Mc Lc

CNG NGH SN XUT PENICILLIN .............................................................................................................2 I. TNG QUAN V PENICILLIN ...............................................................................................................2 Gii thiu v penicillin.......................................................................................................................2 Cng thc cu to ca penicillin ....................................................................................................2 Ging vi sinh vt .................................................................................................................................3 C ch sinh tng hp penicillin ca vi sinh vt .........................................................................5 Nguyn liu sn xut .........................................................................................................................6

CNG NGH SN XUT PENICILLIN: ........................................................................................................8 1. 2. iu kin ln men: ..............................................................................................................................8 Quy trnh sn xut penicillin t nhin:..........................................................................................9

III. THNG PHM PENICILLIN ................................................................................................................18 1. 2. Penicillin nhm G: ............................................................................................................................18 Penicillin nhm M (ly meticillin lm cn bn). ........................................................................20 Penicillin nhm A (ly ampicillin lm cn bn). ........................................................................20

1

CNG NGH SN XUT PENICILLINI. TNG QUAN V PENICILLIN Gii thiu v penicillin Penicillin l i din tiu biu cho cc khng sinh c ngun gc t nm mc , l loi khng sinh ph rng, c ng dng rng ri trong iu tr v c sn xut ra vi lng ln nht trong s cc cht khng sinh c bit hin nay. Chng tc dng ln hu ht cc vi khun Gram dng v thng c ch nh iu tr trong cc trng hp vim nhim do lin cu khun, t cu khun, th d nh vim mng no, vim tai - mi - hng, vim ph qun, vim phi, lu cu, nhim trng mungn cn vic tng hp thnh t bo vi khun.

Pht hin tnh c vo nm 1928 do Alexander Fleming, khi nhn thy mt hp petri nui Staphylococcus b nhim nm mc Penicillium notatum c xut hin hin tng vng vi khun b tan xung quanh khun lc nm.M trin khai ln men thnh cng penicillin theo phng php ln men b mt (1931).1947 sn xut ln men chm quy m cng nghip. Cng thc cu to ca penicillin Penicillin gm nhiu loi, chng c cu to gn ging nhau, bao gm mt vng thiazolidine, mt vng -lactam v ch khac nhau gc R ca mch ngang .tuy nhin c ngha ln nht trong iu tr cng nh thng mi l penicillin dng G v V

2

Ging vi sinh vt

Nhng vi sinh vt sinh penicillin thuc cc ging nm mc penicillium v Aspergillus l nhng loi nm mc c kh nng tit ra penicilin. Nhng cc chng thuc nhm Penicillium notatum, Penicillium chrysogenum v P.baculatum c hot lc cao v c dng trong cng nghip khng sinh.Ngy nay trong cng nghip s dng chng ca loi P.chrysogenum do c hoat lc cao nht .Ging nm mc penicillin chrysogenum l loi hiu kh bt buc. Hn th na qu trnh tng hp penicillin xy ra trong iu kin hiu kh mnh. . Do trong sut qu trnh ln men, vic thi kh l iu ht sc cn thit. Penicillium chrysogenum trn mi trng Raistr ik to thnh hai kiu khun lc: Kiu I: khun lc trn trn, cc np nhn r nt. Khun ty kh sinh mc tt v c mu xanh; theo ra khun lc c ng vin rng 2-5 mm ca nhng khun ty bc trng khng c bo t; cc3

khun ty c cht mu nu; cht mu khng ho vo mi trng. Kiu II: khun lc c nhng khun ty mu trng, pht trin yu; khun ty c cht cng c mu nu. Khun lc kiu I cho hot lc cao, kiu II cho hot tnh khng sinh thp. V vy cn phi tch nhng khun lc kiu I trn mi trng ny v thng xuyn kim tra chn nhng khun lc c hot lc cao, gi c c tnh ca ging S pht trin h si v c im hnh thi h si nm c quan h hu c vi hiu qu sn xut. S tng trng v kch thc h si (tng di si, s ln ln v kch thc, mc phn nhnh ca h si ... ) lng khm si nm trong mi trng hnh thnh cc khm si nm(pellet- bi si cun xon): Pellet xp (fluffy loose pellets) l dng pellet c phn bn trong h si cun thnh

khi chc v mn, lp si pha bn ngoi cun lng lo to thnh cu trc xp hn. Pellet chc v mn (compact smooth pellets) c c im l phn si pha bn

trong pellet cun tng i cht ch ra n gn st lp si pha ngoi, lp si pha ngoi cng cng cun chc thnh lp si mn. Pellet rng (hollow pellets) l dng pellet c phn si bn trong b t phn to

thnh khong rng, h si pha bn ngoi cun rt cht thnh lp si mn v chc chn. - Hiu qu chung ca qu trnh ln men c quan h hu c vi s lng, kch thc v cu trc pellet nm. Trong thc tin sn xut cng nghip, ngi ta thng iu chnh cc thng s cng ngh theo hng u tin to ra dng pellet nh v mn, hn ch to pellet xp v ngn nga hnh thnh cc pellet rng. iu kin cng ngh tng ng vi mc tiu trn thng p dng l : t l cy ging 10%, vi mt dch ging (2-10).1011 bo t /m3; phi hp iu chnh gia sc kh v khuy trn m bo cung cp oxy ha tan d so vi nhu cu tng ng vi thi im ln men, v to ra pellet mn v nh (kch thc pellet thch hp nht khong 0,2 0,5mm), trong iu kin cn i vi nhu cu tit kim mc tiu tn nng lng do khuy trn.

4

C ch sinh tng hp penicillin ca vi sinh vt Theo quan im ph bin hin nay, qu trnh sinh tng hp penicillin nm mc P. chrysogenum c th tm tt nh sau: t ba tin cht ban u l -aminoadipic, cystein v valin s ngng t li thnh tripeptit -(- aminoadipyl) - cysteinyl - valin ; tip theo l qu trnh khp mch to vng -lactam v vng thiazolidin to thnh izopenicillin-N; ri trao i nhm -aminoadipyl vi phenylacetic (hay phenooxyacetic) to thnh sn phm penicillin G (hay penicillin V, xem s tng hp penicillin G.

Hnh 2.3. S c ch sinh tng hp penicillin t axit L-- aminoadipic, L-cystein v L-valin5

Nguyn liu sn xut Thnh phn mi trng dinh dng bao gm nhng ngun chnh sau: Ngun carbon: glucose hay lactose l ngun nng lng chnh nm pht trin,chng s dng glucose trong pha pht trin tng sinh khi(48 gi u)ca qu trnh,nm ng ha hu nh ton b glucose.V vy,nn khi chuyn sang pha sinh tng hp penicilin th ngun nng lng cn kit dn n gim hiu sut sinh tng hp . khc phc ta cn b sung lactose trong mi trng ln men Trong pha ln men th nht ging pht trin mnh, s dng glucoza v axit lactic ca cao ng. Sau lactoza mi c s dng (ch yu trong pha to penicillin). Khi trong mi trng cn lactoza v khng b sung cc cht dinh dng, h si nm bt u t phn, nu tip tc ln men nng penicillin s gim, trong thc t sn xut cn phi kt thc ln men trc thi im ny. Ngun nito: nm mc c kh nng ng ha cc mui amoni v nitrat,ngun nit hu c l ngun m giu ammino acid nm xy dng nn phn t penicillin ,do mi trng sn xut phi c mt ca cao ng.c th thay th 1 phn cao ng bng bt u tngP.chysogenum c kh nng tit proteinase kh mnh nn hp cht protein trong cao ng hay bt u rt d c nm s dng.Tuy nhin lng N phi va v nu thiu s xy ra hin tng t phn ca si,cn nu tha th si pht trin nhanh qu lm gim hiu sut sinh penicillin Ngun lu hunh:c ngha c bit trong qu trnh sinh tng hp penicillin v n tham gia vo cu trc phn t to nn vng thiazolidin.Ngun lu hunh thng dng l cc mui sulfat ca kali,natri v amoni.cc cht ny tham gia vo tng hp methionin,cystin,biotin,thiaminHay s dng nht l natri thiosulfat(Na2S2O3) Trong mi trng dinh dng c tiosunfat cng vi cao ng hiu sut penicillin c th tng hai ln Sunfat Sunfit Tiosunfit sixtin

Ngun kim loi vi lng: mt s kim loi nh Mg,Mn,Fe,Zn,Na.thng c b sung di dng mui sulfat hoc c sn trong nc my hay ngun nguyn liu to mi trng Cht tin th to nhnh: thm phenylacetic lm cht tin th (cung cp gc R) vo mi trng ln men to penicillin G,v phenoxyacetic to penicillinV.Khi b sung cht tin th th hiu sut sinh tng hp penicillin cao hn(tng thm 30-50%)nhng thc t cho thy 2 cht ny gy c cho nm nn ngi ta thng chn gii php b sung lin tc v khng ch cht ch nng theo yu cu khng lm gim nng lc ln men ca chng sn xut.

6

Ch : v nguyn tc nu ngun dinh dng y th s tch t penicillin s xy ra mnh m khi h si t trng thi cn bng .Nu thiu thc n s xy ra hin tng t phn ca si,cn nu tha th si pht trin nhanh qu s khng tch t penicillin m tch t nhiu acid gluconic v acid malic Mi trng nhn ging c thnh phn gm: Cao ng Glucose KH2PO4 NaNO3 MgSO4 CaCO3 Nc Ph 1l 6-6.1 20g 40g 0,5G 3g 0,125g 5g

7

CNG NGH SN XUT PENICILLIN: 1. iu kin ln men: Nhit l thng s c nh hng ln n s pht trin ca nm mc, kh nng sinh tng hp v nng lc tch t penicillin ca chng. Nhn chung nm mc pht trin thun li hn di nhit khong 30 0C. Tuy nhin, di nhit ny tc phn hu penicillin cng xy ra mnh m. Trong thc t, giai on nhn ging sn xut ngi ta thng nhn di nhit 300C; sang giai on ln men thng p dng ch nhit : Giai on ln men bt u tin hnh 300C cho n khi h si pht trin t yu cu v hm lng sinh khi th iu chnh nhit sang ch ln men penicillin di nhit 22 - 250C (c cng ngh iu chnh xung 22 - 230C, gi nhit ny tip hai ngy ri chuyn sang ln men tip 250C cho n khi kt thc qu trnh ln men). pH mi trng thun li cho s pht trin h si v cho qu trnh sinh tng hp penicillin thng dao ng trong khong pH = 6,2 - 7,4. Tuy nhin iu kin pH cao xu hng phn hu penicillin cng tng ln. V vy, trong sn xut pH mi trng thng c khng ch cht ch gi tr la chn trong khong pH = 6,2 6,8. pH ca mi trng c xu hng gim nn ta dng CaCO3 iu chnh Nng oxy ho tan v cng khuy trn dch ln men: nng oxy ha tan thun li cho qu trnh sinh tng hp penicillin dao ng quanh mc 30% nng oxy bo ha. Nng CO2 trong dch ln men mc nht nh cng cn thit cho qu trnh ny mm ca bo t nm mc; tuy nhin nu nng CO 2 qu cao s lm cn tr qu trnh hp thu v chuyn ho c cht ca chng, ngha lm lm cn tr qu trnh sinh tng hp penicillin Thi gian ln men: thng ko di trong vng 6-7 ngy

8

2. Quy trnh sn xut penicillin t nhin: C 2 phng php ln men penicillin: Ln men b mt Ln men chm

QUY TRNH LN MEN B MT:

9

p dng t lu, hin nay hu nh khng cn c trin khai trong sn xut ln na. Gm 2 phng php: Ln men trn nguyn liu rn (cm m, cm ng c b sung ng lactose) Ln men trn b mt mi trng lng tnh (ph bin s dng mi trng c bn lactose - nc chit ng).. Qu trnh nhn ging Qu trnh nhn ging bt u t ging c trong ng nghim. Trong cc nh my, mi ln cy truyn ging, ngi ta thng cy lm 3 ng. Mt ng dng kim tra trc khi sn xut, mt ng dng sn xut v mt ng dng bo qun. Song song , ngi ta chun b mt bnh tam gic dung tch 200 250 ml v chun b 50 g mi trng nh phn trnh by trn. Mi trng c thanh trng v lm ngui n 30oC. 10ml thanh trng v lm ngui vo ng ging, dng que thy tinh nh cho bo t ha trn vi nc. Bng bin php v trng (thc hin trong cc t nui cy v trng) chuyn ton b vo bnh tam gic trn lc cho tht u v chuyn chng sang t m 30 37oC. Nui trong iu kin ny chi n khi bo t nm xut hin v pht trin u khp mi trng. Ta gi qu trnh thc hin nh trn l qu trnh nhn ging cp 1. C ln lt thc hin tip ta c ging cp 2, cp 3cho n khi 5 10% ging cho sn xut. Mi mt cp nhn ging t cp ny sang cp khc, khi lng mi trng tng t 10 15 ln. Qu trnh ln men i vi phng php ln men trn nguyn liu rn (cm m, cm ng c b sung ng lactose), khi mi trng c kh trng v lm ngui n 30 oC, tin hnh trn ging vo vi t l t 5 10%. Cc khay c xp chng ln nhau trn nhng gi c mt khong cch nht nh thong kh v thong nhit. Qu trnh ln men ko di 6 7 ngy nhit 24 28oC. u im ca phng php ny l ng lactose c nm mc ng ha chm nn khng xy ra hin tng d tha ng trong t bo, cn dch nc chit ng cung cp cho nm mc ngun thc n nit, cc cht khong v cc cht sinh trng, trong phenylalanin khi b thy phn s to thnh phenylacetic cung cp tin cht to mch nhnh cho phn t penicillin.10

Khi ln men trong mi trng lng, p dng cng ngh b sung lin tc phenylacetic vo mi trng ln men, hm lng b sung ph thuc pH mi trng thng l 0,2-0,8 kg phenylacetic/m3 dch ln men. Dung dch ln men sau khi c kh trng s c phn phi vo cc khay c kch thc ging cc khay nui cy b mt vi mi trng bn rn. y cc khay ny khng c c l v phi cha mi trng lng. Chiu cao ca dung dch mi trng trong cc khay l 3 4 cm. ngi ta cng tin hnh ln men trong khong thi gian 6 7 ngy nhit ln men l 24 28oC. Tin hnh ln men trong iu kin mi trng lng ny, lng penicillin G c tng hp tng r rt cn hm lng cc penicillin khc cng gim i. hn ch qu trnh oxy ha tin cht, thng phi b sung vo mi trng mt lng nh axit axetic. Trong k thut ln men lng gin on khng iu chnh pH mi trng thng tng nh, sau tng i n nh v vo cui qu trnh ln men thng trong khong pH = 6,8 7.4. Khi s dng c cht chnh l lactose, ngi ta xc nh c penicillin ch c tng hp v tch t mnh m trong mi trng khi nm mc s dng ng ny v khi lactose c du hiu cn kit th si nm cng bt u t phn. V vy ngi ta thng kt thc qu trnh ln men vo thi im sp ht ng lactose. QUY TRNH LN MEN CHM:

11

a. Chun b ln men (Chun b mi trng nhn ging v ln men):

Nhn ging ngi ta cng chun b nh mi trng ln men nhng chng khng cha lactose (nu c ch cha mt lng rt nh), mt s khong cht v tin khong cht. Mt khc thnh phn mi trng nhn ging cn c tnh ton m bo cung cp ngun thc n C, N, cc cht khong v cc thnh phn khc, m bo cho s hnh thnh v pht trin thun li ca pellet

Mi trng ln men:

Thanh trng mi trng: mi trng ln men v nhn ging u c Thanh trng gin on 1210C ( hay thanh trng lin tc khong 140-1460C) trong 30 pht

Kh trng thit b; Phi c v khun trc khi a vo s dng. Thng thanh trng bng hi qu nhit 2,5 3,0 at trong thi gian 3 gi. ng thi kh khun nghim ngt tt c cc h thng ng dn, khp ni, van, phin lc v tt c cc thit b ph tr khc.Trong qu trnh ln men luun c gng duy tr p sut d trong thit b nhm hn ch ri ro do nhim tp. Khng kh thng c kh khun s b bng nn on nhit, sau qua mng lc v khun hay mng siu lc .12

Nhn ging: Trong qu trnh ln men chm ngi ta nhn ging trong mi trng lng. Mc ch ca qu trnh nhn ging l thu nhn c s lng t bo cao( thng tnh tng lng t bo/ml). t l cy ging 10%, vi mt dch ging (2-10).1011 bo t /m3; phi hp iu chnh gia sc kh v khuy trn m bo cung cp oxy ha tan d so vi nhu cu tng ng vi thi im ln men, v to ra pellet mn v nh (kch thc pellet thch hp nht khong 0,2 - 0,5mm). Ngi ta thng nhn ging vo cc bnh ln men dung tch t 1 lt cho n hng ngn lt. Nhit trong qu trnh nhn ging duy tr khong 26 1oC v thi gian nhn ging mi cp khong 72 gi.

b. Qu trnh ln men: Qu trnh ln men trong mi trng lng bng phng php ln men chm sn xut penicillin c vn hnh theo phng php ln men hai pha: Pha th nht nui thu sinh khi trong khong 2 3 ngy. Trong pha ny h si pht trin rt mnh v cc cht dinh dng d ng ha s c t bo hp th rt mnh, tc sinh sn ca nm xy ra rt nhanh, s to thnh penicillin mi bt u. pha ny penicilium cn c b sung lien tc lng glucose h si pht trin pellet t s lng v yu cu. ngoi ra cn b sung du bo ph bt. nhit trong pha ny ta gi 30 C. Pha th hai ln men thu sn phm. thi gian pha ny l 144-180 gi. pha ny h si pht trin chm li, pH tng dn v t n gi tr khong 7,5. Trong pha ny penicillin c to thnh vi mc cc i. lng penicillin c to ra nhiu cn b sung lng lactose cng cc tin cht kch thch to ra penicillin v hay penicillin G(ty vo mc tiu sn xut). nhit ti u trong qu trnh ny l 22 25C. Ngoi ra trong sut qu trnh ln men lu : thng kh: sc kh(1,2-1.5V/phut) v khuy trn Ngun dinh dng N v S: Ngoi ngun nit trong nc chit ng, ngi ta thng s dng phi hp (NH4)2SO4 va cung cp thc n N v S, va s dng iu chnh pH trong qu trnh ln men (pH dch len men ban u thng

13

c iu chnh v khong pH = 6,5 6,8 bng dung dch NaOH hoc H3PO4); nng NH4 + thng khng ch trong khong 0,3 0,4 kg/m3 dch ln men. pH iu chnh iu kin: 7-7,4

Kt thc qu trnh ln men ngi ta c gng lc sm dch ln men, lm lnh ri chuyn sang cng on trch ly v tinh ch thu penicillin.

c. Qu trnh thu nhn v tinh ch: C ba phng php thu nhn v tinh ch penicillin t mi trng nui cy, l: Trch ly bng dung mi hu c Hp ph Trao i ion Trong ba phng php trn th phng php trch ly bng dung mi hu c c s dng nhiu hn c. phng php ny da trn nhng u im sau: Mui ca penicillin rt d tan trong nc Acid penicillic rt d tan trong dung mi hu c

14

Trong qu trnh thu nhn v tnh ch cn lu gim st cht ch cc thng s cng ngh nh: nhit pH, v khun.... hn ch tn tht do phn hu penicillin. Lc : Penicillin l sn phm ln men ngoi bo. V vy, ngay sau khi kt thc qu trnh ln men ngi ta thng tin hnh lc ngay gim tn hao do phn hu penicillin v gim bt kh khn khi tinh ch, do cc tp cht to ra khi h si nm t phn. Hin tng t phn h si nm thng ko theo hu qu lm cho dch kh lc hn. thit b lc ht kiu bng ti hoc kiu thng quay. Thng thng, ngi ta ch cn lc mt ln ri lm lnh dch ngay chuyn sang cng on tip theo. Trch ly ln 1: trch ly penicillin khi dch ln men. Dch ln men sau khi lc c bm trn ng thi vi dung dch H2SO4 hoc H3PO4 long c b sung thm cht chng to nh v bm song song cng vi dung mi trch ly vo trong thit b. T l dch lc: dung mi thng chn trong khong 4 - 10V dch lc /1V dung mi. Trn nc v dung mi tng b mt tip xc. Lm nh vy cc phn t khng sinh tip xc cht ch vi dung mi. Tin hnh khuy lin tc m bo qu trnh tip xc ny t c mc cao nht. Sau khi tip xc gia khng sinh v dung mi s tao ra kt ta. cc dung mi sau tin hnh thu nhn khng sinh: o Cc ancol: butanol, isopropanol, propanol.15

o Cc ester: acetate etyl, butyl, amyl. o Cc ceton: metyl etyl aceton, metyl butyl ceton. o Cc ete: ete isopropylic, dioxan. o Benzen, phenol, pyridin, dicloetan, clorofoc. Ta trch ly pH = 2,0 - 2,5, nhit 0 - 30C. Nhm hn ch lng penicillin b phn hu, qu trnh trch ly c thc hin trong thi gian rt ngn trong thit b trch ly ngc dng lin tc kiu ly tm nhiu tng cnh. Hp ph: ty mu v loi b mt s tp cht khc, ngi ta thng b sung trc tip cht hp ph vo dung mi cha penicillin sau trch ly, s dng ph bin nht l than hot tnh Lc than: than hot tnh c tch v ra li bng s dng thit b lc ht bng ti hoc thit b lc ht kiu thng quay. Phn than sau lc c a i chng thu hi dung mi v x l hon nguyn, phc v cho cc m sau. Trch ly ln 2: trch ly dung mi ra khi penicillin . ngi ta trch ly = dung dch KOH long (hay NaOH long).pH = 7,2 -7,5 C kt tinh: b sung kali acetat hoc natri axetat nhm tch trit dung mi ra khi penicillin. Penicillin t kt tinh khi nhit thp vi s c mt ca BaOH. Cc thng s cng ngh c nh hng ln n hiu qa kt tinh l : nng penicillin, nng mui acetat, pH dung mi hay pH dung dch c c, nhit kt tinh ... Sau khi kt tinh, tinh th penicillin c lc tch bng my lc ht thng quay. m bo tinh khit cao hn, c th tin hnh ha tan v kt tinh li penicillin. Khi sn phm t tinh sch theo yu cu, thng tinh khit khng di 99,5% Lc tinh th: lc tnh tinh th; tip theo ra v lm kh s b bng dung mi k nc nh izopropanol hay butylalcohl; ht chn khng tch dung mi trn my lc bng ti ri sy bng khng kh nng n dng sn phm bt mui penicillin. Sn phm ny, mt phn c s dng trc tip pha ch thuc khng sinh penicillin; cn li, phn ln c s dng lm nguyn liu phc v cho vic sn xut cc sn phm penicillin v cephalosporin bn tng hp khc.

-

-

-

-

d. Qu trnh tng hp penicillin bn tng hp: Peniciliin t nhin d b phn hy bi pH thp v b enzyme penicilase lm mt hot tnh. Nn ngi ta nghin cu sn xut ra cc penicillin bn tng hp v tng hp c hot tnh v tnh bn vng cao hn T penicillin t nhin chng ta c th chuyn i thnh 6 APA hay 7-ADCA. Trong 6APA l nhn ca penicillin, phn trung tm ca phn t khng c gc axyl, ko c hot tnh khng khun v ging penicillin l ko bn vng vi penicilase. Nhng t 6-APA ta c th tng hp rt nhiu loi khng sinh khc.16

chuyn ha penicillin thnh 6-APA ta dng enzyme penicilase c sn xut t cng ngh sn xut enzyme.

17

Quy trnh tng hp penicillin bn tng hp t penicillin t nhin:

III. THNG PHM PENICILLIN Hin nay trn th trng c bn cc loi penicillin, bao gm: Penicillin c ngun gc t nhin (do nm si to ra). Penicillin tng hp. Penicillin bn tng hp. Penicillin G ch c kh nng chng vi khun gram (+) v khng chng c h enterobacteriaceae v cc chng thuc pseudomonas. 1. Penicillin nhm G: y l nhm penicillin c in, tm thy u tin. a s trch t nm v mt s bn tng hp. Cc penicillin G c tc dng vi khun gram dng v cu khun gram

18

m. Sau 60 nm s dng, penicillin G mt phn no hiu lc do to ra nhiu chng ln thuc. a s penicillin G b axit ca dch v ph hu nn ch dng tim m khng ung. Thuc chn lc tr ph cu, lin cu, t cu khng tit penicillinaz, clostridium, neisseria, khun k kh ming, xon cu. G.1 Benzylpenicillin = Penicillin G: Bt mu trng, mi v c bit, d tan trong nc. Dung dch thuc d b thu phn. Ch pha khi dng. Dc in quy nh dung dch penicillin G ch c tn tr 3 ngy trong t lnh.. Nhit cng cao cng d b hng. G.2 Penicillin G-procain: y l benzylpenicillin-procain c tac dng chm. c ch: depocillin, allocillin, duracillin, hydracillin, luetopen, novocillin, solucillin. Bt trng, khng ht m, t tan trong nc.

G.3 Bipenicillin: V penicillin-procain khuch tn chm nn ngi ta kt hp penicillin G vi penicillinprocain c tc dng va tc thi va lu bn. G.4 Benzathin-penicillin: Benzathin-penicillin = benzathin-benzylpenicillin. c ch: extencillin, benapen, leomypen, penadin, tardocillin. Kt hp hai phn t penicillin G vi mt phn t dibenzyl-ethylen diamin. G.5 Benethamin-penicillin. Bt kt tinh, t tan trong nc. Tc dng chm trung bnh. G.6 Clemizol-penicillin: c ch: largopenyl, neocural. Clemizol l cht khng histamin, nhng mui clemizol ca axit benzylpenicillinic l dng thuc tc dng chm. S hin din ca clemizol lm gim bt d ng v t nguy c gy tai bin.19

G.7 penethacillin: c ch: neopenyl, leocillin, estopen, bronchocillin. Bt trng, t tan trong nc. G.8 Penicillin V = phenomycillin = phenoxymethyl-penicillin: c ch: oracillin, alphacillin, berocilli, calciopen K, icipen, isocillin, oracil, oragen, penigen, sumagen, bantogen, calcipen V, penavlon V. G.9 Phenethicillin=phenoxyethyl penicillin: c ch: broxil, chemipen, maxipen, syncillin. G.10 Propicillin=phenoxypropyl penicillin: c ch: baycillin. G.11 Clometocillin: Tc dng lu di hn cc penicillin ung khc. 2. Penicillin nhm M (ly meticillin lm cn bn). Nm 1957, J.C.Sheeham tng hp c penicillin. Nm 1959, Doyle v Robinson a vo sn xut cng nghip. Bng chc thay dy ngang R, ngi ta tm c nhiu cht mi c hot ph rng, t gy tr ngi khi dng, t to chng khngiu ng ch nht l tng hp c cc cht khng penicillinaz do t cu tit ra, v nhng penicillin ung tt hn penicillin V. Penicillin nhm M c hai cht chnh l meticillin v cloxalin. Chng khng b hy bi penicillinaz. Do cc cht ny thng dng tr cc bnh t cu. Tuy nhin khong 20-25% chng t cu vn khng vi penicillin nhm M, y l do khng nhim th. Do cc penicillin ny vn cha c gi tr tuyt i vi t cu. Hiu lc khng khun ch bng 1/10 penicillin G vi cc khun nhy cm penicillin Oxacillin, cloxacillin, dicloxacillin t c tnh thn hn meticillin. Meticillin ch dng tim, cc cht khc ung c. Penicillin nhm A (ly ampicillin lm cn bn). y l penicillin bn tng hp. Hot ph rng hn cc penicillin trc kia: dit c cc khun gram dng v m, cu khun gram m, nhng li tr khng hu hiu t cu. Ngi ta chia lm ba nhm nh: Aminopenicillin: amicillin v dn cht. Carboxypenicillin: carbonicillin v dn cht. Ureidopenicillin v imidinopenicillin.

20