Aveptadil peptideyog ib qho hluavtaws, ruaj khov polypeptide analog ntawm vasoactive plab hnyuv peptide (VIP), muaj zog tiv thaiv kab mob, meej immunomodulatory, thiab cov ntaub so ntswg tiv thaiv. Cov peptide no inhibits kev ua haujlwm ntau dhau ntawm neutrophils thiab macrophages, yog li tiv thaiv cytokine cua daj cua dub thiab txo qis pulmonary inflammatory infiltration. Nws qhia tau hais tias tus nqi kho mob tshwj xeeb hauv kev mob hnyav, mob ntsws, thiab kev tiv thaiv kab mob tiv thaiv kab mob, ua haujlwm ua cov tshuaj polypeptide tshwj xeeb nrog cov tshuaj tiv thaiv kab mob thiab tiv thaiv kab mob.
Peb Cov Khoom Muag Khoom
AviptadilCOA
Pharmacological Mechanism of Action
(1) Muaj peev xwm tiv thaiv kab mob thiab tiv thaiv cytokine cua daj cua dub
Raws li ib tug synthetic analog ntawm vasoactive plab hnyuv peptide (VIP),aviptadil peptide tshuajnthuav tawm muaj zog tiv thaiv kev ua haujlwm thiab tiv thaiv cov lus teb inflammatory thiab cytokine cua daj cua dub. Nws cov haujlwm tseem ceeb suav nrog peb yam: Nws ua rau muaj kev cuam tshuam loj heev ntawm kev tsim cov cytokines xws li IL-6, TNF- , IL-1 , thiab IFN- , txo cov teeb meem inflammatory, thiab txo qhov mob-kho cov ntaub so ntswg puas tsuaj, tshwj xeeb tshaj yog txo qis pulmonary o.
Nws inhibits overactivation ntawm neutrophils thiab macrophages, txo infiltration ntawm cov inflammatory hlwb mus rau hauv lub ntsws thiab lwm cov ntaub so ntswg o, txo cov nqaij mos raug mob los ntawm inflammatory infiltration, tiv thaiv alveolar epithelial hlwb, thiab txo pulmonary edema. cascades, yog li comprehensively txwv tsis pub dhau o thiab tiv thaiv kev puas tsuaj loj los ntawm cytokine cua daj cua dub.
Cov ntaub ntawv qhov chaw: NCI nkag rau Aviptadil; InvivoChem khoom daim ntawv rau Aviptadil acetate; Pharmological profile ntawm Aviptadil ntawm ards.mindspacetech.com.
(2) Immunomodulatory teebmeem
Nws exerts immunomodulatory teebmeem feem ntau los ntawm kev tiv thaiv homeostasis thiab tiv thaiv cov ntaub so ntswg:
Nws hloov kho qhov sib npaug ntawm T-cell subsets los ntawm kev txhawb nqa cov lus teb los tiv thaiv Th2, tiv thaiv kev tiv thaiv kab mob ntau dhau, kho lub cev tsis muaj zog, thiab txo kev puas tsuaj los ntawm kev tiv thaiv tsis zoo. Nws kuj tswj hwm qhov sib npaug ntawm Treg / Th17 txhawm rau txhim kho lub cev tiv thaiv kab mob ntxiv.
Los ntawm kev txo cov kev tso tawm ntawm cov kab mob sib kis, nws txo qis kev tiv thaiv kab mob hauv lub cev, nrog kev tiv thaiv kev tiv thaiv ntawm cov kab mob tsis zoo xws li lub ntsws.Nws khaws cov plab hnyuv mucosal barrier kev ncaj ncees, txhawb kev kho mucosal, tswj lub plab barrier homeostasis, thiab mitigates plab hnyuv kab mob hauv kev tshawb fawb-i.
Cov ntaub ntawv qhov chaw: Kev Koom Tes thiab Lub Luag Haujlwm ntawm Vasoactive Peptides hauv Kev tshwm sim thiab kev loj hlob ntawm cov kab mob autoimmune, Cov Ntaub Ntawv Tshuaj, 2024.Encyclopedia nkag rau Aviptadil.
Daim ntawv thov hauv Kev Kho Mob erectile Dysfunction
(1) Dual Synergistic Relaxation ntawm Corpus Cavernosum Smooth Muscle
Cov txheej txheem tseem ceeb ntawm nws hauv kev kho erectile kawg (ED) nyob rau hauv nws ua ke nrog phentolamamine, uas synergistically relaxes penile corpus cavernosum smooth nqaij ntawm txoj kev sib txawv, txhim kho hemodynamics, thiab restores erectile muaj nuj nqi.
Raws li ib tug hluavtaws VIP, nws xaiv activates VPAC1 thiab VPAC2 receptors ntawm cavernous vascular endothelial thiab du leeg hlwb, nkoos adenylate cyclase, tsub kom intracellular cAMP theem, activates protein kinase A, thiab inhibits calcium influx, ncaj qha relaxing cavernous du nqaij thiab penile hlab ntsha. Meanwhile, nws optimizes veno-occlusive mechanism, txo venous outflow thaum lub sij hawm erection, tswj cavernous ntshav siab, thiab prolongs erection lub sij hawm.
Phentolamine, ua yeeb yam luv luv-adrenergic antagonist hauv kev sib xyaw ua ke, blocks 1 thiab 2 receptors ntawm cov leeg nqaij leeg, inhibits norepinephrine-mediated vasoconstriction, ntxiv dilates cov hlab ntsha, thiab ua rau cov hlab ntsha tuaj yeem nce ntxiv. Qhov kev txiav txim ntawm ob qho tib si ntawm cov leeg nqaij ncaj nraim ntxiv rau kev thaiv ntawm cov cim kev cog lus kov yeej cov kev txwv ntawm kev kho mob monotherapy: Aviptidal qhia txog veno-occlusion thiab kev so ntev ntev, thaum phentolamamine txhim kho arterial perfusion, ua ke txhim kho erectile rigidity thiab ntev.
Tsis zoo li qhov ncauj PDE5 inhibitors (piv txwv li, sildenafil), kev sib xyaw aviptidal ua ntawm nws tus kheej ntawm txoj kev nitric oxide (NO) thiab tseem muaj txiaj ntsig tiv thaiv refractory ED ntawm neurogenic, vasculogenic, lossis ntshav qab zib, tshwj xeeb tshaj yog rau cov neeg mob uas tsis ua haujlwm lossis tsis kam rau PDE5 inhibitors.
(2) Clinical Indications
Covaviptadil peptide tshuaj/phentolamine ua ke (Invicorp) tau pom zoo rau cov tsos mob ntawm erectile kawg hauv cov txiv neej laus, suav nrog neurogenic, vasculogenic, psychogenic, thiab mixed-etiology ED. Nws yog siv los ua txoj kab thib ob rau cov neeg mob uas muaj contraindications rau, intolerance ntawm, los yog tsis txaus cov lus teb rau qhov ncauj PDE5 inhibitors, nrog rau cov ED muaj feem xyuam rau cov hlab ntsha raug mob xws li post-prostatectomy phais thiab tus txha caj qaum raug mob.
(3) Kev kho mob txoj haujlwm thiab qhov zoo
Sau qhov sib txawv ntawm kev kho mob rau refractory ED: muab ib qho kev xaiv zoo rau neurogenic, vasculogenic, thiab ntshav qab zib ED tsis teb rau PDE5 inhibitors.
Kev txhaj tshuaj zoo heev: tsis tshua muaj mob tshwm sim, kev lees txais neeg mob siab, tsim nyog rau kev tswj tus kheej mus ntev.
Kev pib nrawm nrawm thiab lub sijhawm tswj tau: pib hauv 10 feeb, kav ntev li 1 teev, ua raws li kev sib deev ntuj tsim.
Tsis muaj kev cuam tshuam cov tshuaj txaus ntshai: tsis ua rau tuag taus hypotension nrog nitrates, muaj kev nyab xeeb dua rau cov neeg mob plawv comorbidities.
(4) Clinical Development Prospects
Tam sim no aviptidal formulations feem ntau yog kev txhaj tshuaj ua ke. Kev loj hlob tsom mus rau kev xa tsis pub koob, kev npaj ua haujlwm ntev, thiab ua ke nrog kev kho mob qia cell:
Kev txhaj tshuaj tsis muaj koob ntxiv txo qhov mob thiab txhim kho kev ua raws.
Kev sib xyaw nrog cov koob tshuaj qis alprostadil txhim kho kev ua tau zoo hauv refractory ED.
Kev siv ua ke nrog cov qia hlwb lossis platelet-nplua nuj plasma (PRP) kho neural thiab vascular puas ib txhij, ua kom muaj kev kho mob ntawm ED.
Cov ntaub ntawv qhov chaw: NHS Bedfordshire Tshuaj Optimization Team, Aviptadil/phentolamine Intracavernosal Txhaj (Invicorp) rau Erectile Dysfunction; Scottish Medicines Consortium 2017 daim ntawv ntsuam xyuas; European Urology 2021 kev kawm ntawm refractory ED; HortWeek 2015 cov ntaub ntawv kho mob ua tau zoo.
Daim ntawv thov hauv Asthma
Kev mob ntsws asthma yog pathologically tus yam ntxwv los ntawm cov kab mob hauv cov hlab ntsws ntev, cov hlab ntsws hyperresponsiveness, thiab kho cov hlab cua, sib txuas nrog Th2-mediated allergic responses, inflammatory cell infiltration, thiab tso tawm inflammatory mediators. Cov kab mob muaj xws li allergens, kab mob, thiab ib puag ncig stimuli, nrog rau kev tawm tsam hnyav uas ua rau muaj kev tsis taus. Kev txhaj tshuaj Aviptadil modulates asthma pathogenesis ntawm ntau lub hom phiaj, qhia txog cov txiaj ntsig zoo hauv kev tswj kev mob, txo cov hlab ntsws hyperresponsiveness, thiab tiv thaiv kev mob hnyav.
Ua ntej, aviptidal suppresses mob ntsws ntsws o nyob rau hauv mob hawb pob los ntawm kev khi rau receptors ntawm cov hlab ntsws epithelial thiab inflammatory hlwb, txo cov kev tso tawm ntawm IL-4, IL-5, thiab IL-13-tus neeg sawv cev tseem ceeb ntawm kev ua xua rau cov hlab ntsws.
Cov qib qis ntawm cov cytokines no txo qis kev nkag mus ntawm eosinophils thiab mast hlwb, tshem tawm cov hlab ntsws mucosal edema thiab mucus hypersecretion. Thib ob, nws rov ua kom Th1 / Th2 tshuav nyiaj li cas, txo qis kev tsis haum tshuaj, txo qis kev ua pa ntawm txoj hlab ntsws, thiab txo qis kev cuam tshuam rau kev ua xua thiab cua txias, yog li tiv thaiv kev mob hawb pob.
Tsis tas li ntawd, aviptidal tiv thaiv cov kab mob hauv cov hlab ntsha hauv cov hlab ntsha, inhibits epithelial apoptosis thiab hauv qab daus membrane thickening, slows airway remodeling, thiab zam tsis txhob hloov cov qauv irreversible, khaws cia ib txwm ua pa so. Nws cov nyhuv me me bronchodilatory sai relieves bronchospasm thaum lub sij hawm mob hnyav, alleviating hawb pob thiab hauv siab nruj. Kev siv ua ke nrog cov pa bronchodilators txhim kho kev ua tau zoo.
Cov ntaub ntawv qhov chaw: Aviptadil profile ntawm ards.mindspacetech.com; Aviptadil: Ib txoj kev kho mob zoo rau kev mob ua pa nyuaj (Zuventus); Bronchial Asthma (CNKI Clinical Assistant).
I. Rov qab-Phase High-Kev Ua Haujlwm Ua Kua Dej Chromatography (RP-HPLC)
Rov qab-theem siab-kev ua tau zoo ua kua chromatography yog txoj hauv kev tseem ceeb rau kev txheeb xyuas qhov ntau ntawmaviptadil peptide tshuajthiab saib xyuas nws cov khoom degradation. Txoj kev no ua tiav kev sib cais raws li qhov sib txawv ntawm hydrophobicity ntawm peptides, nrog rau qhov zoo ntawm kev ua haujlwm yooj yim, siab precision, thiab zoo reproducibility. Hauv kev sim, C18 nyob ruaj khov theem yog siv, thiab theem mobile muaj cov theem aqueous uas muaj 0.1% trifluoroacetic acid thiab acetonitrile. Gradient elution ua rau muaj txiaj ntsig zoo sib cais ntawm aviptidal los ntawm impurities, nrog lub sijhawm sib cais tswj ntawm 4.5 ± 0.1 feeb. Cov txheej txheem tau raug lees paub raws li cov lus qhia los ntawm International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) thiab US Food and Drug Administration (FDA). Lub calibration nkhaus qhia tau hais tias zoo linearity nyob rau hauv lub concentration ntau ntawm 2–10 ug / mL (r²=0.9996), tus nqi rov qab yog 99.65%, thiab intra-hnub thiab inter{16}}hnub txheeb ze tus qauv sib txawv (RSD) yog ob qho tib si tsawg dua 1.0%. Txoj kev no tso cai rau tib lub sijhawm nrhiav kom pom ntawm aviptidal thiab nws cov khoom degradation hauv acidic thiab alkaline media.
II. Capillary Electrophoresis–Mass Spectrometry (CE-MS)
Capillary electrophoresis-mass spectrometry yog ib qho tseem ceeb ntxiv cov txheej txheem rau kev tsom xam impurity ntawm cov khoom, tshwj xeeb tshaj yog tsim nyog rau kev txheeb xyuas qhov tseeb ntawm kab impurities. Txoj kev no siv cov coated capillary ua ke nrog ib pawg spectrometer los ntawm lub sheathless interface, thiab kev sib cais yog tiav raws li qhov sib txawv ntawm peptide nqi thiab kev txav mus los. Piv nrog nano- thim rov qab- theem siab- ua haujlwm ua kua chromatography-mass spectrometry (nanoRP-HPLC- MS), nws muaj kev nkag siab ntau dua thiab muaj zog impurity txheeb xyuas lub peev xwm. Cov kev sim tau lees paub tias qhov txwv ntawm kev kuaj pom (LOD) ntawm CE-MS yog kwv yees li 1 fmol, uas yog 2500-fold siab dua li ntawm nanoRP-HPLC-MS (3 pmol). CE-MS tuaj yeem kuaj tau 15 impurities, qhov nanoRP{17}}HPLC-MS kuaj pom tsuas yog 2; Ntxiv mus, cov impurities pom los ntawm ob txoj kev tsis sib tshooj, tso cai rau kev sib koom ua ke.
III. Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS)
Cov kua chromatography-tandem huab hwm coj spectrometry yog tsuas yog siv rau kev txheeb xyuas cov qauv thiab cov amino acid sib lawv li kev txheeb xyuas ntawm cov khoom, ua raws li cov txheej txheem tseem ceeb los xyuas kom meej cov tshuaj peptide zoo. Nyob rau hauv txoj kev no, cov qauv xeem yog thawj desalted thiab sib cais los ntawm siab -kua kua chromatography. Cov peptide yog tam sim no tawg ntawm peptide bonds rau hauv b/y ions siv lub siab - daws teeb meem loj spectrometer. Ua ke nrog cov ntaub ntawv theoretical sequences thiab UNIFI software, cov amino acid sequence raug txheeb xyuas raws li cov ntaub ntawv tseem ceeb thiab theem nrab pawg spectral fragment, thaum post-kev hloov pauv xws li phosphorylation thiab oxidation kuj tuaj yeem kuaj pom. Txoj kev no ua ke nrog kev sib cais siab thiab kev txheeb xyuas qhov tseeb, ua kom muaj tseeb ntawm cov qauv molecular ntawm aviptidal kom ntseeg tau tias nws cov kev ua haujlwm lom neeg thiab kev nyab xeeb. Nws yog dav siv rau kev tswj kom zoo hauv kev tsim tshuaj thiab kev tsim cov aviptidal.
Cov ntaub ntawv qhov chaw: Kev tsim kho thiab kev siv tau ntawm RP-HPLC txoj hauv kev rau kom muaj nuj nqis ntawm Aviptadil Acetate thiab nws cov khoom degradation (Asian Journal of Biological thiab Life Sciences); Daim Ntawv Qhia Sib piv rau HPLC Txoj Kev rau Peptide Purification thiab Analysis (Benchchem).
Kev ceev faj tshwj xeeb
Tsav tsheb thiab ua haujlwm tshuab: kiv taub hau, qaug zog, lossis hypotension tuaj yeem tshwm sim tom qab kev tswj hwm; zam kev tsav tsheb, ua haujlwm tshuab, lossis ua haujlwm ntawm qhov siab.
Cawv: Cawv potentiates vasodilatory thiab hypotensive teebmeem, ua rau muaj kev pheej hmoo ntawm kiv taub hau thiab hnyav hypotension. Kev haus cawv yog txwv tsis pub thaum kho.
Kev tuav tshuaj: Rau kev siv tshuaj xwb; tsis txhob qhia rau lwm tus. Pov tseg cov tshuaj uas tas sij hawm ua cov pov tseg kho mob.
Cov ntaub ntawv qhov chaw: Oxyptadil® cov lus qhia; Apollo Pharmacy cov lus qhia kev nyab xeeb.
FAQ
Kev txhaj tshuaj aviptadil ua haujlwm li cas?
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Aviptadil yog ib daim ntawv hluavtaws ntawm tib neeg vasoactive plab hnyuv peptide (VIP) thiab theoretically zoo nkaus li hais txog tag nrho plaub lub hypoxemia mechanisms hauv ARDS. Qhov no yog ua tiav los ntawmrestores cov kev ua ntawm puas alveolar epithelial hom 2 hlwb, ua rau kom muaj zog surfactant ntau lawm thiab txo shunting..
Puas yog aviptadil yog ib qho tshuaj tiv thaiv - mob?
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Lub presumed thawj kho mechanism ntawm kev txiav txim ntawm inhaled aviptadil yogkev sib xyaw ua ke ntawm cov tshuaj tiv thaiv -inflammatory zogthiab induction ntawm tolerogenic tiv thaiv kab mob ntawm lub cev tiv thaiv kab mob nyob rau hauv lub ntsws.
Cim npe nrov: Tuam Tshoj aviptadil peptide manufacturers, lwm tus neeg
