Acetyl Hexapeptide

1. Lub hauv paus ua rau wrinkle tsim: "sib nqus saw" ntawm neuromuscular junctions
Yuav kom nkag siab txog cov txheej txheem ntawm kev txiav txim, nws yog thawj zaug uas yuav tsum tau ua kom meej meej yuav ua li cas wrinkles, tshwj xeeb tshaj yog cov kab dynamic (kab lus qhia), yog tsim.
Muaj ntau tshaj 40 lub ntsej muag nqaij hauv tib neeg lub cev, thiab thaum twg peb luag nyav, frown, los yog ntsais muag, lub hlwb xa ib tug "contraction" hais kom ua rau lub ntsej muag nqaij los ntawm lub cev muaj zog neurons. Cov txheej txheem kis tau tus mob ntawm cov lus qhia no yog nyob ntawm tus neeg xa xov chemical tseem ceeb - acetylcholine (ACh).

Cov txheej txheem tshwj xeeb yog raws li hauv qab no:
Kauj Ruam 1: Cov hlab ntsha impulse ncav cuag cov paj hlwb. Thaum lub paj hlwb xa tawm "frown" teeb liab, cov teeb liab hluav taws xob tau xa mus raws li lub cev muaj zog paj hlwb mus rau presynaptic membrane ntawm neuromuscular hlws ris.
Kauj Ruam 2: Calcium ion influx ua rau vesicle fusion. Lub teeb liab hluav taws xob qhib qhov hluav taws xob -gated calcium ion channel, thiab Ca ² ⁺ rushes mus rau hauv lub paj hlwb. Kev nkag mus ntawm calcium ions yog "ignition switch" rau tag nrho cov txheej txheem tso tawm.
Kauj Ruam 3: SNARE complex sib dhos, vesicles tso acetylcholine. Qhov no yog cov kauj ruam tseem ceeb tshaj plaws - synaptic vesicles uas muaj acetylcholine yuav tsum tau fuse nrog presynaptic membrane thiaj li "pom" acetylcholine mus rau hauv lub synaptic cleft.

Thiab cov txheej txheem fusion no tso siab rau lub tshuab molecular hu ua SNARE protein complex.

Kauj Ruam 4: Acetylcholine khi rau cov leeg nqaij thiab ua rau cov leeg nqaij. Acetylcholine dhau los ntawm synaptic cleft thiab khi rau receptors ntawm cov leeg nqaij daim nyias nyias, ua rau cov leeg nqaij fiber ntau contraction - yog li, wrinkles yog tsim. Ib hnub dhau ib hnub, ib xyoos dhau ib xyoos, rov ua cov leeg nqaij hlav tawm tsis pom cov cim ntawm daim tawv nqaij.
Los ntawm qhov no, nws tuaj yeem pom tias SNARE complex yog "tus tswv hloov" rau kev tsim wrinkle. Leej twg tuaj yeem tswj tau qhov hloov pauv no tuaj yeem tswj cov cim ntawm wrinkles.

2. Core mechanism: Sib tw inhibition ntawm SNARE complexes
2.1. Kev sib xyaw thiab kev ua haujlwm ntawm SNARE complex
Lub SNARE complex muaj peb core proteins:
SNAP-25 (Synaptosome Associated Protein-25): nyob rau ntawm lub presynaptic membrane, nws yog "anchoring scaffold" ntawm lub complex;
Syntaxin (synaptic fusion protein): kuj nyob rau ntawm lub presynaptic membrane, nws tsim t-SNARE ua ke nrog SNAP-25;
VAMP (vesicle txuam membrane protein, tseem hu ua synaptobrevin): nyob rau ntawm lub synaptic vesicle membrane, nws ua v-SNARE.

Thaum neural impulses tuaj txog, v-SNARE (VAMP) thiab t-SNARE (SNAP-25+Syntaxin) nruj nreem qhwv thiab sib sau ua ke zoo li zippers, ua kom ruaj khov plaub helix bundle qauv - qhov no yog SNARE complex. Qhov tsim ntawm qhov complex no ua rau muaj kev ntxhov siab heev, rub lub vesicle membrane los ze zog thiab fusing nrog presynaptic membrane, thaum kawg tso acetylcholine.
Txhawm rau muab qhov zoo sib xws, SNARE complex yog zoo li "molecular zipper". Thaum lub zipper kaw, cov hlab ntsha qhib, acetylcholine nchuav tawm, cov leeg nqaij daim ntawv cog lus, thiab daim ntawv wrinkles.

2.2. Acetyl hexapeptide"Disguise Technique": Simulating N-terminus ntawm SNAP-25
Nws cov amino acid ib ntus - Ac Glu Glu Met Gln Arg Arg NH ₂ - tsis yog tsim los, tab sis raug ua raws li rau 6 amino acid fragments ntawm N-terminus ntawm SNAP-25 protein. Qhov no yog lub hauv paus ntawm tag nrho cov mechanism ntawm kev ua.
N-qhov kawg ntawm SNAP-25 yog ib cheeb tsam tseem ceeb koom nrog hauv kev sib sau ua ke ntawm SNARE complexes. Raws li 'molecular forgery', nqa cov qauv zoo ib yam li N-terminus ntawm SNAP-25, infiltrating paj hlwb xaus thiab sib tw nrog SNAP-25 los khi rau tib qhov chaw hauv SNARE complex.

3. Kev sib tw ua ke: maj mam thiab meej "pob foob pob"
Thaum nws nyob hauv qhov chaw sib khi uas yuav tsum tau nyob los ntawm N- qhov kawg ntawm SNAP-25, kev sib dhos ntawm SNARE complexes cuam tshuam:
Cov qauv ntawm cov khoom sib xyaw ua tsis tiav;
Lub fusion efficiency ntawm vesicles thiab presynaptic membranes txo qis;
Kev tso tawm ntawm acetylcholine txo qis heev - tab sis tsis thaiv tag nrho.
Qhov no yog nws qhov kev txawj ntse tshaj plaws: nws tsis yog hais txog "tua tawm" qhov hloov pauv, tab sis hais txog "txo" qhov rhiab heev ntawm qhov hloov.

Kev tso tawm ntawm acetylcholine tsis muaj zog, thiab qhov kev siv ntawm cov leeg nqaij contraction txo qis raws li. Cov leeg nqaij ntawm lub ntsej muag tsis yog "ntev", thiab cov kab dynamic maj mam flatten tawm los ntawm kev so maj mam hnub dhau hnub.

Hais lus nrog cov ntaub ntawv: Hauv ob qho - qhov muag tsis pom kev sim nrog 20 tus poj niam noj qab haus huv Asmeskas cov neeg ua haujlwm pab dawb, siv cov roj hauv cov tshuaj pleev dej uas muaj Aquirelin ob zaug hauv ib hnub txo qis qhov tob ntawm 17% tom qab 15 hnub thiab 30% tom qab 30 hnub; Hauv lwm qhov kev sim qhib lub hom phiaj orbital wrinkles, 10 tus poj niam thov Akirelin cream ob zaug ib hnub, thiab tom qab 30 hnub, cov tawv nqaij periorbital tau txhim kho los ntawm 27%.

Kev tshawb fawb ntxiv tau pom tias ntawm qhov tshwj xeeb, qhov tob ntawm qhov quav tuaj yeem txo los ntawm 59% mus rau 71%, thiab qhov loj me tuaj yeem txo los ntawm 41% mus rau 50%.
Cov ntaub ntawv no eloquently qhia tau hais tias nws cov kev sib tw inhibition mechanism tsis yog ib tug theoretical speculation, tab sis ib tug scientific qhov tseeb uas tau rigorously clinically validated.

4. Kev sib piv nrog botulinum toxin: 'kev hloov maj mam hloov' nrog txoj kev sib txawv ua rau tib lub hom phiaj
Kev nkag siab txog cov tshuaj no yuav tsum tau hais txog nws cov qauv '- Botulinum toxin type A.

Lub hom phiaj ntawm ob qho tib si zoo ib yam, ob qho tib si yog SNARE complexes, tab sis lawv cov qauv kev ua haujlwm yog qhov sib txawv. Botulinum toxin yog "molecular txiab" uas ncaj qha cleaves SNAP-25 protein, nrog tam sim ntawd tab sis irreversible cuam tshuam, thiab muaj kev pheej hmoo ntawm cov leeg nqaij leeg ntau dhau ua rau "facial tuag tes tuag taw". Akirelin, ntawm qhov tod tes, yog "molecular spacer" uas tsis ua rau muaj protein ntau, tab sis maj mam nyob ntawm qhov chaw thiab ua kom tsis muaj zog ntawm qhov chaw. Nws cov nyhuv yog maj mam tab sis muaj kev nyab xeeb thiab tswj tau.

Raws li qhov tshwm sim, cov tshuaj no tau qhuas tias yog "kev nyab xeeb dua, pheej yig dua, thiab lwm txoj hauv kev rau botulinum toxin" thiab tau dhau los ua thawj qhov kev xaiv rau cov neeg siv khoom suav tsis txheeb uas tsis kam txhaj tshuaj tab sis xav tau tshuaj tiv thaiv kab mob.

5. Tshaj li wrinkle kuj: collagen remodeling thiab elastin ua kom
Lub mechanism ntawm kev txiav txim tsis txwv rau neurotransmitter inhibition ib leeg. Cov kev tshawb fawb tsis ntev los no tau qhia tias nws tseem muaj "thib ob sib ntaus sib tua" - txhawb nqa cov tawv nqaij matrix rov tsim kho.
Wang Yun et al. los ntawm Lub Tsev Kho Mob Thib Ob ntawm Xi'an Jiaotong University tau kho cov laus qauv nas nrog cov tshuaj Ajirelin, thiab cov txiaj ntsig tau zoo siab: txhua tus nas tau kho rau rau lub lis piam muaj sia nyob yam tsis muaj kev phiv.

Daim tawv nqaij seem staining pom tau tiasacetyl hexapeptideCov pab pawg kho mob muaj cov tawv nqaij tuab, ntau dua collagen fibers, thiab denser collagen fibers. Cov tawv nqaij ntawm cov nas laus ib txwm yog nyias thiab xoob, thaum daim tawv nqaij ntawm pab pawg Akirelin qhia txog kev ua hluas thiab nruj.

Qhov no qhia tau hais tias nws muaj peev xwm tsis tsuas "so cov leeg nqaij thiab txo cov wrinkles", tab sis kuj reorganize lub collagen elastic network, ua rau kom cov kev ua ntawm elastin, thiab txhim kho daim tawv nqaij zoo ntawm cov txheej txheem ntawm lub dermis txheej. Lub mechanism yuav muaj feem xyuam rau cov hauv qab no:

Txo cov neeg kho tshuab kev nyuaj siab rau collagen: Tom qab cov leeg nqaij contraction tsis muaj zog, rov qab txhua yam rub tawm ntawm cov dermis txheej txo, thiab collagen fibers tsis dhau stretched los yog tawg;
Kev ua kom cov fibroblasts: Kev tswj cov teeb liab me me tuaj yeem cuam tshuam ncaj qha rau fibroblast synthesis ntawm cov collagen tshiab thiab elastin;
Txhim kho microcirculation: Qhov txo qis ntawm kev tso tawm neurotransmitter tuaj yeem txhim kho cov ntshav ncig hauv zos thiab muab cov khoom noj kom txaus rau daim tawv nqaij.

6. Kev Txawj Ntse ntawm Kev Tsim Molecular: Vim Li Cas Hexapeptide?
Qhov laj thawj ntawm kev xaiv rau 6 amino acids tsis yog qhov yuam kev. Lub N-terminus ntawm SNAP-25 muaj 206 amino acids, tab sis thaj chaw tseem ceeb koom nrog kev sib sau ua ke ntawm SNARE complexes nyob rau hauv thawj 9 amino acids ntawm N-terminus. Rau ntawm cov ntsiab lus tseem ceeb tshaj plaws (Glu Glu Met Gln Arg Arg) tau muab rho tawm, thiab ib pawg acetyl (Ac -) ​​tau ntxiv rau N-terminus los txhim kho kev ruaj ntseg thiab lipophilicity, thaum ib pab pawg amide (- NH ₂) tau ntxiv rau C-terminus peptides.

Lub tswv yim tsim ntawm "tsawg kawg ua haujlwm zoo" muab nws cov txiaj ntsig hauv qab no:

Qhov hnyav molecular tsuas yog hais txog 889 Da, deb ntawm qhov tsis sib haum xeeb ntawm 500 Da rau transdermal absorption. Txawm li cas los xij, nws qhov hnyav me me thiab lipophilicity tau txais txiaj ntsig los ntawm acetyl kawg muab nws qee qhov kev nkag mus ntawm daim tawv nqaij muaj peev xwm;
Tsis yooj yim degraded los ntawm cov proteases zoo tib yam thiab muaj sijhawm txaus rau ntawm daim tawv nqaij;
Nrog rau cov dej zoo solubility, nws yog ib qho yooj yim los npaj cov tshuaj pleev ib ce, essence kua, lub ntsej muag daim npog qhov ncauj thiab lwm yam ntau npaum cov ntaub ntawv;
Chemically ruaj khov, nws tswj kev ua haujlwm nyob rau hauv nruab nrab rau me ntsis acidic ib puag ncig (pH 4.43 ± 0.10) thiab tuaj yeem khaws cia rau lub sijhawm ntev hauv qhov kub thiab txias hauv qhov tsaus ntuj.

Txoj kev tshawb no kuj pom tias cyclic peptides muaj kev tiv thaiv wrinkle zoo dua thiab tiv thaiv - cov teebmeem kev laus piv rau linear peptides, uas taw qhia txoj hauv kev rau yav tom ntej molecular optimization.

Kev sib koom tes ua haujlwm: "golden ua ke" ntawm ntau- phiaj los tiv thaiv wrinkle
Hauv kev siv tswv yim, cov tshuaj no tsis tshua ua haujlwm ib leeg. Nws feem ntau yog siv ua ke nrog lwm cov peptides ua haujlwm los tsim ntau yam - phiaj los tiv thaiv wrinkle regimen:

Palmitoyl Pentapeptide-4: nkoos collagen synthesis, tsim ib tug zoo meej ntxiv rau Akirelin "cov leeg nqaij so + collagen txhawb";
Tripeptide-1 Copper (GHK Cu): Txhawb kev kho qhov txhab thiab kho daim tawv nqaij, txhim kho cov ntaub so ntswg reconstruction ntawm Ajirelin;
Palmitoyl tripeptide-1 thiab Palmitoyl tripeptide-5: Cov teeb liab peptides uas qhib fibroblasts thiab tsim ib qho kev cai ob ntawm "sab sauv + downstream" nrog rau cov kev tiv thaiv neuroprotective ntawm Akirin.
Qhov no peb hauv ib lub tswv yim ntawm "neural inhibition + collagen regeneration + cell kho" qhia tau zoo heev los ntawmacetyl hexapeptidekho qhov muag, caj dab tiv thaiv- laus, thiab tes rejuvenation.