhim kho cov ntshav txaus, yog li nthuav dav qhov zoo ntawm cov hnyuv, ncua kev zom zaub mov kom nkag mus rau lub sijhawm thiab kev nqus dej. Rau cov neeg mob uas mob plab hnyuv loj xws li mob plab hnyuv loj uas tso siab rau tag nrho cov khoom noj khoom haus parenteral, tus nqi tseem ceeb ntawm Teduglutide yog nyob rau hauv nws lub peev xwm maj mam rov ua kom lub cev tsis muaj zog ntawm txoj hnyuv, txhawm rau txo lossis txawm tias tshem tawm txoj sia nyob mus ib txhis rau kev noj zaub mov noj, thiab txo cov kev pheej hmoo ntawm daim siab puas, kab mob, thiab thrombosis. Nws tsis yog tsuas yog lwm txoj kev kho mob nkaus xwb tab sis kuj yog ib qho kev kho mob rov tsim dua tshiab txhawm rau txhim kho txoj hnyuv plab, txhim kho kev mob mus ntev thiab kev ua neej zoo.
|
Customized Bottle Caps Thiab Corks:
|
|
Teduglutide tau ua kom pom qhov ua tau zoo tshaj plaws hauv kev kho mob plab plob tsis so tswj (SBS). Cov txheej txheem tseem ceeb ntawm kev nqis tes ua, kev siv tshuaj kho mob, thiab kev txhawb nqa txoj cai rau cov tshuaj no yog raws li hauv qab no:
Cov txheej txheem tseem ceeb ntawm kev ua: Txhawb txoj hnyuv plab thiab txhim kho kev nqus dej
Teduglutide yog lub ntiaj teb thawj GLP-2 analogue pom zoo siv hauv SBS. Nws ua raws li cov teebmeem ntawm ntuj GLP-2 los ua kom cov receptors nyob rau saum npoo ntawm cov hnyuv, ua rau cov lus teb tseem ceeb hauv qab no:
Txhawb txoj hnyuv mucosal loj hlob
Txhawb kev loj hlob ntawm crypt hlwb, nce villus qhov siab thiab mucosal thickness, yog li nthuav cov plab hnyuv nqus.
Inhibit gastric acid secretion
Txo cov stimulation ntawm gastric acid nyob rau hauv txoj hnyuv mucosa, tiv thaiv txoj hnyuv ua haujlwm.
Txhim kho plab hnyuv peristalsis
Ua rau qeeb qeeb ntawm cov kab mob hauv plab hnyuv, ncua lub sijhawm sib cuag ntawm cov as-ham, thiab txhim kho kev nqus tau zoo.
Txhawb nqa angiogenesis
Txhim kho txoj hnyuv plab, txhim kho cov xwm txheej rau kev thauj mus los.
Cov txheej txheem no ua haujlwm ua ke los pab SBS cov neeg mob ua tiav kev rov ua haujlwm ntawm txoj hnyuv hauv plab thiab txo qhov kev cia siab ntawm cov khoom noj khoom haus parenteral (PN).
Cov txiaj ntsig kho mob: txo qis qhov xav tau ntawm PN, txhim kho lub neej zoo
|
|
|
|
Ntau qhov kev sim tshuaj ntsuam xyuas tau txheeb xyuas qhov ua tau zoo ntawm Teduglutide hauv kev kho mob ntawm SBS:
Cov neeg laus:
Kev kho mob 24-lub lim tiam: 63% ntawm cov neeg mob tau txo qis ntau dua lossis sib npaug li 20% hauv PN kom tau txais ib lub lis piam; 39% ntawm cov neeg mob tuaj yeem txiav tawm PN / parenteral txhaj rau ntau dua lossis sib npaug li 3 hnub hauv ib lub lis piam.
30-hli kev kho mob: 33% ntawm cov neeg mob tau tshem tawm tag nrho ntawm PN dependence, thiab tshaj 90% ntawm cov neeg mob tau txo qis ntau dua los yog sib npaug li 20% hauv PN kom tsawg.
Cov neeg mob menyuam yaus:
Kev kho mob 24-lub lim tiam: 12% ntawm cov menyuam yaus tau tshem tawm PN dependence tag, thiab 69% ntawm cov me nyuam tau txo qis dua los yog sib npaug li 20% hauv PN kom tsawg; Qhov nruab nrab txhua hnub PN infusion lub sij hawm rau cov menyuam hauv pawg sim tau raug txo los ntawm 3 teev, txo qis ntawm 42% piv rau cov hauv paus.
Cov ntaub ntawv kawm: Ib tug me nyuam muaj hnub nyoog 4- xyoo SBS uas tau txais kev kho Teduglutide tau txo qis 50% hauv cov ntim txhua hnub, nce 20.4 kilograms hauv qhov hnyav, loj hlob 2 centimeters nyob rau hauv qhov siab, pom kev txhim kho tseem ceeb hauv lub hlwb, thiab muaj peev xwm kawm tau ib txwm thiab nyeem cov paj huam thaum ub, nrog kev txhim kho ntawm lub neej zoo.
Kev txhawb nqa txoj cai: Kev ua kom nrawm nrawm, ua tiav qhov kev kho mob hauv tsev
|
|
|
|
Kev lees paub thoob ntiaj teb:Teduglutide tau txais kev pom zoo hauv cov tebchaws thiab cheeb tsam xws li Europe, Amelikas, thiab Nyij Pooj rau kev kho mob SBS cov neeg mob hnub nyoog 1 xyoos thiab siab dua, thiab kuj tau pom zoo siv rau cov menyuam hnub nyoog 4 hli thiab siab dua hauv Nyij Pooj.
Txoj kev loj hlob hauv tsev:
Pilot project: Cia siab rau txoj cai ntawm Hainan Boao Lecheng International Medical Tourism Pilot Zone, Teduglutide ua tiav nws thawj daim ntawv thov kev kho mob hauv Suav teb thaum lub Tsib Hlis 2023, tau txais txiaj ntsig ntau tus neeg mob SBS.
Kev pom zoo raug cai: Lub Ob Hlis 2024, Tuam Tshoj National Medical Products Administration (NMPA) tau pom zoo Teduglutide rau cov neeg laus thiab cov menyuam hnub nyoog 1 xyoos thiab siab dua nrog SBS, dhau los ua thawj SBS tshuaj kho mob hauv Suav teb.
Txoj cai nqa tshuaj rau kev tso tawm: Tom qab kev soj ntsuam, cov neeg mob tuaj yeem siv tsis pub dhau 12 lub lis piam ntawm cov tshuaj tawm ntawm Boao thiab txuas ntxiv kev kho mob ntawm qhov chaw kho mob qub, txhim kho kev kho mob yooj yim heev.
Kev nyab xeeb thiab kam rau ua: Zuag qhia tag nrho zoo, nrog kev saib xyuas tsis tu ncua
|
|
|
Kev tsis zoo tshwm sim:Xws li xeev siab, mob taub hau, mob plab, thiab kab mob ua pa sab saud, feem ntau me me mus rau nruab nrab thiab zam tau.
Ntev -kev pheej hmoo ntev:Kev saib xyuas tsis tu ncua ntawm cov kab mob hauv plab hnyuv (vim muaj peev xwm txhawb kev loj hlob ntawm tes los ntawm GLP-2 analogues), tab sis cov ntaub ntawv kho mob tam sim no tsis pom muaj qhov tshwm sim ntawm cov qog.
Cov pejxeem tshwj xeeb:Cov neeg mob me me yuav tsum tau saib xyuas qhov ntsuas kev loj hlob thiab kev loj hlob zoo kom ntseeg tau tias cov tshuaj muaj kev nyab xeeb.
Teduglutideyog ib qho tseem ceeb bioactive tshuaj uas muaj ntau yam physiological thiab biochemical functions. Hauv chav kuaj, tiglutide tuaj yeem ua ke los ntawm ntau txoj hauv kev. Cov hauv qab no yog ib qho ntawm feem ntau siv cov txheej txheem synthesis:
Chemical Equation:
(Equation 1) C5H9TSIS MUAJ4+C3H10N2.HCl → - Glutamoyl propanediamine hydrochloride
(Equation 2) - Glutamoyl propanediamine hydrochloride + C14H10O3→ niam txiv compound ntawm Tidulutide
(Formula 3) Cov niam txiv compound ntawm Tidulutide + H4N2→ cysteine derivative ntawm Tidulutide
(Formula 4) Cysteine derivative ntawm Tidulutide + HCl → Thioamino acid derivative ntawm Tidulutide
(Formula 5) Thioamino acid derivative ntawm Tidulutide + BrCN → Tidulutide
Pib cov ntaub ntawv thiab reagents
Cov ntaub ntawv pib: L-glutamic acid, malondiamine hydrochloride, benzoic anhydride, thiab lwm yam.
Synthesis cov kauj ruam
(1) Sib tov L-glutamic acid nrog propylene diamine hydrochloride, ntxiv concentrated sulfuric acid ua catalyst, thiab cua sov rau reflux xeev. Thaum lub sijhawm txheej txheem no, L-glutamic acid dhau los ua cov tshuaj tiv thaiv condensation, tsim cov khoom nruab nrab - Glutamoyl propanediamine hydrochloride (formula 1).
(2) Tsim cov khoom nruab nrab - Sib tov glutamylpropylenediamine hydrochloride nrog benzoic anhydride, ntxiv triethylamine ua catalyst, thiab cua sov rau reflux xeev. Thaum cov txheej txheem no, cov khoom nruab nrab tau dhau los ua cov tshuaj tiv thaiv esterification nrog benzoic anhydride los tsim cov niam txiv compound ntawm Dideluptin (Formula 2).
(3) Sib tov cov niam txiv compound ntawm cov generated tilurutide nrog hydrazine hydrate, ntxiv triethylamine ua catalyst, thiab tshav kub rau reflux xeev. Thaum lub sij hawm tus txheej txheem no, cov niam txiv compound tau txo qis cov tshuaj tiv thaiv nrog hydrazine hydrate los tsim ib qho cysteine derivative ntawm tigurotide (formula 3).
(4) Sib tov cov cysteine derivative ntawm cov generated tilurutide nrog hydrogen chloride gas thiab cua sov rau reflux xeev. Thaum lub sijhawm ua haujlwm no, cysteine derivatives tau hloov pauv cov tshuaj tiv thaiv nrog hydrogen chloride gas los tsim cov thioamino acid derivative ntawm Dideluptin (Formula 4).
(5) Sib tov cov thioamino acid derivatives ntawm generated tilurutide nrog cyanide bromide thiab tshav kub rau reflux xeev. Thaum cov txheej txheem no, thioamino acid derivatives tau hloov pauv cov tshuaj tiv thaiv nrog cyanide bromide los tsim tilurutide (formula 5).
Cov saum toj no yog ib hom tshuaj synthesis ntawm tiglutide. Txoj kev no yuav tsum tau tswj cov tshuaj tiv thaiv xws li qhov kub thiab txias, pH tus nqi, lub sijhawm tshuaj tiv thaiv, thiab lwm yam.Teduglutide.
Kev npaj Tedroside
Ntxiv 1220g (2mol) Fmoc Nws (Trt) - OH thiab 230g (2mol) HOSu mus rau 10L peb lub caj dab iav cov tshuaj tiv thaiv lub khob, yaj hauv 4000ml DMF rau 30 feeb, tom qab ntawd ntxiv 412g DIC thiab do hauv chav sov li 2 teev. Thaum kawg, ntxiv 402g (2mol) Gly OBzl. HCl thiab 300ml (2mol) triethylamine thiab react rau 10 teev kom tiav cov tshuaj tiv thaiv thiab synthesize Fmoc Nws (Trt) - Gly. OBzL tiv thaiv dipeptide. Siv 10 npaug ntawm cov kua tshuaj tiv thaiv los nag, lim thiab sau cov dej nag, ntxuav nrog dej ntau, thiab qhuav hauv qhov txo qis. Tom qab dhau qhov kev tshuaj xyuas, cov khoom tau yaj hauv 50% ethanol aqueous tov, 50g ntawm 5% Pd / c tau ntxiv, thiab catalytic hydrogenation tau ua tiav rau 16 teev kom tiav cov concentration ntawm ethanol. Cov khoom lim tau qhuav nyob rau hauv qhov txo qis kom tau 644.2g ntawm Fmoc Nws (Trt) - Gly OH ua cov khoom kawg, nrog cov txiaj ntsig ntawm 47.6%.
Ntxiv 422g (2mol) Fmoc Asp (OtBu) - OH thiab 230g (2mol) HOSu mus rau 10L peb lub caj dab iav cov tshuaj tiv thaiv lub khob, yaj hauv 4000ml DMF rau 30 feeb, tom qab ntawd ntxiv 412g DIC thiab do hauv chav sov li 2 teev. Thaum kawg, ntxiv 402g (2mol) Gly OBzl. HCl thiab 300ml (2mol) triethylamine thiab react rau 10 teev kom tiav cov condensation synthesis ntawm Fmoc Asp (OtBu) - Gly. OBzL tiv thaiv dipeptide. Siv 10 npaug ntawm cov kua tshuaj tiv thaiv los nag, lim thiab sau cov dej nag, ntxuav nrog dej ntau, thiab qhuav hauv qhov txo qis. Tom qab dhau qhov kev tshuaj xyuas, cov khoom tau yaj hauv 50% ethanol aqueous tov, 50g ntawm 5% Pd / c tau ntxiv, thiab catalytic hydrogenation tau ua tiav rau 16 teev kom tiav cov concentration ntawm ethanol. Cov khoom lim tau qhuav hauv qhov txo qis kom tau txais cov khoom kawg 402.1g Fmoc Asp (OtBu) - Gly OH, nrog cov txiaj ntsig ntawm 42.9%. wb :468
Noj 500g ntawm 2-Cl Trt Cl resin nrog tus nqi hloov pauv ntawm 0.6mmol / g thiab ntxiv DMF o tuaj. Noj 0.6mol Fmoc Asp (OtBu), yaj nws hauv qhov tsim nyog ntawm DMF, ntxiv rau cov khoom siv saum toj no, do sib npaug, tom qab ntawd ntxiv 1.2mol DIEA, do thiab hnov mob rau 3 teev, tshem tawm cov tshuaj tiv thaiv, ntxuav nws nrog DMF 3 zaug, thiab ntxuav nws nrog DCM 3 zaug kom tau Fmoc Asp (OtBustitution) -2 tus nqi hloov pauv. 0.46 mmol/g
Noj 500g ntawm Wang resin nrog tus nqi hloov pauv ntawm 0.5mmol / g thiab ntxiv DMF o tuaj. Noj 0.5mol ntawm Fmoc Asp (OtBu), yaj nws hauv qhov tsim nyog ntawm DMF, thiab ntxiv rau cov khoom saum toj no. Tom qab sib tov sib npaug, ntxiv 1.0mol ntawm DIC, 0.4mol ntawm HOBt, thiab 0.04mol ntawm 4-N, N-dimethylpyridine. Do cov tshuaj tiv thaiv rau 6 teev, tshem tawm cov tshuaj tiv thaiv, ntxuav nws peb zaug nrog DMF, thiab ntxuav nws peb zaug nrog DCM kom tau Fmoc Asp (OtBu) - Wang resin nrog tus nqi hloov ntawm 0.41mmol / g.
Noj 0.1mol ntawm Fmoc Asp (OtBu) -2-Cl Trt resin los ntawm Piv txwv 4 (nrog kev hloov pauv ntawm kwv yees li 0.46mmol / g), tiv thaiv nws nrog 20% PIP / DMF tov rau 25 feeb, ntxuav thiab lim kom tau H-Asp (OtBu) -2-Cl Trt.
Dissolve 0.3mol Fmoc Thr (tBu) thiab 0.3mol HOBt hauv qhov tsim nyog ntawm DMF; Noj lwm 0.3mol ntawm DIC thiab maj mam ntxiv nws thaum nplawm. Txuas ntxiv rau 30 feeb thiab ntxiv rau H-Asp (OtBu) -2-Cl Trt resin hais saum toj no. Ua ib qho kev sib txuas lus rau 120-300 feeb. Qhov kawg ntawm cov tshuaj tiv thaiv yog txiav txim los ntawm txoj kev indene ketone. Ntxuav thiab lim, ces tiv thaiv nrog 20% PIP / DMF tov rau 25 feeb. Ntxuav thiab lim kom tau H-Thr (tBu) - Lys (Boc) -2-Cl Trt resin. Tau txais peptide fragment 3:
H-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu)-Met-Asn(Trt)-Thr(tBu)-Ile Leu-Asp(OtBu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp(OtBu)-Phe{-}Ile- (Boc)-Leu-Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tBu)-Asp(OtBu)-
H-Nws(Trt)-Gly-Asp(OtBu)-Gly-Ser(tBu)-Phe-Ser(tBu)-Asp(OtBu)-Glu(OtBu )-Met-Asn(Trt)-Thr(tBu)-Ile-Leu-Asp(Ot Bu)-Asn(Trt)-Leu-Ala-Ala-Arg(Pbf)-Asp (OtBu)-Ph-Ile-Asn(Trt)-Trp(Boc)-Leu{{26} }Ile-Gln(Trt)-Thr(tBu)-Lys(Boc)-Ile-Thr(tB u)-Asp(OtBu)-2-Cl Trt- Resin.
FAQ
1. Dab tsi yog qhov sib txawv ntawm Teduglutide thiab cov tshuaj noj ntshav qab zib ntau ntau (xws li GLP-1 agonists)?
Lub hom phiaj tseem ceeb txawv ntawm lub hom phiaj. Nws ua haujlwm ntawm GLP-2 receptor thiab nws lub luag haujlwm tseem ceeb yog txhawm rau txhim kho txoj hnyuv mucosal thiab hloov kho, txhawm rau txhim kho kev nqus cov as-ham, tsis yog tswj cov ntshav qab zib thiab qhov hnyav los ntawm kev tswj cov tshuaj insulin lossis qab los noj mov.
2. Puas yog siv nws txhais tau tias kev noj zaub mov hauv cov hlab ntsha tuaj yeem nres tag nrho?
Tsis tas li. Lub hom phiaj ntawm kev kho mob yog kom txo qis (tshwj tsis yog tshem tawm tag nrho) kev cia siab rau cov khoom noj khoom haus parenteral. Qhov kev ua tau zoo sib txawv ntawm ib tus neeg mus rau ib tus neeg thiab yuav tsum tau hloov maj mam raws li tus neeg lub plab hloov pauv raws li kev soj ntsuam ze ntawm cov khoom noj khoom haus hauv cov hlab ntsha.
3. Cov kev pheej hmoo tseem ceeb yog dab tsi?
Qhov kev pheej hmoo tseem ceeb tshaj plaws uas yuav tsum tau muaj kev txhawj xeeb yog kev nrawm ntawm plab hnyuv hyperplasia, uas tuaj yeem ua rau cov qog nqaij hlav hauv plab uas twb muaj lawm (xws li polyps) kom loj hlob sai lossis ua rau muaj kev pheej hmoo ntawm cov qog nqaij hlav. Kev tshuaj xyuas nruj thiab saib xyuas cov qog nqaij hlav hauv plab yuav tsum tau ua ua ntej thiab thaum kho.
4. Nws cuam tshuam li cas rau lub neej zoo ntawm cov neeg mob?
Los ntawm kev txo lossis tshem tawm qhov kev cia siab ntawm kev txhaj tshuaj ntev ntev txhua hnub, cov neeg mob tuaj yeem txaus siab rau txoj kev ywj pheej ntawm kev txav mus los, tsawg dua kev tso dej ntau dua - cuam tshuam txog cov teeb meem (xws li kab mob, thrombosis), thiab txhim kho kev xav txog kev noj haus. Txawm li cas los xij, qhov no yuav tsum tau hnyav rau qhov muaj peev xwm ntev - kev kho mob thiab saib xyuas lub nra.
Cim npe nrov: Teduglutide CAS 197922-42-2, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom