Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm flibanserin capsule hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo flibanserin capsule muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Flibanserin Capsulebelongs rau cov tshuaj uas tsis yog tshuaj hormonal, thiab lawv cov txheej txheem tseem ceeb ntawm kev ua yog kev tswj hwm neurotransmitter. Los ntawm inhibiting 5-HT1A receptors, lawv indirectly nce dopamine tso tawm, qhib lub hlwb nqi zog chaw, thiab txhim khu kev txaus siab rau kev sib deev cwj pwm. Lub norepinephrine system tuaj yeem qhib 5-HT2A receptors, txhim khu lub hlwb lub peev xwm los teb rau ib puag ncig stimuli, thiab pab tsom ntsoov rau kev sib deev. Lub serotonin system antagonizes 5-HT2A receptors, txo inhibitory signaling, thiab sib npaug excitatory thiab inhibitory yam nyob rau hauv kev sib deev kev ntshaw. Tsis zoo li cov txiv neej uas siv Viagra (sildenafil) los txhim kho erectile muaj nuj nqi los ntawm dilating cov hlab ntsha, Flibanserin ua ncaj qha rau hauv nruab nrab paj hlwb thiab yog ib tug neurotransmitter regulator.
Peb cov khoom
Cov ntaub ntawv ntxiv ntawm chemical compound:
|
|
|
FlibanserinCOA
Flibanserin Capsule, raws li lub ntiaj teb thawj cov tshuaj pom zoo rau kev kho cov poj niam kev sib deev tsis sib haum xeeb (HSDD), tau tsim thiab tsim siv kev txiav- thev naus laus zis los ntawm ntau yam kev qhuab qhia suav nrog neuroscience, organic chemistry, thiab kws tshuaj engineering. Los ntawm kev tsim qauv molecular mus rau kev tsim khoom lag luam, cov tshuaj no tau dhau mus dhau los ntawm kev sim mus rau chaw kho mob, thiab thaum kawg tsim cov saw hlau ua tiav.
Molecular mechanism: kev cuam tshuam meej ntawm kev tswj hwm neurotransmitter
Flibanserin Capsuleregulates neurotransmitter tshuav nyiaj li cas nyob rau hauv lub hauv paus paj hlwb los ntawm ib tug dual mechanism ntawm kev txiav txim:
Ib feem ntawm kev ua haujlwm ntawm 5-HT1A receptor: khi rau postsynaptic membrane 5-HT1A receptor nrog sub nanomolar affinity (Ki=1} nM), inhibiting adenylate cyclase kev ua los ntawm G protein txuas nrog cAMP PKA txoj hauv kev, indirectly txhim kho qhov rhiab heev ntawm dopamine kev sib deev txoj kev. Cov kev tshawb fawb preclinical tau pom tias cov nyhuv no tuaj yeem ua rau cov tshuaj dopamine tso tawm los ntawm 42% thiab txhawb kev sib deev kom muaj zog.
5-HT2A receptor antagonism: Thaiv cov presynaptic membrane 5-HT2A receptor nrog 20 quav xaiv (Ki=24} nM), txo nws txoj kev cuam tshuam ntawm norepinephrine synthesis. Qhov kev sim microdialysis ntawm locus coeruleus tau pom tias cov txheej txheem no tuaj yeem nce qhov tso tawm ntawm norepinephrine los ntawm 37% thiab txhim kho kev coj cwj pwm zoo.
Pharmacokinetic yam ntxwv
Kev nqus thiab kev faib tawm: Lub qhov ncauj bioavailability yog kwv yees li 32%, lub sijhawm siab tshaj plaws ntawm cov tshuaj ntshav siab (Tmax) yog 1-4 teev, thiab qhov pom tseeb qhov ntim (Vd) yog 4-6 L / kg, qhia txog nws qhov kev faib tawm thoob plaws hauv cov ntaub so ntswg.
Metabolism thiab excretion: Feem ntau metabolized los ntawm CYP3A4 thiab CYP2D6 enzymes, tsim cov metabolites tsis ua haujlwm. Ib nrab -lub neej (t1/2) yog 11 teev thiab txhawb nqa kev noj tshuaj ib zaug ib hnub. Cov neeg mob lub raum tsis txaus tsis tas yuav kho qhov koob tshuaj, tab sis nws yuav tsum tau contraindicated rau cov neeg mob uas mob siab heev.
Cov Lus Qhia: Siv los kho HSDD tau txais thiab dav dav hauv cov poj niam premenopausal, yuav tsum ua raws li cov xwm txheej hauv qab no:
Tsawg libido ua rau mob hnyav lossis nyuaj rau kev sib txuas lus ntawm tus kheej
Tsis yog tshwm sim los ntawm kev noj tshuaj, mob, lossis teeb meem kev sib raug zoo ntawm tus khub
Contraindications: mob siab ua haujlwm tsis zoo, haus dej cawv los yog siv cov tshuaj muaj zog CYP3A4 inhibitors (xws li ketoconazole), cov poj niam cev xeeb tub thiab lactating.
API synthesis: technological breakthrough hauv chiral catalysis
Muaj txoj kev tsim khoom
Qhov tseem ceeb nruab nrab qhov kev npaj
Cov kev mob tshwm sim: 5-methoxytryptamine (CAS: 608-07-}1) thiab p-fluorobenzoyl chloride (CAS: 403-43-0) tau condensed hauv anhydrous dichloromethane ntawm 0℃rau 4 teev los tsim Np-fluorobenzoyl 9%.
Kev ua kom zoo tshaj plaws: Los ntawm kev ntxiv 0.1% triethylamine ua cov kua qaub khi, lub sij hawm cov tshuaj tiv thaiv tau luv rau 2 teev, thaum cov khoom purity tau nce mus rau 99.5%.
Chiral catalytic hydrogenation
Catalyst system: Ruthenium phosphine ligand complex (Ru BINAP) tau siv los xaiv txo N-p-fluorobenzoyl-5-methoxytryptamine rau (S) - Libanserin ntawm 50℃thiab 8 MPa hydrogen siab, nrog rau cov txiaj ntsig ntawm 82% purity thiab 9.6% purity 9.
Kev sib piv: Cov tsoos L-proline derivative catalytic system muaj cov txiaj ntsig ntawm tsuas yog 65%, qhov kho qhov muag purity ntawm 98.2%, thiab yuav tsum tau siv cov pa roj carbon monoxide kim heev.
Crystallization thiab Purification
Crystallization tej yam kev mob: Acetonitrile / dej (60:40), txias rau 0℃ntawm tus nqi ntawm 1℃/ min, dawb crystals tau precipitated nrog ib tug D90 particle loj faib<50 μ m.
Txoj kev purification: Supercritical fluid chromatography (SFC) technology yog siv, nrog CO2 / methanol (85:15) raws li theem mobile. Kev sib cais ua tau zoo yog peb zaug siab dua li cov txheej txheem crystallization, thiab kev tswj cov kuab tshuaj seem ua tau raws li qhov xav tau ntawm ICH cov lus qhia Q3C.
Kev Tswj Xyuas Zoo
Heterozygous mass spectrometry tsom xam: HPLC-Q-TOF-MS ua ke siv thev naus laus zis, nrog kev kuaj pom tsis pub dhau 0.01%. Lub hom phiaj yog los saib xyuas cov genotoxic impurities xws li fluoroaniline (tsawg dua los yog sib npaug rau 10 ppm).
Kev kuaj xyuas cov hlau hnyav: ICP-MS txoj kev siv los txiav txim siab cov hlau lead tsawg dua lossis sib npaug ntawm 0.5 ppm, cadmium Tsawg dua lossis sib npaug li 0.3 ppm, thiab mercury Tsawg dua lossis sib npaug li 0.1 ppm, ua raws li USP<231>qauv.
Cov kuab tshuaj seem: Acetonitrile Tsawg dua lossis sib npaug li 410 ppm, dichloromethane Tsawg dua lossis sib npaug li 600 ppm, methanol Tsawg dua lossis sib npaug rau 3000 ppm, tag nrho hauv qab ICH cov lus qhia txwv.
Cov txheej txheem Formulation: Innovative Application ntawm Nanocrystallization Technology
- Kev sib piv ntawm Thawj Kev Tshawb Fawb thiab Kev Tsim Kho Tshuab
| Technical Specifications | Original tshuaj (Sprout) | Lwm yam tshuaj generic tshuaj |
| Cov txheej txheem tseem ceeb | Khoom dispersion (PVP-K30) | Nanocrystallization tshuab (particle loj 200nm) |
| Dissolution tus nqi (30 feeb) | 85% | 95% |
| Bioavailability | 32% | 52% |
| Batch stability | Kev sib hloov pauv ± 8% | Kev sib hloov pauv ± 3% |
- Cov ntsiab lus tseem ceeb ntawm cov txheej txheem nanocrystalization
Kev sib tsoo ntub dej
Cov khoom siv tsis muaj: Siv Netzsch LabStar LS1 grinder, zirconia hlaws (0.2mm) raws li kev sib tsoo nruab nrab, sib tsoo lub sijhawm 4 teev, D50＜300nm, D90＜600nm.
Kev hloov kho saum npoo: Ntxiv 0.5% sodium dodecyl sulfate (SDS) ua tus stabilizer tiv thaiv nanoparticle aggregation.
tshuaj tsuag kom qhuav
Cov txheej txheem txheej txheem: inlet kub ntawm 120 degree, qhov hluav taws xob kub ntawm 65 degree, atomization siab ntawm 0.3 MPa, pub tus nqi ntawm 15 mL / min, sau efficiency ntawm 92%, residual noo noo<2%.
Cov khoom siv txheej: Opadry daj txheej yog siv, nrog qhov hnyav nce ntawm 3%, txheej lauj kaub ceev ntawm 8 rpm, cua kub ntawm 55 degree, thiab uniformity RSD<5%.
Filling thiab Sealing
Capsule specification: 100 mg/capsule, siv gelatin hollow capsules (qauv 0 #), ntim nrog cov av noo tsawg dua lossis sib npaug li 40% RH.
Sealing tshuab: Ultrasonic vuam tshuab yog siv los xyuas kom meej lub sealing ntawm lub capsule, nrog ib tug to ntawm tsawg tshaj li 0.1%.
Quality Control System: Tag nrho traceability los ntawm raw khoom mus rau cov khoom tiav
GMP Kev Ua Raws Cai
Kev Tshawb Fawb Txog Kev Muag Khoom: Ua rau - kev tshuaj xyuas qhov chaw ntawm cov khoom siv raw khoom tseem ceeb (xws li Jiangsu Alpha thiab Zhejiang Xinhecheng) ib xyoos ib zaug, nrog rau kev tsom mus rau kev soj ntsuam kev tswj xyuas zoo, kev tsim khoom, thiab kev hloov pauv.
Kev tswj cov khoom muag: Kev siv thawj zaug hauv thawj qhov tawm (FIFO), qhov ntsuas kub ntawm cov khoom siv raw yog 2-8 degree, cov av noo tsawg dua lossis sib npaug li 65% RH, thiab lub txee lub neej yog 24 lub hlis.
Kev tswj cov txheej txheem ntau lawm
Kev saib xyuas cov txheej txheem tseem ceeb (CPP):
Sib tsoo siab: 0.5-0.8 MPa
Txau kom qhuav kub: 115-125 degree
Tablet hardness: 80-120 N
Kev kuaj pom hauv online: Nyob ze infrared spectroscopy (NIR) yog siv los saib xyuas kev sib cais hauv lub sijhawm tiag tiag, nrog rau kev tshawb pom ntau zaus ib zaug txhua 15 feeb.
Cov khoom tiav tso tawm cov qauv
| Cov khoom kuaj | Txheem tus nqi | Kev kuaj xyuas txoj kev |
| Cov ntsiab lus tsis sib xws | RSD Tsawg dua lossis sib npaug li 5% | HPLC (USP method) |
| Cov khoom muaj feem xyuam | Ib qho impurity Tsawg dua lossis sib npaug li 0.5%, tag nrho impurity Tsawg dua lossis sib npaug rau 1.5% | HPLC{0}}DAD |
| Microbial txwv | Tag nrho cov kab mob aerobic suav tsawg dua lossis sib npaug li 100 CFU / g | Cov ntsiab cai dav dav ntawm Tshooj Plaub ntawm Suav Pharmocopoeia 2020 Edition |
| Moisture | Tsawg dua lossis sib npaug li 3.0% | Karl Fischer txoj kev |
Kev sib koom ua ke hub mechanism ntawm Flibanserin thiab pyramidal neurons hauv prefrontal cortex
Cov qauv thiab cov yam ntxwv ua haujlwm ntawm pyramidal neurons hauv prefrontal cortex
Lub prefrontal cortex nyob rau hauv lub anterior ib feem ntawm lub hlwb thiab yog ib tug tom qab hloov zuj zuj thiab functionally complex cheeb tsam nyob rau hauv lub cerebral cortex. Cone neurons yog hom tseem ceeb ntawm cov neurons nyob rau hauv prefrontal cortex, nrog ib tug tshwj xeeb morphological qauv. Cov cell lub cev ntawm cov neurons no yog cone - zoo li tus, emitting ib tug tuab apical dendrite uas txuas mus rau saum npoo ntawm lub paj hlwb cortex, thaum muaj ntau basal dendrites tawm sab nraud. Sab saum toj thiab hauv paus dendrites yog them nrog ntau dendritic spines, uas yog qhov chaw tseem ceeb rau kev sib txuas synaptic nrog lwm cov neurons, ua rau pyramidal neurons tau txais cov ntaub ntawv tawm tswv yim los ntawm ntau thaj tsam ntawm lub hlwb.
Cov pyramidal neurons nyob rau hauv lub prefrontal cortex muaj ib tug tshwj xeeb hierarchical faib nyob rau hauv lub cerebral cortex. Muaj qhov sib txawv hauv morphology, kev ua haujlwm, thiab kev sib txuas ntawm cov pyramidal neurons ntawm ntau qib. Piv txwv li, cov pyramidal neurons ntiav yog feem ntau koom nrog hauv kev ua cov ntaub ntawv kev hnov lus, thaum cov pyramidal neurons sib sib zog nqus tau koom nrog ntau txoj haujlwm xws li kev paub txog kev tswj hwm thiab kev txiav txim siab- ua. Cov qauv hierarchical no ua rau lub prefrontal cortex sib xyaw thiab ua cov ntaub ntawv sib txawv.
Kev paub tswj kev ua haujlwm: Cov pyramidal neurons hauv prefrontal cortex ua lub luag haujlwm tseem ceeb hauv kev paub txog kev tswj hwm. Lawv tuaj yeem tswj cov txheej txheem kev txawj ntse xws li kev mloog, kev ua haujlwm nco, thiab kev ua haujlwm. Los ntawm kev cuam tshuam nrog lwm thaj chaw hauv lub hlwb, pyramidal neurons tuaj yeem tshuaj xyuas thiab sib koom ua ke cov ntaub ntawv los ntawm kev hnov lus, lub cev muaj zog, thiab lub cim xeeb, ua rau kev npaj thiab kev koom tes ntawm tus cwj pwm. Piv txwv li, hauv kev ua haujlwm nco, pyramidal neurons tuaj yeem tswj hwm lub xeev ntawm cov ntaub ntawv tseem ceeb rau lub sijhawm luv luv txhawm rau ua cov haujlwm kev txawj ntse tom ntej.
Emotional regulation muaj nuj nqi: Lub prefrontal cortex yog ze ze rau kev tswj kev xav. Cone neurons tuaj yeem cuam tshuam lossis txhim kho kev xav los ntawm kev tswj hwm cov haujlwm ntawm kev xav txog lub hlwb thaj tsam xws li amygdala.
Thaum cov tib neeg ntsib kev ntxhov siab lossis kev xav tsis zoo, pyramidal neurons nyob rau hauv prefrontal cortex tuaj yeem inhibit overactivation ntawm amygdala, yog li txo cov kev xav xws li kev ntxhov siab thiab kev ntshai. Ntawm qhov tsis sib xws, thaum lub luag haujlwm ntawm frontal cortex yog qhov tsis zoo, cov tib neeg yuav muaj kev ntxhov siab, ntxhov siab, thiab kev nyuaj siab.
Kev txiav txim siab ua haujlwm: Cov pyramidal neurons nyob rau hauv prefrontal cortex kuj ua lub luag haujlwm tseem ceeb hauv kev txiav txim siab- txheej txheem. Lawv tuaj yeem sib xyaw cov ntaub ntawv los ntawm ntau lub hlwb, suav nrog cov ntaub ntawv xav tau, cov ntaub ntawv nco, thiab cov ntaub ntawv kev xav, los ntsuas thiab sib piv ntau yam kev xaiv thiab txiav txim siab tsim nyog. Piv txwv li, hauv kev txiav txim siab pheej hmoo- ua haujlwm, pyramidal neurons tuaj yeem kho tus neeg txiav txim siab- ua cov tswv yim raws li cov ntaub ntawv txaus ntshai thiab khoom plig.
Kev sib cuam tshuam mechanism ntawm Flibanserin thiab pyramidal neurons nyob rau hauv prefrontal cortex
Kev tswj ntawm excitability ntawm pyramidal neurons
Lub excitability ntawm pyramidal neurons nyob rau hauv lub prefrontal cortex yog ib qho tseem ceeb rau lawv ib txwm ua hauj lwm. Flibanserin tuaj yeem cuam tshuam qhov excitability ntawm pyramidal neurons los ntawm kev tswj cov neurotransmitter system. Piv txwv li, cov nyhuv excitatory ntawm Flibanserin ntawm 5-HT1A receptors tuaj yeem ua rau muaj kev cuam tshuam ntawm cov pyramidal neurons, yog li txo lawv cov excitability. Ntawm qhov tsis sib xws, cov nyhuv antagonistic ntawm Flibanserin ntawm 5-HT2A receptors tuaj yeem txo qhov inhibition ntawm pyramidal neurons thiab nce lawv cov excitability.
Cov kev cai ntawm dopamine thiab noradrenaline systems kuj cuam tshuam rau excitability ntawm pyramidal neurons. Qhov kev tso tawm ntau ntxiv ntawm dopamine tuaj yeem txhim kho qhov excitability ntawm pyramidal neurons, thaum qhov kev tso tawm ntau ntxiv ntawm norepinephrine tuaj yeem tswj hwm kev ceeb toom thiab qib siab ntawm pyramidal neurons. Flibanserin tuaj yeem hloov kho qhov ua kom muaj zog ntawm pyramidal neurons los ntawm kev tswj cov kab mob neurotransmitter, ua rau lawv ua haujlwm tau zoo hauv cov xeev sib txawv.
Qhov cuam tshuam ntawm neurotransmitter tso tawm thiab rov ua dua
Cov pyramidal neurons nyob rau hauv prefrontal cortex sib txuas lus nrog lwm cov neurons los ntawm kev tso cov neurotransmitters. Flibanserin tuaj yeem cuam tshuam rau kev tso tawm thiab rov tsim cov neurotransmitters hauv pyramidal neurons. Piv txwv li, Flibanserin txoj cai ntawm 5-HT system tuaj yeem cuam tshuam rau kev tso tawm thiab rov ua dua ntawm serotonin hauv pyramidal neurons. Los ntawm kev tswj hwm qib ntawm serotonin, Flibanserin tuaj yeem cuam tshuam cov ntaub ntawv xa mus ntawm pyramidal neurons thiab lwm cov neurons, yog li tswj hwm kev txawj ntse thiab kev tswj hwm kev xav.
Kev tso tawm thiab rov ua cov txheej txheem ntawm dopamine thiab norepinephrine kuj tseem tuaj yeem cuam tshuam los ntawm Flibanserin. Flibanserin tuaj yeem hloov pauv cov neurotransmitter ib puag ncig ntawm pyramidal neurons los ntawm kev tswj cov kev tso tawm thiab rov ua dua ntawm cov neurotransmitters, yog li cuam tshuam rau lawv cov haujlwm ua haujlwm. Piv txwv li, nce qhov tso tawm ntawm dopamine thiab txo nws cov reuptake tuaj yeem ncua lub sijhawm ua haujlwm ntawm dopamine hauv synaptic cleft thiab txhim kho nws cov kev tswj hwm ntawm pyramidal neurons.
Qhov cuam tshuam rau neural plasticity
Neuroplasticity yog hais txog lub peev xwm ntawm lub paj hlwb kom hloov mus rau ib puag ncig kev hloov pauv hauv cov qauv thiab kev ua haujlwm. Cov pyramidal neurons nyob rau hauv lub prefrontal cortex muaj siab neural plasticity, uas yog ib qho tseem ceeb heev rau txoj kev loj hlob ntawm kev kawm, nco, thiab kev txawj ntse ua hauj lwm. Flibanserin tuaj yeem txhawb nqa neural plasticity los ntawm kev tswj cov kab mob neurotransmitter thiab cuam tshuam rau kev ua haujlwm ntawm pyramidal neurons.
Piv txwv li, Flibanserin txoj cai ntawm dopamine system tuaj yeem cuam tshuam cov txheej txheem neuroplasticity xws li ntev -lub sij hawm potentiation (LTP) thiab ntev -lub sij hawm kev nyuaj siab (LTD). LTP thiab LTD yog cov txheej txheem tseem ceeb rau kev hloov pauv hauv synaptic kev sib txuas lub zog ntawm cov neurons, thiab lawv ua lub luag haujlwm tseem ceeb hauv kev kawm thiab kev nco. Flibanserin tuaj yeem txhim kho kev sib txuas synaptic ntawm pyramidal neurons thiab txhim kho kev txawj ntse hauv prefrontal cortex los ntawm kev txhawb nqa LTP lossis inhibiting LTD.
Cim npe nrov: flibanserin capsule, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom