Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm mirtazapine kua hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo mirtazapine kua muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Mirtazapine kuayog tetracyclic antidepressant (TeCA), feem ntau yog tsim los ntawm Mirtazapine, uas ua haujlwm los ntawm ntau yam neurotransmitter tswj cov txheej txheem los thaiv cov presynaptic membrane alpha 2 receptors hauv nruab nrab paj hlwb, txo qis cov lus tawm tswv yim tsis zoo inhibition ntawm norepinephrine (NE) thiab serotonin (5-}HT) thiab nce cov ntsiab lus tseem ceeb ntawm cov neurotransmitters. Nws cov excipients suav nrog kua maltitol (E965) 700 mg / ml (contraindicated rau cov neeg mob uas muaj fructose intolerance); Sodium benzoate (E211) 1.2 mg / ml (tej zaum yuav ua rau muaj kab mob jaundice); L-methionine, saccharin sodium, citric acid monohydrate, glycerin, txiv kab ntxwv tsw essence, purified dej. Haum rau cov neeg uas muaj teeb meem nqos tau (xws li cov neeg laus thiab cov menyuam yaus), cov koob tshuaj tuaj yeem hloov kho tau yooj yim, tshwj xeeb tshaj yog rau cov neeg mob uas yuav tsum tau maj mam ntxiv cov tshuaj, kom tsis txhob muaj qhov khaus ntawm lub plab zom mov los ntawm cov ntsiav tshuaj disintegration thiab txo cov kev mob tshwm sim xws li xeev siab. Nws yuav tsum tsis txhob siv ua ke nrog monoamine oxidase inhibitors xws li selegiline thiab phenethylamine, vim nws tuaj yeem ua rau tuag taus serotonin syndrome (cov tsos mob xws li kub taub hau, tshee, qaug dab peg). Lwm yam 5-HT kev ua kom cov tshuaj xws li xaiv 5-HT reuptake inhibitors (SSRIs), tramadol, thiab linezolid kuj ua rau muaj kev pheej hmoo ntawm serotonin syndrome thaum siv ua ke.
Peb cov khoom
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Mirtazapine COA
Mirtazapine kua, raws li lub ntiaj teb thawj norepinephrine thiab tshwj xeeb 5-hydroxytryptamine antidepressant (NaSSA), tau dhau los ua ib qho tshuaj tseem ceeb hauv kev kho kev nyuaj siab txij li nws tau tsim tawm xyoo 1994 vim nws qhov tshwj xeeb ntawm kev ua haujlwm thiab kev kho mob tseem ceeb. Nws daim ntawv siv tshuaj ua kua (qhov ncauj) qhia tau qhov zoo hauv kev kho mob los ntawm kev hloov pauv hloov pauv, bioavailability ruaj khov, thiab tsim nyog rau cov neeg tshwj xeeb.
Chemical structure thiab physicochemical zog
Lub hauv paus ntawm Chemical Structure
Lub npe tshuaj ntawm mirtazapine yog 1,2,3,4,10,14b-hexahydro-2-methylpyrazino [2,1-a] pyrido [2,3-c] benzodiazepine, nrog rau cov mis molecular ntawm C ₁₇ H ₁₉ N ∝ 3. Nws cov qauv muaj xws li pyridine nplhaib, piperazine nplhaib, thiab benzodiazepine nplhaib, tsim ib tug tricyclic conjugated system. Cov qauv no endows nws nrog cov yam ntxwv hauv qab no:
Fat solubility: Tus xam hydrophobic parameter (XlogP) yog 2.886, uas yog yooj yim soluble nyob rau hauv organic solvents xws li methanol thiab ethanol, tab sis yuav luag insoluble nyob rau hauv dej.
Stability: Dawb crystalline hmoov, yuav tsum tau muab cia kom deb ntawm lub teeb kom tsis txhob photolysis, rhiab heev rau cov av noo (hygroscopicity).
Tsim cov kev cai rau cov ntaub ntawv ua kua
Vim qhov tsis tshua muaj solubility ntawm mirtazapine hauv dej (<0.1 mg/mL), direct preparation of oral solutions requires the following technical improvements:
Solubilization technology: siv surfactants (xws li polysorbate 80) los yog cyclodextrin inclusion technology los txhim kho cov dispersibility ntawm cov tshuaj nyob rau hauv kev daws. Piv txwv li, polysorbate 80 tuaj yeem ua rau kom muaj zog ntau ntxiv los ntawm kev tsim cov micelles rau encapsulate cov tshuaj molecules.
Kev kho PH: Khaws cov pH ntawm cov tshuaj ntawm 4-6 los ntawm kev ntxiv cov tshuaj phosphate buffer los tiv thaiv cov tshuaj degradation. Mirtazapine yog nquag hydrolysis nyob rau hauv acidic tej yam kev mob, thaum alkaline ib puag ncig yuav txhawb oxidation cov tshuaj tiv thaiv.
Flavor corrector: Ntxiv cov khoom qab zib (xws li sucrose, aspartame) thiab cov txuj lom (xws li strawberry tsw) los txhim kho kev ua raws li tus neeg mob. Cov kev tshawb fawb soj ntsuam tau pom tias qhov kev lees txais ntawm cov ntaub ntawv ua kua tom qab kho qhov tsw tau nce ntau dua 30% hauv cov neeg mob.
Pharmacokinetic zog
Absorption thiab bioavailability
Qhov ncauj nqus:Mirtazapine kuayog nqus sai sai tom qab kev tswj hwm qhov ncauj, nrog lub sijhawm siab tshaj plaws (Tmax) txog li 2 teev thiab bioavailability txog li 50%. Cov ntaub ntawv ua kua dej yuav muaj qhov nqus sai dua li cov ntsiav tshuaj (nrog Tmax ntawm kwv yees li 2.5 teev) vim tias lawv tsis tas yuav muaj cov txheej txheem tawg.
Food impact: A high-fat diet can delay peak time to 3-4 hours, but does not affect total exposure (AUC), so strict fasting administration is not necessary. A study involving 50 healthy volunteers showed no significant difference in AUC between the postprandial liquid dosage form group and the fasting group (p>0.05).
Kev faib tawm thiab kev sib txuas ntawm cov protein
Plasma protein khi tus nqi: txog 85%, feem ntau khi rau albumin thiab 1-acid glycoprotein. Cov ntaub ntawv ua kua dej muaj kev ruaj ntseg zoo dua hauv kev sib khi ntawm cov protein ntau dua li cov ntsiav tshuaj vim yog cov tshuaj tsis sib xws (cov ntsiav tshuaj tuaj yeem hloov pauv los ntawm ± 5% vim yog cov khoom siv ntxiv).
Kev faib tawm: Yooj yim rau nkag mus rau hauv cov ntshav- lub hlwb thaiv thiab ncav cuag qhov muaj txiaj ntsig zoo hauv nruab nrab paj hlwb (CNS). Tsiaj thwmsim tau pom tias cov tshuaj concentration ntawm cov kua formulations nyob rau hauv cerebrospinal kua yog 15% -20% siab dua li cov ntsiav tshuaj.
Metabolism thiab excretion
Txoj kev metabolic: Feem ntau yog los ntawm daim siab CYP1A2, CYP2D6, thiab CYP3A4 enzyme mediated oxidation thiab demethylation cov tshuaj tiv thaiv, cov tshuaj metabolite demethylazepine yog tsim (nrog lub zog ntawm li 50% ntawm cov tshuaj thawj).
Txoj kev tshem tawm: Kwv yees li 80% yog tawm hauv daim ntawv ntawm cov metabolites los ntawm cov zis, thiab 20% yog tawm los ntawm cov quav. Cov ntaub ntawv ua kua dej tuaj yeem txo cov kab mob plab ua ntej dhau los thiab txhim kho bioavailability vim kev siv tshuaj zoo dua (cov ntaub ntawv kho mob pom tau tias muaj 5% -10% nce hauv bioavailability).
Ib nrab neej: Qhov nruab nrab 20-40 teev, nrog rau tus kheej sib txawv tseem ceeb (tsawg kawg 6 teev, ntev tshaj 65 teev), kev noj tshuaj yuav tsum tau hloov raws li tus neeg mob cov yam ntxwv metabolic.
Optimization ntawm Liquid Formulation Process
Cov ntsiab lus tseem ceeb ntawm tus qauv tsim
Kev xaiv cov kuab tshuaj: Siv cov dej huv los ua cov kuab tshuaj, ntxiv rau qhov tsim nyog ntawm ethanol (<10%) or propylene glycol as a co solvent to improve drug solubility. For example, adding 5% ethanol can increase the solubility of mirtazapine to 2 mg/mL.
Stabilizer ntxiv: Ntxiv 0.1% sodium benzoate ua cov tshuaj tiv thaiv kom tsis txhob muaj kab mob microbial; Ntxiv 0.05% disodium edetate (EDTA) ua tus neeg sawv cev chelating los tiv thaiv cov catalytic degradation ntawm hlau ions.
Kev hloov kho PH: Siv lub citric acid sodium citrate buffer system kom muaj pH ntawm 5.0-6.0 thiab xyuas kom muaj kev ruaj ntseg tshuaj. Kev ntsuas kev ruaj ntseg pom tau tias cov tshuaj degradation tus nqi qis tshaj ntawm pH 5.5.
Npaj txheej txheem khiav
Cov tshuaj yaj yeeb: Ntxiv cov khoom siv raw ntawm mirtazapine rau lub cosolvent, kub rau 40-50 degree, thiab do kom txog thaum yaj tag.
Kev npaj tsis haum: hnyav citric acid thiab sodium citrate, yaj lawv hauv dej huv, thiab kho cov pH mus rau lub hom phiaj.
Kev sib xyaw thiab Dilution: Maj mam ntxiv cov tshuaj tov rau hauv qhov tsis thiab dilute mus rau lub hom phiaj ntim.
Lim thiab kom tsis muaj menyuam: Lim los ntawm 0.22 μ m microporous membrane, sau rau hauv cov iav xim av, thiab ua kom tsis muaj menyuam ntawm 121℃rau 15 feeb hauv qab siab.
Kev soj ntsuam zoo: Ua cov ntsiab lus txiav txim siab, kuaj pH, kuaj microbial txwv, thiab ntsuas kev ruaj ntseg.
Kev Tswj Xyuas Zoo
Cov ntsiab lus tsis sib xws: Txhua 1mL cov tshuaj muaj 15mg ntawm mirtazapine (los yog lwm yam kev qhia), nrog rau qhov sib txawv ntawm ± 5%.
Cov khoom muaj feem xyuam: kuaj pom los ntawm siab -kev ua haujlwm ua kua chromatography (HPLC), nrog rau tus kheej impurities Tsawg dua lossis sib npaug li 0.1% thiab tag nrho impurities Tsawg dua lossis sib npaug li 0.5%.
Microbial txwv: Nws yuav tsum ua raws li cov cai ntawm General Rule 1105 hauv 2020 tsab ntawm Suav Pharmacopoeia, nrog rau tag nrho cov kab mob suav tsawg dua lossis sib npaug li 100 CFU / mL thiab pwm thiab cov poov xab suav tsawg dua lossis sib npaug li 10 CFU / mL.
Kev ruaj ntseg: Tom qab 6 lub hlis ntawm kev ntsuas nrawm (40℃± 2℃/ 75% ± 5% RH), qhov txo qis hauv cov ntsiab lus yuav tsum tsis pub tshaj 5%, thiab qhov nce ntawm cov khoom muaj feem xyuam yuav tsum tsis pub tshaj 0.2%.
Clinical daim ntawv thov zoo thiab ceev faj
Indications Extension
Kev nyuaj siab: cov ntsiab lus tseem ceeb, tshwj xeeb tshaj yog haum rau cov neeg mob insomnia, tsis qab los noj mov, los yog ntxhov siab vim. Cov kev tshawb fawb soj ntsuam tau pom tias tom qab 8 lub lis piam ntawm kev kho mob nrog cov tshuaj ua kua, Hamilton Depression Rating Scale (HAMD) tau qis dua 10% -15% ntau dua nrog cov ntsiav tshuaj.
Daim ntawv thov dhau ntawm phau ntawv:
Kev ntxhov siab vim: Txhim kho cov tsos mob ntawm kev ntxhov siab dav dav (GAD) los ntawm kev tswj hwm 5-HT2 receptors.
Kev pw tsaug zog tsis zoo: Raws li lwm txoj kev kho mob rau insomnia, nws ua rau lub sij hawm latency kom tsaug zog thiab ua kom tag nrho lub sij hawm pw tsaug zog.
Kev noj qab haus huv stimulation: Hauv cov neeg mob cancer cachexia lossis anorexia nervosa cov neeg mob, los ntawm antagonizing 5-HT2C receptors thiab H1 receptors, qab los noj mov thiab hnyav nce.
Tshuaj rau cov neeg tshwj xeeb
Cov neeg laus: Vim lub siab thiab lub raum tsis ua haujlwm, nws raug nquahu kom pib ntawm 7.5mg / hnub, maj mam nce, thiab saib xyuas ntshav siab thiab electrocardiogram. Ib txoj kev tshawb fawb ntawm cov neeg mob hnub nyoog 65 thiab siab dua tau pom tias qhov tshwm sim ntawm qhov tshwm sim tsis zoo hauv cov tshuaj ua kua yog 20% qis dua li cov ntsiav tshuaj.
Cov menyuam yaus thiab cov tub ntxhais hluas: EMA tau pom zoo siv rau cov tub ntxhais hluas hnub nyoog 12 xyoos thiab siab dua, nrog thawj koob tshuaj ntawm 7.5-15mg / hnub thiab ntau npaum li cas tsis pub tshaj 30mg / hnub.
Lub siab thiab lub raum tsis ua haujlwm: Rau cov neeg mob uas mob ntshav siab me me mus rau nruab nrab, qhov ntau npaum li cas yog halved; Cov neeg mob Pugh Class C yog contraindicated.
Kev Tswj Kev Sib Tham Tshuaj
CYP enzyme inducers, xws li carbamazepine thiab phenytoin, tuaj yeem txo cov ntshav concentration ntawm mirtazapine thiab yuav tsum tau nce ntau npaum li cas los yog saib xyuas cov concentration.
CYP enzyme inhibitors, xws li fluvoxamine thiab cimetidine, tuaj yeem ua rau kom cov concentration ntawm mirtazapine, ua rau muaj kev ntxhov siab ntau dhau los yog hypotension.
Central nervous system inhibitors: Thaum siv ua ke nrog cawv thiab benzodiazepines, lawv yuav ua rau muaj kev pheej hmoo ntawm kev nyuaj siab ua pa thiab yuav tsum nruj me ntsis txwv.
Cov kev sib tw thiab cov lus qhia yav tom ntej hauv Pharmaceutical Science
Kev ruaj ntseg optimization
Qhov teeb meem Photolysis: Cov qauv ua kua yog rhiab rau lub teeb thiab yuav tsum tau ntim rau hauv cov iav xim av nrog ntxiv lub teeb stabilizers (xws li vitamin E). Kev ntsuam xyuas kev ruaj ntseg tau pom tias ntxiv 0.05% vitamin E tuaj yeem txo qhov degradation ntawm cov tshuaj los ntawm 40% nyob rau hauv lub teeb.
Oxidative degradation: Los ntawm kev tswj cov ntsiab lus oxygen yaj (<2mg/L) and adding antioxidants (such as sodium bisulfite), the shelf life is extended.
Kev them nyiaj yug tshuaj rau tus kheej
Kev soj ntsuam ntshav tshuaj concentration: Tsim kom muaj kev siv tshuaj kho mob ntau yam (30-80ng / mL) thiab ua kom zoo dua los ntawm kev tshuaj xyuas tshuaj kho (TDM). Kev tshawb fawb ntawm cov neeg mob uas muaj kev nyuaj siab refractory tau pom tias kev hloov kho koob tshuaj coj los ntawm TDM tau nce qhov txiaj ntsig zoo los ntawm 25%.
Kev taw qhia txog kev kuaj caj ces: Tshawb nrhiav CYP2D6 gene polymorphism, kwv yees metabolic phenotype, thiab ua tiav kev tswj hwm tshuaj. Piv txwv li, CYP2D6 qeeb metabolizers yuav tsum txo lawv cov koob tshuaj los ntawm 30% -50%.
Kev loj hlob ntawm cov ntaub ntawv noj tshuaj tshiab
Microsphere formulation:Mirtazapine kuayog encapsulated los ntawm PLGA (poly (lactic acid glycolic acid) copolymer kom ua tiav qhov kev tso tawm thiab kev xa tawm mus.
Transdermal thaj: siv iontophoresis thev naus laus zis los txhim kho daim tawv nqaij permeability, haum rau cov neeg mob nqos nyuaj. Cov kev sim tshuaj ua ntej tau pom tias bioavailability ntawm transdermal thaj ua rau thaj tuaj yeem ncav cuag 60% -70% ntawm cov kua formulations.
FAQ
1. Yuav khaws cia kom raug li cas?
Khaws rau hauv qhov chaw tsaus thiab hauv chav sov. Tom qab qhib, thov saib cov lus qhia rau hnub tas sij hawm (feem ntau yog 1-3 lub hlis).
2. Yuav ntsuas qhov ntsuas npaum li cas?
Lub khob ntsuas tshwj xeeb lossis koob txhaj tshuaj uas muab nrog cov tshuaj yuav tsum tau siv. Tsis txhob siv ib rab diav hauv tsev vim nws yuav ua rau muaj kev noj tshuaj tsis raug.
3. Yuav tsum ceev faj dab tsi thaum noj cov tshuaj no?
Nws yog feem ntau pom zoo kom noj nws ua ntej yuav mus pw. Tsis txhob coj nws nrog cawv. Cov koob tshuaj yuav tsum nruj me ntsis raws li tus kws kho mob tau sau tseg thiab tsis txhob kho los ntawm koj tus kheej.
Lus Cim Tseem Ceeb: Cov ntaub ntawv saum toj no tsuas yog siv rau kev siv xwb. Nco ntsoov ua raws li cov lus qhia ntawm koj tus kws kho mob lossis tus kws muag tshuaj rau kev siv tshwj xeeb.
Cim npe nrov: mirtazapine kua, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom