Yuav ua li cas Trilostane Tablets Tswj Cortisol Synthesis Pathways

Cortisol yog lub luag haujlwm tseem ceeb ntawm cov metabolism, cov tshuaj tiv thaiv kab mob thiab kev hloov pauv kev ntxhov siab. Ntau dhau ntawm nws los ntawm cov qog adrenal tuaj yeem ua rau lub cev tsis zoo ntawm cov tshuaj hormones hauv txoj hauv kev uas ua rau muaj kev cuam tshuam loj rau kev noj qab haus huv. Cov tshuaj trilostane yog ib qho ntawm cov tshuaj tshawb fawb tshaj plaws hauv kev tswj hwm qhov tsis sib xws, hais txog cov txheej txheem enzymatic uas tswj cov tshuaj steroid hormone synthesis nrog.trilostane ntsiav tshuaj. Kev paub txog cov txheej txheem no pab tus kws kho tsiaj thiab tus kws tshawb fawb nkag siab tias vim li cas trilostane tau dhau los ua qhov tseem ceeb ntawm kev kho endocrine.

Trilostane ntsiav tshuaj

1. General Specification (hauv Tshuag)
(1) Txhaj tshuaj
Customizable
(2) Tablet
Customizable
(3) API (Ntshiab hmoov)
PE / Al foil hnab / ntawv lub thawv rau cov hmoov ntshiab
HPLC Ntau dua lossis sib npaug rau 99.0%
(4) Pill press machine
https://www.achievechem.com/pill-xwm
2.Customization:
Peb yuav sib tham tus kheej, OEM / ODM, Tsis muaj hom, rau kev tshawb nrhiav kev ruaj ntseg nkaus xwb.
PIB: BM-2-016
Trilostane CAS 13647-35-3
Kev tshuaj xyuas: HPLC, LC-MS, HNMR
Kev them nyiaj yug Technology: R&D Dept.-4

Lub Enzyme ntawm Qhov Chaw ntawm Txoj Kev

Lub adrenal cortex tsim cortisol nyob rau hauv ntau - kauj ruam metabolic cascade. Lub enzyme 3 -hydroxysteroid dehydrogenase (3 -HSD) yog ib qho tseem ceeb enzyme ntawm txoj kev hla ntawm txoj kev no, hloov pregnenolone mus rau progesterone, ib qho tseem ceeb precursor hauv synthesis ntawm cortisol. Trilostane ntsiav tshuaj yog qhov sib tw, thim rov qab inhibitor ntawm cov enzyme no. Trilostane haum rau hauv qhov chaw nquag ntawm 3 -HSD thiab thaiv cov cortisol ntau lawm nyob rau hauv txoj kev tswj tau thiab thim rov qab, yam tsis tas ua rau lub enzyme mus tas li.

Qhov kev thim rov qab no yog qhov tseem ceeb hauv kev kho mob. Thaum piv rau cov tshuaj adrenolytic irreversible, trilostane ua rau tus kws kho mob titrate koob tshuaj rau tus neeg mob cov qib cortisol nyob rau lub sijhawm. Tias yog vim li cas nws tau pom zoo los kho cov kab mob tshwm sim los ntawm kev tsim tawm ntau dhau ntawm glucocorticoids, vim tias nws ua raws li lub hom phiaj.

Cov teebmeem hauv qab ntawm Mineralocorticoid Synthesis

Trilostane kuj inhibits qhov tsim ntawm aldosterone. 3 -HSD koom nrog hauv kev sib txuas ntawm glucocorticoids thiab mineralocorticoids. Aldosterone tswj cov sodium thiab potassium sib npaug thiab yog li nws txoj kev tswj hwm muaj kev cuam tshuam rau cov ntshav siab thiab kua dej sib npaug. Cov ntsiav tshuaj Trilostane hloov pauv hauv kev tswj hwm ntawm adrenal endocrine vim lawv ob leeg inhibition ntawm ob txoj hauv kev cortisol thiab aldosterone, raws li qhia hauv kev tshawb fawb qhia hauv cov ntaub ntawv kho mob tshuaj.

Cov kws kho mob saib xyuas cov neeg mob no yuav tsum tau siv qhov kev txwv ob zaug no rau hauv kev txiav txim siab, tshwj xeeb tshaj yog rau kev saib xyuas cov electrolytes thiab cortisol. Qhov sib xyaw ua ke qhov tshwj xeeb khi profile ntawm Δ5,4-isomerase kauj ruam ntxiv txhawb nqa nws lub hom phiaj tshuaj.

Lub Hypothalamic{0}}Pituitary-Adrenal Axis Txuas

Cortisol ntau lawm tsis tshwm sim hauv kev sib cais. Nws ua rau hypothalamic-pituitary-adrenal (HPA) axis, lub voj voog tawm tswv yim uas lub hlwb saib xyuas cov cortisol thiab qhia cov qog adrenal. Trilostane tshuaj thaiv adrenal enzymes, txo cov qib cortisol. Lub caj pas pituitary tuaj yeem them rov qab rau qhov no los ntawm kev txhawb nqa cov tshuaj hormone adrenocorticotropic (ACTH), uas txhawb nqa cov qog adrenal. Qhov nyiaj them rov qab ntawm qhov cuam tshuam ntawm trilostane txhais tau hais tias nws yog qhov zoo dua li kev hloov kho dua li kev kaw tag nrho.

Qhov kev sib cuam tshuam me me no hais txog kev saib xyuas nyob ze thiab txuas ntxiv thaum kho trilostane. Cov kws kho mob feem ntau siv ACTH stimulation tests los ntsuam xyuas adrenal cia thiab kom paub meej tias cortisol suppression yog kho, tsis txaus ntshai.

Sib piv Cortisol Regulation Strategies

Muaj ntau yam kev kho mob tshuaj muaj los txo cortisol ntau lawm suav nrog cov tshuaj adrenolytic thiab inhibitors ntawm adrenal enzymes. Qhov tshwj xeeb feature ntawmtrilostane ntsiav tshuajyog thim rov qab thiab xaiv qhov kev txiav txim ntawm ib kauj ruam hauv steroidogenic cascade. Txawm hais tias qee cov tshuaj tuaj yeem thaiv ntau tshaj ib kauj ruam enzymatic, lossis ua rau muaj kev pheej hmoo siab dua ntawm kev tawm tsam adrenal tsis tu ncua, trilostane qhov kev sib tw inhibition profile txhais tau hais tias cov ntaub so ntswg adrenal tuaj yeem rov ua haujlwm thaum cov tshuaj raug tshem tawm ntawm lub cev.

Cov cuab yeej tshuaj no tau ua rau trilostane ib lub ntsiab lus ntawm kev kho mob txuas ntxiv, tshwj xeeb hauv cov kws kho tsiaj, qhov twg qhov kev hloov pauv ntawm koob tshuaj rau lub cev sib txawv yog qhov xav tau.

Lub hauv paus ntawm cov Enzyme Inhibition

Cov qauv molecular ntawm nws (4 ,5 -epoxy-2-cyano-androst-2-ene-3,17 -diol) yog txaus zoo ib yam li lub ntuj substrate ntawm 3 -HSD kom haum nyob rau hauv lub active site ntawm lub enzyme. Cov tshuaj formula ntawm cov tshuaj yog C20H27NO3 thiab nws qhov hnyav molecular yog 329.43. Cov pob txha steroid yog compact thiab yuav txuas mus rau lub enzyme binding hnab tshos nrog zoo affinity. Qhov no steric mimicry muab lub hauv paus molecular rau cov kev kho mob ntawm trilostane.

Thaum khi, trilostane inhibits cov txheej txheem dehydrogenation uas hloov Δ5-3 -hydroxysteroids rau lawv Δ4-3-ketosteroid counterparts, uas yog qhov tseem ceeb rau kev sib txuas ntawm cortisol thiab aldosterone tom qab. Cov tshuaj inhibition yog nyob ntawm koob tshuaj, piv txwv li qhov ntau dua cov qib ntshav plasma trilostane ntsiav tshuaj, qhov ntau ua tiav qhov kev tawm tsam ntawm theem hloov dua siab tshiab no.

Reversibility thiab Therapeutic Precision

Trilostane inhibits 3 -HSD ntawm tsis yog-covalent binding, ib qho kev ua uas ploj lawm thaum cov ntshav plasma concentration tsawg. Cov cuab yeej tshuaj pharmacodynamic no muab rau tus kws kho mob nrog kev tswj hwm kev tswj hwm cortisol. Qhov tseeb tiag, qhov no txhais tau hais tias txoj kev kho mob uas hloov pauv ntau npaum li cas tuaj yeem hloov pauv cov tshuaj hormones hauv cov hnub ntau dua li lub lis piam.

Cov ntaub ntawv los ntawm kev soj ntsuam kws kho tsiaj pom tau hais tias kev saib xyuas ntawm adrenal muaj nuj nqi, tshwj xeeb tshaj yog qhov ACTH stimulation test, yog ib txoj hauv kev zoo los saib xyuas cov koob tshuaj no - teb kev sib raug zoo. Kev soj ntsuam qib cortisol ntawm 1 thiab 4 teev tom qab ACTH stimulation tau dhau los ua qhov kev ntsuam xyuas niaj hnub rau cov neeg mob noj cov tshuaj trilostane.

Tailoring Dosage rau cov neeg mob Canine

Hyperadrenocorticism los yog Cushing's syndrome yog ib qho kev mob tshwm sim nyob rau hauv nruab nrab - cov dev laus thiab cov laus Nws yog vim hypersecretion ntawm cortisol. Nws ua rau muaj kev nqhis dej ntau ntxiv, tso zis ntau ntxiv, hloov hauv qab los noj mov thiab tawv nqaij txawv txav. Cov ntsiav tshuaj Trilostane tau ntawv tso cai raug cai los ntawm kws kho tsiaj cov cai tswj xyuas kev mob nkeeg thiab cov ntaub ntawv kho mob qhia tau tias ntau dua 90% ntawm cov dev uas muaj qhov teeb meem no txo ​​lawv cov tsos mob uas ntsuas tau nrog kev noj kom haum.

Kev pom zoo thawj zaug yog 0.8 txog 1 mg / kg PO q12h nrog zaub mov. Cov lus teb ntawm tus kheej sib txawv nrog lub cev qhov hnyav, qhov hnyav ntawm kev mob thiab cov kab mob siab metabolism thiab yog li tus neeg siv tshuaj titration yog qhov tseem ceeb rau cov txiaj ntsig zoo tshaj plaws. Ua raws li- cov kev ntsuam xyuas feem ntau tau ua 10 mus rau 14 hnub tom qab pib kho lossis hloov ntau npaum li cas.

Saib xyuas cov txheej txheem thiab kev txiav txim siab txog kev nyab xeeb

Kev saib xyuas kev nyab xeeb ntev ntev yog ib qho tseem ceeb ntawm kev kho trilostane hauv cov dev. Lub siab thiab lub raum panels, CBCs, thiab cortisol cov lus teb kuaj muab ib daim duab sib xyaw ntawm tus tsiaj zoo li cas rau kev kho mob ntev. Tej zaum yuav xav tau kev hloov pauv ntau npaum li cas lossis kev ncua ib ntus vim muaj kev cuam tshuam tsis zoo (xws li qaug zog, anorexia, electrolyte cuam tshuam).

Qhov "reversibility" ntawm trilostane kev txiav txim ntawm enzymes muaj tswv yim siv ntawm no. Hauv cov ntaub ntawv pov thawj ntawm adrenal tsis txaus, cov tshuaj yuav raug tso tseg, tso cai rau adrenal rov qab, tsis zoo li kev kho mob mus tas li adrenolytic. Cov yam ntxwv kev nyab xeeb no qhia txog qhov kev xav tsis tu ncua ntawmtrilostane ntsiav tshuajraws li thawj - kab xaiv hauv kev kho mob ntawm canine hyperadrenocorticism los ntawm kws kho tsiaj endocrinologist.

Kev koom ua ke hauv Veterinary Clinical Practice

Kev tswj hwm endocrine kws kho tsiaj tau dhau los ua qhov nyuaj, thiab kev saib xyuas cortisol tam sim no tau txais los ua qhov ntsuas ntau ntawm cov tshuaj teb. ACTH stimulation test yog tus qauv kub rau kev ntsuam xyuas ntawm adrenal cov zis hauv cov dev ntawm cov tshuaj trilostane. Lub hom phiaj qib cortisol tom qab stimulation feem ntau yog nyob nruab nrab ntawm 40-150 nmol / L, qhia txog kev tswj kab mob zoo yam tsis muaj kev cuam tshuam tsis tsim nyog ntawm adrenals.

Cov kev ntsuas tau muab tso rau hauv cov kev saib xyuas tsis tu ncua los ntawm tus kws kho mob, feem ntau txhua txhua 10 hnub, ib hlis, peb hlis thiab tom qab ntawd txhua rau lub hlis. Hom kev kho no tso cai rau kev sib npaug ntawm cov tshuaj hormones txuas ntxiv yam tsis muaj kev txhim kho ntawm iatrogenic adrenal insufficiency.

 

 

Supply Chain thiab Compound Quality hauv Veterinary Siv

Lub purity thiab stability ntawm trilostane raws li ib tug active tshuaj muaj yog ib qho tseem ceeb rau kev kho mob. Cov tshuaj ua raws li cov cai nruj GMP thiab tau lees paub los ntawm ntau- cov txheej txheem tswj kev ua tau zoo txwv tsis pub muaj qhov sib txawv hauv cov tshuaj lom neeg lom neeg. Rau cov chaw kho tsiaj thiab cov chaw tshawb fawb nrhiav trilostane hauv API lossis daim ntawv ntsiav tshuaj tiav, kev ntseeg siab ntawm tus neeg muag khoom thiab cov ntaub ntawv tshuaj ntsuam xyuas zoo, suav nrog HPLC daim ntawv pov thawj purity ntau dua lossis sib npaug li 99.0% thiab LC-MS characterization yog qhov tseem ceeb hauv lawv qhov kev txiav txim siab yuav khoom.

Lub cortisol- tswj kev ua ntawmtrilostane ntsiav tshuajyog tshwm sim los ntawm ib qho tshwj xeeb thiab thim rov qab ntawm 3 -hydroxysteroid dehydrogenase nyob rau hauv txoj kev adrenal steroidogenic. Trilostane txawv los ntawm cov adrenal suppressors tshwj xeeb hauv cov txheej txheem molecular tshwj xeeb uas nws ua thiab muab cov tswv yim kho raws li kev saib xyuas tas li thiab kev hloov kho tus kheej. Kev siv tau siv nyob rau hauv kev kho tsiaj kho tsiaj endocrine, tshwj xeeb tshaj yog rau cov dev nrog hyperadrenocorticism, qhia nws cov txiaj ntsig kho mob thiab kev ruaj ntseg tshuaj. Thaum tau txais high-purity trilostane rau kev tshawb fawb lossis kev siv tshuaj, cov kws tshaj lij nyob ntawm qhov ua tau zoo thiab kev ntseeg siab ntawm cov neeg siv khoom kom ntseeg tau tias muaj txiaj ntsig zoo sib xws.

Thaum kev tswj hwm hormonal nyob ntawm qhov ua tau zoo, koj xav tau atrilostane ntsiav tshuajtus neeg muag khoom koj tuaj yeem tso siab rau kev ntseeg siab. Bloomtechz tau xa cov kws tshuaj ntsuam xyuas - qib tshuaj sib xyaw ua ke txij li xyoo 2008, ua haujlwm rau 24 tus neeg koom tes thoob ntiaj teb tsim nyog thoob plaws cov tshuaj, kev tshawb fawb, thiab cov tshuaj tshwj xeeb. Peb cov ntsiav tshuaj trilostane thiab API yog tsim los ntawm 100,000 m² GMP- cov chaw muaj ntawv pov thawj tuav US-FDA, EU, JP, thiab CFDA ntawv pov thawj, nrog triple - txheej txheej validation ntawm txhua theem tsim khoom. Peb muab cov ntsiav tshuaj customizable ntau npaum li cas - 5 mg, 10 mg, 20 mg, 30 mg, thiab 60 mg - nrog rau cov hmoov ntshiab API nrog HPLC purity Ntau dua lossis sib npaug li 99.0%. Txawm hais tias koj xav tau cov khoom siv ntau lossis OEM tsim kev txhawb nqa, Bloomtechz muab tus nqi raug, lub sijhawm ua haujlwm pob tshab, thiab kawg -rau-kawg cov ntaub ntawv rau kev lis kev cai tsis sib haum xeeb. Hu rau hnub no ntawmSales@bloomtechz.com thiab cia peb pab koj ua tau raws li koj qhov R&D lossis cov hom phiaj kev lag luam.

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3. Fracassi F, Corradini S, Floriano D, et al. Prognostic factors for survival in dogs with pituitary-dependent hypercortisolism treated with trilostane. Veterinary Record, 2015, 176(2): 49.

4. Helm JR, McLauchlan G, Boden LA, et al. Kev sib piv ntawm yam uas cuam tshuam rau kev ciaj sia nyob rau hauv cov dev nrog adrenal -dependent hyperadrenocorticism kho nrog mitotane lossis trilostane. Phau ntawv Journal of Veterinary Internal Medicine, 2011, 25(2): 251–260.

5. Ramsey I K. Trilostane hauv dev. Veterinary Clinics of North America: Small Animal Practice, 2010, 40(2): 269–283.

6. Wenger M, Sieber-Ruckstuhl NS, Muller C, et al. Kev cuam tshuam ntawm trilostane rau cov ntshav ntshav ntau ntawm aldosterone, cortisol, thiab potassium hauv cov dev nrog adrenal-nyob ntawm hyperadrenocorticism. American Journal of Veterinary Research, 2004, 65(9): 1245–1250.