Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm nicotinamide riboside nasal spray hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo zoo nicotinamide riboside nasal spray rau muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Nicotinamide Riboside Nasal Sprayyog cov tshuaj los yog cov khoom kho mob uas xa cov Nicotinamide Riboside (NR) hauv daim ntawv ntawm cov tshuaj tsuag qhov ntswg. Nws qhov zoo dua yog nyob rau hauv cov hlab ntsha uas muaj ntau nyob rau hauv lub qhov ntswg mucosa, tso cai rau cov tshuaj nkag mus rau hauv cov hlab ntsha ncaj qha, bypassing thawj cov nyhuv (qhov ncauj tshuaj yuav tsum tau metabolized los ntawm lub siab), thiab txhim kho bioavailability. Tej zaum yuav ua ncaj qha rau ntawm lub hlwb (los ntawm txoj kev olfactory paj hlwb) thiab tej zaum yuav siv tau raws li ib tug adjuvant therapy rau neurodegenerative kab mob xws li Alzheimer's kab mob. Nyob rau tib lub sijhawm, nws kuj muaj kev yooj yim thiab tsis tas yuav tsum tau txhaj tshuaj lossis kev tswj xyuas qhov ncauj, ua rau nws tsim nyog rau cov xwm txheej uas nqos tau yooj yim lossis yuav tsum tau ua sai.
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Nicotinamide Riboside Chloride COA
Keeb kwm ntawm no nas tsuag tsuag nyob rau hauv kev kho mob ntawm neurological kab mob
Nicotinamide Riboside (NR), raws li ib tug derivative ntawm vitamin B3, tau sai heev los ua ib tug kev tshawb fawb hotspot nyob rau hauv lub teb ntawm anti- kev laus thiab metabolic noj qab haus huv txij li thaum nws nrhiav tau nyob rau hauv thaum ntxov 21st caug xyoo uas nws muaj peev xwm ho nce intracellular theem ntawm nicotinamide adenine dinucleotide (NAD+). NAD + yog ib qho tseem ceeb coenzyme koom nrog hauv mitochondrial zog metabolism, kho DNA, thiab cov teeb liab ntawm tes. Nws qib txo qis thaum muaj hnub nyoog thiab muaj feem cuam tshuam nrog cov kab mob neurodegenerative, metabolic syndrome, thiab lwm yam mob. Txawm hais tias qhov ncauj NR tau pom qee qhov muaj peev xwm tiv thaiv neuroprotective, nws qhov tsis muaj bioavailability thiab qhov cuam tshuam thawj zaug tseem ceeb txwv nws cov concentration hauv lub hlwb. Nyob rau hauv xyoo tas los no,Nicotinamide Riboside Nasal Spray(NR tshuaj tsuag qhov ntswg), raws li txoj kev xa tawm tshiab, yog ncaj qha absorbed los ntawm qhov ntswg mucosa thiab bypasses daim siab metabolism, muab lub tswv yim tshiab rau kev kho mob ntawm neurological kab mob.
Kev tshawb pom ntawm NR thiab lub hauv paus lom neeg ntawm NAD + metabolism
Chemical Essence thiab Discovery Process ntawm NR
NR yog ib txwm tshwm sim pyridine nucleotide uas yog thawj zaug cais tawm ntawm cov mis nyuj hauv xyoo 1940, tab sis nws tsis yog txog xyoo 2004 uas Charles Brenner pab pawg thawj zaug tau nthuav tawm nws txoj haujlwm ua ntej rau NAD+. Kev tshawb fawb tau pom tias NR tuaj yeem raug phosphorylated thiab hloov mus rau hauv nicotinamide mononucleotide ntxiv (NMN), tom qab ntawd tuaj yeem hloov mus rau hauv nicotinamide mononucleotide. NAD+. Nws nthuav tawm cov txiaj ntsig NAD + txhim kho muaj peev xwm hauv ob qho tib si poov xab thiab tsiaj txhu. Qhov kev tshawb pom no tau qhib txoj hauv kev tshiab rau kev tiv thaiv - kev tshawb fawb txog kev laus.
Lub luag haujlwm tseem ceeb ntawm NAD + hauv lub paj hlwb
NAD + ua si ntau lub luag haujlwm hauv lub paj hlwb:
Lub zog metabolism: Raws li ib qho tseem ceeb coenzyme nyob rau hauv lub mitochondrial tricarboxylic acid voj voog thiab oxidative phosphorylation, nws tswj neuronal zog mov;
Kev kho DNA: Koom nrog hauv DNA kev puas tsuaj kho thiab kev tswj hwm epigenetic los ntawm poly (ADP ribose polymerase) (PARP) thiab sirtuins tsev neeg cov proteins (xws li SIRT1-3);
Calcium signaling: regulating neuronal excitability thiab synaptic plasticity;
Oxidative stress resistance: Ua kom cov superoxide dismutase (SOD) los ntawm SIRT3 txo cov neuronal oxidative puas.
Qib ntawm NAD + hauv lub hlwb cov ntaub so ntswg ntawm cov neeg mob uas muaj kab mob neurodegenerative xws li Alzheimer's kab mob thiab Parkinson tus kab mob tau txo qis, qhia tias ntxiv NAD + precursors yuav muaj peev xwm kho tau.
Kev tshawb nrhiav neuroprotective ntawm qhov ncauj NR: kev tshawb nrhiav ua ntej los ntawm kev kuaj mus rau kev siv tshuaj kho mob
Kev ua tau zoo validation nyob rau hauv cov qauv tsiaj
Alzheimer's disease (AD): Hauv xyoo 2013, pab pawg MIT pom nyob rau hauv APP/PS1 transgenic nas qauv uas qhov ncauj NR tuaj yeem txo - amyloid (A) deposition thiab txhim kho kev txawj ntse, uas muaj feem xyuam rau SIRT1 activation thiab neuroinflammation inhibition.
Parkinson's disease (PD): Hauv xyoo 2016, kev tshawb fawb los ntawm Johns Hopkins University tau qhia tias NR tuaj yeem tiv thaiv dopaminergic neurons los ntawm MPTP toxin induced degeneration los ntawm kev txhim kho mitochondrial muaj nuj nqi los ntawm kev nce NAD + thiab SIRT3 qhia.
Cerebral ischemia / reperfusion raug mob: Hauv xyoo 2018, Suav cov kws tshawb fawb tau tshaj tawm tias NR pretreatment tuaj yeem txo qhov ntim ntawm cerebral infarction hauv nas, inhibit neuronal apoptosis, thiab nws cov nyhuv yog nyob ntawm SIRT1 / PGC-1 txoj hauv kev.
Cov txiaj ntsig ua ntej ntawm Human Clinical Trials
Kev nyab xeeb thiab kam rau ua: Ntau theem I sim tau lees paub tias qhov ncauj NR (250-1000 mg / hnub) muaj kev nyab xeeb rau cov neeg tuaj yeem noj qab haus huv thiab tsuas yog ua rau mob plab tsis zoo.
Kev paub txog kev ua haujlwm cuam tshuam: Hauv xyoo 2018, ob - qhov muag tsis pom kev sim tsom rau cov neeg mob uas muaj kev paub tsis meej me me (MCI) pom tias 12 lub lis piam ntawm NR ntxiv (500 mg / hnub) tsis tau txhim kho cov qhab nia kev txawj ntse, tab sis nce qib ntawm NAD + metabolites hauv cerebrospinal fluidment lub hom phiaj.
Kab mob neuron lub cev muaj zog: Hauv xyoo 2020, kev sim theem II (NCT03489169) rau amyotrophic lateral sclerosis (ALS) raug txiav tawm ntxov ntxov vim qhov ua tau zoo tsis txaus, qhia txog cov kev txwv ntawm qhov ncauj NR hauv kev nkag mus rau cov ntshav - hlwb barrier (BBB).
Yug ntawm NR tshuaj tsuag qhov ntswg: los ntawm ntau npaum li cas daim ntawv tshiab rau paj hlwb xa
Cov txiaj ntsig zoo ntawm qhov ntswg qhov ntswg
Tag nrho thaj tsam ntawm qhov ntswg mucosa yog li 160 cm ², nrog cov hlab ntsha ntau thiab kev sib txuas ncaj qha rau lub hlwb (los ntawm txoj kev olfactory thiab trigeminal hlab ntsha). Nws muaj cov yam ntxwv hauv qab no:
Bypassing thawj qhov tshwm sim: cov tshuaj nkag mus rau hauv cov kab mob ncaj qha, thiab lawv cov bioavailability yog 3-5 npaug ntau dua li kev tswj hwm qhov ncauj;
Kev pib sai: Ib nrab- lub neej ntawm qhov ntswg nqus yog li 15-30 feeb, tsim nyog rau kev cuam tshuam rau cov hlab ntsha raug mob (xws li mob stroke);
Lub hom phiaj ntawm lub hlwb: Qee cov tshuaj tuaj yeem thauj mus rau qhov muag olfactory thiab cerebral cortex los ntawm olfactory paj hlwb axons, txo cov kev raug mob.
Kev txhim kho keeb kwm ntawm NR nasal spray
Kev sim thaum ntxov: Xyoo 2015, Swiss lub tuam txhab Chromatex thawj zaug thov rau patent rau NR qhov ntswg xa (US20150320742A1), thov kom muab NR nrog rau kev nkag mus (xws li cyclodextrin) los txhim kho mucosal permeability.
Kev ua kom zoo ntawm cov qauv: Xyoo 2018, pab pawg MIT tau tshaj tawm txoj kev tshawb fawb hauv Nature Communications, uas tau npaj NR nanoparticles siv cov tshuab microfluidic thiab ua ke nrog cov kua ntsev ua kom haum, ua rau 8-fold nce hauv NAD + qib hauv lub hlwb tom qab kev tswj qhov ntswg hauv nas piv rau kev tswj hwm qhov ncauj.
Kev kuaj mob ua ntej: Hauv 2020, pab pawg ntawm University of California tau ua qauv qhia hauv AD nas qauv uasNicotinamide Riboside Nasal Spray(100 mg / kg / hnub) tuaj yeem txo cov quav hniav thiab txhim kho kev nco, thiab nws cov txiaj ntsig zoo dua li qhov sib npaug ntawm qhov ncauj NR.
Kev tshawb fawb soj ntsuam kev nce qib ntawm NR nasal spray nyob rau hauv cov kab mob neurological
Alzheimer's disease: los ntawm kev paub txog kev txhim kho mus rau kev hloov kho kab mob
Theem I kev nyab xeeb xeem: Xyoo 2021, pab pawg Australian ua tiav thawj theem kuv xeem (NCT04504669) ntawmNicotinamide Riboside Nasal Spray(250 mg / zaug, ob zaug ib hnub) rau cov neeg laus noj qab nyob zoo. Cov txiaj ntsig tau pom tias kev ua siab ntev ntawm cov tshuaj tau zoo, tsis muaj qhov tshwm sim tsis zoo tshwm sim, thiab lub sijhawm ua kom ntshav siab tshaj plaws (Tmax) yog 30 feeb, nrawm dua qhov ncauj (1-2 teev).
Kev Tshawb Fawb Txog Phase IIa Kev Ua Tau Zoo: Hauv 2023, Biogen, lub tuam txhab Asmeskas, tshaj tawm cov txiaj ntsig ua ntej ntawm Phase IIa sim (NCT04914613) rau cov neeg mob AD thaum ntxov. Tom qab 12 lub lis piam sib law liag ntawm kev tswj qhov ntswg, qhov sib piv A 42/40 hauv cov kua cerebrospinal ntawm cov neeg mob tau nce ntxiv (p=0.03), qhia txog qhov txo qis hauv A deposition; Txawm li cas los xij, qhov kev txhim kho hauv MMSE cov qhab nia tsis ncav cuag qhov tseem ceeb (p=0.07), uas tej zaum yuav cuam tshuam rau cov qauv me me (n=45).
Parkinson tus kab mob: kev tiv thaiv mitochondrial thiab alleviation ntawm lub cev muaj zog cov tsos mob
Tsiaj qauv validation: Nyob rau hauv 2022, lub Karolinska lub koom haum nyob rau hauv Sweden tau qhia tias NR tshuaj tsuag qhov ntswg yuav rov qab tau cov dopaminergic neurons nyob rau hauv lub substantia nigra ntawm MPTP induced PD nas thiab txhim kho lub cev muaj zog kev sib koom tes. Cov txheej txheem tau cuam tshuam nrog kev txhim kho ntawm mitochondrial autophagy mediated los ntawm SIRT3.
Kev hloov pauv ntawm kev kho mob mus rau qhov chaw kho mob: Xyoo 2023, Tuam Tshoj yuav tshaj tawm qhov kev sim theem II (NCT05876543) rau cov neeg mob PD thaum ntxov, uas yuav tau kho nrog NR qhov ntswg tsuag (500 mg / hnub) ua ke nrog levodopa. Lub ntsiab lus kawg yog qhov kev hloov pauv ntawm qhov qhab nia ntawm ntu III ntawm Unified Parkinson's Disease Rating Scale (UPDRS), uas xav kom ua tiav hauv 2025.
Mob stroke cuam tshuam: neuroprotection thiab ua haujlwm rov qab
Ischemic stroke: Hauv xyoo 2021, ib pab neeg German pom nyob rau hauv tus qauv nas ntawm nruab nrab cerebral artery occlusion (MCAO) uas qhov ntswg tswj ntawm NR (50 mg / kg) 2 teev tom qab mob stroke tuaj yeem txo qhov ntim ntawm 40%, txhawb kev tsim cov hlab ntsha, thiab nws cov txiaj ntsig yog nyob ntawm SIRT1 / VEGF txoj hauv kev.
Kev sib tw kev txhais lus kho mob: Txawm hais tias cov ntaub ntawv tsiaj zoo, qhov ua tau ntawm kev tswj hwm intranasal tom qab mob stroke hauv tib neeg tseem yuav tsum tau lees paub. Xyoo 2023, US StrokeNet network yuav tshaj tawm theem II mus sib hais (NCT05689121) los ntsuas kev nyab xeeb thiab kev pom zoo lub sijhawm ua haujlwm ntawm NR qhov ntswg tshuaj tsuag rau cov neeg mob uas mob stroke ischemic.
Kev sib tw thiab kev tsis sib haum xeeb: Qhov sib txawv ntawm chav kuaj mus rau kev xyaum kho mob
Bioaccumulation thiab tus kheej sib txawv
Kev txwv qhov ntswg mucosal: NR muaj qhov hnyav molecular (255.23 g / mol) thiab nqa cov pawg polar. Tej yam ntuj tso mucosal permeability yog tsawg thiab tso siab rau kev nkag mus rau enhancers, uas yuav ua rau qhov ntswg irritation (xws li kub hnyiab tau).
Metabolic enzyme polymorphism: Cov metabolism hauv NR hauv vivo nyob ntawm lub plab microbiota thiab daim siab enzymes (xws li CD38, NUDT12), nrog rau cov neeg sib txawv tseem ceeb uas yuav cuam tshuam rau kev kho mob.
Lub sij hawm ntev kev nyab xeeb thiab tawm lub hom phiaj cuam tshuam
Kev pheej hmoo ntawm NAD + overload: Lub sij hawm ntev siab - koob tshuaj NR ntxiv tuaj yeem ua rau ntau dhau ntawm NAD + los ntawm kev ua kom PARP lossis CD38, uas ua rau muaj kev ntxhov siab ntawm tes.
Kev tiv thaiv kab mob tsis sib haum xeeb: Xyoo 2022, Cell tau tshaj tawm tias NR tuaj yeem txhawb CD38 kev qhia hauv cov qog hlwb, txhim kho cov kab mob tiv thaiv kab mob microenvironment, thiab ceeb toom cov neeg mob qog noj ntshav kom siv ceev faj.
Qhov tsis xws luag hauv Clinical Research Design
Cov qauv tsis txaus: Feem ntau cov kev sim thaum ntxov suav nrog tsawg dua 50 tus neeg mob, ua rau nws nyuaj rau kev kuaj xyuas me me tab sis kev kho mob tseem ceeb.
Qhov kawg xaiv qhov kev tsis ncaj ncees: AD cov kev sim siab feem ntau yog qhov tseem ceeb ntawm cov qhab nia kev txawj ntse, thaum PD thiab mob stroke tsom ntau dua rau lub cev muaj zog thiab tsis muaj kev sib koom ua ke ntau qhov kev ntsuam xyuas.
Nicotinamide Riboside (NR), raws li ib daim ntawv tshiab ntawm vitamin B3, tau dhau los ua ntau theem ntawm kev tshawb fawb txij li thaum nws nrhiav tau nyob rau hauv nruab nrab-20th caug xyoo, los ntawm kev tshawb fawb yooj yim mus rau kev kho mob daim ntawv thov kev txhais lus. Kev yug me nyuam ntawm NR tshuaj tsuag qhov ntswg yog cov khoom siv thev naus laus zis thiab kev xav tau tsav hauv daim teb no.
Qhov kev tshawb pom ntawm NR tuaj yeem tshawb pom rov qab mus rau xyoo 1944, thaum cov kws tshawb fawb Asmeskas kawm Haemophilus influenzae pom tias cov kab mob no tsis tuaj yeem siv cov vitamin B3 uas paub ua ntej xws li niacin thiab nicotinamide, tab sis tuaj yeem tau txais cov khoom noj tsim nyog rau kev loj hlob los ntawm qee yam khoom tawm los ntawm cov ntshav. Tom qab ua kom huv ntxiv, cov kws tshawb fawb tau txheeb xyuas peb yam khoom siv: NAD + (nicotinamide adenine dinucleotide), NMN (nicotinamide mononucleotide), thiab NR. Ntawm lawv, NR tau lees paub tias yog daim ntawv zoo tshaj plaws los txhawb kev loj hlob ntawm cov kab mob, tso lub hauv paus rau kev kawm txog nws txoj haujlwm lom neeg.
Nrog rau kev sib sib zog nqus ntawm kev tshawb fawb ntawm vitamin B3 (niacin), cov kws tshawb fawb tau maj mam nthuav tawm nws txoj kev metabolic hauv tib neeg lub cev. Vitamin B3 koom nrog hauv cov txheej txheem tseem ceeb xws li cellular zog metabolism, kho DNA, thiab cov teeb liab hloov los ntawm kev hloov mus rau nicotinamide mononucleotide (NMN) thiab ntxiv synthesizing NAD+. Txawm li cas los xij, cov tshuaj vitamin B3 ib txwm (xws li niacin) muaj cov kev mob tshwm sim (xws li tawv nqaij flushing) thiab txwv bioavailability rau kev tshawb fawb ntau dua. NAD + precursors.
Xyoo 2004, Xib Fwb Charles Brenner pab neeg ntawm Dartmouth Medical School tau tshawb pom los ntawm kev tshuaj ntsuam genomic uas NR tuaj yeem hloov mus rau NAD + los ntawm txoj hauv kev tshwj xeeb hauv metabolic. Tshwj xeeb, NR yog phosphorylated los ntawm nicotinamide ribose kinase (NRK) rau NMN hauv hlwb, ua raws li kev sib txuas ntawm NAD + los ntawm NMN adenosyltransferase (NMNAT). Qhov kev tshawb pom no tawg los ntawm cov kev txwv ntawm ib txwm muaj vitamin B3 metabolic txoj hauv kev thiab muab lub hauv paus theoretical rau daim ntawv thov NR ua NAD + ntxiv. Xib Fwb Brenner txoj kev tshawb fawb kuj tau lees paub tias NR tuaj yeem nce qib NAD + hauv ob qho tib si poov xab thiab mammalian hlwb, nrog tsawg dua kev phiv.
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