OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications

OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development Organisation. DISCLAIMER This document has been produced without formal United Nations editing. The designations employed and the presentation of the material in this document do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations Industrial Development Organization (UNIDO) concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries, or its economic system or degree of development. Designations such as “developed”, “industrialized” and “developing” are intended for statistical convenience and do not necessarily express a judgment about the stage reached by a particular country or area in the development process. Mention of firm names or commercial products does not constitute an endorsement by UNIDO. FAIR USE POLICY Any part of this publication may be quoted and referenced for educational and research purposes without additional permission from UNIDO. However, those who make use of quoting and referencing this publication are requested to follow the Fair Use Policy of giving due credit to UNIDO. CONTACT Please contact [email protected] for further information concerning UNIDO publications. For more information about UNIDO, please visit us at www.unido.org UNITED NATIONS INDUSTRIAL DEVELOPMENT ORGANIZATION Vienna International Centre, P.O. Box 300, 1400 Vienna, Austria Tel: (+43-1) 26026-0 · www.unido.org · [email protected] 2ooq~ .. ' PROGRAMA REGIONAL OE BIOTECNOLOGIA PARA AMERICA lATINA Y EL CARIBE DP/RLA/83/003 PROOUCCION INDUSTRIAL OE PENICIUN AMIDASA Y SU USO PARA lA OBTENCION OEL. ACIOO 6-AMINOPENICll.ANIC (~A) N=ORME FINAL CONTRATO No. 91/142 Centro de lngenieria Genl!tica y Biotecnologia La Habana, Cuba .. ,,. ' -.. -·- -·• 74& . .. .... . ., .. , . . . . . . . . . .. .. ............ . ._ REPORTE TECNICO FINAL DEL PROYECTO ONUDI No. DP/RLA/831003 "PRODUCCION INDUSTRIAL DE PENICILIN-APtJDASA Y SU USO PARA LA OBTENCION DEL ACIDO 6~1NOPENICILANIC0" QUE PRESENTA 1 ll'IEFA-C IBI ( DJ8A) LA HAIANA, CUBA, ABRIL DE 1992 ..... ,,.; I _/ I I ' I I II II ' I I El present• informe DP/RLA/931003, c:ut-.r~ al lerc9r 01~0 del pr-oyecto ONUDl No. "ProducciOn i.nduatricsl ne penic:i l in-acru.da!la uso p•r• la obtenci6n del Acido a~o Durante •l primer do y au b-aminooenicil~ni~o". •~tividad~~ se ent•P.nO al personal cubano an la5 instillaciones de Genin S.A. de c.v. l• producci6n del bioc•talizador y del 6-:plir.adas en el biocatali~~dor de petnici.l in• can el y de 2,0 kg Bjnter.noloyi• de Cuba. para Cubo en m.arzo de 1990, primer· infonne. biocatal iziidor Pilra eat.& Cl,~ kg (an etapa pos.terior), da an in5talacion•• cubana•; la (en p@nicilin-ilmida~a se en las instala- per iodo d• •ct.iv idad•a, se programt. 1 a pr oducci.'in de un.-i prim•ra etape1) Adam.is, en u110 produt:ido. Se progr.amo adecn&-., \.a participaci~n de un especial iet• cutJano err la c:onfecciOn del ., .. En lo& primera• aeiti me••li de trabaJo, ali prodLtjli!ron le• primeroa •• r.omenzO la producciOn de 2,0 kg reat•nt••t •• canLluy~ lo refAre~te ~l potonci~l de lo• tr~n~- ,· .. !Htg1.\ndo dor-, aPio ~ &e t.er·mtno les prodl..1Cci6n incluyondo in&t~laci6n pe:

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OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

OCCASION DISCLAIMER FAIR USE POLICY CONTACT. Please contact for further information concerning UNIDO publications
OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development O

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OCCASION This publication has been made available to the public on the occasion of the 50th anniversary of the United Nations Industrial Development Organisation.

DISCLAIMER This document has been produced without formal United Nations editing. The designations employed and the presentation of the material in this document do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations Industrial Development Organization (UNIDO) concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries, or its economic system or degree of development. Designations such as “developed”, “industrialized” and “developing” are intended for statistical convenience and do not necessarily express a judgment about the stage reached by a particular country or area in the development process. Mention of firm names or commercial products does not constitute an endorsement by UNIDO.

FAIR USE POLICY Any part of this publication may be quoted and referenced for educational and research purposes without additional permission from UNIDO. However, those who make use of quoting and referencing this publication are requested to follow the Fair Use Policy of giving due credit to UNIDO.

CONTACT Please contact [email protected] for further information concerning UNIDO publications. For more information about UNIDO, please visit us at www.unido.org UNITED NATIONS INDUSTRIAL DEVELOPMENT ORGANIZATION Vienna International Centre, P.O. Box 300, 1400 Vienna, Austria Tel: (+43-1) 26026-0 · www.unido.org · [email protected]

2ooq~

.. '

PROGRAMA REGIONAL OE BIOTECNOLOGIA PARA AMERICA

lATINA Y EL CARIBE DP/RLA/83/003

PROOUCCION INDUSTRIAL OE PENICIUN AMIDASA Y SU USO PARA lA OBTENCION OEL. ACIOO 6-AMINOPENICll.ANIC (~A)

N=ORME FINAL CONTRATO No. 91/142 Centro de lngenieria Genl!tica y Biotecnologia La Habana, Cuba

.. ,,.

'

-..

-·- -·•

74&

. .. .... .

., .. , . . . . . . . . . ..

.. ............ . ._

REPORTE TECNICO FINAL DEL PROYECTO

ONUDI No.

DP/RLA/831003

"PRODUCCION INDUSTRIAL DE PENICILIN-APtJDASA Y SU USO PARA LA OBTENCION DEL ACIDO 6~1NOPENICILANIC0"

QUE PRESENTA 1 ll'IEFA-C IBI

( DJ8A)

LA HAIANA, CUBA, ABRIL DE 1992

.....

,,.;

I

_/ I

I

'

I

I

II

II

'

I

I

El

present• informe

DP/RLA/931003,

c:ut-.r~

al

lerc9r

01~0

del

pr-oyecto ONUDl No.

"ProducciOn i.nduatricsl ne penic:i l in-acru.da!la

uso p•r• la obtenci6n del Acido

a~o

Durante •l primer

do

y

au

b-aminooenicil~ni~o".

•~tividad~~

se ent•P.nO al

personal

cubano an la5 instillaciones de Genin S.A. de

c.v.

l• producci6n del bioc•talizador y del

6-:plir.adas en el

biocatali~~dor

de

petnici.l in• can el

y

de 2,0 kg

Bjnter.noloyi• de Cuba.

para Cubo en m.arzo de 1990, primer·

infonne.

biocatal iziidor

Pilra eat.& Cl,~

kg

(an

etapa pos.terior),

da

an in5talacion•• cubana•;

la

(en

p@nicilin-ilmida~a

se

en las instala-

per iodo d• •ct.iv idad•a, se programt. 1 a pr oducci.'in de un.-i prim•ra etape1)

Adam.is,

en

u110

produt:ido.

Se progr.amo adecn&-.,

\.a participaci~n de un especial iet• cutJano err la c:onfecciOn del

., ..

En lo& primera• aeiti me••li de trabaJo, ali prodLtjli!ron le• primeroa •• r.omenzO la producciOn de

2,0 kg reat•nt••t ••

canLluy~

lo

refAre~te ~l

potonci~l

de

lo•

tr~n~-



.. !Htg1.\ndo

dor-,

aPio ~ &e t.er·mtno les prodl..1Cci6n

incluyondo

in&t~laci6n

pe:-ni.cilina l?n

par~

con

au le

E?l

c.ont.r f.Jl

reali=~~iOn

1990~

en •9osto de

y

pruducido.

Lolho

en el

Pr·ime,-

foca •n

~'='

•lcanzados por los partir.ipanta&

~n

en San

prea&ntaron

Costa

el proyectu.

c:1onaa d•

procai>ar

p•r•

Jes~.

Ibvr-o-

los result.ado•

pruyE?cto ""' adecuaron

industri-'

particip6

Congreso

Durante •ate tercer ano dP.l la

se

,.t:-.alizesdil an Bogo • .i, Colom-

celgbrado

dondP

l•

hidrOliaia de

Adeinc\s

lati.noalftericano di! &iotl!cnologia, novi•mbre de 199(1,

conc:ibiO

Bl!

las prueba& de

prny~cto,

e&.f

los 2 kQ de biocet•l ize-

calidad

dP

biocal&ill~c.dor·

l& reunion t6cnice del

bia,

do

d~

1•)0

kg

de

has

inst.ala-

peniciline.

Se

r1;paJ izaron lea hidr6lisi& r.o,-,eepondit?ntes y 6e puri fic:6 t!l b-APA

producido.

se

Ad&mas,

cart fecc:ionO

un

estud1o

dE?

tac:tibi 1 id ad

tocnico-•con6niit:a, CJL•e inc:J uye tianto l • prodL,CCi6n di?! biocatal i -

c:i 11 ina en Cub.a.

A continuacion && aRo de

d~sr.riban

activid•d~•~

~n

m~yor

lus ohjP.tivo& f ijados gradn

d~

detalle.

par~

el tQrcer

...

-------------------------------~ ~Q_&,JETIVQS

Lo& obJet.ivo& de trebiiiljo y

en

eat~

et•P• fuRron lDa

B-Adctcu•ciOn

desarrollada

a.1

de

ltt!r»

l•u• ac:tivid•dt:~ ~ de~.ar·rol l~r por Cuba

aigui•nt~5t

ins;talacionl!s

de

.ac.uento

Cl

l

.USIS

8 I

9

l SECADO EN BANDEJAS DEL 6 APA

I

7

' tt :I t \

6

I

I

1

I I le.,,

i'

/

I I

~

KITASAlO CON BJCHNER

/,

,

/;

REACTOR

"~'

,_ ""-"

I I

TANOUE DE RECEPCtON

~·;trA·· el. cumpl imiento de?l

objP.li VO D dcl Pr oyecto, se toinaron

lllhp1cill1na

6-Af·A,



Empresa Med1cub.a,

E9IRAIUI8

dw

p•rtir

importador~ ~e

jur1tu

ll•ri

6-APA

'l

l• ias hi;:ir"Ol .i.-is

considerando

que

Ia

de

velct:.HSad

el

( si

evaporac10n

podr !a 59,- &l J.1•50 l imi tanl~ d9l pr tKPSO. 5. -Rntoav.apo.~•dores d~ ~· L,

ODJCTJVO:

con l.JC\rio tenno~ ti:l ~.~du.

L.i ~oll1rinn

Conc&ntr•r

t11

r1rnJ i .-:•d• hi:\= tn 1.111 :i(> I. del

vnlumen inicial. "'--TOlh(tU•

d•

~¢ L de

volUlr1Pn

cit:Lll ... t>,

~~h.;.queta\ y

valvulri

rifl'

fondo.

OBJETIV01 Alm•cem:ue de 111 sol11c;i6n conc..entr actA. 7 .-Ra.actor de 2:5 L

total.

volumen

b~fflea, .ag1t.aci6n 1

puttrtos

VAlvul.a de de•c•rga.

Tape..

para

con

cH•nte~ .,;-~gta el fondo por·a

lni

'.2.0 t ..

du~.:.

I.

volumen et9ct1vo,

l~ctrlic.lt:• !Ji.:: w·if11;1oi;

pH

y

ontrc!ldft tie HCl

4

t.er·m6mt!tr·o,

/

tul.ic:i!-i

,;al

con

correapQn-

~·O % y EtOH,

V i.aor.

nBJETIV01

Acidific.ar

la

sol.11c:i6n

Lu11l'.&r11

r~d•

y

po6tE1riormente

precipitar el 6-APA can et.anol al 9h %. B. -l equ.ipo de mayo!' tamano, o en su lugar sust:it:u1rlo

por

otro

~ido op11rar

11quipo de

que ae

cult.•d•a,

Otra

al terna.tiva

c:on 1.ir.a dli! la~ vt.u·itt11L~~ ~ir1 Lunr.entreir

de hidr6lisis.

a

conc:t!ntr acitln.

hubiar.;a

la soluc:i6n

No ob~ta~te. no ~~ ~iqui6 esla olternativa debido

rpporta

qllt.=.-

lo~

rcndimient.os

.:i

esc:ele d~

laborat.orio

per un accidonte d~ l1dG~jo l~ cary~ d~ biocatalizador

ae deterior6 parcialn11rntc. Es lo ul.ur r 16 pr·ouuL tu d~ C!Uli &l t•nqu~

que contenia al

baj6 haste 6,8.

ag~~

para el

amaniacal

La 60l\1C.10n que UQ

tom(•

~ontrol

par11

del

r:ontinuar

pH en

el

adelante

fue la de ~t.~l..ama1:ter..-5(1(\. g.d~ lJic.ali:.i.\dor.. al .re.:u:lor:, p~r:~.c::oltl----· pens•~

El

le p•rdida do •ctividad de la c~rg~ original del

porc•n'lej&- promedio ds;i

convcr·~i6n de

tue de un 93.8 'l.. En l• r-bl• 1

tanque.

J tali hidr61 isi• real izadi&5

~v mue~~ran

lo& resultadoa de la&

l"UdP"6l i•i •.

....

Le purificaci6n del 6-AF'A,

En 9•n•r•l 5e trat..it

cJ~

u11

r.:omn

SP.

mF:-r1c:ior10

pn1lf"11:i.n1l~rd.. u

anterinrm•nt•,

~tmc.illu

y

ta&

reprmJuc;.i.ble.

1 ·..

(

grandtt•

volumen~'!I.

id~~)

Aqu.i lo

~.ido ~~tudiar

hubiera

la poaibi··

c.entr:lfugo.

l iof i 1 i~.acion, tr~beJc

Ed

Y•

QUE

sv emple6 une

e!!Sto e6tuf~

@ncarth.t:-r

dP-

v~cic.

l"'ecobr•do promedio em pe!iD de

del

85.4 Y.,

tl

diferenr:ia

del

i..

al

J..

~P.cando

ft

30-32

la Pl•r1ficaci6ri del c.an7.~rlo

~l

~s te

En

J" 1.nluLLi6u.

•c. 6-APA

ldbur-atorio,

fu&

que se

l"'epo..-ta de un 95 %. Ac:hac:.amos l• di. tF.rer;C:icl obtenid.a al ca111bio d@ et>c;ala.

En la Tabla 2 se

~Je~tra

el

r-esum~n

rle

!dG

puriti~acione~

del 6-

APA. £1 control de talidad

d~l

6-APA

obt~nido

liC

reali26 determinando

el punto d• fut1.i.6n del produLto c.1l·lun1no en lcna difar•nte& lotR&,

aGi como l• concentraLi6n de 6-APA pur dimetilaminob•n%aldahido p~tr6n

(Bala~ingham

el

1972).

m•todo del

contra

una

p-

curve

pr•parada con 6-APA de caliditd o::trroformo~

que

~•

(FAIO,

proyecto,

un J.nsumo de

i11po,..tac:i.on. d) Per.- producir 1 kg deo h f'tPA '"1U•·1..1r· cunfi.j dwr·ar~,.: Qllk ...., conau1n1tn ".•.0047

tr:g c1,. hinri11ttAl i 7ol'c1nr .FKt'1 au ban~ en

n.r·g• d• bioc•tal12ador"' µuetdt>

ut1

J

\h

L7O· 2:"'' mg i.:osto U.~.D

500 lf•O

C~lculo per 1001.1 c•ptiulati

C05t.O U.5.CJ

37.3Y~~

Ampicillina

Trihidrat.o EtPSO

1.9119

I 01:.Al

&:"·. o~BB USD/ ~9

..

"

,.

"

"

"

..

II

"

tr i t.j rlr~to •I

"

10CJ() cap. de Afl'•P.

,,

"

.•..

El ·.,.alor d• 1• 111\portac.:iOn dP 1 f, ArA thtnden

m1tnt.•

•ft

II

dR Amp ....Pao

,,

~:u cJ~

a e&t.abiliO!:lr~o on 75.(• y

~(''·' &P6(J

4~ .1255 USO

2~0 B~SO

23.0126

c111Jo11.1c.ill1na y da

71_1.r.t lJ.'.LD.

1 Y.g de

n'?t:.pert1vll'-

!-

•l mercada internac1on~l.

El precio de eMporteci6n d«' 1000 r.#lp~1..1l9'fP pued1t

II

alc:anzar el v.alor ri• 65 U.!::>.I>.

mg. d• •mpicillin• el d~ ~:

u.s.D.

t . .'

(jo

•urpicil)Jna ~()0 mg.

I:

'

' r



µra la producciOn del 1>1ncahli?.ador pu"" fue

2do allO de •cUvidadeS l

primer

r~cnico aooalo 1990

l •

Para el nosto d•I proceso &en" ad.,LUor.ilri• de IM insta\ac1om•s

glltCI

••UIU

d•I &-APA obtenido fu• de 91,7 •· kl prc.ices.o d• pur-1ficaci6n d111l &-flPA tuo

:;,-LOS eatudiD" dR fact1bilidad C..

d~

••~obrana 05.4 'l•.

~niw-pcon0lll1C.a ..u~sCr•n

able. No ob•t.ante. el margen dA r-entahil1u.-d ' (

que el

. .,

~ow to

Jw .uno•

~nla

110

U:JD I kg ,

.a l• producciOn

c~

L

d~ ampicillina.

·,I)

qua la

muy ompl10, y.a

b-A~'A pcu "'" t.. tacnu \ c•g i • mi en tr a~ qn~ -.n pro: lQ '", •I

de produLciOn de l

t. &

promedio d•I

resu l to ,.., rcarlo

REfERENGIAS 1.- Ec.al•sin~halft •• Wi'\rlmrton

Biophys. Act•. 2.-Lowry,O.H.,

27~1

2~0

D. ~l,unr11ll

26~

Lilly

y

M.D. :E:tiochem

:icn, morzo de 1C/'7v.

4.-Gvnin S.A. de C.V.1

lecnico del Pr·oyecto ONUl>l

Pr-irrur Repurte

No. DP/~LA/83/o03 (2Q anode .-ctiviucdJt.-!1)

1

Mt!i~ico, D.~., diciem-

br• d• 19SC/.

:-i.-t..r.lk ••1.f' •• Pr-ojects,

I "nnlvti~P.A,f. i

t;u~t ~~tl.mitiGn for

Etiotechnt"lf.UJY·.

in M~nueal of Industrir.l Microbiology and 81otechnolo9y~

Ed•· A.L. Oemtilin y N.A Sololhon. Am. l:.ioc. Microb •• Wa&fiI'hgtbn

i:r.c:,

1qsb.

b.-Ulrich.

G.D. 1A Guide

to

Ch&mit:;al

•nd Economica, Johr. Wiley 4c Sons, 7.-Petera,

M.S.

y

Timmer-haue,

t.IRw

lf..U.1

Engineer

in~ Procaa5 DesiQn

Vork, 1984. t-·l~rit

L>rnu.gn

fol'" Chem1:C9'1 E"ngin&Rrs, Mc Gra1r•-Hi 11, New Yor-~,

and

Economic~

1900.

·•.· 8.-f.1prry,

J.H.,

y

Ch.ilton.C.H •• Cl"1P.mJ.r.al

E.rt1;;iincc-rs'

Hondbook,

5th

edition, Mc Gr~w-Hill, N~w Vork, 1~73. 9. -Rw9uwru-Rw2,;,r; Ma:-·1 titrasa: · 1 n forn-re· c;r-1bre· pttri ti c.r.c.:i6n· ·dt!- ·tiAf'•A· ·y ·

AFA, Cuernav~c~, MoreJos, M•xico. Nu~.-Di~. 1909 •

. 'I

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