S

TS. PHAN QUC KINH

CC HP CHAT THIEN NHINC HOT TlNH SINH HC

NH XUT BN GIO DC VIT NAM

Cng ty c phn Sch i hc - Dy ngh, Nh xut bn Gio dc Vit Nam giqyn cng b tc phm

M s: 7K890Y1- DAI

196 -2011/CXB/10-14 0/G D4

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LI GII THIU

T xa xa, con ngi bit s dng mt s cy c lm thc phm v lm thuc iu tr bnh tt v cc vt thng. Theo dng lch s hnh thnh cc nn y dc hc c truyn ni ting La M, Ai Cp, Trung Quc, n , chu u, Bc M, M Latnh,...

T ch ch bit khai thc cc cy c hoang di s dng, dn dn con ngi bit trng trt nhiu loi cy lng thc, thc phm v cc cy c dng lm thuc, m phm.

u th k XIX, sau khi Friedrich Sertrner chit xut c morphin t nha qu thuc phin vo nm 1805 th cc nh khoa hc m ch yu l cc nh ho hc v sinh hc tp trung nghin cu cc hp cht thin nhin c hot tnh sinh hc t cy c v l tin cho s ra i ca ngnh Ho hc thc vt - Phytochemistry.

Cc nh ho thc vt chit xut v xc nh c nhiu hp cht c hot tnh sinh hc cao t cy c nh quinin trong v cy canh kina iu tr st rt, cafein t l ch, ht c ph c tc dng kch thch h thng thn kinh trung ng. Vitamin c t qu chanh, cam c tc dng phng v iu tr bnh chy mu di da cho cc thu th i bin lu ngy. Ngoi ra cn pht hin c nhiu hp cht c hot tnh tr su ph hoi cy trng nh nicotin t cy thuc l, Pyrethrin t hoa cc tr su, roten on t cy duc c.

Trong nhng nm gia th k XX, khi ngnh Ho hc hu c pht trin v t c nhiu thnh tu rc r trong vic pht minh cc sulfamit, aspirin, paracetamol, veronal, gardenal,... v tng hp ton phn c nhiu nhm thuc ho hc m, c hiu qu iu tr cao th ch yu cc nhm thuc quan trng l cc thuc tng hp ho hc ton phn t cc nguyn liu c bn c trong than , du m,...

Nhng sau cc nh khoa hc pht hin ra rng nhiu thuc tng hp ho hc ton phn c cu trc ho hc xa l, ngoi lai vi cu trc ho hc ca cc hp cht thin nhin nn sinh ra nhiu tc dng ph c hi cho c th con ngi m ch yu l gy qui thai, ung th v cc tai bin nguy him khc nh d ng, ic, rng tc,...

V vy, nhiu nh khoa hc quay li nghin cu cc hp cht thin nhin, v cc cht ny c sn trong thin nhin, c ngun gc thin nhin, t gy cc phn ng c hi, c bit l khng gy tc dng xu ln h thng gen ca ngi s dung, khng gy cc t bin gen. Cc hp cht thin nhin khng ch c nghin cu t cc cy c, m cn ly t ng vt, vi sinh vt v c gi chung l cc hp cht thin nhin c hot tnh sinh hc. T hnh thnh ngnh Ho hc cc hp cht thin nhin - Chemistry of Natural Products v sau pht trin thnh ngnh Ho hu c sinh hc - Bioorganic Chemistry.

Nh nhng pht minh mi ca cc nh khoa hc. ngnh Ho hc cc hp cht thin nhin cung cp cho con ngi nhiu loi thuc qu gi c tc dng phng v iu tr nhiu bnh tt nguy him nh cc cht khng snh iu tr cc bnh nhim khun nguy him, cc corticosteroid chng vim, chng d ng, cc hormon steroid sinh dc chng lo ho, tng sinh lc, ko di tui th, cc thuc iu tr ung th nh vincaleucoblastin, vincaleucocristin t l da cn, taxol t thng , camptothecin t cy Camptotheca acuminate. Nhiu nh khoa hc nghin cu trong lnh vc cc cht alcaloid, vitamin, steroid, prostaglandin, hormon peptid,... c nhn gii Nobel.

Cc hp cht thin nhin c hot tnh sinh hc khng nhng c s dng rng ri trong y hc m cn c dng ph bin trong chn nui, trng trt, th y v m phm.

c bit trong 20 nm tr li y, cc hp cht thin nhin cn c s dng rng ri v c hiu qu trong sn xut cc thc phm chc nng (functional food), b sung dinh dng (dietary supplements) hay thc phm thuc (neutraceuticals) l cc sn phm nng cao sinh lc, nng cao sc kho cho con ngi, chng oxy ho, chng lo bo, tng cng min dch, phng v h tr iu tr bnh tt, nng cao tui th nh cc carotenoid, cc flavonoid, cc vitamin, cc acid amin, cc enzym.

Cng cn ch rng, trong khoa hc khm ph v s dng c nhiu hp cht thin nhin c hot tnh sinh hc qu gi t cy c. ng vt v vi sinh vt, nhng th gii sinh vt rt phong ph v a dng v cn nhiu loi sinh vt cha c nghin cu khai thc, c bit l cc sinh vt bin, nht l cc sinh vt bin su.

Tp sch ny s trnh by cc hp cht thin nhin c hot tnh sinh hc ang c s dng lm thuc, m phm, thc phm chc nng cho ngi, cc sn phm dng cho nng nghip, cc cht ny c phn loi theo cu to ho hc thnh cc nhm chnh sau:

Chng 1. Cc cht alcaloid

Chng 2. Cc cht terpenoid

Chng 3. Cc cht steroid

Chng 4. Cc cht flavonoid

Chng 5. Cc cht vitamin

Chng 6. Cc cht khng sinh

Chng 7. Cc acid bo cha no v cc prostaglandin

Chng 8. Cc hormon

Chng 9. Cc cht khc

H Ni 2011,

TS. PHAN QUC KINH

Chng

CC ALCALOID

GII THIU CHUNG

Cc alcaloid l cc hp cht hu c trong thc vt c cha mt hay nhiu nguyn t nit trong phn t v chng c tnh kim. chit xut v xc nh cu to ho hc ca khong 10.000 cht alcaloid khc nhau trong cy c. Mt t alcaloid cn c xc nh t mt s ng vt nh kin, cc hay nm ca, lo mch.

Nhiu alcaloid l nhng cht c c tnh rt cao nh aconitin trong u, strychnin trong ht m tin, gelsemin trong l ngn, solanin trong mm khoai ty v nhiu trng hp ng c dn n t vong do dng nhm cc cht ny.

phn loi cc alcaloid ngi ta da vo v tr ca N trong phn t ca alcaloid:

+ Cc alcaloid c N mch nhnh, khng c N trong nhn nh capsaicin trong qu t, ephedrin trong ma hong.

+ Cc alcaloid c N trong nhn d vng nh nicotin trong thuc l. morphin trong thuc phin.

Tu theo bn cht ca cc vng cha nit m ngi ta chia ra cc nhm alcaloid d vng khc nhau nh sau:

PyridinPiperidin

* Cc alcaloid l dn xut ca vng pyridin hay pperidin nh mcotin trong thuc l, arccolin trong ht cau, lobelin trong cy Lohelia infalata.Ephedrin

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* Cc alcaloid l dn cht ca tropan nh atropin v scopolamin trong c c dc, cocain trong l coca.

Tropan

Quinolin

Isoquinolin

* Cc alcaloid l dn xut ca qunolin nh quinin, quinidin trong v cy canh kina.

Cc alcaloid l dn xut ca isoquinolin nh L-tetrahydropalmatin trong c bnh vi, berberin trong hong lin gai, morphin trong nha thuc phin, emetin trong r Ipeca, nuciferin trong l sen, tubocurarin trong cy Chondodendron tomentosum.

Indol

Cc alcaloid l dn xut ca indol nh strychnin trong ht m tin: reserpin trong r ba gc; vinblastin, vincristn trong l da cn.

H

Purin

* Cc alcaloid l dn xut ca purin nh cafein, theobromin trong ch.

V cc alcalod c'cc d vng khc nh a-dichroin (l thng sn) c nhn quinazolin, solanidin (trong mm khoai ty) c nhn steroid, aconitin (trong u) c nhn cu trc terpenoid,...

- Cn c vo s' ho tr ca nit, ngi ta cn chia ra cc nhm alcaloid khc nhau;

+ Cc alcaloid c nit ho tr ba hu ht l cc alcaloid nm trong nhm ny. V d: ephcdrm trong ma hong.L-tetrahydropalmatin trong c binh vi.

+ Cc alcaloid c nitd hoa tri 5. Co hai nhom nh, cc alcaloid bc 4 nhii palmatin trong hong dang, berberin trong hong lien gai. Cc cht ny c mu vng dam.

Cc Noxyt alcaloid nhii genoscopolamin

NO

Genoscopolamin

Di tc dng ca nc oxy gi cng c th chuyn nhiu alcaloid thnh cc N-oxytalcaloid (genoalcaloid) nh genoatropin, genostrychnm. Khi chuyn sang genoalcaloid th c tnh ca alcaloid s gim i nhiu ln nhng vn gi c cc hot tnh iu tr ca chng.

L HO7NH CA CC ALCALOID

a phn cc alcaloid di dng th rn v khng c mu. Cc alcaloi ch c cc nguyn t c, H, N th thng th lng nh nicotin. i b phn cc alcaloid c c cc nguyn t" c, H, N, o trong phn t v thng th rn, khng tan trong nc, tan trong cc dung mi hu c. Chng thng c mu trng hay khng c mu. Chng c th to mui vi cc acid v c v hu c, cc mui ny tan trong nc nhng khng tan trong cc dung mi hu c. Ngi ta thng s dng cc c tnh ny chit xut v tch ring cc alcaloid t dc liu.

Trong khi cc alcaloid c nitd ho tr 5 (amin bc 4) th thng c mu vng cam hay vng . Bn thn cc alcaloid ny tan c trong nc v khng tan trong cc dung mi hu c. Cc mui ca chng cng tan c trong nc v trong cc dung dch cn long.

CC PHNG PHP IU CH CC ALCALOID

Ch c vi chc alcaloid c s dng rng ri trong y hc v nng nghip nh nicotin, anabasin, atropin, hyoscyamin, scopolamin, quinin, quinidin, L-tetrahydropal matin, berberin, morphin, codein, papaverin, emetin, tubocurarin, strychnin, vincamin, vinblastin, vincristn, yohimbin, cafein, theobromin, theophylin, ephedrin, colchicin,...

Cc quv trnh iu ch cc alcaloid da vo cc c im ho l ca tng alcaloi ring bit. V d: vi alcaloid nicotin th dng phng php bc hi cng hi nc. C th: tn nh sdi thuc l sau khi sy kh, kim ho bng ammoniac hay Na2COn hoc dung dch NaOH long chuyn cc mui alcaloid trong cy thnh dng base ri ct ko bng hi nc. Thng dung cc dung dch acid chuyn nicotin lng thnh cc mui phn lp ring v tinh ch.

Vi cc alcaloid bc 3 dng rn th s dng cc phng php sau:

- Chit cc alcaloid di dng mui bng cc dung dch acid long.

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Nguyn liu sau khi tn nh c chit xut bng dung dch acid acetic long hay dung dch acid sulfuric long, c th un nng chit th s t c hiu sut cao hn.

Cc dung dch chit c cha cc alcaloid di dng mui c bc hi di p sut gim thnh cao c. Sau kim ho chuyn cc alcalod thnh dng base v dng dung mi hu c chit cc alcaloid ny. Bc hi cc dung mi s c hn hp cc alcaloid.

Chit xut cc alcaloid di dng cc base bng cc dung mi hu c.

Tn nh nguyn liu, lm m v trn vi Na2C03 hay NaOH chuyn cc alcaloid thnh dng base. Sau chit bng dung mi hu c thch hp hoc bng phng php ct hi lu hay bng phng php ngm kit. Thng s dng cc dung mi hu c nh xng nh. benzen, chlorofoc, dichloromethan chit.

Sau khi nhn c dch chit th bc hi bt dung mi di p sut gim ri ho dch chit c c vi cc dung dch acid long. Nh vy cc alcaloid s chuyn sang cc dng mui tan c trong dung dch. Kim ho dung dch acid ny chuyn cc alcaloid sang dng base. Cc alcaloid s kt ta, c th lc ly ring hay c th dung cc dung mi hu c thch hp chit xut chng.

Sau khi ct thu hi dung mi th s nhn c hn hp cc alcaloid th.

Cng c th dng cn ethylic chit xut thng cc alcaloid di dng mui trong cy c. Sau bc hi cn thnh cao c ri kim ho chuyn cc alcaloi dng mui thnh cc alcaloid base v tip tc chit xut nh. cc phn trn.

Hm lng cc alcaloid trong cy c c th c t vi phn trm (c khi trn 20%) cho n vi phn vn hay phn mi vn. V d: trong l da cn c cha mt phn vn vinblastin v mt phn mi vn vincristin l nhng alcaloid c tc dng iu tr ung th mu. Trong da cn c khong 150 alcaloid khc nhau nn vic tch ring v tinh ch cc alcaloid l rt kh khn v phc tp.

tch ring cc alcalod th ch yu s dng cc phng php kt tinh khc nhau bng cc dung mi khc nhau trong cc diu kin pH khc nhau. Cng c th s dng phng php sc k ct hay phng php trao i ion.

Trong phm vi phng th nghim th thng s dng phng php sc k bn mng iu ch, sc k ct, sc k lng cao p tch ring tng alcaloid tinh sch. Sau s dng cc phng php o nhit nng chy, o nng sut quang cc, o ph t ngoi, ph hng ngoi, ph cng hng t ht nhn v khi ph xc nh tng alcaloid.

Mt s" phng php chit xut v xc nh cc alcaloid s c trnh by trong cc phn sau.

HOT TNH SINH HC CA CC ALCALOID

Nhiu alcaloid c c tnh cao, ch vi liu vi miligram l c th gy t vong cho ngi. Cc alcaloid nh cocain, morphin l nhng cht ma tu nguy him. Ephedrin v cc dn cht ca chng l cc cht thuc nhm doping.

Ni chung alcaloid c cc tc dng snh hc ri\t a dng, ch yu cc alcaloid c s dng lm thuc nh:

Cc thuc c ch thn kinh trung ng nh: morphin, scopolamin, Ltetrahydropalmatin.Cc thuc kch thch thn kinh trung ng nh: strychnin, cafein.Cc thuc iu tr bnh tim nh: quindin, amalin.Cc thuc iu tr bnh cao huyt p nh: reserpn, ajmalixin.Cc thuc chhg co tht nh: papaverin.Cc thuc tr hen suyn nh: atropin, theophylin, ephedrin.Cc thuc chng st rt nh: quinin, chng l amp nh emetin.

-Cc thuc chng ung th nh: vinblastin, vincristin, colchamin,

ellipticin.

Cc thuc c tc dng khng sinh, chng vim nh: berberin.Cc thuc cng ng nh: yohimbm.Cc thuc tr ho nh: codein.Thuc lm mm c nh: tubocurarin.Cc alcaloid ca thuc l, thuc lo, ca c bch b v ca l na, ht na cn c s dng lm thuc tr su, bo v ma mng.

Tm li, tng alcalod khc nhau c cc hot tnh sinh hc khc nhau v cng ch khong vi chc alcaloid c s dng rng ri trong y hc v trong nng nghip.

Trong ti liu ny ch i su vo cc alealoid sau: Atropin v scopolamin, cocain, quinin v quinidin, L-tetrahydropalmatin v palmatin, berberin, morphin, codein, emetin, tubocurarin, strychnin, reserpin, vincamin, vinblastin, vincristin, cafein, theobromin, colchicin, aconitin,...

Atropin v cc alcaloid nhm tropan

N

D,L-tropintropat

(D,L-hyoscyamin)

Cc alcaloid nhm tropan l (-) hyoscyamin v ng phn raxemic atropin v hyoscin (scopolamin). l cc este. Khi thu phn chng bng nc baryt nhit nng 60c th atropin s cho acid tropic v tropin, cn hyoscin th cho acid tropic v oscin (hay scopn).

Cc alcaloid ny c trong cc cy h C Solanaceae cng vi khong 40 alcaloid khc. Cc alcaloid tropan khc cn c trong mt s cy h Erythroxylaceae nh cocan trong l cy coca v mt s" cy thuc nhiu h khc nh Convolvulaceae, Dioscoreaceae, Rhizophoraceae, Cruciferae v Euphorbiaceae. Hin nay bit khong 200 alcalod l dn cht ca tropan nhng trong y hc ch s dng hyoscyamin, atropin, scopolamin, v trc y c s dng cocain lm thuc gy t.

Cc nguyn liu d chit xut cc alcaloid tropan l:

L cy Datura stramonium c cha 0.2 - 0,45% alcaloid ton phn, trong ch yu c hyoscyamm v scopolamin v mt t atropin do hyoscyamin c racemic ho.

L cy Hyoscyamus niger c cha 0,045 - 0,14% alealoid ton phn, trong ch yu c hyoscyamn v scopolamin.

nh hoa v l cy Atropa belladonna cha 0,3 - 0,6% alcaloid ton phn, trong ch yu l scopolamin, cn r ca cy ny cha 0,4 - 0,8% alcaloid ton phn m ch yu l hyoscyamin.

Cc cy trn khng c Vit Nam, nc ta c cv C c dc (Datura metel) c cha scopolamin v atropin l, hoa v r. T lu, C c dc c s dng trong v hc c truyn lm thuc iu tr hen suyn.

C c dc cn c gi l lc lc, mn la thuc h C Solanaceae. Cy ny mc hoang nhiu ni khp Vit Nam, nht l cc tnh Trung B.

C c dc l cy c.

ng Th Hng Vn, Phan Quc Kinh, Nguyn Vn Ix>ng (Trng i hc Dc H Ni) chit c scopolamin l alcaloid ch yu ca l C c dc Vit Nam. Sau Vin Dc liu chit c hyoscvamin v atropin.

Alcaloid ton phn trong l l 0,1 - 0,5%, trong hoa l 0,25 0,6%, trong r l 0.10 0,20% v trong qu l 0,12%.

Y hc c truyn dng cc b phn ca cy C c dc diu tr ho, hen, thp khp, chng co tht, gim au trong lot d dy, rut, cha tr, chng say sng.

Atropin di dng tinh th hnh lng tr, kt tinh trong aceton. Nhit d nng chy 114 - 116uc. t tan trng nc, d tan trong alcol. chlorofoc, te v aceton. Trong y hc thng s dng dng mui a tropin Sulfat tan c trong ntc pha thuc tim.

Atropin c tc dng c ch i vi giao cm v chng tit cholin, chng co tht c trn nn c tc dng lm gim au. Kch thch c, gin ng t nn c th dng to gin ng t trong vi g.

Ch yu dng iu tr cc cn au tht ng tiu ho v tit

niu. Ngi ln dng 0,25 lmg chia lm 4 liu nh, ung trong 1 ngy. Tim di da 0,25 0,5mg chia lm 2 liu trong 1 ngy d di dng atropn sulfat. Cn dng ung phng say tu, xe, my bay v dng cp cu trong iu tr ng c cc thuc tr su ln hu c.

N o

Trong y hc cn s dng genoatropin, cht ny c tc dng cha bnh nh atropin nhng c tnh li gim i nhiu ln, dng an ton cho ngi bnh hn atropin.

Hyoscyamin c hot tnh v c tnh mnh hn atropin 2 ln, nn c dng nh atropin nhng ch vi liu 1/2 liu ca atropin.

Trong y hc cn s dng scopolamin di dng bromhydrat. Scopolamin base l cht lng sn st. [a]^ = 28c tan c trong 9,5 phn nc, d tan trong nc nng, alcol.

Scopolamin bromhydrat nng chy 195c. Kt tinh trong nc di dng trihydrat, d tan trong nc, t tan trong chlorooc, khng tan trong te. Scopolamin c tc dng lm lit i vi giao cm hn atropin, nhng c tc dng c bit an thn lm du h thn kinh trung ng, v vy c tc dng trong iu tr chng au dy thn kinh v bnh lit rung (Parkinson), dng phng chhg say my bay, tu, xe.

Ch yu dng iu tr au do co tht, sung huyt cc b, do chn thng hoc vim, au lng, bong gn. Cn dng lm thuc an thn, gim au giai on tin m, tiu phu thut, ni soi. Cn ctc dng chng d ng. Liu ung hay tim di da cho ngi ln l 0,3 - 0,6mg/ngy, chia lm 4 ln. L thuc c tc dng rt c.

OCOC6H5

Cocain

Cocain

L alcaloid chnh ca l cy Erythroxyon coca v l cy Erythrocyon truxiUense. cc cy ny c trng bt hp php Nam M. Cy coca c trng t xa xa bi th dn Inca. Nm 1860 chit c cocain t l coca.

Trong l coca c t 0,7 1,5% cc alcaloid chnh l cocain, cinamoyl cocain v atruxihn cocain. L coca trng Nam M v Sri Lanca c cha nhiu cocain, trong khi l coca trng Nht Bn li c nhiu cinamoyl cocain.

Cocain kt tinh hnh phin trong cn, nng chy 0 nhit 98c, [a]p8 = 35 (cn 50), t tan trong nc, d tan trong chlorooc, te.

Trong V hc c dng di dng cocain hydroclorua, tinh the khng mu, khng mi, v ng sau gy t li v mi, nng chy 195c, d tan trong nc, khng tan trong te. c dng lm thub gy t ti ch, dng trong phu thut v nht l dng trong nha khoa.

1.3.3. Quinin v Quinidin

H3CO

Cocain l cht ma tu gy nghin nguy him, thng con nghin s dng di dng ht. Cocain l alcaloid c, gy nghin.

L hai alcaloid ca cy canh kina (Cinchona sp.), thuc h C ph (Rubiaceae). y l cy thuc v nguyn liu sn xut quinin v quinidin ngun gc Nam M, vi 4 loi quan trng nht l.

Cinchona succirubra Pavon c cha 6,5% alcaloid ton phn, trong c 30 - 60% l cc alcaloid nhm quinin.

Cinchona ledgeriana Moens.

Cinchona calisaya Weddell.

Cinchona officinalis L.

T lu, v cy canh kina c dng lm thuc tr st rt Nam M. T nm 1630, ngi ta bit dng v cy ny tr seit v t nm 1677 c s dng London vi tn V Pru.

T cy mc hoang, nm 1792, cc nh khoa hc t chc trng trt cy canh kina nhiu vng khc nhau trn th gii, nht l Angeri, Pru v Java, Bollivia v sau l Malaysia, Vit Nam v chu Phi (Camrun, Ghin).

Vit Nam, cy canh kina c trng Lm ng ch yu l loi Cinchona ledgeriana. L cy g cao 10 15m, l mc i nguyn, gn l hnh lng chim, phin l hnh trng hoc hnh mc, mu xanh lc hay nht, cm hoa l chm sim hay ng u cnh mu trng hoc hi hng, lng tnh, bu di. Bu c 2 ngn, nhiu non. Qu nang, ht c cnh. B phn dng l v cy. Canh kina Vit Nam c cha 6 10% alcaloid ton phn, trong ch yu l quinin, quinidin ch c vi hm lng nh, ngoi ra cn c khong 20 alcaloid khc.

V canh kina c tc dng b, v ng, kch thch tiu ho, h nhit, c bit c tc dng dit k sinh trng st rt (tc dng ca quirn). v cy canh kina l nguyn liu sn xut quinin v mt phn nh quinidin. i b phn quinidin - thuc iu tr lon nhp rung tim c bn tng hp t quinin bng 2 phn ng oxy ho v sau hydrogen ho tr li e thay i li cu hnh khng gian.

Quinin di dng cc tinh th hnh kim, nng chy 177wc, [a] - -169 (cn 97). Dung dch quinin trong H.^SCb long cho hunh quang mu xanh. t tan trong nc, tan trong alcol chlorofoc. Hu nh khng tan trong te du m.

c dng di dng quinin Sulfat ung v quinin dihydroclorid tim. Quinin c tc dng dit th phn lit ca k sinh trng st rt trong mu. Hu nh khng c tc dng ln th giao t nn ch c tc dng iu tr m khng c tc dng phng bnh st rt.

Ngi ln ung 1 - l,5g/ngy, uhg lin tc 5-7 ngy dng mui quinin Sulfat. Tim 0,6g/mi tim, 2 3 ln/ngy di dng mui quinin hydroclorid hay quinin dihydroclorid.

Hin nay quinin vn l thuc ch yu iu tr st rt, nht l st rt c tnh, c th dng phi hp vi Fansidar. Dng quinin c th c tc dng ph gy tai v c th gy ic. Liu cao trn 8g c th gy t vong cho ngi.

Cn dng Quinidin gluconat:

C tc dng iu tr bnh lon nhp rung tim.c dng di dng thuc tim, lml c cha 80mg quinidin gluconat,Quinidin cng c th gy cc phn ng ph nh quinin.

Cc alcaloid l dn ch't ca isoquinolin

L-tetrahydropalmatin v palmatin ciorua

L-tetrahydropalmatin - mt alcaloid nhm isoquinolin l alcaloid chnh ca c Bnh vi Vit Nam (Stephania glabra).

Cy ny mc hoang cc vng ni, nht l ni vi min Bc, min Trung v ng Nam B. B phn dng l c. Phan Quc Kinh v cc cng s (1965) xc nh alcaloid chnh ca c binh vi Vit Nam l Ltetrahydropalmatin ch khng phi l Rotundin nh TS. Kondo (Nht Bn) xc nh sai. Cc nh khoa hc Nht sau d nh chnh li sai lm ny.

Phng php chit xut:

C bnh vi c thi mng, nh v sy kh, sau tn thnh bt. Bt c lm m vi dung dch bo ho Na2COa chuyn ccalcaloid dng mui sang dng base v chit nng bng benzen (un nng bng hi nc). Sau tch dch chit benzen v d ngui.

Acid ho dch chit benzen vi dung dch acid sulfuric long, lc k nhiu ln, e lng v tch phn nc acid c cha cc alcaloid di dng sulfat. Lm tip 2 ln vi dung dch acid sulfuric long, tch dch acid. Gp cc dch acid, kim ho n pH -11 bng Na2C03. S xut hin ta trng ca cc alcaloid base khng tan trong nc. qua m. lc ly ta. Sy kh, tn nho (thng t t l 1,5 - 2% tnh t dc liu kh).

Sau d kt tinh bt alcaloid ton phn nhiu ln bng cn th s tch dc Ltetrahydropalmatin tinh khit (t t 1 - 1,5%). Ri cho alcaloid vo dung dch acid hydrochloric long cho tan ht, bc hi dung dch cn li 1/10 th tch. nhit lnh th s xut hin ta L-tetrahydropalmatin-hydroclorua di dng bt trng.

NaBH4

D,L- tetrahydropalmatin

(khng c hoat tnh sinh hoc)

IjC v sau sy kh 80. Alcaloid base nng chy 141 142c, [] - -291 (cn 95), kt tinh trong methanol. un L-tetrahydropalmatin trong methanol vi od v KH th n s b oxy ho to thnh palmatin di dng iodua. Sau hydrogen ha palmatin iodua bng natriboro hydrd th dc: 1) v L - tctrahydropalmatin.

Palmatin cng c vi mt lng nh trong c bnh VI. Palmatin c nhiu trong cy hong dng (Vibraurea tinctoria), cy ny mc

hoang nhiu ni nc ta. Palmatin c dng lm thuc khng sinh phng chng dch l, tr bnh au mt di dng palmatin clorua. em hydrogen ho bng natri borohydrit th s nhn c D,L-tetrahydropalmatin. Cht ny ch c hiu lc an thn bng a ^-tetrahydropalmatin v ng phn Dtetrahydropalmatin khng c hot tnh sinh hc. D,Ltetrapalmatin c s dng nhiu Trung Quc di dng thuc ung v thuc tim gim au, an thn.

Cng dng chnh ca L-tetrahyropalmatin l an thn, gim dau, chng co tht, gin c. Ngi ln uhg 30 60mg/ngy, chia lm 2 ln. Dng qu liu quv nh s b ng c. Palmatin clorua c dng di dng dung dch 0,3 - 0,5% lm thuc nh mt do c tc dng khng sinh v chng vim.

1.3.4f2. Berberin clorua

L alcaloid chnh ca cc cy:

Hong lin gai (Berberis wallichiana D.CJ.Hong lin chn g (Coptis teeta Wall).Hong b (Phelodendron amurense), mc hoang v c trng xung quanh dy Hong Lin Sn.Vng ng (Coscinum fenestratum), mc hoang Nam Trung R v cc tnh ng Nam B. '

nc ngoi, berberin c sn xut t cc loi cy Berberis vulgaris, Berberis aquifolium, Hydratis canadensis v Coptis chinensis Franck (Hong lin bc). Trong y hc s dng berberin dng mui clorua hay mui Sulfat.

* Phng php chit xut:

Bt dc liu c chit bng cn etylic 70 theo t l 1 dc liu - 8 dung mi (kg/lt) v c un hi lu si trong 2 gi. Lc nng dch chit, bc hi dch chit cho n thnh cao sn st.

Thm dung dch NaCl bo ho, trn du 30 pht, qua m. Lc ly ta berberin clorua mu vng cam sm. Kt tinh li nhiu ln trong cn etylic 75 th s nhn c berberin clorua mu vng da cam.

T v r hong lin gai chit c berberin clorua vi hiu sut 11%. T thn cy vng ng chit c berberin clorua vi hiu sut 2 - 3%.

Berberin clorua c di dng tinh th hnh kim, rt t tan trong nc lnh, tan nhiu trong nc nng, hu nh khng tan trong cn lnh, chlorofoc, te. e c ch phm tan trong nc th iu ch berberin sulfat (C2qHihN0i).^S0.1, cht ny di dng tinh th hnh kim mu vng, tan trong nc, tan trong cn.

* Phng php diu ch:

Ho berberin clorua vo nc nng, cho thm Na2CO;! cho n pH = 9. Sau li cho thm dung dch H2S04 10% cho n pH = 3 (acid). Bc hi dung dch thnh dng c, ngui v lm lnh th s ta berberin su 1 fat, Lc ly ta, kt tinh li trong cn 70.

em hvdrogen ho berberin sulfat bng NaBH,| th s nhn c D,L-tetrahydroberberin, cn gi l canadin. Canadn c tc dng an thn. Alcaloid canadin t nhin c trong cy Hydratis canadensis, bn cnh berberin v hydrastin.

C. Lutein dipalmitrat kt tinh hnh kim, mu , cn c tn l helenien, adaptinol. Lutein hp ph nh sng xanh, cn c kh nng hp ph nh sng vng v nh sng d cam. Lutein cn c cho vo thc n nui g rut trng g c mu m hn v da g c mu vng. Trong y hc, lutein c dng lm thuc, thc pham chc nng v cn c dng lm m phm.

Trong c th ngi, lutein tp trung im vng ca mt, mt s vng mc v l mt cht thit yu cho kh nng nhn ca mt. Ngi ta cho rng, lutein bo v mt trc cc tc hi stress, oxy ha v nng lng photon cao ca nh sng xanh. Lutein c tc dng phng v h tr iu tr bnh thoi ha im vng ngi cao tui. xc nh nguvn nhn gy ra bnh thoi ha im vng l do hm lng lutein mt b gim st v tui cao v c th dn ti m la. Theo thng k M c 10% ngi tui 66 - 74 b bnh thoi ha dim vng v 30% ngi c tui t 75 85 b bnh ny.

Nguyn nhn ca cn bnh ny l con ngi c cung cp lutein t thc n nh rau, qu. Cn ngi gi do gim kh nng hp th thc n nn dn ti hm lng lutein mt b gim ht.

T nm 1996, lutein c dng lm thc phm chc nng phng v h tr iu tr bnh thoi ha dim vng mt. Lng s dng lutein hng ngy t 2 - lOmg.

V hot tnh ca lutein t do v lutein este th c kin cho rng, lutein este c d hp th km hn lutein t do (Alexandra A.R., 2001, Kemin Health). Trong cng nghip, lutein c sn xut t cnh hoa cc vn th (Tagetes erecta). Ngoi ra, lutein cn c 0 rau chn vt, ci Brussel, sp l xanh,...

Tm li, lutein c dng e phng v h tr iu tr bnh thoi ha im vng mt, phng chng m la. Ngoi ra, cn c tc dng phng v h tr iu tr bnh qung g, phng v chng li tc hi ca nh sng xanh. Vi liu t 2 lOmg/ngy, lutein cn c dng lm m phm bo v da v lm cht chng oxy ha.

Gi tr thng mi hng nm trn th gii v lutein nh sau:

Th trng Dc phm: 190 triu USD.

Th trng Thc phm chc nng: 110 triu USD.

Th trng thc n cho g v cc lnh vc khc: 175 triu USD.

Cc vn th c trng nhiu Tin Giang, ng Thp, Thnh

ph H Ch Minh, Bnh Thun v H Ni ly hoa trang tr v cng bi. Vit Nam cha c ti u no d cp ti lutein trong hoa cc vn th. T nm 2003, Vin Khoa hc Cng ngh mi, B Quc phng bt u nghin cu chit xut lutein t hoa vc vn th trng thnh ph' H Ch Minh, thnh ph" Phan Thit, Tin Giang v H N.

Thiu tng Phm Sn Dng ch tr ti cp Vin KH-CN Qun s, B Quc phng v nghin cu chit xut lutein t hoa cc vn th v iu ch thc phm chc nng Ocpola cha 3mg lutein/vin. Ocpola c B Y t cho php sn xut. Giy chng nhn tiu chun sn phm s" 559/2007/YTCNTC do Ph Cc trng Cc An ton V sinh Thc phm Hong Thy Tin k ngy 24/01/2007. ti nghin cu v Ocpola c nghim thu v hon thnh nm 2008.

T nm 2004, Khoa Thc phm, Trng i hc Bch khoa H Ni v Khoa Sinh hc, i hc Khoa hc T nhin (i hc Quc Gia H Ni) cng TS. Phan Quc Kinh hng dn hai smh vin lm Lun vn tt nghip k s v nghin cu chit xut lutein t hoa cc vn th v mt nghin cu sinh hon thnh Lun n Tin s Sinh hc v nghin cu cc carotenoid t cy c Vit Nam, trong c hoa cc vn th.

Nm 2009, TS Phan Quc Kinh, cng ty Kinhphar nghin cu bo ch vin nang mm Kinhphar Ocula c cha lutein chit xut t hoa cc vn th Vit Nam v piperin, alcaloid ca ht h tiu, lm tng s hp th lutein vo c th. B Y t cho php cng ty Kinhphar sn xut vin nang mm Kinhphar Ocula theo giy chng nhn tiu chun sn phm s 1476/2010/YT-CNTC.

Trn th trng Vit Nam, B Y t cho php Cng ty CP Sn xut v Thng mi Hng Bng sn xut mt s sn phm TPCN c cha lutein nhp ni v cho php lu hnh nhng sn phm nv trn th trng.

Astaxanthin

Astaxanthin l mt carotenoid nhm terpen xanthophyl vi tn L vng.

Ging nh nhiu carotenoid, n c mu, tan trong lipid. N c trong cc loi vi to, nm men, c, tm, chim,...

Basil Weedon l ngi u tin xc nh cu to ha hc ca astaxanthin. Astaxanthin l mt carotenoid khng c hot tnh vitamin A trong cd th ngi. Nh bit, liu vitamin A qu cao l c cho cd th, cn astaxanthin c c tnh thp. N c hot tnh chng oxy ha. Astaxanthin c dng lm cht b sung dinh dng cho ngi, gia '.'m v chn nui thy sn. Trong cng nghip s dng c astaxanthin thin nhin v astaxanthin tng hdp.

Astaxanthn thin nhin c ly t cc loi tm, cua, s, hn d bin nh Euphausia pacifica, Euphausia borealis, Tm Pandalus borealis, nm men Xant.hophyllomyces dendrorhous v vi to Haernatococcus pluvialis. Vi to l ngun nguyn liu giu astaxanthin nht sn xut astaxanthn thin nhin, t lkg sinh khi kh vi to ny c -lOg astaxanthin.

Ngun nguvn liu quan trng khc chit xut astaxanthin l nm men Xanthophyllomyces dendrorhous cha 100% astaxanthin t do. Astaxanthin tng hdp t cc cht ha du m c gi 2.000 USD/kg, hng nm c th gi dng khong 200 triu USD cho astaxanthin.

Do astaxanthin tng hdp c ln cht ng phn, nn ngi ta thch s dng astaxanthin thin nhin hn. lkg astaxanthin thin nhin c gi 7.000 USD.

Nm 1948, nh khoa hc George Wald (t gii Nobel) s dng astaxanthin lm phm mu thc phm v cht b sung dinh dng cho gia cm, tm, c v cho ngi.

Astaxanthin dng cho ngdi c tc dng chng oxy ha, tt cho h thng tim mch, min dch, chng vim v cc bnh thoi ha thn kinh. X cn c tc dng chng ung th.

CU HI N TP CHNG 2

Tinh du bc h c cha cc monoterpenoid no? Cng thc ha hc v cng dng ca chng.Monoterpenoid chnh ca cy thng l cht g? Cu to ha hc ca cht .Cc hot cht chnh ca Cc tr su. Cng dng ca chng.Cy n long c cha cc cht terpenoid loi g? Cng dng ca chng.Parthenoid c trong cy no? Cng thc ha hc v cng dng ca Parthenoid.Cng dng ca cc La M v cc c.Artemisinin c trong cy no? Cc dn cht tr st rt ca artemsinin.Cng thc ha hc v c tnh ca hot cht c cy bng.Cc thuc tr ung th t cy thng . Cu to ha hc ca chng.Cc hot cht v cng dng ca l ngn hnh.Cc saponin ca cam tho c hot tnh sinh hc nh th no? Cu to ha hc ca chng.Nhn sm c cha cc saponin thuc nhm no? Cng dng chnh ca nhn sm,Pcaroten c trong cv c no? Cng dng ca p-caroten.Lutein c trong nguyn liu no? Cu to ha hc v cng dng ca lutein.Cholesterol

76

75

Chng3 CC STEROID

74

GII THIU CHUNG

Phenantren

Perhydrophenantren

Cyclopentan perhydrophenantren (Gonn)

Cc cht steroid l mt nhm ln cc hp cht c cu to vi khung c bn l cyclopentan perhydrophenantren, cn gi l gonan.

Cc cht steroid cn c thm 2 nhm -CH3 vi cu to nh sau:

Cholesterol l cht sterod c nhiu trong cc ng vt, cn thc vt c cc cht sitosterol, stigmasterol v campesterol.

Trong c th ngi, cholesterol c chuyn ha sinh tng bp cc acid mt, cc hormon sinh dc, cc hormon v tuyn thng thn. Cholesterol c cng thc ha hc nh sau:

Drfa vao cau true hoa hoc cua cholesterol, cac nha hoa hoc da quy dinh cac danh so cac cacbon trong phan trl steroid nhp sau:

20 22 24

Khung cd ban va each danh so cac cacbon trong phan tii steroid: Tuy vao vi tri khong gian cua H 6 C5> cl hiidng a hay p ma chung ta co cac chat 5acholestan va 5pcholestan.

Co ba nhom hormon steroid la dan chat 5a-cholestan, do la: 5-apregnan, 5a-androstan, 5-aestran. Dan chat 5apregnan gom co: progesteron noi tiet to" sinh due nO va hydrocortison noi tiet to cua tuyen thpdng than. Dan chat 5a-androstan co testosteron - noi

t t sinh dc nam. Dn cht 5-aestran c 17--estradiol ni tit t sinh dc n.

5--androstan

OH

5-cx-estran

OH

D. Barton, nh ho hc t nn mng cho cu hnh khng gian ca cc phn t ho hu c nhn gii Nobel v chuyn ngnh ny xc nh cu hnh khng gian ca cc cht steroid'nh sau:

Trc ht l cu hnh ca cu hnh hai vng: trans decalin v cis decalin. V sau l cu hnh 4 vng trong phn t cc cht steroid.

90

89

H

77

^ Trans decalin

Cu hinh steroid 4 vng:

Trn cc c s thit lp c cc khung c bn ca cc nhm, loi cc cht steroid nh sau:

Phn loi cc steroid:

Cc steroid bao gm nhiu loi thuc v thc phm chc nng quan trng c dng phng v iu tr cc bnh him ngho nh thp khp, chong, d ng, suy tim, cc cht steroid cn dng iu tr cc bnh thiu nng cc tuyn sinh dc, iu tr v sinh, ung th v c bit l cc thuc chng th thai gip cho nhn loi hn ch c kh nng sinh qu mc.

Cc cht steroid c phn loi theo cu to ha hc v mt phn theo hot tnh sinh hc, bao gm cc nhm sau:

CC STEROL

Gm cc steroid ng vt nh cholegterol c trnh by phn gii thiu chung v cc sterol thc vt.

Cc sterol thc vt (Phytosterol) c nhiu trong cc loi cy c v nm men nh sitosterol c trong la m, go, g; stigmasterol c trong ht u tng; ergosterol c trong nm ca la mch, men bia.

Trong cng nghip Dc phm hin nay, cc steroil ny c sn xut t ph liu cng ngh lm x phng t du u tng v cng ngh sn xut giy t g.

Hn hp sterol ca u tng ch yu c dng lm nguyn li bn tng hp cc hormon steroid, nht l cc thuc chng th thai. Y hc cn s dng hn hp cc sterol thc vt lm thuc ung phng v iu tr x va ng mch (tranh chp cholestrol trong c th ngi) v iu tr bnh nh chu vim. Trong cm go c cha yoryzanol, l este ca sitosterol vi acid erulic. yoryzarol c tc dng chng oxy ha, chng lo ha. N cn c tc dng iu tr cc ri lon h sinh dc n. Cc cht ny c s dng nhiu d Nht, c, Hn Quc.

OH

Ecdvsteron l mt cht c trong su b (nh tm) v trong mt s" loi thc vt. Trong thc vt, ecdysteron c sinh tng hp t cholestol. Hin ti, ecdysteron c dng tng sinh lc. tng qu trnh ng ha, tng dng v tng thnh tch thi u cho cc vn ng vin th dc th thao.

CC ACID MT

Ti mt cha dch mt l tc nhn gip cho c th hp th cc cht dinh dng. Dch mt c cha nhiu acid mt c cu to steroid nh acid cholic trong mt gia cm, acid ursodeoxycholic trong mt gu, mt chut v c mt ngi.

Y hc hin i dng acid cholic lm thuc thng mt, li mt dng cho nhng ngi vim gan, ri lon chuvn ha acid mt. dng acid chenodeoxycholic c trong mt gia cm lm thuc tan si mt di dng urig ngy 0,5 - lg ngy. Cc nh khoa hc bn tng hp cng nghip c acid ursodeoxycholic hot cht chnh t acid chenodeoxycholic. Acid ursodeoxvchplic c dng lm thuc lm tan si mt, tr vim gan, x gan. Ngi ln ung 0,2 - 0.4g/ngy.

CC SAPONIN STEROID

Cc saponin steroid c nhiu trong cc cv Mt l mm nh cc cy h C nu - Dioscoreaceae, Thy tin - Amaryllidaceae. Hnh - Lliaceae, Ru hm - Tacacea.

Trong thc vt, cc saponin ny dng glycosid, cha cc aglcon steroid, gn vi cc phn dng (glucose, galactose,...). Khi thv phn bng acid long hay bng enzym th s nhn c cc aglvcon steroid c gi l cc sapogcnin steroid. Cc saponin stcroid th tan trong nc v c kh nng to bt.

Cc sapogenin steroid th khng tan trong nc nhng tan trong cc dung mi hu c v cn cao . Da vo cc tnh cht ny. ngi ta tin hnh chit xut cc saponin steroid trong dc liu. Trong thc vt cc saponin steroid cng c sinh tng hp t cholesterol.

Diosgenm l nguyn liu hn tng hp cc hormon steroid.

Ngun nguyn liu sn xut diosgenin trn th gii gm cc cy sau:

Mexico v Trung M: Dioscorea mexicana, Dioscorea composite.

Trung Quc: Dioscorea collettii, Dioscorea pathaica, Dioscorea nipponica.

Guatemala: Dioscorea floribunda.

n : Dioscorea deltoidea, Dioscorea prazeri, Dioscorea speciosus.

Nht: Dioscorea tokoro.

Hecogenin - l saponin streoid c dng e bn tng hp cc thuc glucocorticoid th h mi nh {1methason li c chit xut t cc cy sau:

Da M: Agave mexicana.

Nam M, Israel, Kenia, Trung Quc: Agave sisalana:

Mexico: Agave rgida.

T l hecogenin ch c 0,01% trong l cy da M. Nhng n l dit phm ca cng ngh sn xut si t l cy ny.

Chit xut diosgenin t c Dioscorea sp.

Vit Nam c nhiu cy c cha dosgenin, nh c mi gng, c nm gng, ru hm, ma d, hi u tho,... v cc cy di thc Dioscorea deltoidea v D. composita Mexico.

l nhng nguvn liu chit diosgenin. Nguyn liu ti (cu. re) d ra sch, thi mng v sy kh, sau xay thnh bt.

Chit saponin bng nc nng hoc cn long. Sau bc hi dung mi th c hn hp saponin, thy phn hn hp ny bng dung dch acid sulfuric long th nhn c sapogenin khng tan trong nc, tan trong dung mi hu c.

Lc ly diosgenin, tinh ch bng cch ha vo dung mi hu c hay cn cao , sau bc hi v cho sy kh. Hm lng diosgenin c th c t 2 7% tnh t nguyn liu kh.

Sau y trnh by cc thuc Steroid c bn tng hp t diosgenin.

S bn tng hp cc hormon steroid t diosgenin:

S bn tng hdp cc thuc chng th thai v cc thuc chng vim, chng d ng t diosgenin:

Cc saponin steroid ca nhn sm

Nhn sm Triu Tin Panax ginseng l v thu c b, tng sinh lc, thch nghi sinh hc tt nht trong y hc c truyn ng v ng Nam . c nhiu cng trnh nghin cu cc hot cht ca Nhn sm, trong d ch yu c:

Cc saponin triterpenoid (dn cht acid oleanolic) trnh by phn cc cht terpenoid.

Mt s" cc saponin steroid khi thy phn thnh cc genm l panaxodiol, panaxotriol; 20-Sprotopanaxodiol (genin ca ginsenoid Rb,).

20-S-prtopanaxodiol

Ngoi ra trong nhn sm cn c cc cht Polysaccharid (cc glycan) v cc cht axetylenic. Cc glycan ca nhn sm c gi l Panaxan.

Cho n nay, nhn sm vn ch yu c dng di dng dc liu hay cc dng cao chit ton phn m thi. V cc saponin nhn sm (k c loi triterpenoid v loi steroid) c hot tnh sinh hc cao nhng li c trong nhn sm vi mt t l kh nh.

Nht, cho php s dng cc sn phm nui cy m nhn sm. V c bn, cc sn phm ny c hot tnh nh nhn sm nhng ngi tiu dng vn thch s dng nhn sm Triu Tin nhiu hn.

Cc saponin steroid ca cy Tt l - Tribulus terrestris L.

L dc liu c tc dng kch thch v tng cng hot dng tnh dc cho c hai gii: nam v n. Dc liu nv dc s dng hng ngn nm nav n , Trung Cn ng, Trung Quh v Vit Nam. Cc nh khoa hc Bulgaria l nhng ngi u tin chng minh cc saponin streoit ca cy Tt l c tc dng lm tng lng testosteron trong c th nam, estradiol trong c th n v lm tng cc hormon LH v FSH trong c th. Nu nh y hc c truyn Trung Qub ch dng ht Tt l lm thub th Bulgaria v min Nam Trung B Vit Nam li dng ton phn trn mt t ca cv.

Cc saponin steroid ca Tt l gm c cc cht sau y:

(i- rhamnose

V nhiu saponin khc cha cc sapogenin l diosgenin, hecogenin.

Cc san phm Tribestan, Tribiol, Povvcr Men cha cao Tt l c s dng rng ri Au M e lm thuc chng lo ha, tng cng hot ng tnh dc, tng cng sc khe v hot ng cho cc vn dng vin. Phan Quc Kinh v cc cng s d nghin cu thnh phn ha hc v hot tnh sinh hc ca cy Tt l mc hoang Nam Trung B Vit Nam. Tc gi xc nh cy Tt l Vit Nam c cc glvcosid l dn cht ca diosgenin, hecogenin, neohecogenin,... nghin cu sn xut thuc Tribelus cha cao Tt l tng sinh lc cho c nam v n, v Kingphar Tribelus l thc phm chc nng cha cao Tt l v piperin v nhiu thc phm chc nng khc.

CC HORMON STEROID SINH DCCc hormon steroid sinh dc n

Cc hormon nv c 2 nhm :

Cc estrogen v progestogen. Cc estrogen l cc cht steroid c cha 18 nguyn t cacbon v c 4 vng A, B, c, D trong vng A l nhn thm. Estrogen chnh l estradiol, ngoi ra cn c estron, estriol, equilin, equilenin,...

Cc estrogen l nhng cht quyt nh trong vic hnh thnh v pht trin cc c quan sinh dc n, chu k kinh nguyt, s pht trin ca bung trng, t cung, tuyn v v cc biu hin th cp, cc t chc, m sinh dc n gii v to dng v hp dn 3 vng cho phi p, lm cho da d mn mng, mm mi, ging ni cao v nh nhng.

Progcsteron l mt progestogen thin nhin c 21 nguvn t caebon trong phn t. Progesteron l cht quyt nh cho chu k kinh nguyt cho qu trnh sinh sn, tit sa, nui con b v s pht trie 11 hi ha cho c th n gii, nu thiu progesteron th c th n khng th sinh con.

Chu k kinh nguyt n gii c hnh thnh tui dy th (12 - 16 tui), trong nhng ngy u, hm lng estradiol tng du trong c th v t n inh cao nht ngv th 14 ca chu l> l thi gian trng chn v rng vo vi t cung. Nu gp Linh trng th trng s th thai v pht trin thnh thai nhi t cung. Cn nu khng xy ra qu trnh th tinh th hm lng estradiol s gim dn.

Hm lng progesteron cng tng cao ngy sau trng rng, nu khng xy ra qu trnh th thai th hm lng progesteron s gim, cn nu c s th tinh th hm lng progesteron vn duy tr n nh mc cao, bo v s pht trin ca bo thai trong t cung.

Cc hnh sau trnh by s lin quan ca tuyn yn v bung trng, ng sinh sn v chu k kinh nguyt vi hm lng estradiol v progesterone trong chu k v hm lng testosterone trong cuc sng ca nam gii, hm lng estradiol trong cuc sng ca n gii.

S lin quan ca Hypothalomus, bung trng v dng sinh sn

r

s rng ca trng chn

(pha rng trng)

Trng thnh v pht trin th vngS to thnh

(pha bung trng)vt th vng

Vt th vngthoi ha

Vong rng trng

Hm lng o Testosteron trong c th nam gii Hm .ng Estradiol trong c th n gii

Cc cstrogen

OHoo

Nm 1923, Allen v IDoisy pht hin cao ca bung trng c hot tnh gy ng dc (estras). Ngun giu cc cht estrogen l nc tiu ca ph n.c thai. Sau tch chit c estron di dng kt tinh. Tip theo tch chit c I7-p-estradiol v estrio.9]

9]

Trong c th, cc estrogen c sinh tng hp t cholesterol:

Sinh tng hp cc hormon steroid sinh dc:

Qu trnh nhn thm ha vng A to thnh estron t androstendion#

93

92

Nh tc ng ca cc enzym m estron chuyn ha thnh estradiol v ngc li. cng nh quan h to thnh estnol t estradiol v estron:

Estradiol:

L estrogen c hot tnh nht trong cd th n gii, n b oxy ha v chuyn ha thnh estron v estriol. Trong cng nghip Dc, estradiol c sn xut bng hydrogen ha estrol bng natri borohydrua. Estradiol thin nhin l dng phn 17POH. Estradiol tng hp c ng phn 17-p-OH c tch ring khi 17-a- estradol. V 17a-estradiol ch c hot tnh estrogen bng 1/40 hot tnh ca 17pestradiol.

ho v v tng tui th ca thuc, ngi ta thng dng estradiol monobenzoat, l estradiol b kha nhm OH phenolic bng acid benzoic, c dng di dng dung dch 0,1% trong du e tim bp. Liu tim l-2ml/ngy. Cng dng nh estron nhng c hiu lc cao hn.

Do cc estrogen t nhin t bn vng nn ch yu phi dng di dng thuc tim ha tan trong du thc vt. khc phc tnh trng , cc nh khoa hc tng hp c ethinyl estradiol c hot tnh rt cao v dng c di dng vin nn.

Estradiol l estrogen thin nhin c hot tnh cao nht v l estrogen ch yu tui sinh . Estradiol cng vi progesteron c lin quan mt thit n qu trnh thai nghn. Estradiol ch yu c dng iu tr hi chng tin mn kinh v mn kinh nh cc triu chng bc ha, ra m hi qu nhiu, lo lng, bun phin, teo dn ng sinh dc tit niu, iu tr chng long xng. Thng dng ung di dng thuc vin: 0,5mg, lmg, 2mg, v cc dng kem bi m o, cao dn m do. Dng tim di dng Estradiol monobenzoat tan trong du. Estron v estriol c tc dng yu hn. Estriol c dng di dng thuc vin lmg. Premarin l hn hp cc estrogen thin nhin di dng este, sn xut t nc tiu ca nga ci c thai l estrogen c s dng rng ri, chng c tc dng nh estradiol nhng yu hn nhiu ln c dng di dng thuc vin ung.

Vin cha 0,625mg, cui th k XX doanh thu hng nm trn th trng quc t ca premarin ln n 2 t la, ch yu dng trong bin php thay th hormon cho ph n cao tui.

Cc nh khoa hc tng hp ton phn c estron quy m cng nghip. Nm 1959, I.u. Torgov v cc cng s tng hp ton phn D-homoestrogen t Vinyl1-methoxy6tetralol1 vi methyl- 2cyclohexandion1,3 vi xc tc l Triton B. Dn cht Vinyl c tng hp t methoxy-6tetralon.

o

3.4.1.2. Cc progestogen

98

97

94

Da trn c s phn ng , I.u. Torgov v S.N. Ananchenco tng hp c ton phn estron. Phng php ny c ng dng vo cng nghip tng hdp estron M v c vi s dng cht methyl2-cyclohexan-dion-l, 3 to vng D ca estron.

Methyl-2-cyclohexadion-1,3Qo

Cc dn cht i t cyclohexandion-1,3:

Nm 1965, Phan Quc Kinh, I.u. Torgov v cc cng s tng hp ton phn mt sc cht D-homonorestrogen mi theo phng php mi vi cc cht to vng D ca estrogen l cyclohexandion-1,3 v dimethyl-5,5cyclohexandion-1,3 to ra cc cste methylic l dn cht ca D-homo18-n ores tron c hot tnh chng khi u.

Cc dn cht i t dimethyl-5,5-cyclohexandion1,3.

Dimethyl-5,5-cyclohexandion-1,30

Ethinyl estradiol (E.E.):

L estrogen tong hp c hot tnh cao nht. Cho estron tc dng vi kali acetylua trong ammoniac lng th nhn c ethinyl estradiol (E.E.).

E.E. l estrogen tng hp ton phn c hiu lc rt mnh c dng vi liu ung 0,03 - 0,lmg v c dng rng ri lm thuc chng th thai (kt hdp vi cc progestogen).

oOH

i din cho nhm ny l progesteron. L mt hormon steroid c cha 21 nguyn t cacbon, c vai tr quyt nh trong cc chu k kinh nguyt ca n gii, trong thai nghn (pht trin thai nghn) v sinh sn ca ngi v mt s ng vt khc.

Progesteron thuc nhm cc hormon sinh dc n c gi l cc progestogen v n l progestogen thin nhin chnh c trong c th ngi. Trong cng nghip, progesteron c bn tng hp t diosgenin, c trong mt s loi c mi Dioscorea sp. Willand Myron Allen M nm 1933 chit xut v t tn cho hormon ny l progestational steroidal keton. Cn pht hin c progesteron trong cy Juglans regia. Progesteron cn c tc dng bo v no do c tc dng chng vim ging nh tin cht ca n l pregnenolon. Progestcron l hormon sinh dc n lin quan n qu trnh sinh sn v tit sa nui con b. Trong c the n, progesteron c sinh tng hp t cholesterol v hm lng progesteron cao nht tui 2 - 30, sau gim dn theo tui tc.

Progesteron di dng bt tinh th trng, khng tan trong nc, tan trong du, cn, te, chlorooc, nng chy 126 131c. Dng b sung thay th trong bin php b sung hormon cho ph n cao tui. Dng cho cc bnh nhn n thiu nng vt th vng, ri lon kinh nguyt, chy mu khi hnh kinh v khi c thai, v kinh, au khi hnh kinh, chy mu d con, cc c quan sinh dc km pht trin, km hot ng, v sinh.

Dng phng sy thai, tim bp dung dch du 102mg/ngy, cn dng diu tr ung th ni mc t cung vi liu cao, c th dng dng vin e ung hay t d m o.

0 Vit Nam, GS. Nguyn Vn n nghin cu sn xut progesteron t diosgenin di dng thuc tim.

106

107

Cc progestogen bn tng hp

99

Cc nh khoa hc bn tng hp v tng hp ton phn c nhiu dn cht mi t progcsteron vi cc tiu ch: tng cao hiu lc, rt nh liu iu tr, tng cao vng bn ca thuh, m rng ph iu tr, tm thuc trnh th thai, chng th thai, gy sy thai, iu tr ung th....

c bit pht sinh ra cc thuc trnh th thai dng ung, dng tim hay t vo m o. Vic sn xut v s dng rng ri cc thuc trnh th thai cho hng trm triu ph n tui sinh s dng hn ch dn s l mt bc ngot lch s ca y hc, dc hc.

Cc progestogen c s dng nhiu nht T norethndron acetat, c bn tng hp t estron di dng bt tinh th mu trng hay trng ng, khng mi, khng tan trong nc, tan trong cn, chlorofoc.

Norethndron acetat c dng mt mnh lm thuc trnh th thai vi liu 0,6mg/ngy hay phi hp vi levonorgestrel vi liu norethindron acetat 0,lmg, levonorgestrel 0,003mg. Dng kt hp 1 vin/ngy, ung 21 ngy trong chu k kinh nguyt tnh t ngy th 5 ca chu k.

Levonorgestrel c sn xut bng phng php tng hp ton phn di dng bt tinh th trng, khng tan trong nc, tan trong methylcn clorua. L progesteron c hot tnh mnh nht dng phng v diu tr thiu progesteron. Dng trnh th thai dng vifm kt hp vi ethinvlestradiol. Dng lm thuc chng th thai khan cp -

chng lm t. Ucmg 0,75mg (trong vng 72 gi sau khi giao hp) v sau 12 tng ung tip 0,75mg levonorgestrel.

Trn th trng cn c norgestrcl raxemic c cha tng ng lng levonorgcstrel v dcxtronorgestrel, do dextronorgestrel khng r hiu lc nn phi dng liu norgestrel raxemic gp 2 ln liu le von 01 gostrel.

c bit mifepriston, mt dn cht ca nortcstosteron c tc dng gy sy thai cho ph n mang thai trong 2 thng u.

Ung liu 600mg mifepriston v sau 36 gi tim 0,4mg misoprostol (mt loi prostoglandin c tc dng gv co bp t cung) th s xy ra sy thai.

I V1 ph n chu , chu Phi v chu M Latinh gp kh khn khi phi ung thuc trnh th thai hng ngy (d b qun) th s dng thuc ticm trnh thai medroxyprogesteron acetat. Ch cn lim 0.150g mcdroxyprogesteron acetat trong thi gian 3 thng th s c tc dng trnh th thai. Phng php ny c li th l ph n khng th t mnh b d liu php trnh thai (v nu ung Lhuc hay t. vng th c th t ngng c).

Medroxyprogesteron acetat

Cht ny cn dng iu tr chng da kinh hoc v kinh th pht, bnh lc mng tii cung, ung th v, ung th ni mc t cung. Cn dng iu tr ung th tyn tin lit cho nam gii (0,5g/ln).

Cc androgen

Testostoron l mt hormon steroid thuc nhm androgen c trong ng vt c v, chim, b st,... Testosteron dc sinh tng hp tinh hon nam gii v bung trng n gii v mt lng rt nh tuyn thng thn. N l hormon nam chnh v l mt cht steroid tng dng.

nam gii, testosteron dng vai tr quan trng trong vic hnhthnh v pht trin cc c quan sinh dc nh tinh hon, tuyn tin ht v cc biu hin th cp sinh dc c trng cho nam gii nh pht trin c bp, xng, mc tc, ru.

lin th na, testostcron l mt cht m bo sc khe v cuc sng khe mnh v c tc dng phng long xng. Trong c th nam gii trng thnh c hm lng testosteron 10 ln cao hn trong c th n gii trng thnh. Nhn chung cc androgen lm tng tng hp protem v pht trien cc c bp. Testosteron l mt cht cn thit cho cuc sng v tng dng.

Tc dng tng dng l pht trin cc c bp v rn chc ca chng, lm tng chc ca xng, lm cho xng pht trin. Tc dng androgen l pht trin cc c quan sinh dc nam, c bit l quy u v hnh thnh ging ni nam, mc lng, tc, ru.

Laqueur E v cc cng s chit c testosteron t tinh hon b nm 1935. Butenand A v Ruzicka xc nh c cu to ha hc ca testosteron v bn tng hp testosteron t cholesterol v c hai d nhn c gii Nobel ha hc 1939.

OHo

Sinh chuyn ha ca testosteron trong c th

Testosteron

c dng iu tr suy gim tuyn sinh c nam do thiu nng tuyn yn hay tinh hon hay do ct b 2 tinh hon.

Cn dng iu tr dy th mun nam, chng suy gim hot ng sinh dc nam, lit dng, v sinh, ri lon cng dng, lm tng kh nng lao ng chn tay v lao ng tr c, chng lo ha, chng thiu mu khng ti to, tng kh nng ng ha, tng dng, chng lnh cm cho n gii, gp phn iu tr ung th v cho n gii. Dng di dng dung dch trong du tim di dng testosteron propionat 2mg/ng. Dng ung di dng testosteron undecanonat 'lOmg/vin, methyl testosteron 5mg.

Testostcron c tc dng androgen (hot tnh sinh dc nam) mnh v cn c tc dng tng dng (anabolisant). Dng cho nam gidi cao tui thiu androgen trong c th, cho nhng ngi suy gim chc phn sinh dc, thiu nng sinh dc, ri lon cc chc nng sinh dc, lit dng, v sinh, ri lon cng dng.

Cn dng cho n gii iu tr bnh lnh cm tnh dc, ung th v, d con, bung trng. Testosteron cn c tc dng tng ddng, lm tng qu trnh tng hp protein trong c th, gi nit, gim bi tit ur Lheo nc tiu v kt qu l tng cn, chc c bp. Ch yu dng tim di dng testosteron propionat tan trong du 5 - lOmg/ngy. Dng ung di dng testosteron undecanoat hay tethyl testosteron v hai cht ny vng bn trong ng tiu ha.

OH

Vit Nam, TS. Phan Quc Kinh nghin cu sn xut methyl testosterone di dng vin metet i t diosgenin.

Cc cht tng dng

Testosteron c tc dng tng dng nhng li c hot tnh androgen mnh nn dng khng thch hp cho ph n hay c nam gii c chc, phn androgen bnh thng v s lm tng mc ru, mc lng, mc tc, ni mn trng c,...

khc phc iu , cc nh khoa hc ci tin cu to ha hc ca testosteron nhn c cc cht c hot tnh androgen ti thiu v tng hot tnh anabolisant. l oxymetholon v nandrolon phenylpropionat.

Oxymetholon c hot tnh androgen yu, hot tnh tng dng mnh hn testosteron 3 ln. Dng cho bnh nhn suy yu sau chn thng, sau phu thut, bng, nhim trng nng, thiu mu. long xng.

o

Nandrolon phenylpropionat c hot tnh tng dng mnh hn testosteron 6 ln. Dng cho bnh nhn suv mn, yu t v dng iu tr ung th v cho n gii.

Cc tin hormon sinh dc

DHEA (Dehydroepiandrosteron):

DHEA l mt tin hormon steroid ch yu c tit bi cc tuyn thng thn v cn c cc c quan sinh dc v no.

Trong c th nam, DHEA chuyn ha thnh testosteron; trong c th n n chuyn ha thnh estron v estradiol. DHEA l mt cht ph tr sigma-1 hot tnh cao. N cn c gi l mt cht steroid thn kinh (neurosteroid).

Trong c th. DHEA dc sinh tng hp t cholesterol. DHEA c hot tinh di khng vi cortisol. N c tc dng chng trm cm v bo v c th trc tai hi ca liu cao cortisol. DHEA lm tng tr nh, lm tng khi lng c bp.

Androstendion:

Androstendion l mt tin hormon steroid c 19 nguyn t cacbon c sinh tng hp tuyn thng thn v cc tuyn sinh dc, l cht trung gian sinh tng hp androgen-testosteron v cc cstrogen-cstron v estradiol.

Androstendion l tin cht ca cc hormon sinh dc nam v n, mt lng nh androstendion c tit ra t huyt tng v n s chuyn ha thnh tcstosteron v estrogen d cc m ngoi bin.

o

Androstendion

Androstendion c dng lm cht b sung dinh dng thng gi l andro (hay andros). Bc M, dng androstendion cho cc vn ng vin the dc th thao. N c tc dng lm tng hm lng testosteron trong huyt tdng sau 8 gi, sau khi nam gii ung VI liu 300mg/ngv, cn hm lng estradiol s c tng cao sau khi ung 100 300mg.

Pregnenolon:

Pregnenolon l tin hormon steroid, tin cht ca progesteron, cc mineralocorticoid cc glucocorticoid, cc androgen v cc estrogen. Pregnenolon l mt cht i khng ca GABA (acid aminobutyric).

Phn t c 4 vng, 21 nguyn t cacbon v c nhm -OII c th este ha thnh pregnenolon sulat, chl ny tan trong nc. Trong c th, prcgnenolon dc sinh tng hp t Cholesterol.

Prcgnenolon chuvcn ha trong cd the theo ba hng sau:

Pregnenolon chuyn hoa thnh progesteron. Progesteron s chuyn ha thnh 17a-hydroxv-progosteron v anrostcndion, tin cht ca testosteron v estron. AloUeron v cc corticosteroid cng c sinh tng hp t progcsteron hay cc dn cht ca n.Pregnenolon c chuyn ha thnh 17hyroxy pregnenolon. sau chuyn ha thnh DHEA, DHEA l tin cht ca androstendion.Pregnenolon c th chuyn ha thnh androsta; chuycn ho thnh 5.16dien3ol bang 16en synthetase.

Pregnenolon v dng Sulfat ca n, ging nh DHHA v Sulfat DHEA v progesteron thuc nhm neurosteroid (Steroid thn kinh), do vy chng c hm lng cao mL vi vng ca no v cng dc sinh tng hp 0 d. Neurosteroid c tc dng bo v cc chc phn ca no lm Lng cc chc phn ghi nh.

Pregnenolon dc gi l "b ni" ca cc hormon Steroid, c hot tnh trong bin php thay th hormon, iu tr thp khp v chng stress, lm chm qu trnh lo ha, lm tng chc phn ca no.

tng tr nh, chng mt mi, tng cng cc kh nng hot ng tnh dc. Pregnenolon c dng ung mt mnh hay kt hp vi mt s cht khc chng lo ha, gy ng, lm tng cc hot ng ca no. Liu hng ngy l 25 - 600mg pregnenolon.

CC ADRENOCORTICOSTEROID

Tuvn thng thn nm trn 2 qu thn c chia lm 2 phn: phn li tit cc cht catecholamin, cn phn v tit cc steroid, c gi l cc adrenocorticosterod.

Cc adrenocorticosteroid li chia lm hai nhm ph thuc vo tc dng dc hc v chuyn ha sinh ha hc ca chng l: cc glucocorticoid (hydrocortison), cc mineralocorticoid (aldosteron).

C th thiu cc hormon ny s b bnh Addison, th hin s mt mi. thiu mu, nn ma, huyt p h, da xanh hin cc vt c mu, suy gim hot dng tr no, Trung bnh c 100.000 dn th c mt ngi b bnh Addison (bnh qun cho c nam v n gii, cho cc la tu).

Nu loi b cc tuyn thng thn trn c th sc vt s gy ra cc hiu qu rt nghi m trng: hm lng ur mu tng, cc c yu (asthenia), gim glycogen gan, gim phn ng bo v vi insulin; giam phn ng bo v vi chn thng, nh l qu lnh, sc c hc, sc ha cht, r lon chuyn ha mui, tng loi ion kali, gim thi Na', CT v nc. Sc vt nh b ct b tuyn thng thn s cht sau t ngy sau khi phu thut. Cc nh khoa hc, c bit l Rogoff v Stewart xc nh tim cao tuyn thng thn cho ch b loi tuyn thng thn th ch vn sng.

Cc nh khoa hc d xc nh c 47 hot cht c hot tnh sinh hc cao t tuyn thng thn nh: hydrocortison, corticosteron, aldosteron, Cortison, 11desoxycorticosteron, 11dehydrocorticosteron, 17uhydroxyl11desoxycorticosteron l nhng cht c hot tnh cao nht. Trong c th, cc cht ny dc sinh tng hp t cholesterol.

i din in hnh ca nhm glucocorticosteroid l corCson v hyrocortison. i din cho nhm mincradocorticosteroid l 1 1deoxycorticosteron v aldosteron.

Cc cht ny ch c hm lng rt nh trong cc v tuyn thng thn, cng nghip dc sn xut cc cht ny bng bn tng hp t cholestrol, diosgenin.

Cortson

Ln u tin nh ha hc M Edward Calvin Kendall, lm vic ti bnh vin Mavo chit c cortison. Nm 1950, ng v Philip s. Henoh v Tadeus Reichten c nhn gii Nobel v y hc do pht hin cu to ha hc, chc phn ca cc hormon v tuyn thng thn.

Cortison ln u tin c sn xut vo nm 1949 bi hng Merok and Co t cc acd mt.

Cortson v adrenalin l cc hormon chnh ca c th gy ra cc stress. N c tc dng chng vim, chng chong, chng d ng. Vic pht hin cortison c xem nh mt bc ngot lch s y hc v diu tr c bnh thp khp m thi im 1949 cha c thuc no c hiu qu e iu tr bnh ny..0

110

111

108

Nhng qua thc t lm sng, Cortison thng c dng di dng acetat ch c tc dng cha triu chng, khng C tc dng lm mt cn nguyn ca bnh nn phi dng lu di, cn neu dng lu di th s c nhiu bin chng ph nh b ph thng, lot v thng d dy,... nn hin nay c s dng rt hn ch.

Thng dng Cortisol acetat trong hn dch tim bp. Tim 200 - 300mg/ngy.

Hydrocortison acetat (Cortisol acetat)

Hydrocortison l hormon corticoid chnh c trong c th ngi v ng vt, ngoi corLsol cn c cortison, cht ny c hot tnh sinh hc yu hn Cortisol.

Trong y hc s dng Cortisol di dng acetat lm thuc.

o

Hydrocortison acetat di dng bt kt tinh trng, khng tan trong nc, kh tan trong alcol. Hydrocortison acetat v cc glucocorticos-teroid khc c tc dng:

+ Chng vim.

+ Chng d ng.

+ Chng chong.

+ c ch min dch.

Ch yu dc dng iu tr thp khp, vim khp, vim gan, vim thn, vim tng, cc bnh d ng hen suyn, vim da,... Cn dng trong ghp cc c quan ni tng do c tc dng c ch min dch.

Qua s dung lu di, th cc glucocorticosterod c cc nhc icm:

+ Ch c tc dng iu tr triu chng, khng c tc dng iu tr lm mt cn nguvn bnh, nn phi dng thuc lu di, ngng dng thuc th bnh li ti din, c khi cn nng hn.

+ Do c tc dng gi ion Naf v nc nn gy ph. Do lm tng tit pepsin v trvpsin ncn c th gy chy mu hay thng d dy. V vy nn s dng phi theo chi dn ca thy thuc.

Cch dng:

+ Dng ung c cc vin nn 5, 10, 20mg.

+ Dng tim hn dch 1 l 5ml hydrocortison acetat.

+ Dng iu tr thiu nng thng thn (bnh Addison) hoc sau khi ct b thng thn. Ngy ung 30mg chia lm 2 ln.

iu tr:

+ iu tr d ng nng, hen c tnh, chong th dng thuc tim 100 500mg/ngy.

+ diu tr vim khp, thp khp th c th tim vo khp 5 - 50mg/ln. Dng ngoi di dng kem chhg vim.

hn che bt cc tc dng ph bt li v lm .ng hot tinh ca thuc, cc nh khoa hc bn tng hp c cc glucocorteroid mi. dc s dng rng ri trong y hc nh prednison, prensolon - th h 2; dexamethason, methason th h 3. V thuc c tr bnh hen suyn Beclomethason dipropionat.

Beclomethason dipropionat Ct cn hen (phun 0,4 mg/ngy)

Pregnenolon

Qu trinh sinh tng hp corticosteroid trong cd th

Cc mineralocorticosterod

Aldosteron:

Aldosteron l mt mincralocorticosteroid c hot tnh lm tng s ti hp th sodium, nc v tng tit, loi b kali thn, Nh vy, s tng th tch mu v lm tng huyt p. c dng iu tr bnh Addison.

Aldosteron c Simpson v Tait chit xut ln u tin vo nm 1953. Trong c th, aldosteron c sinh tng hp t cholesterol. Dng lm thuc iu tr thiu nng tuyn thng thn, liu tim tnh mch 0,5mg ln, ngy 3 ln.

CC STEROID CNG TIM

Trong V hc hin i, cc thuc steroit cng tim ngun gc thc vt l nhm thng dng nht c dng iu tr cc bnh suy tim.

Cc steroid cng tim ch yu c trong cc loi Dng i hong Digitalis purputea L, Digitalis lanata Ehrh. Cc cy Strophanthus nh Strophanthus gratus, Strophanthus kombe. V cc cy c Vit Nam nh ay, Trc o, Thng thin, Sng d, Sng tru.

L cc glycosid c tc dng c hiu ln tim dng iu tr suy tim. T 1.500 nm trc Cng ngu vn, con ngi bit n bnh suy tim v cc thuc iu tr bnh ny. Nm 1783, William Withering vit v cc glycosid cng tim.

V ngv nay, cc glycosid cng tim l nhng hp cht c 2 phn:

Phn ng.Phn khng ng aglycon.

R'

Cc aglvcon ca cc glycosid cng tim c nhn cu to steroid, c 4 vng. Cc vng A-B v CD c lin kt cis, cn B-C c lin kt trans. Cu trc ny to nn s c o v cu to ha hc ca cc aglycon. Cc aglycon li c phn thnh hai nhm ty theo vng lacton ni v tr 17 ca khung steroid. Vng lacton 5 cnh, 1 dy ni i l cardenolid; vng lacton 6 cnh, 2 dy ni i l bufadienolid.

Cc cardenolid c trong mt s loi cy c. Cc cardenolid chnh c hot tnh iu tr cao l:

1 10

1 10

DigitoxigeninDigoxigenin

o

Cardenolid digitoxigeninBuadienolid hellebrigenin

Cc cu to c trng ca cc glycosid cng tim:

A/B C1S, C/D cis.14p-hydroxyl.Lacton cha no C17p.Kt hdp vi phn ng 3phydroxy.

Cc phn ng: cn gi l cc oligosaccharid gm c ng glucose v nhiu dng deoxy (cn gi l cc ng him).112

113

-0. OH

OH

OH

OH

OH

[-D-digitoxose

OH

u-D-rhamnose[-D-digitoxose|>-D-cymarose

Cc cht genin nh strophanthidin v hellebrigenin c sinh tng hp trong cy t cholesterol qua pregrenolon hay progesteron nh sau:

Cc ng thng gp trong cu to ha hc ca cc steroid cng tim:

Ngoi cc genin trn, trong Dng a hong cn c cc cht genin khc nh gitoxigenin, digoxgenin v trong cy Strophanthus gratus c uabaigenin.

Cc thuc cng tim c hot tnh tt nht c dng trong V hc hin i l digitoxin, digoxin, dn cht p-methyldigoxin v uabain.

Sau y trnh by mt s cht streroid cng tim c trong mt s thc vt.

Cc steroid cng tim ca cc loi Dng a hong

Digitalis purpurea L v Digitatis lanata Ehrh, thuc h Hoa mm ch Scrophulariaceae.

Mao a hong, cn gi l Dng a hong ta, Digitalis purpurea L l cy tho sng mt hay nhiu nm, cao t 0,5 l,5m. L mc quanh gc hnh trng di, mp l c rng ca, gn l hnh mng ni r mt trn. Mt trn l mu xanh thm, mt di xanh xm, c lng, cung l di. L gn ngn c cung ngn hoc khng cung. Cm hoa mc thnh chm lch v mt pha. Trng hoa hnh chung, mu tm n tm nht ri trng dn. Qu hnh di, t nt khi chn. Ma hoa thng 5 6. Cv c ngun gc chu u hin c trng i tr nhiu nc.

Ngoi ra, ngi ta cn s dng Dng a hong lng Digittalis lanata Ehrh c trng nhiu chu Au. B phn dng l l, trong d c cha nhiu cc glycosid cng tim.

Do cu to ha hc ca cc glycosid rt phc tp, trong qu trnh chit xut cc glycosid th cp v cui cng sau khi thy phn th cho cc gemn,

Sau y trnh by cc glycosid ca cc loi Dng a hong.

o

Digitalis lanata:

Cc glycosid nguyn cp

R,

R,

R:1

Lanatosid A

- H

- H

- coch3

Lanatosid B

- OH

- H

-COCHj

Lanatosid c

- H

- OH

- COCH,

ct phn ng glucose ca chng th c 3 glycosid th cp tng ng: acetyl digitoxin; acetyl gitoxin; acetyl digoxin.

Ct phn acetyl ca 3 cht ny th c cc glycosid th cp tng ng: digitoxin, gitoxin, digoxin.

ct 3 phn ng digitoxose ca 3 cht ny th c cc aglycon tng ng: digitoxgenin, gitoxigenin, digoxigenin cn trong l Digitalis purpures L th c cc glucosid nguyn cp l: purpurea glycosid A (= deacetyl lanatosd A), purpurea glycosid B (- deacetyl lanatosid B).

Trong y hc ch yu s dng digitoxin, digoxin v dn cht bn tng hp p-metyldigoxon.

Digitoxin:

Thng di dng bt kt tinh trng, khng mi, v ng, nng chy 270'C. Thc t khng tan trong nc, lg digitoxin c 8.000 10.000 dn v ch (tc l c tc dng ngng tim ca 8.000 10.000 con ch); 1.911 2.271 dn v mo (tc l c tc dng lm ngng tim ca cc con mo, tng khi lng t 1.911 - 2.271kg). Ch yu c dng iu tr bnh suy tim, nht l suy tim mn tnh vi liu 0,5 lmg/ln, 3 4 ngy/ln, v sau gim vi liu 0,05 - 0,lmg/ln, 1 2 ln/ngy. Ngoi ra, cn dng dng tim 1 ng lml c cha 0,2mg hot cht. Bnh suy tim l bnh him ngho nn ch c s dng thuic di s ch dn trc tip ca thy thuc, v nu dng qu liu c th ng c v t vong.

Digoxin cn gi l lanicor l thuc iu tr suv tim c dng nhiu nht hin nay. Ch phm .di dng bt kt tinh trng, thc t' khng tan trong nc, rt kh tan trong cn.

lg ch phm c 1.950 - 2.600 n v ch, 4.000 n v mo. So vi digitoxin, digoxin c tc dng nhanh, thi tr nhanh v t c hn.

Dng ung cho ngi ln 0,25mg/ln, ung 4 5 ln/ngy, sau gim dn. Tim tnh mch 0,25 0,5mg.

-methyldigoxin

bn tng hp dn cht methyldigoxin, cht ny c u im tan nhiu trong nc hn digoxin v c bo ch di dng thuc tim 0,5mg/lml.

Uabain

Uabain

Cn gi l Strophanthin G, l cht chit t ht cy Strophanthin gratus (Asnaud, 1888).

Uabain di dng cc tinh th hnh phin vung mng, khng mu, v hi ng, t tan trong nc nhit thp, tan nhiu hn trong nc un si, tan trong cn, khng tan trong trong chlorooc, te. [a] - -30,6flc n -32,5c. Thy phn bng acid th c uabaigenin c mu d.

L thuc c tc dng cng tim siu nhanh, lm cho c tim co bp mnh hn, lm hi phc cc si c tim b yu. Thng dng e iu tr suy tim, vim c tim cp tnh. Dng tim chm vo tnh mch. Ngi ln 0,25mg/ln, 0,5mg/ngy.#

115

Acetylstrophanthidin

L thuc cng tim c tc dng nhanh tng t nh uabain nhng hot tnh yu hn. T ht ay Corchorus olitorius L.( Phan Quc Kinh v cng s chit c glycositolitorosid. em thy phn glycosid ny th nhn c genin strophanthidin.

OH

Acetyl strop h an th id i n

em acetyl ha strophanthidin bng hn hp anhydrid acetic trong pyridin th nhn dc cc sn phm thuc. Qu trnh acetyl ho to ra acetylstrophanthidin nh sau:

Dng pha thuc tim, lml/ng cha 0,2mg acetylstrophanthidin. Ngy tim truvn tnh mch 1-2 ln, mi ln lml.

Cc bufadienolid nc cc Vit Nam

Nc cc (Bufo melanostiatue, cc Vit Nam) c cha nhiu bufadienolid rt dc Vit Nam, dn gian s dng tht, xng cc e lm thub tr ci xng, gy m, nhng mt s ngi n tht cc c ln nc cc d b ng c v a s l t vong.

Nm 1980, R. Verpoorte v Phan Quc Kinh cng b" trn bo Cc hp cht thin nhin" M v nghin cu cc bufadienolid t nc cc Vit Nam.

Nc cc c ly t hai tuyn gn mang tai ca cc. xc r.h hot cht chnh ca nc cc Vit Nam l 19-hydroxybufalin. Khc vi cc hot cht bufadienolid chnh ca nc cc Trung Quc, Nht Bn,

chu u, chu M c cng b. Ngoi ra cn c bufalin, resibufogenin, bufotalin, cinobufagin, hellebrigenol, hellebrigenin, marinobufagin,... cc cht ny c cng thc ha hc nh sau:

Cc bufadienolid

R,

r2

Ra

Rj

H

H

s

I2

I2

Tm li, tuyt i b phn cc cephalosporin bn tng hdp c d

t' s v tr 5.

Ngoi ra cn c mt s' cht nh latanocef v tr 5 thuc nhm oxacaphem v loracarbef c nhm -NH2 v tr 5 thuc nhm carbacephem. Nhng cht ny cng vi cc cht c cha d t' s nhng li c nhm CH v tr th 7 th khng c xp vo cc cht cephalosporin chnh hiu.

TT

Tn

R,

r2

R>

R13 reduction

I |(-oxidat*on

I

if b oxidation

o.

^oxidation

'~ WyCBUdation^. COOM*. "v,tuUM