procapıl - Are İlaç

(VDVDODELOHFH÷LQL]\HQLOLN™
Procapil™
Türkçe
PROCAPIL™
ÖZET
$oÕNODPD d|]HOWLLoHULVLQGHWDPDPOD\ÕFÕDNWLIPDGGHNRPELQDV\RQX
,1&, DGÕ: Butylene Glycol (ve) Water (Aqua) (ve) PPG-26-Buteth-26 (ve)
PEG-40 Hydrogenated Castor Oil (ve) Apigenin (ve)
Oleanolic Acid (ve) Biotinoyl Tripeptide-1
Objektif olarak gösterilen dermokozmetik aktivite:
ƒ
In vitro oDOÕúPDODU
• Peptitbiyotinil-GHK
QÕQVDoIROLNO]HULQGHNLYDUOÕ÷ÕoDOÕúPDVÕ%,2$/7(51$7,9(6oDOÕúPDVÕ
• .OWUOHQPLúVDoIROLNOOHUL]HULQGH\DúODQPD\ÕJHFLNWLUPHoDOÕúPDVÕ
(BIO-(&oDOÕúPDVÕ
2 ppm biyotinil-GHK (yani, %1 PROCAPIL™ YDUOÕ÷ÕQGD SSP
—0 0LQR[LGLOŠ YDUOÕ÷ÕQGD RODQD EHQ]HU úHNLOGH kontrolde
ROGX÷XQGDQGDKDVWQELUE\PHHOGHHGLOPLúWLUSSP
biyotinil-GHK (yani, %2.5 PROCAPIL™) ile büyüme kontrolde
ROGX÷XQGDQGDKDID]ODROPXúWXU
• PROCAPIL™ ile gen aktivasyonu (DNA dizisi)
%,2$/7(51$7,9(6oDOÕúPDVÕ
ƒ
In vivo oDOÕúPDODU
D\OÕNSODVHERNRQWUROONOLQLNGHQH\'(506&$1/DERUDWXYDUODUÕ
Telojen DúDPDVÕQÕQELUG|QJVQNDSVD\DQD\OÕNNOLQLNGHQH\LQ
VRQXoODUÕPROCAPIL™ ile tedavi edilen grupta oral Finastéride®
WHGDYLVLQH NÕ\DVOD DQDMHQWHORMHQ RUDQÕQGD EHOLUJLQ ELU DUWÕú
J|VWHUPLúWLU
gQHULOHQNXOODQÕPGR]X
%3
*YHQOLN81,7,6&KDUWHUED÷ODPÕQGDRQD\ODQPÕúWÕU
Talep üzerine sunulacak raporlar:
HET CAM testi
uzman raporu
øQVDQODU]HULQGHSDWFKWHVWL
RIPT
Ames testi
PROCAPIL™
ødø1'(.ø/(5
1. *ø5øù
1 - 7/41
2. 6$d'g.h/0(6ø1ø*(&ø.7ø50(<(<g1(/ø.6('(50$.216(37ø 8 - 9/41
3. (7.ø1/ø.7(67/(5ø
10 - 35/41
In vitro oDOÕúPDODU
.OWUOHQPLúVDoIROLNOOHULHNVSODQWODUՁ]HULQGHoDOÕúPD
(Saç folikülü üzerinde peptit Biyotinil-GHK¶QÕQYDUOÕ÷Õ %,2$/7(51$7,9(6oDOÕúPDVÕ
.OWUOHQPLúVDoIROLNOOHUL]HULQGH\DúODQPD\ÕJHFLNWLUPHoDOÕúPDVÕ
(BIO-(&oDOÕúPDVÕ
PROCAPIL™ ile gen aktivasyonu (DNA dizisi)
In vivo oDOÕúPD
D\OÕNSODVHERNRQWUROONOLQLNGHQH\'(506&$1/DERUDWXYDUODUÕ
4. SONUÇ
36 - 37/41
5. REFERANSLAR
38 - 40/41
EK
41/41
12/2009/V3
PROCAPIL™
1/41
1.
*ø5øù
6DoÕQ VRQXQGD VDo oL]JLVL EHOLUJLQ ELU úHNLOGH JHULOH\HQH NDGDU JQEHJQ
LQFHOPHVL EX HUNHN QIXVXQXQ |QHPOL ELU RUDQÕQÕQ KHU JQ \DúDGÕ÷Õ
GHQH\LPGLU (QGLúH YH KD\DO NÕUÕNOÕ÷Õ VRQUDVÕQGD WHVOLP ROPD ELUH\LQ NDID
DUNDVÕE|OJHKDULoWPNDIDWDVÕQÕHWNLOH\HQNHOOLNOHELUOLNWHN|Wüleyici bir öz-imaj
belirlemesine neden olur.
$ORSHVL \DúÕQGDQ LWLEDUHQ HUNHNOHULQ VLQL HWNLOHU YH RQ \ÕOGD ELU DUWDU%XGD\DúÕQGDNLHUNHNOHULQ\DUÕVÕQGDQID]ODVÕQÕQNHOOLNWHQPX]GDULS
ROGX÷XDQODPÕQDJHOLU
Kozmetik segmentindeki erkek WDOHELQLQJFNROD\OÕNODDQODúÕODFDNWÕU
%DúODQJÕoWD RUWD VHYL\HGH RODQ DORSHVL JHQo HULúNLQOHUGH PH\GDQD JHOHELOLU
YHYDNDODUÕQ
LQGHDQGURMHQLNHWL\RORML\HVDKLSWLU
0LODWWDQ \ÕO |QFH +LSRNUDW KDUHP D÷DODUÕQÕQ DVOD NHOOHúPHGL÷LQL
J|]OHPOHPLú GROD\ÕVÕ\OD NHOOL÷LQ |]HO RODUDN HULO IDNW|UH ED÷OÕ ROGX÷XQX
NHúIHWPLúWLU
%X DQGURMHQH ED÷OÕ ROJX NDGÕQODUGD NHOOL÷LQ QHGHQ GDKD D] ROXúWX÷XQX GD
DoÕNODPDNWDGÕU %X GH]DYDQWDM \DOQÕ]FD KDVWDOÕN VWUHV \D GD ED]HQ
|VWURMHQOHULQ EHOLUJLQ ELU úHNLOGH GúS GRODúÕPGDNL testosteronun
GHQJHOHQHPHGL÷L menopoz VRQUDVÕ G|QHP JLEL EHOLUOL NRúXOODU DOWÕQGD RUWD\D
oÕNPDNWDGÕU
%XHUNHNYHNDGÕQHúLWVL]OL÷LNDGÕQODUÕNRUXPDNWDGÕUYHNDGÕQODUÕQ
GHQD]Õ
DúÕUÕVDoG|NOPHVL\DGD\HUOHúLNNHOOLNWHQúLND\HWetmektedir.
.DGÕQODUÕQ VDoÕQÕQ OHKLQH ELU EDúND IDUNOÕOÕN GD YDUGÕU \ÕOD NDGDU RODQ VDo
|PU EHOLUJLQ ELU úHNLOGH GDKD X]XQGXU HUNHNOHUGHNL VDo |PU LVH RUWDODPD
RODUDN EX VUHQLQ \DUÕVÕ NDGDUGÕU %X GXUXP NDGÕQ VDoÕQÕQ XODúDELOHFH÷L
PDNVLPXPX]XQOX÷X GDDoÕNODPDNWDGÕU
PROCAPIL™
2/41
)DNDW VDo E\PH G|QJV KHU LNL FLQVL\HWWH GH D\QÕGÕU YH DUGÕúÕN
DúDPDGDQ ROXúXU
Her iki saç da, keratinositlerin hücre bölünmesiyle saç N|NYHDUGÕQGDQVDo
DODQÕROXúWXUDQELUGHUPDOSDSLOODVHYL\HVLQGHROXúXU
6Do IROLNOQQ WDEDQÕQGD \HU DODQ KHU ELU SDSLOOD GDKLOL ELU VDDWH
X\DUDN
GR÷DOVDo\HQLOHQPHVLQLWHWLNOHPHNLoLQJHUHNHQELUE\PHPHVDMÕDOÕU
øON DúDPD \D GD E\PH DúDPDVÕ anajen RODUDN ELOLQLU YH LOD \ÕO
sürer.
øNLQFLDúDPDLVHLODKDIWDVUHQ E\PHGXUPDVÕQGDQROXúXU%X
katajen DúDPDVÕGÕU
hoQF DúDPD LVH VDoÕQ GÕúDUÕ\D oÕNWÕ÷Õ telojen DúDPDVÕGÕU. Yüzeye
oÕNÕú|QFHVLQGHN|NDODQÕQÕQJHULOH\LSVDoNÕOÕ\XYDVÕQÕQKLSRGHUPLVWH
\DNODúÕN PP GHULQOLNWH \HU DOÕU D\UÕOPDVÕ JHUHNWL÷L LoLQ EX DúDPD
ROGXNoD\DYDúJHUoHNOHúLU%XVUH\DNODúÕNLODD\GÕU
-
%XG|QJ|PUER\XQFD\DNODúÕNNH]WHNUDUODQÕU
ƒ
S$d025)2-(1(=ø
Saç \D GD YFXW NÕOODUÕ GHUPLV YH HSLGHUPLV DUDVÕQGDNL HWNLOHúLPOH RUWD\D
oÕNDU
Epidermal mesajla harekete geçirilen fibroblastlar, primer bir filiz (2)
ROXúWXUPDNLoLQGHUPLVLLoHGR÷UXNDWOD\DQELUHSLGHUPDOSODNDROXúXPXQX
tetikleyen keratinositlere ELUVLQ\DOKD]ÕUODUYHLOHWLU
%|\OHFHSULPHUILOL]JHOHFHNWHNLGHUPDOSDSLOOD\ÕROXúWXUPDNLoLQoHYUHGHNL
ILEUREODVWODUÕVWDELOL]HHGHQPHVDMODUJ|QGHULU
6RQRODUDNILOL]GHUPDOSDSLOODWDUDIÕQGDQJ|QGHULOHQPHVDMODUÕQHWNLVLDOWÕQGD
kademeli olDUDNYHVDoIROLNOQHIDUNOÕODúÕU
PROCAPIL™
3/41
3$86DUGÕQGDQVDoPRUIRMHQH]LQLQIDUNOÕHYUHOHUL
.HUDWLQRVLWOHUGHQJHOHQELUVLQ\DOLQDUGÕQGDQ
HSLGHUPDOSODNDQÕQKD]ÕUODQPDVÕ
1. Evre
3ULPHUILOL]ROXúXPXLOHSODNRGXQGHUPLV
LoLQGHLoHGR÷UXNDWODQPDVÕ
2. Evre
)LEUREODVWODUGDQJHOHQELUVLQ\DOLQDUGÕQGDQ
GHUPDOSDSLOODQÕQ\HQLEDúOD\DQROXúXPX
3. Evre
4. Evre
)DUNOÕODúPD'HUPDOSDSLOODGDQJHOHQELU
VLQ\DOHFHYDEHQVDoIROLNOROXúXPX
5. Evre
dRNVD\ÕGDKDEHUFLEXGHUPDO-HSLGHUPDOGL\DORJGDHWNLOHúLPHJLUHUYH
EXQODUÕQNHVLQUROOHULKHQ]DoÕ÷DNDYXúWXUXODPDPÕúWÕU
PROCAPIL™
4/41
ƒ
S$d9(+h&5(',ù,0$75ø6
Saç büyümesinin temel ELOHúHQOHULQGHQ ELUL GH NHUDWLQRVLW YH ILEUREODVWODUÕQ
\R÷XQODúWÕ÷ÕGHUPDOSDSLOODLoHULVLQGHNLGHUPLVYHHSLGHUPLVDUDVÕQGDNLIL]LNVHO
HWNLOHúLPGLU
'HUPDOSDSLOODLNLKFUHSRSODV\RQXDUDVÕQGD\DNÕQWHPDVÕNRUX\DQYHVDo
NÕOÕ\XYDVÕQÕQE\PHVLLoLQJHUHNHQNLP\DVDOLOHWLúLPLGHVWHNOH\HQNRODMHQOHU
YH JOLNR]DPLQRJOLNDQODU DoVÕQGDQ |]HOOLNOH ]HQJLQ ELU E|OJHGLU %X PDWULV
ELOHúHQOHULQLQVDoE\PHVLLoLQELUPDWULVPRWRUXRODUDNGúQOHELOHFHNRODQ
GHUPRHSLGHUPDOELUOHúLPYHGHUPDOSDSLOODQÕQE\NNÕVPÕQÕQILEURQHNWLQLOH
WDEDQ PHPEUDQÕQÕ GD ROXúWXUPDVÕ GROD\ÕVÕ\OD NRODMHQ ,9 YH ODPLQLQH LOLúNLQ
|QHPLQYXUJXODQPDVÕJHUHNLU-$+2'$ve ark., 1992), (ALMOND-ROESLER
B. ve ark., 1997).
$UD\] PDWULVL PROHNOOHULQLQ FLOW YH X]DQWÕODUÕQÕQ E\PHVL YH
IDUNOÕODúPDVÕQGDR\QDGÕ÷ÕPHUNH]LUROLQVDQFLOGLQLQHPEUL\RMHQH]LKDNNÕQGDNL
7$0,2/$.,6oDOÕúPDVÕLOHDoÕNELUúHNLOGHUHVPHGLOPLúWLU
YHKDIWDDUDVÕQGDNLLPQRIORUHVDQHWLNHWOHPHVDoNÕOÕ\XYDVÕQÕQN|N
NÕQÕQGDJoOODPLQLQNRODMHQ,9YHILEURQHNWLQ\R÷XQODúPDVÕJ|VWHUPHNWHGLU
%X ELOHúHQOHU EDúODQJÕoWD \DOQÕ]FD VDo N|NQQ HSLWHO JHUPLQDO KFUHOHULQGH
PHYFXWWXU KDIWD EXQODU NDGHPHOL RODUDN N|N NÕQÕQÕ HOH JHoLULU YH
DUGÕQGDQ VDoÕQ RUWD\D oÕNWÕ÷Õ DODQD YH GHUPRHSLGHUPDO ELUOHúLPe göç eder
(21. haftada DEJ).
KDIWDGDQ |QFHNL EDúODQJÕo HYUHVLQGH GHUPRHSLGHUPDO ED]DO ODPLQD
VHYL\HVLQGHYLPHQWLQPHYFXWWXUYHLONKHPLGHVPR]RPROXúXU-9. hafta).
0DWULV ELOHúHQOHULQLQ NOWUOHQPLú LQVDQ VDoÕ IROLNOOHULQLQ KD\DWWD NDOPDVÕ YH
büyümesindeki önemi WARREN R. ve ark.WDUDIÕQGDQGDJ|VWHULOPLúWLU
PROCAPIL™
5/41
Arayüz matris proteinlerinin rolü, özellikle yeni saç rekonstrüksüyonuna yol
açDQ ROD\ODU GL]LOLPLQGH DoÕN ELU úHNLOGH UHVPHGLOPLúWLU .|N \DSD\ RODUDN
NÕVÕPODQGÕUÕOÕSDOÕQGÕ÷ÕQGDGÕúN|NNÕQÕQÕQNHUDWLQRVLWOHULULVNOLDODQÕQDúD÷ÕVÕQD
göç eder. )LEUREODVWODU NHUDWLQRVLWOHULQ NDUúÕVÕQD \HUOHúLU Bu yeni arayüz
DODQÕQGDNRODMHQ,9ODPLQLQYHILEURQHNWLQLoHUHQELUPDWULVROXúXU<HQLELU
GHUPDOSDSLOOD\DSÕODQGÕUÕOÕUYHIDDOL\HWHJHoHU&2/,1ve ark., 1992).
.RODMHQ,9YHODPLQLQ
LQJHQHOOLNOHNHUDWLQRVLWOHUWDUDIÕQGDQVHQWH]OHQGL÷LYH
laminin 5'in dermoepidermal kohezyon ve \DUD L\LOHúPHVL VÕUDVÕQGD
NHUDWLQRVLWOHULQ J|oQGH NULWLN YH \HUL DOÕQDPD] ELU URO R\QDGÕ÷Õ J|] |QQGH
EXOXQGXUXOPDOÕGÕU52866(//(3
ƒ
S$d9((.6ø./ø./(5
%L\RWLQ\DGD+YLWDPLQLEHVOHQPH\ROX\ODYFXGDDOÕQDQWHPHOELUYLWDPLQGLU
%L\RWLQHNVLNOL÷LFLOWYHX]DQWÕODUÕQGDDQRPDOLOHUH\RODoDULQFHµWDUDQDPD\DQ¶
saç (SHELLEY ve ark.DORSHVLSXOODQPDNDúÕQWÕYHGHUPDWLW)5,**
ve ark., 1989; FRITSCHE ve ark., 1991).
%L\RWLQ HNVLNOL÷LQH HQ KDVVDV KFUHOHU Q|URQODU YH NHUDWLQRVLWOHUL LoHULU
(SUORMALA ve ark., 2002). Erkekteki fizyolojik eksiklikler mental gerilik ve
cilt anomalilerine yol açar. Cilt ve beyinin ortak embriyolojik kökeni dikkate
DOÕQGÕ÷ÕQGDEXWDPDPHQEHNOHQPHGLNELUGXUXPGH÷LOGLU
(SLGHUPLVWH EL\RWLQ |]HOOLNOH IDUNOÕODúPDQÕQ JHo G|QHP VLWRNHUDWLQOHULQLQ
ROXúXPXQXG]HQOHU)5,76&+(ve ark., 1991).
PROCAPIL™
6/41
%L\RNLP\DVDO ELU EDNÕú DoÕVÕQGDQ EL\RWLQ NHQGLVL LoLQ SURVWHWLN JUXEX
ROXúWXUGX÷XPLWHNRQGUL\DONDUERNVLOD]ODUÕQGR÷UXLúOHYJ|UPHVLLoLQNDoÕQÕOPD]
bir enzimatik kofaktördür.
Mitekondriyal enzimlerin (piruvat, propiyonil-CoA, 3-metil krotinil-CoA ve
asetil-&R$NDUERNVLOD]ODUÕOLVLQNDOÕQWÕODUÕQDNRYDOHQWED÷OÕEL\RWLQDNWLIIRUPD
d|QGUOPú KDOL\OH LVH NDUERNVLEL\RWLQ SLUXYDW .UHEV G|QJV YH
oksaloasetat (lipojenez) gibi akseptörlere CO2 JUXSODUÕQÕQDNWDUÕOPDVÕQÕVD÷ODU
bu nedenle biyotin mitekondriyal metabolizmada kritik bir kofaktördür.
ƒ
S$d'g.h/0(6ø1ø<$9$ù/$70$.ødø1.8//$1,/$1675$7(-ø.+('()/(5
Birinci hedef
%LULQFL KHGHIEHOLUJLQELUúHNLOGHDQGURMHQLNWLU: amaç dihidrotestesteron (DHT)
üretimini 5α-UHGNWD] \DYDúODWPDNWÕU g]HOOLNOH GHUPDO SDSLOODGD \HU DODQ
DQGURMHQ UHVHSW|UOHULQH E\N \DNÕQOÕ÷Õ ROPDVÕ QHGHniyle bu metabolit (kan
WDUDIÕQGDQVD÷ODQDQWHVWRVWHURQGDQGDKDDNWLIWLU$1'(566216
'+7VDoIROLNOQN|UHOWHUHNYH\DNÕQ]DPDQGDJHOLúWLULOHQELUKLSRWH]HJ|UH
(SAWAYA ve ark., 2001), kaspaz 3 YDVÕWDVÕ\OD pro-apoptotik bir mekanizma
ile hareket eder.
Ciltte 5α-UHGNWD]ÕQL]RIRUPXPHYFXWWXUIDNDWα1 formunun yüz seviyesinde
EN] DNQH YH GHUPDO SDSLOOD VHYL\HVLQGH VDo IROLNOQGH GDKD DNWLI ROGX÷X
görülürken, αIRUPXQXQLoYHGÕúN|NNÕQÕVHYL\HVLQGHGDKDoRNYDUROGX÷X
UDSRUHGLOPLúWLU%$<1(ve ark., 1999).
PROCAPIL™
7/41
/¶2UpDO HNLEL *(567 ELU \DSÕDNWLYLWH LOLúNLVL oDOÕúPDVÕQGD α2UHGNWD]ÕQVSHVLILNLQKLELW|UOHULQLQVSHVLILNα1-UHGNWD]ODUÕya da karma α1- ve
α2-UHGNWD]ODUÕQÕQDNVLQHNOWUOHQPLúVDoIROLNOOHUL]HULQGHDNWLIROPDGÕ÷ÕQÕ
J|VWHUPLúWLU
Finasterid (5α2-UHGNWD]Õ ]HULQGHNL H\OHPLQGHQ GROD\Õ DVOÕQGD SURVWDWLN
KLSHUWURIL LoLQ JHOLúWLULOHQ ELU LODo JLEL NDUPD α1- ve 5α2-redüktaz
LQKLELW|UQQ NXOODQÕPÕ EHOLUJLQ ELU úHNLOGH JHULOH\HQ ELU VDo oL]JLVL J|UOHQ
KDVWDODUGDNLVDoG|NOPHVLQGHEHOLUJLQELUD]DOPDVD÷ODPÕúWÕU
Böylelikle 5α-UHGNWD]ÕQÕQ EDVLW LQKLELV\RQX DUDFÕOÕ÷Õ\OD \ÕO VRQUD DQDMHQ
DúDPDGDVDoDUWÕúÕHOGHHGLOPLúWLU9$11(67(ve ark., 2000).
%X HWNLQLQ '+7 VHYL\HOHULQGHNL ORNDO GúúH ED÷OÕ ROGX÷X
GúQOPúWU %X VD\HGH '+7 QRUPDO VDo GHULVLQGHNL NRQVDQWUDV\RQGD
PHYFXWKDOHJHOPLúWLU'$//2%ve ark., 1994).
øNLQFLKHGHI
øNLQFL KHGHI NDQGÕU: iyi NDSLOHU SHUI]\RQ DVOÕQGD ELU DQWLKLSHUWDQVLI RODUDN
NXOODQÕODQ ELU SHULIHUDO YD]RGLODW|U RODQ 0LQR[LGLOŠ
LQ EHNOHQPHGLN EDúDUÕVÕQÕ
DoÕNODPDN LoLQ JHOLúWLULOHQ PHNDQL]PDGÕU øOJL oHNLFL \DQ HWNLVL RODQ \HQL VDo
E\PHVL LODFÕQ KLSHUWDQVL\RQX WHGDYL HWPHN LoLQ NOLQLN NXOODQÕPÕ\OD
NHúIHGLOPLúWLU
$UWÕUÕOPÕú NDSLOHU SHUI]\RQD ED÷OÕ HWNLQLQ D]ÕPVDQPDPDVÕ JHUHNPHVLQH
UD÷PHQ 0LQR[LGLOŠ
LQ IROLNOGH KDOL KD]ÕUGD IDUNOÕODúPÕú RODQ NHUDWLQRVLWOHULQ
DNWLISUROLIHUDV\RQXQXVD÷OD\DUDNKDUHNHWHWWL÷LGHELOLQPHNWHdir (BOYERA N.,
1997).
Üçüncü hedef
Minoxidil®'in hiper-proliferatif etkisine (100 µM'den az konsantrasyon) ek
olarak, yüksek dozda (milimol düzeniyle) bir pro-IDUNOÕODúPD HWNLVL GH UDSRU
HGLOPLúWLU %X HWNL IROLNOOHUGHNL ORNDO DNPODV\RQ LOH X]XQ Vreli tedavide
HOGH HGLOHELOLU 6RQXo RODUDN VDo G|NOPHVL JHFLNWLULOLU 'ROD\ÕVÕ\OD hiperproliferatif etki ve pro-IDUNOÕODúPDHWNLVL KHGHILROXúWXUXU
PROCAPIL™
2.
8/41
6$d'g.h/0(6ø1ø*(&ø.7ø50(<(<g1(/ø.6('(50$.216(37ø
Günümüzdeki saç morfojenezi DQOD\ÕúÕ YH DORSHVL\L WHWLNOH\HQ \D GD
úLGGHWOHQGLUHQ SRWDQVL\HO VHEHSOHULQLQ SURJUHVLI NHúIL ÕúÕ÷ÕQGD ROGXNoD
NDUPDúÕN YH oRN IDNW|UO ELU PHNDQL]PDQÕQ EXOXQGX÷X DoÕNWÕU )ROLNO MHQH]L
YH VDo E\PH G|QJVQQ LOHUOHPHVLQL NRQWURO HWPH\H oDOÕúPDN EDKVH
girmek gibi ELUúH\GLU.
'DKDVÕ oRN \DNÕQ ]DPDQGD \DSÕODQ MHQHULN oDOÕúPDODU PXWDV\RQODUÕ DORSHVL
LOHLOLúNLOL|QHPOLELUJHQPLNWDUÕHQD]J|VWHUPLúWLU6('*:,&.-RKQ*4
Magazine, 1999).
%X QHGHQOH úX DQD NDGDU \DSÕOPÕú LOHUOHPHOHUL özellikle anti-androjenik ve
YD]RGLODW|U ELOHúHQOHU NRQXVXQGD RODQODUÕ LKPDO HWPHPHQLQ |QHPOL ROGX÷X
RUWD\DoÕNPDNWDGÕU
'ROD\ÕVÕ\OD 6('(50$ EH KHGHIOHU ]HULQGH H\OHP J|VWHUHQ ELWNL N|NHQOL LNL
DNWLIPDGGH VHoPLúWLU α1- ve 5α2-UHGNWD]ODUÕQÕQ LQKLELV\RQX LoLQ oleanolik
DVLW/RYH\O\+HPVOH\DN|NOHULQGHQ|]WOHQPLúYHYD]RGLODV\RQLoLQDSLMHQLQ
QDUHQFL\HGHQ|]WOHQPLúIODYRQRLG
$UGÕQGDQ 6('(50$ VDo DQNRUDMÕ NRQVHSWL KHGHIOL H\OHPH VDKLS EX LNL
\DNODúÕPÕJoOHQGLUPLúWLU
6DoÕQFLOWLoLQGHGDKDL\L³N|NOHQPHVL´VD÷ODQDELOL\RUVDDUD\]VHYL\HVLQGHNL
NLP\DVDO KDEHUFLOHULQ DOÕúYHULúOHULQGHNL L\LOHúPH LOH ELUOLNWH WXWXQPD DUWÕúÕ
(dermal papilla - VDo IROLNO HOGH HGLOHFHNWLU %X DUD\]OHPH DUWÕúÕ DQDMHQ
DúDPDVÕQÕQNDOLWHVLYHVUHVL]HULQGHSR]LWLIELUHWNL\HVDKLSRODFDNWÕU%HQ]HU
úHNLOGH VDo NÕQÕ YH GHUPLV DQNRUDMÕQGDNL DUWÕú WHORMHQ DúDPDQÕQ
EDúODQJÕFÕQÕQJHFLNWLUHFHNWLU
Bu amaçla, pro-matris aktiviteleri verilen bir peptit dizilimi seçtik: Matrikinler
serisinin bir üyesi olan Glisil-Histidil-Lisin peptiti (MAQUART ve ark., 1999) ve
EXQX+YLWDPLQLQHEL\RWLQED÷ODGÕN%XYLWDPLQLQHNVLNOL÷LLQFHDORSHVLNVDo
FLOWVDUNPDVÕYHGHUPDWLWH\RODoDU
Bu Ɣekilde, çift matris ve metabolik eylem beklentisiyle yeni bir teƔekkül
oluƔturulmuƔtur: vitamin taƔŦyan bir peptit olan Biyotinil-GHK.
PROCAPIL™
9/41
%XQHGHQOHĮ-UHGNWD]ÕQÕLQKLEHHWPHNLoLQROHDQROLNDVLWNDQSHUI]\RQXQX
DUWÕUPDN LoLQ DSLMHQLQ YH JoOHQGLULOPLú E\PH LOH VDo DQNRUDMÕQGD DUWÕú LoLQ
biyotinil-GHK olmak üzere üç aktif madde yeni konseptte bir araya
JHWLULOPLúWLU
PROCAPIL™
352&$3,/ŒELOHúHQKHGHIOHUL
Biyotinil-GHK →
øoN|NNÕQÕ
Biyotinil-GHK →
'ÕúN|NNÕQÕ
Biyotinil-GHK →
Dermal papilla
Oleanolik asit→5-αredüktaz antagonizmi
Apijenin →
vazodilasyon
%HOLUOLJHQOHULQ'1$GL]LVLDNWLYDV\RQXLOHRQD\ODQDQH\OHPPHNDQL]PDVÕ
matris güçlendirici HWNLOHU NOWUOHUGH LQVDQ VDoÕ IROLNO HNVSODQWODUÕQÕQ
E\PHVLYHD\OÕNSODVHERNRQWUROONOLQLNGHQH\LQVRQXoODUÕEXGRV\DQÕQ
NRQXVXQXROXúWXUPDNWDGÕU
PROCAPIL™
10/41
3.
(7.ø1/ø.7(67/(5ø
In vitro oDOÕúPDODU
.OWUOHQPLúVDoIROLNOOHULHNVSODQWODUՁ]HULQGHoDOÕúPD
(Saç folikülü üzerinde peptit Biyotinil-GHK¶QÕQYDUOÕ÷Õ%,2$/7(51$7,9(6oDOÕúPDVÕ
Prensibi
dDOÕúPD ƒ&¶GH ELU QHPOHQGLUPH E|OPHVL LoLQGH 3%6 RUWDPGD NOWUOHQPLú
RODQLQVDQFLOGLHNVSODQWODUÕDEGRPLQDOSODVWLNRQXVXQGD\UWOPúWU
(NVSODQWODUÕQSHSWLWWe bekletilmesini müteakip, piliyal bölge çevresinin seçilen
ORNDOL]DV\RQXQX LQFHOHPHN ]HUH NÕVÕPODUÕQ LPQRKLVWRNLP\DVDO oDOÕúPDVÕ
\UWOPúWU
Protokol
6Do IROLNOO FLOW HNVSODQWODUÕ VDDW SSP SHptit mevcudiyetinde inkübe
edilir ve peptitsiz eksipiyana PDUX] EÕUDNÕOPÕú RODQ NRQWURO HNVSODQWODUÕ LOH
NDUúÕODúWÕUÕOÕU
Tespitler ELUELULQLQD\QÕVÕSDUoDüzerinde yürütülür.
VDDW VRQUD KHU ELU ND\QD÷ÕQ PHUNH]LQGHQ -PP EL\RSVL oÕNDUWÕOÕU YH VÕYÕ
nitrojen içinde hemen dondurulur.
—P NDOÕQOÕ÷ÕQGDNL NÕVÕPODU GRQDQ ELU PLNURWRP NULRVWDW NXOODQÕODUDN
\DSÕOPÕú ROXS VRQUD NXUXWXOPXú YH VDELWOHQPLúOHUGLU Biyotinil-GHK,
VWUHSWDYLGLQSHURNVDWÕNDYUDPÕúRODQLPQRHWLNHWOHPHLOHWHVSLWHGLOPLúWLU
PROCAPIL™
11/41
Sonuçlar
.ÕVÕPODUSHSWLWBiyotinil-*+.¶QÕQ DoÕNSHUL-SLOL\DOORNDOL]DV\RQXQXJ|VWHUPLúWLU
ANRQWUROHNVSODQWÕQÕQUHVPLVDo
NÕOÕ\XYDVÕHWUDIÕQGDHWLNHWOHPH\RN
(büyütme 20X)
BELWLúLNVDoNÕOÕ\XYDVÕHWUDIÕQGD
belirgin biyotinil-GHK lokalizasyonu
(büyütme 20X)
C;E\WPHLOHVDoÕQSHULIHUDO
HúPHUNH]OLDODQÕbiyotinil-GHK
WDUDIÕQGDQJoOELUúHNLOGH
DER\ODPVDONÕVÕPVDoX]XQOX÷X
ER\XQFDL\LELUGD÷ÕOÕPLOHVSHVLILN
biyotinil-GHK lokalizasyonu ve çevre
dokuda etiketleme yok (büyütme 20X)
dÕNDUÕP
Biyotinil-GHKKHGHILRODQVDoIROLNOOHULoHYUHVLQGH|]HOYDUOÕNJ|VWHUHQ
GD\DQÕNOÕSHSWLWWLU
PROCAPIL™
12/41
.OWUOHQPLúVDoIROLNOOHUL]HULQGH\DúODQPD\ÕJHFLNWLUPHoDOÕúPDVÕ
(BIO-(&oDOÕúPDVÕ
Prensibi
0LNURJUDIW WUDQVSODQWDV\RQX GHYUHVL ED÷ODPÕQGD KD]ÕUODQPÕú RODQ çok
miktarda saç folikülleri PHILPOTT ve ark.WDUDIÕQGDQUDSRUODQPÕúRODQD
EHQ]HUELURUWDPDNOWUOHPHNLoLQWRSODQPÕúWÕU
Protokol
6DoIROLNOOHUL KDYD DUWÕ &22 DWPRVIHU DOWÕQGD ƒ&¶GH JQ D\UÕ D\UÕ
LQNEHHGLOPLúWLU
(NVSODQWODU PXKWHOLI JUXSODUD E|OQPúOHUGLU \DOQÕ]FD NOWU RUWDPÕQGDNL
kontrol grubu, pozitif kontrol gurubu (pozitif referans ürünü) ve peptit biyotinilGHK¶\DPDUX]EÕUDNÕODQWHVWJUXEX
KüOWURUWDPÕJQGHELUGH÷LúWLULOPLúWLU
Genel morfoloji gün EDúODQJÕoYHJQWDULKOHULQGHJ|]OHPOHQPLúWLU
(ú ]DPDQOÕ RODUDN IROLNOOHULQ ELU NÕVPÕ GDKD LOHUL LPQRKLVWRNLP\DVDO
oDOÕúPDODUÕ\UWPHN]HUHGRQGXUXOPXúWXU
Büyüme bir dijital NDPHUD NXOODQÕODUDN ' ' ' ' ' YH '
WDULKOHULQGHDOÕQDQJ|UQWOHUOHL]OHQPLúWLU
PROCAPIL™
13/41
*HQHOPRUIRORMLVRQXoODUÕ
16DoNÕOÕ\XYDVÕE\PHVL
%\PHWHVSLWOHULVDoNÕOÕ\XYDVÕQÕQVHUEHVWNÕVPÕQGD\DSÕOPÕúWÕUVDo
kökünün alt NÕVÕPODUÕKDULo
Kontrol folikülünün büyümesi,
T0 ile T14 günleri
Biyotinil-GHK¶\DPDUX]EÕUDNÕODQ
folikülün büyümesi, T0 ile T14
T0
T7
T14
PROCAPIL™
14/41
(OGHHGLOHQVRQXoODUDúD÷ÕGDNLJUDILNWHUDSRUODQPDNWDGÕU
'
GDQ'
HVDoNÕOÕ\XYDVÕE\PHVL
+%121
+%58
Kontrol
+%58
Pozitif kontrol Biyotinil-GHK Biyotinil-GHK
Minoxidil® 2 ppm 2 ppm
5 ppm
(%1 PROCAPIL™) (%2.5 PROCAPIL™)
dÕNDUÕP
2 ppm peptit etkisi (yani %1 PROCAPIL™DOWÕQGDNRQWUROJXUXEXQGDQ
GDKD ID]OD E\PH HOGH HGLOPLú ROXS SSP 0LQR[LGLOŠ¶LQ —0
PHYFXGL\HWLQGHNLQH EHQ]HU ELU E\PH J|]OHQPLúWLU SSP Biyotinil-GHK
(yani %2,5 PROCAPIL™LOHE\PHNRQWUROGHQGDKDID]ODROPXúWXU
PROCAPIL™
15/41
2.
.|NNÕQՁ]HULGH\DúODQPDJHFLNWLULFLIDDOL\HW
Prensibi
Hücre oR÷DOPD IDDOL\HWLQLNDQÕWODPDNLoLQPLWRWLNPDUN|U.øNXOODQÕOPÕúWÕU
Protokol
D0 ve D14 tarihlerinde GRQGXUXODQPLNURWRPNÕVÕPODUÕSHURNVLGD]ED÷OÕDQWL.LDQWLNRUXQDPDUX]EÕUDNÕOPÕúWÕU
.ÕVÕPODU ]HULQGH oR÷DODQ KFUHOHU NR\X NDKYHUHQJL ER\DQPÕúODUGÕU
0LNURVNRS DOWÕQGD VDo NÕOÕ \XYDVÕQÕQ N|N NÕQÕQÕQ GDKD DOW NÕVPÕQGD ELU VD\ÕP
\DSÕOPÕúWÕU.LPDrkörünün J|VWHUGL÷LEWQKFUHOHU VD\ÕOPÕúWÕUE|OJH
Ki67 mitoz kontrolü
D14
3.
Ki67 mitozu
Minoxidil® D14
2.
1.
.LPLWR]VD\ÕP
Ki67 mitozu BiyotinilGHK D14
PROCAPIL™
16/41
Sonuçlar
Kültürün 14. gününde kontrol sac kökünde mitotik keratinositlerde azalma
J|UOPúWU. Bu durum hücre \DVODQPDVÕQÕ\DQVÕWÕU
Minoxidil® (BOYERA ve ark. WDUDIÕQGDQ\ÕOÕQGDUDSRUODQGÕ÷ÕJLEL—0
biyotinil-GHK¶QÕQ YH \DNODúÕN —0 SSP biyotinil-GHK¶QÕQ \DSWÕ÷Õ JLEL
proliIHUDWLI IDDOL\HWLQL PXKDID]D HWPLúWLU Biyotinil-GHK ile elde edilen etki 10
—0 SSP 0LQR[LGLO Š NRQVDQWUDV\RQXQXQ LOH NDW DOWÕQGDNL
NRQVDQWUDV\RQODUGDHOGHHGLOPLúROPDVÕQDUD÷PHQoRNVWQGU
3.
.|NNÕQÕYHGHUPDOSDSLOODbölgesinde bulunan ED÷OD\ÕFÕ
proteinlerin stimülasyonu
Prensibi
DermoepiGHUPDO NDYúD÷ÕQ NDOLWHVL NHUDWLQRVLWOHULQ LON ED]DO NDWPDQ GD\DQD÷Õ
]HULQGHNL YH \DSÕúDFDN ROGXNODUÕ ODPLQLQ YH NRODMHQ ,9 DoÕVÕQGDQ ]HQJLQ
oRN\R÷XQED]DOODPLQDQÕQIRUPDV\RQXQDED÷OÕGÕU
PROCAPIL™
17/41
Epidermis
Laminin 5
Bazal lamina
Kolajen IV
Dermis
'HUPRHSLGHUPDOELUOHúLP
PROCAPIL™
18/41
a)
.OWUOHPHGHQ JQ VRQUD PRUIRORMLN J|]OHP NRQWUROQ GÕú NÕQ
WDUDIÕQGDG]OHúHQYHED]DOODPLQDVÕQÕND\EHGHQELUGHUPRHSLGHUPDOELUOHúLP
J|VWHUPLúWLU
Aksine, saç folikülü biyotinil-GHK LOH JQ LQNEH HGLOGL÷L ]DPDQ ED]DO
ODPLQD NDOPÕú YH VLQ]RLGDO NDUDNWHULQL J|VWHUHUHN DoÕNoD oL]LOPLúWLU %X LNL
EXOJXJoOH\DSÕúDQYH\DúD\DQGHUPRHSLGHUPDOELUOHúLPL\DQVÕWÕU
Saç
DŦƔ kŦn
Dermoepidermal
ELUOHúLP
Dermoepidermal
birleƔim
Kontrol: 14 gün
Dermis
Tedavi Edilen: 14 gün
b)
/DPLQLQ YH NRODMHQ ,9 ED]DO PHPEUDQÕQ HSLGHUP YH GHUPLVLQ
HNOHQPHE|OJHVLQLQROXúXPXQGDYHVDoODUÕQROPDVÕGXUXPXQGDLVHN|NNÕQÕLOH
GHUPLV DUDVÕQGDNL E\N |QHPH VDKLS LNL SURWHRJOLNDQGÕU 0DWULV ELOHúHQOHUL
LPQRHWLNHWOHPHLOHKLVWRORMLNNÕVÕPODU]HULQGHQWHVSLWHGLOHELOLUOHU
PROCAPIL™
19/41
.OWUOVDoIROLNOOHULQLNXOODQDUDN'WDULKLQGH\DSÕOPÕúRODQNRQWURONÕVÕPODUÕ
LOH J|VWHULOPLú ROGX÷X ]HU ODPLQLQ YH NRODMHQ ,9 D\UÕFD GHUPDO SDSLOODGD
JoOúHNLOGHPHYFXWWXUODU-DKRGDve ark.,1992).
øoN|NNÕQÕQGDODPLQLQ
dermal papilla ile arayüz
øoN|NNÕQÕQGDYHGHUPDO
papillada kolajen IV
Protokol
'YH'|UQHNOHULQGHQGRQGXUXODQPLNURWRPNÕVÕPODUODPLQLQH7HEXYH
NRODMHQH ,9 &OLQLVFLHQFH |]J IORUHVDQ DQWLNRUODUD PDUX] EÕUDNÕOPÕúODUGÕU
(OGH HGLOHQ ER\DPD IORUHVDQ \HúLO ROPXúWX 1NOHLQLQ NDUúÕ ER\DPDVÕ
SURSLGL\XP L\RW NXOODQÕODUDN JHUoHNOHúWLULOPLú YH NÕUPÕ]Õ ER\DPD VRQXFX
YHUPLúWLU
*|]OHPOHU NÕO N|NQQ DOWÕQGDNL YH VWQGHNL IROLNOQ Lo E|OJHVL ]HULQGH
\UWOPúWUYHE|OJHEN]úHPDVD\IDVÕ
PROCAPIL™
18/41
Sonuçlar
a) Laminin 5
Kontrol folikülünde,
ODPLQLQúHULGLGÕúN|N
NÕQÕWDUDIÕIROLNOQ
periferi), 14 gün sonra
ND\ERODQNDOÕQOÕN
a: D0
b: D14
%XEL]L'¶WHPXKWHOLIUQOHULQPHYFXGL\HWLQGHODPLQLQND\EÕQÕLQFHOHPH\H
J|WUPúWU
c: D14’te dermal papilla
d: D14’te kök kŦnŦ
SSP—00LQR[LGLOŠPDUX]L\HWLDUGÕQGDQIROLNOJQVRQUDNDOÕQYH
LSEHQ]HULúHNLOGHNDODQELUODPLQLQúHULGLJ|VWHUPLúWLU
e: D14’te dermal papilla
f: D14’te kök kŦnŦ
2 ppm (0.3 µM) Biyotinil-GHK PDUX]L\HWLDUGÕQGDQODPLQLQJQVRQUD
SDSLOODVHYL\HVLQGHYHGÕúN|NNÕQÕQGDJoOELUúHNLOGHPHYFXWRODUDN
NDOPÕúWÕU
PROCAPIL™
21/41
b)Kolajen IV
Kontrolde kolajen T0'da çok
NDOÕQRODQ,9úHULGL7
JQQGH\DSÕVÕER]XQPXú
YH\R÷XQOX÷XQX
ND\EHWPLúWLU3DSLOOD
HWLNHWOHPHVLQLND\EHWPLúWLU
IRWR÷UDIODUJ|VWHULOPHPLúWLU
a: D0
b: D14
%XEL]L'¶WHPXKWHOLIUQOHULQPHYFXGL\HWLQGHNRODMHQ,9ND\EÕQÕ
LQFHOHPH\HJ|WUPúWU
c: D14’te dermal papilla
G'¶WHN|NNÕQÕ
2 ppm (10 µM) Minoxidil®'e maruziyet, 14 gün sonra dermal papillada ve
N|NNÕQÕQGDNRODMHQ,9\R÷XQOX÷XQGDND\EÕWHWLNOHPLúWLU
e: D14’te dermal papilla
f'¶WHN|NNÕQÕ
Biyotinil-GHK YDUOÕ÷ÕQGD JQ VRQUD NRODMHQ ,9 GHUPDO SDSLOODGD JoO
ELUúHNLOGHPHYFXWRODUDNNDOPÕúHYHN|NNÕQÕVHYL\HVLQGHROGXNoDNDOÕQ
YH\DSÕODQGÕUÕOPÕúKDOGHROPXúWXUI*|]OHPOHQHQ\DSÕNRQWURO'
da (a)
RODQLOHQHUHGH\VHD\QÕGÕU
PROCAPIL™
20/41
dÕNDUÕP
.|N NÕQÕQÕQ YH GHUPDO SDSLOODQÕQ NRODMHQ ,9¶Q YH ODPLQLQ LQ
ELOHúHQOHUL]HULQGHSHSWLWbiyotinil-GHK¶QÕQNRUX\XFXYHRQDUÕFÕHWNLOHUL
DoÕNoD J|VWHULOPLúWLU JQ ER\XQFD NOWUOHQPLú RODQ VDo IROLNO
HNVSODQWODUÕ
]HULQGH
%Lyotinil-GHK¶QÕQ
etkisi
Minoxidil®
NRQVDQWUDV\RQXQGDQNDWGDKDGúNROPDVÕQDUD÷PHQ0LQR[LGLOŠ
H
J|UHGDKDEHOLUJLQROPXúWXU
*HQHO PRUIRORML DoÕVÕQGDQ biyotinil-GHK FDQOÕ ELU N|N NÕQÕQÕQ PLWR]
Ki67) muhafaza edilmesiyle ve dermis üzerine ankorajdan sorumlu olan
SURWHLQOHULQ NRODMHQ ,9 YH ODPLQLQ \DSÕúPDVÕQGDQ VRUXPOX
\DSÕODQPDODUÕ DUWWÕUPDN RODQ VDo IROLNO NHUDWLQRVLWOHUL JQON
NOWU ]HULQGH oRN EHOLUJLQ ELU \DúODnma geciktirme faaliyeti
VD÷ODPÕúWÕU
PROCAPIL™
22/41
352&$3,/ŒLOHJHQDNWLYDV\RQODUÕ
%,2$/7(51$7,9(6oDOÕúPDVÕ
Prensibi
'1$ GL]LVL oDOÕúPDVÕ KFUH IRQNVL\RQODUÕ LOH LOJLOL \DUDUODUÕ LoLQ VHoLOHQ JHQGHQ ROXúDQ ELU SDQHOL NXOODQÕU dDOÕúPD \XNDUÕ-UHJOH YH DúD÷Õ-regüle
PDUN|U JHQOHUL J|VWHUPLú ROGX÷XQGDQ NHUDWLQRVLW YH ILEUREODVW SRSODV\RQ
]HULQGHNR]PHWLNHWNHQPDGGHVLQLQHWNLVLQLQWDQÕPODQPDVÕQÕRODQDNOÕNÕODU
Protokol
'1$ GL]LVL oDOÕúPDVÕ 6NLQ(WKLFŠ \HQLGHQ ROXúWXUXOPXú LQVDQ HSLderm
örneklerinin PROCAPIL™’in (3 etken madde içeren kompleks: biyotinil-GHK,
ROHDQROLNDVLWYHDSLMHQLQPHYFXGL\HWLQGHLQNEHHGLOPHVL\OH\DSÕOPÕúWÕU
øQNEDV\RQ VDDW VUPúWU +FUHOHUGH PHYFXW P51$ '1$ VD÷ODPDN
LoLQWHUV\|QOND\GHGLOPLúYHNRQWUol kültürlerine NDUúÕ RNXQDNOÕELUVLQ\DOHOGH
HWPHNLoLQE\WOPúWU57-PCR).
Sonuçtaki görüntü PROCAPIL™ WDUDIÕQGDQ \XNDUÕ UHJOH HGLOPLú RODQ YH\D
DúD÷Õ UHJOH HGLOPLú RODQ JHQOHULQ VDDW VRQUDNL görüntülerinden bir
enstantanedir.
Sonuçlar
Takip eden sayfalardaki tablolar kontrole NDUúÕ EHOLUJLQ ROGX÷X GLNNDWH DODQ
VRQXoODUÕJ|VWHULUHQD]SR]LWLIYH\DQHJDWLIGH÷LúLNOLN
øOJLOL oHúLWOL KFUHOHUGH GDKD NoN GH÷LúLNOLNOHU LOH DUDVÕQGD
J|]OHQGL÷L]DPDQEXGH÷LúLNOLNOHUELU|OoGHPHNDQLN|QHPLRODQGH÷LúLNOLNOHU
RODUDNGLNNDWHDOÕQPÕúWÕU
PROCAPIL™
23/41
Kontrole NDUúÕ \XNDUÕUHJOHJHQOHUYH
SURWHLQNRGODPDODUÕ
PROCAPIL™’e maruz kalma
DOWÕQGD3URFDSLOŒ¶\HPDUX]NDOPD
Kompleks proteinlerin yapŦƔmasŦ
Desmozomal proteinler 1&3 (Dezmogleinler)
Dezmokollin 1
Fibronektin reseptörüβ-alt ünitesi
Vimentin
Laminin baŒlama proteini
øQWHJULQβ1 &β2
Antioksidan enzimler
Tiyoredoksin peroksidazlarŦ (TDPX2 & AO372)
SOD (mitokondriyal & sitosolik)
Metalotiyoneinler MTH & HMT
CYP b-UHGNWD]Õ
Stres proteinleri
HSP 27
HSP 90
Anti-enflamatuar proteinler
ĀQWHUIHURQγ antagonisti
Hücre metabolizmasŦ enzimleri
Mitokondriyal trifonksiyonel protein & Asil CoA prekürsörü
Ornitin dekarboksilaz
Glutamin sentetaz
Asil CoA transferaz
ø]RVLWUDWGHKLGURMHQD]
iNOS
NADP izositrat dehidrojenaz
3UROLIHUDV\RQIDUNOÕODúPDPDUN|UOHUL
Proliferasyon hücresi nükleer antijeni (PCNA)
Sitokeratinler 10, 14 ve 16
Steroid reseptör koaktivatörü
%
%135 / %138
%146
%134
%138
%146
%134 / %144
%152 ve 174
%150 ve 169
%188 ve 190
%160
%164
%139
%135
%123 ve 128
%132
%136
%137
%189
%143
%189
%191
%154 / 150 / 144
%160
PROCAPIL™
24/41
Kontrole NDUúÕ DúD÷ÕUHJOHJHQOHU
(100%)YHSURWHLQNRGODPDODUÕ
PROCAPIL™’e maruz kalma
DOWÕQGD3URFDSLOŒ¶\HPDUX]NDOPD
Pro-enflamatuar proteinler
øQWHUIHURQγ reseptörü
Anjiyojenik ve matris-yeniden modelleme faktörleri
Vitronektin
TIMP1/TIMP2
Antikimotripsin α1
Lisil hidroksilazlar 1&2
Heperan sülfat proteoglikan
Kolajen 1 alt ünitesi
Hücre proliferasyonu regülasyonu
5HWLQRLNED÷ODPDSURWHLQOHUL&5$%3&5$%3
Vit. D3. reseptörü
%
-%57
-%52
-%43 / -%24
-%43
-%50 / -%29
-%40
-%46
-%34 / -%63
-%40
Yorum
<XNDUÕ\DGR÷UX UHJOHHGLOHQKFUHPHWDEROL]PDVÕHQ]LPOHUL\OHHQ]LPHED÷OÕ
RODUDNLOHDUDVÕQGD\NVHNE\PHIDDOL\HWLQH\|QHOPLúRODQELU
KFUH SURILOLQL \DQVÕWÕU +FUHOHULQ \NVHN VHYL\HGH PHWDEROLN DNWLYLWH
WDUDIÕQGDQ VLVWHPDWLN RODUDN UHWLOHQ VHUEHVW RNVLMHQ UDGLNDOOHULQH NDUúÕ
NRUXPDNJHUHNWL÷LLoLQDQWLRNVLGDQNRUX\XFXHQ]LPOHUGHLOLúNLOHQGLULOPLúWLU
Hücre proliferasyonu nükleer antijeni (PCNA), streoid reseptör ortakDNWLYDW|UOHULYHYHVD\ÕOÕSrROLIHUDV\RQYHD\UÕOPDVitokeratinleri gibi
hücre proliferasyonunun markörleri pro-D\UÕP IDDOL\HWLQL J|VWHUHUHN -21$.
EHOLUJLQ úHNLOGH DQFDN D\UÕFD SURWHLQ +63 ¶OH LOJLOL RODUDN
\XNDUÕUHJOHROPXúODUGÕU
)DUNOÕODúPD\D ED]Õ \DSÕúWÕUPD SURWHLQOHULQGH ELU DUWÕú HúOLN HWPLúWLU KFUHQLQ
ED]DO ODPLQD\D ODPLQLQ ED÷ODPD SURWHLQL YLPHQWLQ LQWHJULQ α ve β)
ED÷ODQPDVÕQÕ NDSVD\DQ KFUHOHU YH \DSÕúPD\Õ YH KFUH NDWPDQODUÕQGDNL
NHUDWLQRVLWOHULQGH]PRJOHLQOHUGH]PRNROLQOHU\D\ÕOPDVÕQÕRODQDNOÕNÕODQODUYH
son olarak çeviUHQ GHUPLVH GH]PRJOHLQOHU GH]PRNROLQOHU DQNRUDMÕ
VD÷OD\DQODUDUDVÕQGDED÷ODQWÕ\ÕRODQDNOÕNÕODQODU
PROCAPIL™
25/41
Her ikisinin güçlü anti eQIODPDWXDU ELU NDWNÕ \DSWÕ÷Õ DúD÷Õ UHJODV\RQOX DUWDQ
interferon antagonisti (+%135) ile birlikte gen interferon reseptörünün azalan
ifadesiyle (-\DQVÕWÕOPÕúWÕU
Bu nedenle, hücre proliferDV\RQX \RODNODUÕQÕQ EX \RODNODU ]HULQGHNL QHJDWLI
HWNLVL\OH IDNW|UOHUGH ELU D]DOPD\OD \R÷XQODúÕUNHQ PDWULV \HQLGHQ
modellemesinin ve anjiyojenezLQNDSVDPÕúROGX÷XJHQOHUJHoLFLRODUDNDúD÷Õ
UHJOHGLUOHU &5$%3 VLWRSOD]PLN UHWLQRWLN DVLW ED÷ODPD SURWHLQOHUL YH
vitamin D3 reseptörü (hücre proliferDV\RQX YH D\UÕPÕ LoLQ WUDQVNULSVL\RQ
faktörü).
Markörlerin güçleri:
Dezmogleinler NHUDWLQRVLW DUDVÕ \DSÕúPD LoLQ YD]JHoLOPH] RODQ YH VDoÕQ GÕú
N|NNÕQÕQÕQIRUPDV\RQXQDNDWNÕGDEXOXQDQ\DSÕúWÕUPDSURWHLQOHULGLU*$552'
ve ark., 2002; NUBER ve ark., 1996)
%XQODU D\UÕFD GHUPDO \DSÕODUÕQ N|N NÕQÕQÕ VDELWOHPH\L GH NDSVDUODU
dezmoglein genlHUL|OGUOPúRODQIDUHQLQWHORMHQVDoODUÕQÕprematüre olarak
kaybeder. (HANAKAWA Y., 2002).
Vimentin HSLWHO\DO GRNX YH VDoÕQ PRUIRMHQezlerinde bir rol oynayan
PHVHQNLPD GHUPLV NHUDWLQRVLWOHU LOH VHQWH]OHQPLú RODQ PDWULVWHQ ROXúXU
(TAMIOLAKIS ve ark., 2001).
6LWRNHUDWLQOHU IDUNOÕODúPD YH VDoÕQ PRUIRMHQ YH NHUDWLQRVLW
proliferasyonu) ve metabolik enzimler ve hücre mitozu (proliferasyon hücresi
QNOHHU DQWLMHQ PDUN|UOHUL \HQL GRNXODUÕQ PRUIRMHQL GR÷UXOWXVXQGD
keratinositik hiperaktiviteyi karakterize ederler.
Retinoik asit için D3 vitamini reseptörünün ve reseptörlerinin (CRABP 1/2)
JHoLúL RODUDN DúD÷Õ UHJOH ROGX÷XQX QRW HWPHN LOJLQoWLU 7UDQVNULSVL\RQ
inhibisyonu de novo '1$ VHQWH] WHúYLNLQL KFUH proliferasyonunu (KROHN
ve ark., 2003) YHIROLNOHULGDPH\L%,//21,NDOGÕUÕU
5HVHSW|UIDDOL\HWLD\QÕ]DPDQGDGLKLGURWHVWRVWHURQXQ'+7DQGURMHQOHULJLEL
VWHURLGOHUH GH ED÷OÕ ROGXNODUÕQGDQ UHVHSW|UQ GúN VHYL\H LIDGHVL D\UÕFD
KRUPRQDODNWLYDV\RQXQ\RNOX÷XQX\DQVÕWÕU
PROCAPIL™
26/41
5HWLQRLG VWHURLG YH ' YLWDPLQL UHVHSW|UOHUL DUDVÕQGD YH NR-efektörlerinin
PHYFXGL\HWLQGH YH\D \RNOX÷XQGD KDILI HWNLOHúLPOHU YDUGÕU %X UHVHSW|UOHU
bundan ötürü saç folikülü morfojenezinde önemi faktörlerdir.
Bu nedenle PROCAPIL™’in etkisi saçmorfojeni ve büyümesi için esas olan
faktörleri kapsar.
<XNDUÕ UHJOH PXKWHOLI JHQOHU DUDVÕQGD SHSWLW biyotinil-GHK JHQH \DSÕúWÕUPD
ve proliferasyonu), biyotin (güçlü mitokondriyal faaliyet) ve oleanolik asit
(CRABP 1 ve 2’nn ve D3 vitamini \ROODUÕQÕQGHDNWLYDV\RQXSDWHQWWLU
In vitroYHULOHU]HULQGHQoÕNDUÕP
6HQWHWLN HSLGHUP ]HULQGH '1$ GL]LVL oDOÕúPDVÕ YH NOWUOHQPLú LQVDQ
VDoÕ HNVSODQWODUÕ KDNNÕQGDNL PRUIRORMLN oDOÕúPD LOH UHWLOHQ YHULOHULQ
ND\GDGH÷HUWXWDUOÕOÕ÷ÕDúD÷ÕGDNLOHULQRWHWPH\HGH÷HUGLU
•
•
•
.L LOH \NVHN \DúODQPD JHFLNWLUPH IDDOL\HWL DUWDQ JHQHO
PRUIRORML N|N NÕQÕ YH SDSLOOD DQWLRNVLGDQ VHOOHU HQ]LPOHU YH
proliferDV\RQXQ3&1$PDUN|UOHULIDDOL\HWHJHoPLúWLU
<DSÕúWÕUPDNRPSOHNVLQLQ\NVHNde novo protein sentezi (kolajen
IV, laminin 5, vimentin, dezmogleinler ve dezmokolinler).
+FUH PHWDEROL]PDVÕQÕQ PLWRNRQGUL\DO HQ]LPOHU YH E\PH
DNWLYDV\RQXQXQ VDo NÕOÕ \XYDVÕ YH VLWRNHUDWLQOHU YH EHOLUJLQX\DUÕOPDVÕ
<XNDUÕGDNLYHULOHUVDoPRUIRMHQH]LQLWHúYLNHGHQYHN|NNÕQÕQÕQGHUPLVH
DQNRUDMÕQÕQJoOHQGLUHQELUUQQSURILOLLOHWXWDUOÕGÕU
hUQ GD\DQÕNOÕ ROXS |]HOOLNOH VDoD \HUOHúWLULOPLúWLU IROLNO ER\XQFD
imüno-lokalizasyon, çevre dokuda yok).
PROCAPIL™
27/41
In vivo oDOÕúPDODU
D\OÕNSODVHERNRQWUROONOLQLNGHQH\'(506&$1/DERUDWXYDUODUÕ
Prensibi
Sac dökülmesi problemi erkeklerde daha fazla J|UOG÷QGHQ, söz konusu
VRUXQXQPHYFXWROGX÷XHUNHNGHQHNOHUOHELUoDOÕúPDEDúODWÕOPÕúWÕU%LUWHORMHQ
G|QHPLWDPDPHQNDSODPDNLoLQD\OÕNELUoDOÕúPDVUHVLVHoLOPLúWLU
$QDMHQ G|QHPGHNL VDo PLNWDUÕ YH WHORMHQ G|QHPGHNL VDF PLNWDUÕQÕQ $7
parametresi) zaman içiQGHVDSWDQPDVÕYHJ|]OHPOHQPHVLLoLQYLGHRWULNRJUDP
PHWRGXNXOODQÕOPÕúWÕU
Protokol
ƒ
Dahil etme kriterleri
<DúODUÕ LOH DUDVÕQGD GH÷LúHQ .DINDV\D RULMLQOL YH VDoODUÕQÕQ ¶GHQ
ID]ODVÕQÕQ WHORMHQ GRQHPGH ROGX÷X WHVSLW HGLOHQ RWX] EHú HUNHN GHQHN GDKLO
HGLOPLúWLU
ƒ
+DULoEÕUDNPDNULWHUOHUL
9HUWHNVWHJULVDo.DIDGHULVLKDVWDOÕNODUÕ
dDOÕúPDGDQ|QFHNLD\LoLQGHNRUWLNRVWHURLGOHULQLPQRVXSUHVDQODUÕQYH\D
retinoidlerin ya da bir hafta içinde anti-HQIODPDWXDUODUODUÕQDOÕQPDVÕ
6RQD\LoLQGH0LQR[LGLOŠ¶LQ\HUHOX\JXODPDVÕYH\DWRSLNDOYH\DRUDORODUDN
DOÕQDUDNYH\DWURSLNVDoWHGDYLVLúHNOLQGHKHUKDQJLELUORNDOµVDoND\EÕ
önleyici’ tedavisi.
.DIDGHULVLQLQWRSLNDOYH\DRUDOoDOÕúPDEDúODPDGan önce 4 hafta içinde
günlük friksiyon olarak anti-seboreik, kepek önleyici) tedavisi.
dDOÕúPDVÕUDVÕQGDEHVOHQPHYH\DHJ]HUVL]DOÕúNDQOÕNODUÕQÕQ
GH÷LúWLULOPHVL$ONROYHWWQQDúÕUÕNXOODQÕPÕ
PROCAPIL™
28/41
ƒ
Ürün uygulama
Ürün veya plasebo \XPXúDN PDVDM NXOODQÕODUDN EDú FLOGLQH JQGH NH]
X\JXODQPÕúWÕU
PROCAPIL™ UHQNVL] OLNLW J|UQPO ROXS RUDQÕQGD VXODQGÕUÕOPÕú DONRO
ORV\RQXRODUDNIRUPOHHGLOPLúWLU3ODVHERD\ÕUWHGLOHPH]QLWHOLNWHROPXúWXUHN
1'de verilen formül).
ƒ
Uygunluk / Güvenlik
8\JXQOXNYHJYHQOLNNRQWUROOHULWHGDYLQLQYHKDIWDODUÕQGD
\DSÕOPÕúWÕU
7YH7D\ODUÕ]DPDQQRNWDODUÕQGDGHUPDWRORJWDUDIÕQGDQNDIDGHULVLQLQIL]LNL
ELUPXD\HQHVL\DSÕOPÕúYHGHQHNPODNDWÕLOHJYHQOLNGH÷HUOHQGLULOPLúWLU
ƒ
Videotrikogram
.XOODQÕOPÕú RODQ VLVWHP ELU GLMLWDO J|UQW DOPD VLVWHPLQH ED÷ODQPÕú ILEHU
RSWLNOL PRELO ; REMHNWLILQ PRQWH HGLOPLú ROGX÷X 025,7(; 6&23(0$1Š
MS-500 marka bir videomikroskoptur.
*|UQWOHU'(506&$1/DERUDWXYDUODUÕQÕQJHOLúWLUPLúROGX÷X&2UNT-HAIR®
SURJUDPÕLOHDQDOL]HGLOPLúWLU
øúDUHWOHPHVRQUDVÕQGDD\QÕWÕUDúOÕVDoE|OJHVLQGHQRUWDODPDRODUDN\DNODúÕN
1cm2VDo7
GDYHD\VRQUDJ|UQWDOÕQPÕúWÕU
ø]OHQHQ SDUDPHWUHOHU VDoÕQ ER\X YH E\PH RUDQÕ YH DQDMHQ DúDPDGDNL
VDFODUÕQPLNWDUÕYHWHORMHQDúDPDGDNLVDoODUÕPLNWDUÕROPXúWXU
PROCAPIL™
29/41
'PP
\HWÕUDúODPD
D48h: uzama ǻ 'sÕ DQDMHQ
8]DPD\RNOX÷X WHORMHQ
ƒ
Saç Örnekleri: Morfolojik analiz ve kolajen IV ve laminin 5’in imüno
etiketlemesi.
7¶GD YH oDOÕúPDQÕQ VRQXQGD FÕPEÕ]ODU NXOODQÕODUDN DORSHVLN E|OJHQLQ
VÕQÕUÕQGDQ DGHW VDo |UQHNOHQPLúWLU 7HGDYL JXUXEXQGDNL GHQHN YH
SODVHERJXUXEXQGDNLNLúL|UQHNOHPH\HWDELWXWXOPXúWXU
Saçlar, analiz için BIO-EC’e gönderilmeden önce (12 adet saç %RXLQ VÕYÕVÕ
LoLQGHVDELWOHQPLúYH\DDGHWVDoKHPHQGRQGXUXOPXúWXU
PROCAPIL™
30/41
Sonuçlar
a) Klinik deney
dDOÕúPD\DGDKLOHGLOHQGHQHNWHQ¶LPROCAPIL™ grubuna (37 ± \ÕOYH
17’si (38 ± \ÕOplasebo JUXEXQDWDKVLVHGLOPLúWLUPROCAPIL™ ve plasebo
JUXSODUÕQDWDKVLVHGLOHQGHQHNOHUUDVWJHOHVHoLOPLúOHUGLU
ƒ Güvenlik
PROCAPIL™ D\OÕN NXOODQÕP VUHVLQFH WP GHQHNOHU WDUDIÕQGDQ çok iyi
tolere HGLOPLúWLU.
ƒ Videotrikogram
.OLQLN oDOÕúPDODU PXKWHOLI GH÷HUOHQGLUPH NULWHUOHUL NXOODQDUDN VDo derisi
VD÷OÕ÷ÕQGD ELU WHGDYLQLQ HWNLOHULQL |OoPH\L DPDoODU 6Do \R÷XQOX÷X VDo
DGHGLFPð E\PH\HQLGHQ E\PH LGGLDVÕQGDNL UQOHU LoLQ NXOODQÕOÕU
$QDMHQYHWHORMHQDúDPDODUGDNLE\PHYH\DND\ÕSVDo\]GHOHUL\OHELUOLNWH
EX\]GHOHULQRUDQODUÕGDKDoRNVDoGHULVL]HULQGHNLVDoDQNRUDMÕQÕQYHVDo
FDQOÕOÕ÷ÕQÕQ KDOD PHYFXGL\HWLQH X\DUODQÕU %X VRQXQFX SDUDPHWUHOHU V|]
NRQXVXQHGHQOHoDOÕúPDLoLQVHoLOPLúOHUGLU
$QDMHQWHORMHQRUDQÕ
$úD÷ÕGDNL úHNLO EDúODQJÕoWD ve D\ VRQUDNL DQDMHQWHORMHQ RUDQÕQÕQ D\
VUHLOHRUDO\ROODNXOODQÕODQ)LQDVWHULGHŠLoLQ\D\ÕQODQDQYHULOHUOH9DQ1HVWH
YHDUNNÕ\DVODPDVÕQÕJ|VWHULU
PROCAPIL™ WHGDYLVLQLQD\VRQUDVÕQGDJ|QOOOHUDQDMHQDúDPDVDoODUÕQÕQ
RUDQÕQGD 7¶OD NDUúÕODúWÕUÕOGÕ÷ÕQGD ND\GD GH÷HU VWQONWH S EHOLUJLQ ELU L\LOHúPH J|VWHUPLúOHUGLU 3ODVHER IDDO GH÷LOGLU 2UDO \ROOD DOÕQDQ
)LQDVWHULGHŠ LoLQ \D\ÕQODQDQ YHULOHUOe NÕ\DVODQGÕ÷ÕQGDPROCAPIL™’in kayda
GH÷HUELUDNWLYLWHVLQLQROGX÷XQXJ|VWHULU
PROCAPIL™
31/41
Nitekim D\VRQUD)LQDVWHULGHŠLoLQ$7RUDQÕQGD7LOHNÕ\DVODQÕQFDÕOÕPOÕ
ELUIDUNOÕODúPDD\VRQUD¶HXODúDQIDUNOÕODúPDUDSRUODQPDNWDGÕU
T0 ile kŦyaslandŦŒŦnda A/T farklŦlaƔma
40
30
20
Finasteride®
11 ay
10
PROCAPILTM
4 ay
0
Finasteride®
5 ay
352&$3,/Œ JUXEXQGD GHQHNOHULQ ¶VL $7 RUDQÕQGD ELU JHOLúPH
J|VWHUPLúOHUGLU YH GHQHNWHQ ¶ LoLQ $7 DUWÕúÕ \HQL VDo PLNWDUÕQGD
DUWÕúVÕUDVÕ\ODYHROPXúWXU
Aksine, plasebo gurubunda anajen saçlarda bir azalma yönünde bir
H÷LOLPROPXúWXU
A/T oranŦnŦn farklŦlaƔmasŦ
(PROCAPILTM 4 ay sonra)
1.4
1.2
1
0.8
0.6
0.4
0.2
0
-0.2
-0.4
-0.6
18 Denek
%\PHRUDQÕ
dDOÕúPDQÕQ EDúODQJÕFÕ LOH ELWLPL NDUúÕODúWÕUÕOGÕ÷ÕQGD HQH÷LQ RUWDODPD VDo
E\PH KÕ]ÕQGD EHOLUJLQ ELU GH÷LúLNOLN J|UOPHPLúWLU )DNDWPROCAPIL™ ile
WHGDYL HGLOHQ JUXSWD E\PH RUDQÕQGD ELU DUWÕú J|VWHUHQ J|QOOGH
JHOLúPH\HGR÷UXELUH÷LOLP J|UOPúWU
PROCAPIL™
32/41
3ODVHER JUXEXQGD RUWDODPD E\PH RUDQÕ Gúú H÷LOLPOL - ROPXú YH
GHQHNOHULQoR÷XQGDKHUKDQJLELUJHOLúPHJ|UOPHPLúWLUGHQHNWHQ
LQGH
%X VRQXoODU ELU VRQUDNL E|OPGH UHVLPOHUOH NDQÕWODQGÕ÷Õ ]HUH FLOWWHNL
VDo DQNRUDMÕ IDDOL\HWL VD\HVLQGH 352&$3,/Œ
LQ JHQHO ED÷ODPGD VDo
G|NOPHVL LOH LOJLOL JoO ELU PRGHUDW|U ROGX÷X oÕNDUÕPÕ \DSPDPÕ]D \RO
DoPÕúWÕU
b) 4 ay sonra saçtagözlemlenen PRUIRORMLNGH÷LúLPOHU
D\VRQUDJUXSODUDUDVÕQGDVDFÕQ\DSÕVÕQGDNLIDUNOÕOÕNODUWHORMHQVDoçekerek
NRSDUÕODQ|UQHNOHPHNXOODQÕODUDNVHULRODUDNJ|]OHPOHQPLúWLU
ƒ
D\OÕN]DPDQQRNWDVÕQGDSODVHER\DNDUúÕPROCAPIL™¶LQIDUNOÕOÕNODUÕ
PROCAPIL™ ile tedavi edilen grupta saç köklerinin çok daha fazla
\DSÕODQGÕUÕOGÕ÷ÕJ|UOG
Plasebo T4 ay (kök)
PROCAPIL™ T4 ay (kök)
Bunun ötesinde PROCAPIL™ LOHWHGDYLHGLOHQVDoL\LIDUNOÕODúPÕúKFUHED]OÕ
LoVDoNÕOÕ\XYDVÕLOJLOLRODUDNoRNQHWVDELWOHQPLúN|NNÕQODUÕLOHELUOLNWHD\UÕFD
oRNL\LELUNDOLWHGHGÕúDUD\]GHUPLViçinde ankoraj) gösterir.
3ODVHER7D\N|NNÕQÕ
PROCAPIL™ T4 ay (kök kÕQÕ
PROCAPIL™
33/41
ƒ
Anajen ve telojen saçODULoLQ7LOH7D\DUDVÕQGDNLIDUN
'HQHNOHUGHQELULQGH7LOH7D\DUDVÕQGDJ|]HoDUSDQGH÷LúLNOLNOHUJ|]OHQPLúWLU
$úD÷ÕGDJ|VWHULOGL÷L]HUHWHORMHQVDoÕQkök E|OJHVLoRNEHOLUJLQúHNLOGH
L\LOHúPLúWLU
PROCAPIL™ T0 (kök)
PROCAPIL™ T4 ay (kök)
$QDMHQVDoODUÕQN|NNÕQODUÕGDNDOÕQODúDUDNYHDoÕNoDWDQÕPODQDQKFUH
ED]ODUÕ\ODL\LOHúPLúWLU
PROCAPIL™ 7N|NNÕQÕ
PROCAPIL™ 7D\N|NNÕQÕ
PROCAPIL™
34/41
PROCAPIL™ JUXEXQGDN|NNÕQÕVDoÕQGÕúWDUDIÕQÕQ]HULQHRSWLPXPGHUPDOHSLGHUPDO \DSÕúPD\Õ VD÷OD\DUDN PNHPPHO \DSÕODQPÕú ED]DO ODPLQD LOH
\NVHNNDOLWHGHJ|]OHQPLúWLU
øo N|N NÕQÕ WDUDIÕ ]HULQGH LVH VDo NÕOÕ \XYDVÕ EXOXQDQ ankoraj bölgeleri
J|]OHQPLúWLU
$NVLQHSODVHERJXUXEXQGDEXLNLE|OJHoRN\DSÕODQPÕúGH÷LOGLU
Bazal
tabaka
'ÕúN|N
NÕQÕ
øoNÕQVDoNÕOÕ
\XYDVÕQGDNL
ankoraj bölgesi)
Plasebo T4 ay
PROCAPIL™ T4 ay
Kolajen IV ve laminin 5 markörleri ile ilgili imünoflüoransan bulgular
|QFHNLEXOJXODUÕWDNYL\HHWPLúWLU
PROCAPIL™ grubundaki telojen köklerde daha büyük laminin 5 flüoresan
N|NNÕQÕJ|]OHQPLúWLU
Plasebo T4 ay
PROCAPIL™ T4 ay
PROCAPIL™
35/41
$\UÕFDWHORMHQkökün kolajen IV etiketlenmesi de PROCAPIL™ gurubunda
dahaEHOLUJLQROPXúWXU
Plasebo T4 ay
PROCAPIL™ T4 ay
In vivo YHULOHU]HULQGHQoÕNDUÕP
7DP ELU WHORMHQ DúDPD\Õ NDSVD\DQ D\OÕN NOLQLN GHQH\LQ VRQXoODUÕ
PROCAPIL™ ile tedavi edilen gurupta oral Finastéride® tedaisi
X\JXODQDQ WHGDYL\H J|UH DQDMHQWHORMHQ RUDQÕQGD E\N ELU DUWÕú
J|VWHUPLúWLU
%X EXOJX 352&$3,/Œ YH 3/$6(%2 JXUXSODUÕQGDNL ELUNDo GHQHNWHQ
DOÕQPÕúRODQVDo|UQHNOHULkonusundaki morfolojik bulgularla mükemmel
úHNLOGHD\QÕGR÷UXOWXGDGÕU
7HORMHQ VDo ]HULQGH GHUPLVH L\L DQNRUDM LoLQ \DSÕODQPÕú YH G]HQOL
ELU ED]DO ODPLQD LOH PNHPPHO ELU N|N NÕQÕQÕQ \HQLGHQ ROXúXPX
\DSÕODQPÕúWÕU %X \DSÕúWÕUPD NRPSOHNV SURWHLQOHULQLQ kolajen IV’ün
YHODPLQLQ¶LQGDKDE\NPHYFXGL\HWLLOHWH\LWHGLOPLúWLU
øo N|N NÕQÕ VDo NÕOÕ \XYDVÕ YH NÕQ DUDVÕQGDNL \DSÕúPD PRWLIOHULQL
J|VWHUPLúWLU
PROCAPIL™
36/41
4.
GENEL ÇIKARIM
PROCAPIL™, saç dökülmesinden sorumlu üç olguyu hedef alan bir
potent Saç Dökülmesini Önleme kompleksidir:
•
5 -UHGNWD]ÕWHVWRVWHURQX'+7
\HG|QúWUU
•
•
Yetersiz kan perfüzyonu
'HUPDOSDSLOODGDVDoDQNRUDMÕEDúDUÕVÕ]OÕ÷Õ
352&$3,/ŒELUOLNWHKDUHNHWHGHQDNWLIPDGGHGHQROXúXU
• peptit Biyotinil-GHK, narenciyeden özütlenen bir flavonoid
olan ve vazodilatör etkisine sahip tutunma
•
SURWHLQL DSLMHQLQ VD\HVLQGH VDo DQNRUDMÕ ]HULQGH H\OHP
gösterir
•
ROHDQROLNDVLW/RYH\O\+HPVOH\DN|NOHULQGHQ|]WOHQPLúWLU
ve5α−UHGNWD]ÕLOHGLKLGURWHVtosteron üretimini inhibe eder.
øQVDQIROLNOOHUL]HULQGHYHDNWLIOHúWLULOHQJHQOHULQDQDOL]HGLOPHVL\OH
elde edilen in vitro YHULOHUúXQODUÕJ|VWHUPLúWLU
•
•
•
hUQQNDOÕFÕOÕ÷ÕVDoNÕOÕ\XYDVÕYHVHoLcL\HUOHúLPLQGHvisà-vis niteliktedir.
Vimentin, dezmogleinler, dezmokollinler, laminin 5 ve
NRODMHQ,9WXWXQPDSURWHLQOHULWDUDIÕQGDQL\L\DSÕODQGÕUÕOPÕú
\DúD\DQELUN|NNÕQÕLOHVDoPRUIRORMLVLQGHJHOLúPH
.HUDWLQRVLWLN oR÷DOPD YH VDo PRUIRMHQH]L ]HULQGH SRWHQW
aktivite
PROCAPIL™
37/41
Oldukça pozitif olan bu özelliklerin in vivo HWNLOLROGX÷XJ|UOPúWU
7HORMHQHYUH\LNDSVD\DQD\OÕNNOLQLNGHQH\352&$3,/ŒLOHSODVHER\X
NDUúÕODúWÕUPÕúYHNRPSOHNVLQEHOLUJLQVDoG|NOPHVL|QOH\LFi aktivitesini
GR÷UXODPÕúWÕU
•
PROCAPIL™ grubundaki 18 gönüllüden %67'si ortalama
DQDMHQWHORMHQ RUDQGD S RUDO X\JXODPD LOH D\OÕN
WHGDYLGHQ VRQUD )LQDVWHULGHŠ LoLQ UDSRU HGLOHQOH D\QÕ
DUDOÕNWD EHOLUJLQ ELU JHOLúLP J|VWHUPLúWLU D\OÕN
352&$3,/ŒNXOODQÕPÕQGDQVRQUDED]ÕGHQHNOHU KDWWD
GDQID]ODELUJHOLúLPJ|VWHUPLúWLU
•
dDOÕúPDQÕQ EDúÕQGD YH VRQXQGD DOÕQDQ VDo |UQHNOHULQLQ
morfolojik ve imünohistolojik analizleri, telojen saç kökü,
N|NNÕQÕYHODPLQLQLOHNRODMHQ,9\R÷XQOXNODUÕQÕQSODVHER
grubunda gözlemlenenin aksine PROCAPIL™ grubunda
EHOLUJLQELUúHNLOGHJHOLúWL÷LQLJ|VWHUPLúWLU
<XNDUÕGD\HUDODn sonuçlar dizisi, PROCAPIL™'in N|NNÕQÕUHMHQHUDV\RQX
DUDFÕOÕ÷Õ\ODGHUPLVWHWHORMHQVDoDQNRUDMÕQÕQDUWÕúÕQÕGHVWHNOH\HUHNH\OHP
J|VWHUGL÷LQLQ RQD\ODQPDVÕQÕ VD÷ODPDNWDGÕU'ROD\ÕVÕ\OD 352&$3,/Œ
VDoG|NOPHVLQL\DYDúODWÕUYHVDoIROLNOOHULQLQVD÷OÕ÷ÕQÕJHOLúWLULU
Optimum etki için PROCAPIL™'in %3'lük konsantrasyonda
NXOODQÕOPDVÕQÕ|QHULUL]
PROCAPIL™
38/41
REFERANSLAR
ALMOND-ROESLER B ve ark., 1997
Cultured dermal papilla cells of the rat vibrissa follicule. Proliferative activity,
adhesion and reorganization of the extra-cellular matrix in vitro.
Arch Dermatol Res., 289 (12), p698-704
ANDERSSON S., 2001
Steroidogenic enzymes in skin.
Eur J Dermatol., aug, 11 (4), p293-95
BAYNE EK. ve ark., 1999
Immunohistochemical localization of types 1 and 2 5-alpha reductases in
human scalp.
Br J Dermatol., sep, 141 (3), p481-91
BILLONI ve ark., 1997
Expression of retinoid nuclear receptor superfamily members in human hair
follicles and its implication in hair growth.
Act. Derm. Venerol., 77 (5), p350-5
BOYERA N. ve ark., 1997
Biphasic effects of Minoxidil on the prolifération and differentiation of normal
human keratinocytes).
Skin Pharmacol., 10, p206-20
COLIN A.B. ve ark., 1992
Cellular and extracellular involvement in the regeneration of the rat lower
vibrissa follicule.
Development, 114, p887-97 (1992).
DALLOB AL. ve ark., 1994
The effect of Finasteride, a 5 alpha reductase inhibitor, on scalp skin
testosterone and DHT concentrations in patients with male pattern baldness.
J Clin. Endocrinol. Metab. , sep, 79 (3), p 703-6
FRIGG M ve ark., 1989
Clinical study on the effect of biotin on skin conditions in dogs
Schweiz. Arch. Tierheilk, 131, p 621-25
FRITSCHE A. ve ark., 1991
Pharmakologische wirkungen von biotin auf epidermiszellen
Schweiz. Arch. Tierheilk, 133, p 277-83
GARROD ve ark., 2002
Desmosomal adhesion: structural
regulation.
Mol Membr Biol , Apr, 19 (2), p 81-94
basis,
molecular
mechanism
and
PROCAPIL™
39/41
GERST C ve ark., 2002
Type-1 steroid 5α−reductase is functionnally active in hair follicule as
evidenced by new selective inhibitors of either type -1 or type -2 human
steroid 5α-reductase
Exp Dermatol, 11, p52-8
HANAKAWA Y, 2002
Expression of desmoglein 1 compensates for genetic loss of desmoglein 3 in
keratinocyte adhesion.
J Invest dermatol., Jul, 119 (1), p27-31
JAHODA C. ve ark., 1992
Changes in fibronectin,laminin and type IV collagen distribution relate to
basement membrane restructuring during the rat vibrissa follicle hair growth
cycle.
J Anat, 181, p 47-60
JONAK C ve ark., 2002
Subcorneal colocalization of the small heat shock protein, HSP27, with
keratins and proteins of the cornified envelope.
Br J Dermatol., Jul, 147 (1), p13-9
KROHN ve ark., 2003
1,25(OH)(2)D(3) and Dihydrotestoste Interact to regulate Proliferation and
Differentiation of Epiphyseal Chondrocytes.
Calcif. Tissue Int. 2003 Jul. 24
MAQUART FX, ve ark., 1999
Régulation de l’activité cellulaire par la matrice extracellulaire : le concept
de Matrikines
Journal de la Société de Biologie, 193, (4), p 423
NUBER UA ve ark., 1996
Patterns of desmocollins synthesis in human epithelia: immunolocalization of
desmocollin 1 and 3 in special epithelia and in cultured cells
Eur J Cell Biol, sep, 71 (1), p1.13
PAUS R., 1999
A comprehensive guide for the recognition and classification of distinct stages
of hair follicle morphogenesis.
The Society for Invest. Dermatol.
PHILPOTT MP, ve ark., 1996
Whole Hair Follicule culture
Dermatologic Clinics, oct, 14 (4), p595-607
VAN NESTE D ve ark., 2000
Finasteride increases anagen hair in men with androgenetic alopecia.
British J of Dermatol., 143, p804-10
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ROUSSELLE P, 2003
Laminine 5 et réparation de l’épiderme.
COBIP, Séminaire d’enseignement, LYON, 2003
SAWAYA ME ve ark., 2001
Androgen responsive genes as they affect hair growth.
Eur J Dermatol., Aug, 11 (4), p304-8
SHELLEY W.B. ve ark., 1985
Uncombale hair syndrome: observations on response to Biotin and
occurrence in sibbings with ectodermal dysplasia.
J Am Acad Dermatol, 13 (97), p97-102
SUORMALA T ve ark., 2002
Biotin-dependent carboxylase activities in different CNS and skin-derived
cells, and their sentivity to biotin-depletion.
Int J Vitam Nutr Res , 72 (4),p278-86
TAMIOLAKIS D ve ark., 2001
Expression of laminin , type IV collagen and fibronectin molecules is related to
embryonal skin and epidermal appendage morphogenesis.
Clin Exp Obstet Gynecol, 28 (3), p179-82
ZHANG YH ve ark.., 2000
Endothelium – dependent vasorelaxant and antiproliferative effects of
apigenin.
Gen. Phamacol., 35 (6), p341-347
WARREN R ve ark., 1992
Improved method for the isolation and cultivation of human scalp dermal
papilla.
JJ Invest. Dermatol., 98 (5), p 693.
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EK
Klinik deney için kullanŦlan formülasyonlar
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INCI adŦ
Tedarikçi
Plasebo
%
Ürün
%
$úDPD
Demineralize su
Water (Aqua)
Sitrik asit
Citric Acid
0.26
0.26
Sodyum sitrat
Sodium Citrate
1.20
1.20
Inkrokuat CTC 30
Cetrimonium
Chloride
1.00
1.00
Yet. 100 Yet. 100
Croda
$úDPD
Etanol
Ethanol
8.00
8.00
Parfüm
Fragrance
Yet.
Yet.
Krillet 1
Polysorbate 20
Croda
0.40
0.40
(bkz. Özet)
SEDERMA
-
%3
%3
-
$úDPD
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