Cov ntsiab lus tseem ceeb ntawmOctreotide Acetate Solutionyog Octreotide Acetate, ib qho kev sib xyaw ua ke octapeptide derivative nrog cov qauv tshuaj ua kom zoo raws li ntuj somatostatin. Nws cov qauv molecular yog C ₅₁ H ₇₀ N ₁₀ O ₁₂ S ₂, nrog rau qhov hnyav ntawm kwv yees li 1019.3 g / mol. Octreotide txuas ob cysteine residues (Cys ² - Cys ⁷) los ntawm ib daim ntawv cog lus disulfide, tsim ib lub voj voog ruaj khov uas ua rau nws muaj zog receptor affinity thiab ntev dua nyob rau hauv vivo ib nrab - lub neej (kwv yees li 1.7-2 teev). Cov tshuaj no feem ntau muaj nyob rau hauv daim ntawv ntawm kev txhaj tshuaj, suav nrog npaj siv cov tshuaj uas tau ntim rau hauv ampoules lossis koob txhaj tshuaj ntawm qhov ntau ntawm 50 μ g / mL, 100 μ g / mL, 200 μ g / mL, lossis 500 μ g / mL. Kev txhaj tshuaj qhuav qhuav kuj tseem yuav tsum tau kho dua tshiab nrog cov kua qaub ntawm lub cev lossis cov kuab tshuaj tshwj xeeb ua ntej siv, nrog cov lus qhia tshwj xeeb ntawm 0.1 mg, 0.2 mg, lossis 0.5 mg. Kev ua yeeb yam ntev ntev xws li microspheres lossis liposomes tuaj yeem ua kom ntev lub sijhawm tso tshuaj thiab txo qhov ntau zaus.
Peb cov khoom Form
Octreotide Acetate COA
Kev tsis ncaj thiab ncaj qha cuam tshuam ntawm Octreotide Acetate ntawm lub plab microbiota thiab nws cov metabolites
Octreotide Acetate yog ib qho kev sib xyaw ua ke ntawm octapeptide analogue ntawm somatostatin uas inhibits qhov tso tawm ntawm ntau yam kab mob hauv plab thiab pancreatic hormones los ntawm kev ua raws li cov kev xav ntawm lub cev ntawm ntuj somatostatin. Raws li cov tshuaj peptide feem ntau siv hauv kev kho mob, nws daim ntawv txhaj tshuaj (Octreotide Acetate Solution) yog dav siv nyob rau hauv kev kho mob ntawm cov kab mob xws li acromegaly, neuroendocrine hlav (xws li carcinoid syndrome, VIP qog), thiab mob raws plab. Nyob rau hauv xyoo tas los no, plab microbiota tau dhau los ua lub hauv paus tseem ceeb rau kev tswj hwm cov metabolism thiab kev tiv thaiv kab mob, thiab nws cov txheej txheem ntawm kev cuam tshuam nrog tshuaj tau dhau los ua qhov kev tshawb fawb hotspot. Octreotide tuaj yeem ua rau muaj kev cuam tshuam loj ntawm cov plab hnyuv microbiota thiab nws cov metabolites (xws li cov saw hlau luv fatty acids, kua tsib acids, lipopolysaccharides, thiab lwm yam) los ntawm kev tswj lub plab hormonal secretion, hloov lub plab microenvironment, thiab ncaj qha ua rau microbial metabolic txoj kev.
Pharmacological zog thiab mechanism ntawm kev txiav txim ntawm Octreotide Acetate
Cov tshuaj chemical qauv thiab receptor selectivity
Octreotide yog ib qho octapeptide derivative ntawm ntuj somatostatin, uas stabilizes nws ib nrab -lub neej los ntawm ib tug cyclic qauv (kwv yees li 1.5 teev rau intravenous txhaj thiab 2-3 teev rau subcutaneous txhaj). Nws cov qauv tshuaj muaj cov amino acids uas tsis yog ntuj xws li D-phenylalanine thiab L-ornithine, ua kom nws txoj kev sib raug zoo nrog cov somatostatin receptor (SSTR). Muaj tsib hom subtypes ntawm SSTR (SSTR1-5) hauv tib neeg lub cev, thiab octreotide muaj kev xaiv ntau dua rau SSTR2 thiab SSTR5 ntau dua li ntuj somatostatin. Cov yam ntxwv no ua rau nws muaj txiaj ntsig zoo thiab pheej hmoo hauv inhibiting qhov tso tawm ntawm kev loj hlob hormone (GH), glucagon, insulin, thiab gastrointestinal peptides.
Core pharmacological teebmeem
Octreotide activates SSTR, inhibits adenylate cyclase kev ua, thiab txo cov qib cAMP intracellular, yog li thaiv txoj kev taw qhia ntawm cov tshuaj hormone secretion. Nws cov ntaub ntawv kho mob muaj xws li:
Acromegaly: Inhibiting ntau secretion ntawm GH thiab txo cov qog ntim;
Neuroendocrine qog: txo cov kab mob carcinoid (flushing, raws plab), VIP qog mob raws plab, thiab glucagonoma syndrome;
Kev tswj hwm kev ua haujlwm ntawm plab hnyuv thiab pancreatic: txo qis pancreatic exocrine secretion, inhibits gastric acid secretion, thiab qeeb plab hnyuv.
Metabolic thiab excretion pathways
Octreotide feem ntau yog tawm los ntawm ob lub raum (txog 30% -40% hauv nws daim ntawv qub), thaum tus so yog metabolized los ntawm lub siab. Nws cov metabolites (xws li deaminated octreotide) tseem khaws qee cov haujlwm lom neeg, tab sis lawv qhov tseem ceeb hauv kev kho mob yog txwv. Nws tsim nyog sau cia tias cov txheej txheem metabolic ntawm octreotide tuaj yeem cuam tshuam los ntawm lub plab microbiota, tsim lub voj kaw ntawm cov tshuaj microbiota kev sib cuam tshuam.
Kev cuam tshuam ncaj qha rau lub plab microbiota
Direct mechanism ntawm inhibiting kab mob loj hlob
Kev sib tw noj zaub mov thiab kev cuam tshuam metabolic
Octreotide txwv tsis pub cov kab mob loj hlob los ntawm inhibiting pancreatic enzyme secretion thiab txo qhov muaj cov as-ham (xws li carbohydrates thiab cov protein) hauv cov hnyuv. Piv txwv li, hauv cov neeg mob uas muaj mob qog noj ntshav, octreotide tuaj yeem txo cov plab hnyuv pH thiab inhibit qhov kev loj hlob ntawm cov kab mob pathogenic uas yuav tsum tau muaj alkaline ib puag ncig, xws li Clostridium perfringens. Tsis tas li ntawd, octreotide tuaj yeem cuam tshuam ncaj qha rau cov enzymes tseem ceeb hauv cov microbiota, xws li - glucuronidase, txo cov co toxins.
Antibacterial peptide zoo li cov teebmeem
Qee qhov kev tshawb fawb qhia tias octreotide tuaj yeem cuam tshuam ncaj qha rau cov kab mob ntawm tes los ntawm kev ua raws li kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob peptides, xws li kev tiv thaiv. Piv txwv li, hauv vitro kev sim, qhov tsawg kawg nkaus inhibitory concentrations (MIC) ntawm octreotide tawm tsam Staphylococcus aureus thiab Escherichia coli yog 16 μ g / mL thiab 32 μ g / mL, raws li, thiab nws cov txheej txheem ntawm kev ua haujlwm yuav cuam tshuam rau kev cuam tshuam ntawm cov cell membrane lipid bilayer.
Inhibition ntawm cov kab mob adhesion
Octreotide tuaj yeem txo qis kev qhia ntawm adhesion molecules (xws li integrins) ntawm cov kab mob hauv plab hnyuv epithelial, txo cov colonization ntawm cov kab mob pathogenic (xws li Helicobacter pylori). Hauv cov qauv tsiaj, ua ntej-kev kho mob nrog octreotide ua rau txo qis ntawm lub plab microbiota hloov pauv tom qab tus kab mob Salmonella.
Cov ntaub ntawv pov thawj kho mob: Kev hloov pauv hauv cov kab mob microbial
Cov neeg mob uas muaj kab mob neuroendocrine
Ib txoj kev tshawb fawb ntawm cov neeg mob carcinoid syndrome tau pom tias tom qab 6 lub hlis ntawm kev kho mob nrog octreotide, qhov piv ntawm Firmicutes rau Bacteroidetes hauv plab microbiota (F / B ratio) txo qis, thaum muaj ntau ntawm butyrate uas tsim cov kab mob (xws li Roseburia) txo qis, thiab cov txheeb ze ntawm cov kab mob ntau ntxiv (piv txwv. Qhov dysbiosis ntawm microbiota no tuaj yeem cuam tshuam nrog octreotide induced plab hnyuv motility thiab hloov pauv hauv cov kua tsib acid metabolism.
Cirrhotic cov neeg mob nrog portal hypertension
Octreotide Acetate Solutionfeem ntau yog siv los tswj los ntshav los ntawm txoj hlab pas thiab gastric varices. Kev tshawb fawb tau pom tias luv luv - siv octreotide (48 teev) tuaj yeem txo cov plab hnyuv microbiota ntau haiv neeg, tshwm sim los ntawm kev txo qis hauv Bacteroidetes thiab nce hauv Proteobacteria, uas tej zaum yuav cuam tshuam rau kev siv tshuaj -induced plab hnyuv ischemia thiab mucosal barrier puas.
Tsiaj sim tshuaj xyuas
Hauv cov qauv nas rog rog, kev cuam tshuam octreotide txo qis qhov ntau ntawm Akkermansia muciniphila (cov kab mob mucin degrading zoo cuam tshuam nrog kev noj qab haus huv metabolic) hauv plab, thaum nce qhov feem ntawm lipopolysaccharide (LPS) tsim cov kab mob xws li Desulfovibrio. Cov kev hloov pauv no zoo ib yam nrog cov txheej txheem uas octreotide inhibits mucin secretion thiab ua rau lub plab zom mov qeeb.
Indirect cuam tshuam rau metabolites ntawm plab microbiota
Metabolic regulation ntawm luv saw fatty acids (SCFAs)
Mechanism rau Txo SCFA tiam
SCFAs (xws li acetic acid, propionic acid, thiab butyric acid) yog cov khoom lag luam tseem ceeb ntawm cov khoom noj fiber ntau fermented los ntawm plab microbiota, nrog rau kev ua haujlwm ntawm kev tiv thaiv - mob, kev tiv thaiv kab mob, thiab tswj cov kab mob hauv plab hnyuv. Octreotide inhibits SCFA tiam los ntawm cov hauv qab no:
Inhibition ntawm microbial fermentation muaj peev xwm: Octreotide txo qis pancreatic enzyme secretion, txo qhov muaj cov carbohydrates fermentable (xws li cov hmoov txhuv nplej siab thiab cellulose) hauv cov hnyuv, thiab ncaj qha txwv cov substrate mov rau SCFA ntau lawm los ntawm cov microbial zej zog.
Kev hloov hauv microbial muaj pes tsawg leeg: Octreotide induced txo nyob rau hauv butyrate tsim cov kab mob (xws li Faecalibacterium prausnitzii) ua rau txo qis hauv butyrate ntau lawm. Hauv cov neeg mob uas muaj carcinoid syndrome, qhov concentration ntawm fecal butyric acid txo qis los ntawm 30% -40% tom qab 6 lub hlis ntawm kev kho mob nrog octreotide.
Inhibition ntawm mucin degradation: Qhov txo qis ntawm mucin degrading kab mob xws li Akkermansia muciniphila txo qhov kev siv ntawm tus tswv mucin ua ib qho kev hloov pauv carbon, ntxiv inhibiting SCFA tiam.
Clinical tseem ceeb ntawm txo SCFA
SCFA deficiency yog txuam nrog ntau yam kab mob, xws li:
Kev puas tsuaj plab hnyuv: Butyric acid yog lub zog tseem ceeb rau cov kab mob colonic epithelial, thiab nws qhov kev txo qis tuaj yeem ua rau txo qis ntawm cov protein sib txuas (xws li Occludin thiab ZO-1), ua rau plab hnyuv permeability.
Cov lus teb hnyav dua: SCFA inhibits NF - κ B signaling txoj hauv kev los ntawm kev ua kom cov G protein txuas nrog receptor (GPR41/43), uas tuaj yeem txhawb LPS induced systemic inflammatory teb.
Cov kab mob metabolic: Propionic acid tuaj yeem tswj kev noj qab haus huv los ntawm lub plab hauv plab axis, thiab nws qhov txo qis tuaj yeem ua rau cov tsos mob plab zom mov ntau ntxiv los ntawm octreotide, xws li tsam plab thiab thaum ntxov satiety.
Bile acid (BA) kev tswj hwm metabolism
Mechanism ntawm BA lub voj voog hloov
Cov kua tsib yog cov khoom kawg ntawm cov roj cholesterol metabolism, uas tau hloov kho los ntawm lub plab microbiota los tsim cov kua tsib theem ob xws li deoxycholic acid thiab lithocholic acid. Octreotide cuam tshuam BA metabolism los ntawm cov hauv qab no:
Inhibition ntawm cov kua tsib secretion: Octreotide inhibits qhov tso tawm ntawm cholecystokinin (CCK), txo cov gallbladder khoob, thiab ua rau kom txo qis concentration ntawm cov kua tsib acids (xws li cholic acid thiab chenodeoxycholic acid) nyob rau hauv txoj hnyuv.
Hloov cov kev ua ntawm cov kua tsib kua qaub metabolism hauv cov enzymes hauv microbiota: Octreotide tuaj yeem txo qis kev qhia ntawm 7 - dehydroxylase (lub luag haujlwm rau hloov cov kua tsib kua qaub rau hauv cov kua tsib theem nrab) hauv cov hnyuv, txo cov khoom deoxycholic acid. Hauv kev sim tsiaj, kev cuam tshuam octreotide txo qhov feem ntawm cov kua tsib acids hauv cov quav los ntawm 60% mus rau 35%.
Kev ua kom muaj farnesol X receptor (FXR): Thawj cov kua tsib acids (xws li cov kua tsib acids) yog cov ligands ntawm FXR, thiab lawv qhov kev txo qis tuaj yeem cuam tshuam cov kua tsib acid synthesis los ntawm FXR-FGF15/19 axis, tsim cov kev tswj xyuas tsis zoo.
Clinical tseem ceeb ntawm BA metabolic hloov
BA metabolic ntshawv siab yog txuam nrog cov kab mob hauv qab no:
Lipid absorption disorder: Bile acid deficiency ua rau cov roj emulsification tsis txaus, uas yuav ua rau octreotide ua rau mob raws plab thiab noj tsis txaus.
Ua rau muaj kev pheej hmoo ntawm daim siab raug mob: Secondary bile acids (xws li deoxycholic acid) muaj cytotoxicity, thiab lawv qhov kev txo qis tuaj yeem txo qhov kev pheej hmoo ntawm cov kua tsib acid-induced hepatocyte apoptosis; Tab sis qhov sib xyaw ntawm cov kua tsib acids tseem tuaj yeem txhawb lub siab fibrosis los ntawm kev ua kom FXR.
Aggravated dysbiosis ntawm microbiota: BA yog ib qho tseem ceeb taw qhia molecule uas tswj cov muaj pes tsawg leeg ntawm microbiota, thiab nws cov kev hloov pauv yuav ua rau muaj kev nthuav dav ntawm cov kab mob kis tau zoo (xws li Enterobacteriaceae).
Lipopolysaccharide (LPS) thiab kev tswj kev mob
Mechanism ntawm nce LPS ntau lawm
LPS yog cov khoom tseem ceeb ntawm cov phab ntsa ntawm tes ntawm cov kab mob Gram tsis zoo, thiab nws tso rau hauv cov hlab ntsha tuaj yeem ua rau cov kab mob inflammatory. Octreotide tuaj yeem nce qib LPS los ntawm txoj hauv qab no:
Kev puas tsuaj plab hnyuv: Octreotide inhibits mucin secretion thiab SCFA ntau lawm, ua rau lub cev tsis muaj zog (xws li mucus txheej) thiab tshuaj tiv thaiv kab mob (xws li tshuaj tua kab mob peptides) ntawm txoj hnyuv, thiab txhawb LPS translocation.
Microbial dysbiosis: Cov txheeb ze ntau ntawm LPS tsim cov kab mob (xws li Enterobacteriaceae thiab Bacteroidetes) induced los ntawm octreotide nce, ncaj qha nce LPS ntau lawm. Hauv cov neeg mob ntshav siab, kev kho mob nrog octreotide nce ntshav LPS concentration los ntawm 20% -30%.
Immunosuppression: Octreotide ua rau tus tswv tsev tsis muaj peev xwm tshem LPS los ntawm inhibiting qhov kev qhia ntawm Tus Xov Tooj zoo li receptor 4 (TLR4), ua rau lub voj voog tsis zoo ntawm "siab LPS low clearance".
Kev kho mob tseem ceeb ntawm LPS nce
Kev nce qib ntawm LPS yog txuam nrog cov teeb meem hauv qab no:
Systemic Inflammatory Response Syndrome (SIRS): Hauv cov neeg mob uas muaj kab mob neuroendocrine,octreotide acetate dawsinduced LPS translocation yuav ua rau cov tsos mob hnyav dua xws li dej ntws tawm thiab raws plab.
Cov tshuaj insulin tsis kam: LPS cuam tshuam nrog cov teeb liab hloov pauv ntawm insulin los ntawm kev ua kom IKK / NF - κ B txoj hauv kev, uas tuaj yeem cuam tshuam cov nyhuv hypoglycemic ntawm octreotide (txawm tias octreotide nws tus kheej tsis ncaj qha tswj cov ntshav qabzib).
Lub siab raug mob: LPS-TLR4 axis activates Kupffer hlwb, tso pro-inflammatory yam xws li TNF - thiab IL-6, ua kom cov txheej txheem ntawm daim siab fibrosis.
Cim npe nrov: Tuam Tshoj octreotide acetate tov manufacturers, lwm tus neeg
