Etelcalcetide

Inkcazelo emfutshane:

I-Etelcalcetide yi-synthetic peptide calcimimetic esetyenziselwa unyango lwe-hyperparathyroidism yesibili (SHPT) kwizigulane ezinezifo ezingapheliyo (CKD) kwi-hemodialysis. Isebenza ngokuvula i-calcium-sensing receptor (CaSR) kwiiseli ze-parathyroid, ngaloo ndlela inciphisa amanqanaba e-hormone ye-parathyroid (PTH) kunye nokuphucula i-metabolism yamaminerali. I-API yethu ye-Etelcalcetide ephezulu yococeko yenziwa nge-solid-phase peptide synthesis (SPPS) phantsi kweemeko ezithobelayo ze-GMP, ezifanelekileyo kwiifom ze-injectable.

Thumela i-imeyile kuthi

Iinkcukacha zeMveliso

Iithegi zeMveliso

Etelcalcetide API

Etelcalcetideyinoveli, eyenziweyopeptide calcimimeticevunyiweyo kunyango lwehyperparathyroidism yesibini (SHPT)kwizigulane zabantu abadala abaneisifo sezintso esinganyangekiyo (CKD)ukwamkelahemodialysis. I-SHPT yingxaki eqhelekileyo kunye neyona nto inzima yesifo sokugqibela sesifo sezintso, esibangelwa ukuphazamiseka kwe-calcium, i-phosphorus, kunye ne-vitamin D metabolism. Ukuphakama okuzingileyo kweihomoni yeparathyroid (PTH)kunokukhokelela kwii-osteodystrophy yezintso, i-vascular calcification, isifo se-cardiovascular disease, kunye nokunyuka kokufa.

I-Etelcalcetide ibonelela ngeukhetho olujoliswe kuyo, olungelulo utyandoukulawula amanqanaba e-PTH kwizigulane ze-dialysis, ezimele i-calcimimetic yesizukulwana sesibini ngeiingenelo ezahlukeneyophezu konyango lomlomo njenge-cinacalcet.

Indlela yokwenza

I-Etelcalcetide yiI-agonist ye-peptide yokwenziwayei-calcium-sensing receptor (CaSR), ebekwe phezu kweeseli ze-parathyroid gland. Ilinganisa isenzo se-calcium ye-extracellular ngokwenza i-allosterically isebenze i-CaSR, ngaloo ndlela:

Ukunciphisa ukukhuselwa kwehomoni ye-parathyroid (PTH).
Ukunciphisa i-serum calcium kunye ne-phosphorus concentrations
Ukuphucula i-calcium-phosphate homeostasis
Ukunciphisa umngcipheko wokungahambi kakuhle kwamathambo kunye nokubalwa kwe-vascular calcification

Ngokungafaniyo ne-calcimimetics yomlomo, i-Etelcalcetide ilawulwaemithanjeniemva kwe-hemodialysis, ephucula ukubambelela kunyango kunye nokunciphisa iziphumo ebezingalindelekanga zesisu.

Uphando lwezonyango kunye nokusebenza kakuhle

I-Etelcalcetide iye yavavanywa kwiimvavanyo ezininzi zeSigaba sesi-3, kubandakanywaizifundo ezimbini ezibalulekileyo ezilawulwa ngokungenamkhetheipapashwe kwiILancetkwayeNew England Journal of Medicine. Ezi zifundo zibandakanya ngaphezulu kwe-1000 yezigulane ze-hemodialysis ezine-SHPT engalawulwayo.

Iziphumo eziphambili zeklinikhi ziquka:

Ukunciphisa okubalulekileyo ngokweenkcukacha kumanqanaba e-PTH(> 30% kwisininzi sezigulane)
Ulawulo oluphezulu lwei-serum phosphorus kunye nemveliso ye-calcium-phosphate (Ca × P)
Amazinga aphezulu empendulo ye-biochemicalxa kuthelekiswa ne-cinacalcet
Unyango olungcono ngomondengenxa yolawulo lwe-IV lwe-post-dialysis lweveki ezintathu
Ukuncitshiswa kweziphawuli zokujika kwamathambo(umzekelo, i-alkaline phosphatase ethe ngqo kwithambo)

Ezi zibonelelo zixhasa i-Etelcalcetide njengeUmgca wokuqala otofwayo wecalcimimeticyokulawula i-SHPT kwizigulana ze-dialysis.

Ukwenziwa kwe-API kunye noMgangatho

YethuEtelcalcetide APIyenziwa ngei-soli-phase peptide synthesis (SPPS), ukuqinisekisa isivuno esikhulu, ubunyulu, kunye nokuzinza kweemolekyuli. I-API:

Ihambelana nokungqongqoImigangatho ye-GMP kunye ne-ICH Q7
Ilungele ukusetyenziswa kwiiimveliso zamachiza atofwayo
Kwenziwa uvavanyo olubanzi lohlalutyo, kubandakanya i-HPLC, izinyibilikisi ezishiyekileyo, iintsimbi ezinzima, kunye namanqanaba e-endotoxin.
Iyafumaneka kwiukulinga kunye nezikali zemveliso yorhwebo

Amandla oNyango kunye nezinto eziluncedo

Unyango olungekho kwi-hormonalye-SHPT kwizigulana ze-CKD kwi-dialysis
Indlela ye-IV iqinisekisa ukuthotyelwa, ngakumbi kwizigulane ezinomthwalo wepilisi okanye ukunganyamezeli kwe-GI
Inganceda ukunciphisaiingxaki zexesha elideukuphazamiseka kweminerali kunye nethambo (CKD-MBD)
Iyahambelana ne-phosphate binders, i-vitamin D analogues, kunye nokhathalelo oluqhelekileyo lwe-dialysis