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PRODUCING
CEPHALOSPORIN
In 1929,Alexander Fleming had
discovered Peniciline
SETTING PROBLEM
CONTENTS
To inhibit the growth of or to destroy bacteria
Have a specific
Low concentration
Secreted by microoganism
synthetic or semi-synthetic chemical compound
Anti
biotics
The antibiotics have β-lactam structure Penicillin,cephalosporin
The antibiotic containing aromatic ring Chloramphenicol
Aminoglycosid structure antibiotics Streptomycin,gentamicin
The structures of antibiotics have 4 rings Tetracyclins
Polypeptid antibiotics Polymyxin,bacitracin
Macrolid antibiotics Erythromycin,spiramycin
Polyen antibiotics Nystatin,amphotericin B
………………..
PENICILINES
CEPHALOSPORIN
MONOBACTAMS
CARBAPENEMS
-lactams
rings
RESIST BY
β-LACTAMASE ENZYME
PART II:
GENERAL VIEW ABOUT
CEPHALOSPORIN ANTIBIOTICS.
1945
1956
1964
1971DISCOVERED HISTORY
Cephalosporium
acremonium race was
discovered from a sewer
in Sardinia in 1945 by
Italian scientist Giuseppe
Brotzu
Cephalosporin C and penicillin N were
fractionated from fungus growth sap
First introduced in clinal
in 1964 (cephalothin)
Cephamycin was
fractionated
fromNorcadia race,
having same structure
as Cephalosporin
Repressing cell
wall biosynthesis
One of β-lactam
antibiotics
Operating on Gr(+)
and Gr(-) bacteria
CEPHALOSPORIN
1Nature CP have low
antibacterial active
2Cephalosporin includes β-lactam ring
and dihydrothiazin heterocyclic
(cephem core)
3Cephalosporin use for treatment all are synthesis
or semi-synthesis chemical compound
4Cephalosporin is the material to
produce 7-ACA and 7-ADCA
1st gener.
Sensitive with
β-lactamase.
+Cefazolin
+Cephalexin
+Cepoxitin
2nd gener.
Sensitive with
β-lactamase.
+Cefamadole
+Cefaclor
+Cepoxitin
3rd gener.
β-lactamase
inhibit.
+Cefotaxime
+Ceftriaxone
4th gener.
β-lactamase
inhibit,
Repress
Pseudomoas
+Cefepime
+Cefozopran
5th gener.
β-lactamase
inhibit,
Repress
MRSA
+Ceftobiprole
+Ceftaroline
Name
PART III:
PRODUCING CEPHALOSPORIN C BY
MICRORGANIC FERMENTATION METHOD
1. Race.
- Cephalosporium acremonium (Acremonium chrysogenum)
- Low antibiotics active, doesn’t have super-synthetic race.
- Doesn’t have acyltransferase enzyme so can’t use
precursor substance to contribute new product
Pictures of
Cephalosprium Acremonium race
Cephalosporin
acremonium
Ingredient:
Nutrition
Microquantity
pH
Water
Sacharose 36g
Glucose 27g
(NH4)2SO4 7.5g
Oleic acid 1.5g
Methionin 3.0g
K, Fe, Mn, Mg, Zn, Cu,…
7.3
(Adequate add 1liter)
pH
condition
from 6,8 to
7,4.
Temp. pH Oxigen CO2
.
T = 25-300C,
maintain
during
fermentation
process
Concentration
of dissolved
oxygen = 30%
concentration
of saturated
one.
Too high
concentration
of CO2 will
resist the
adsorbtion and
metabolization
of substrate ‘s
races.
 Conserve races and multiplicate races:
 Extremely cold storage at -700C or liquid nitrogen
shielding.
 Races from preservation condition are transplanting
to agar to active and growth to get spore.
 Finally, the multiplicating equipment will produce
the amount of races whose the density in initial ferment
solution is about 1 - 5.109 spores / m3.
• Ferment equipment: Must be in absolute sterility
before using, either to all of the equipments. Sterile
in overheated steam at 2,5 – 3,0 at for 3 hr. Manage
to maitain the excess pressure in the equipment
during the ferment process to limit contaminant.
• The air is usually been antiseptic by adiabatic
compresion, then get through ultrafiltration.
• Surfaced fermentation engineering: Fermenting
on solid materials (corn mash, wheat mash added
lactose)
BIOSYNTHESIS MECHANISM
4. Fractionate,
purify
6.Mass
produce
1.Subdividing,
Selecting
race
2.Preserving,
activating race
3. Produced
ferment
PROCESS
3.Producing Process:
5. Collecting
product
5.Transplant
bacteria into
Mueller-Hinton
agar disk
6. Put in
antibiotic
paper
7. Measure
absolute
sterility
ring
8.Analyse and
answer result
1.Subdeviding
race
2. Transplant
into environment
without
selection
3. Creating
bacteria sap in
normal saline
(108cell/ml)
4.Adjusting
opacity of
bacteria
(106cell/ml)
Cephalosporin
acremonium
UI
 YBS environment ( growth environment)
 Two phases ferment
 First phase (get biomass): 2-3 days, at 28 – 30oC,
pH 6.5-6.8
 Last phase (get product) : 5 -7 days, at 22-25oC,
pH lower than frist phase
Ferment in batch-reactor
Using stirrer blades
Aerating air by power pump
Foam
breaking
Partition
Heat transfer
Flat turbine
Aseptic air
 Volume : 5 m3
 Filled coefficient : 0.75
 Steel component: X18H10T and X17H13M2T
 Stir speed: 110-200 rpm
 Antiseptic at: 130- 140ºC
 Working pressure : 50 kPa – 0.25 Mpa
 Working temprature: 0 – 34ºC
 Blow rate : 12 m/s
FERMENT PROCESS
PLEASE KEEP TRACK OF THIS
FOLLOWING VIDEO
Visit website:
http://www.biocon.com/bioconvirtualtour_v1/submergedfermentation.htm
5. CALCULATING KINETIC
FACTORS OF EQUIPMENT:
Bacterial growth curve in the batch reactor
= k . = max.
CC- Bacterial concentration (biomass)(g/l)
µ particular day growth speed (day-1)
µmax maximun particular day growth speed(day-1)
CA sucrose concentration (g/l)
CM Monod coefficient (g/l).
Monod equation for batch
reactor:
rC = = µCC =
CA (g/l) 3 2.9 1.7 1.2 0.8 0.3 0.2
CC (g/l) 0 0 0.2 0.33 1 1.4 1.6
t 0 1 2 3 4 5 6
y = 1.42x + 0.142
0
1
2
3
4
5
6
7
8
9
0 1 2 3 4 5 6
1/CA 0.59 0.83 1.25 3.3 5
Cc/rc 1 1.57 2.22 3.7 8
We have this from the chart above:
K= 7 day-1
Cm= 9.94 (g/l)
Antibiotics concentration: 1.6 g/l.
Weekly yeild: 30 kg
Anually yeild: 1560 kg
Volume of equipment 18.75 m3
Need 5 serial reactors
With this ouput, about 150.000600.000
Cefpodoxime tablet will be produced per week.
 Nowadays, Cephalosporin is the most important antibiotic
drug. Cephalosporin use to treat a lot of disease, what resisted
another antibiotics such as: penicilin, amoxicilin, ampicilin…
 Ranking 7th / 10 antibiotics to treat infections, it is caused by
staphylococus aureus and typhoid fever in humans.
 Semi-synthetic CPC have antibacterial effect with both β-
lactamase bacteria, gram (-) bacteria and have low toxicity.
›CPC second generation antibiotics is very specially effect
when we use infections of incision after operation.
›Advantage of CPC third generation antibiotics is the most
broad spectrum antibacterial for both bacteria gram (-) and
gram (+),including strains of streptococcus .
›It used to treat severely infections in bronchus and
lung, sepsis, bacterial contamination of bone, urinaly
tract, gonorrhoeae resisted by another antibiotics…
1. Nguyễn Thị Mai 60901525
2. Phạm Thị Hồng Nhật 60901844
3. Thiều Nguyễn Trường Giang 60900680
4. Vũ Viết Văn Thưởng 60802199
5. Phạm Như Quốc Khánh 60901192
6. Hứa Tiến Đức 60900625
7. Trần Ngọc Hưng 60901119
8. Nguyễn Văn Nguyên 60901764
9. Trần Ngọc Kiều Khanh 60901164
INSTRUCTOR :Doctor. Lê Thị Kim Phụng
Nhom 001 nhom 08-sv

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Nhom 001 nhom 08-sv

  • 2. In 1929,Alexander Fleming had discovered Peniciline SETTING PROBLEM
  • 4. To inhibit the growth of or to destroy bacteria Have a specific Low concentration Secreted by microoganism synthetic or semi-synthetic chemical compound Anti biotics
  • 5. The antibiotics have β-lactam structure Penicillin,cephalosporin The antibiotic containing aromatic ring Chloramphenicol Aminoglycosid structure antibiotics Streptomycin,gentamicin The structures of antibiotics have 4 rings Tetracyclins Polypeptid antibiotics Polymyxin,bacitracin Macrolid antibiotics Erythromycin,spiramycin Polyen antibiotics Nystatin,amphotericin B ………………..
  • 9. PART II: GENERAL VIEW ABOUT CEPHALOSPORIN ANTIBIOTICS. 1945 1956 1964 1971DISCOVERED HISTORY Cephalosporium acremonium race was discovered from a sewer in Sardinia in 1945 by Italian scientist Giuseppe Brotzu Cephalosporin C and penicillin N were fractionated from fungus growth sap First introduced in clinal in 1964 (cephalothin) Cephamycin was fractionated fromNorcadia race, having same structure as Cephalosporin
  • 10. Repressing cell wall biosynthesis One of β-lactam antibiotics Operating on Gr(+) and Gr(-) bacteria CEPHALOSPORIN
  • 11.
  • 12. 1Nature CP have low antibacterial active 2Cephalosporin includes β-lactam ring and dihydrothiazin heterocyclic (cephem core) 3Cephalosporin use for treatment all are synthesis or semi-synthesis chemical compound 4Cephalosporin is the material to produce 7-ACA and 7-ADCA
  • 13. 1st gener. Sensitive with β-lactamase. +Cefazolin +Cephalexin +Cepoxitin 2nd gener. Sensitive with β-lactamase. +Cefamadole +Cefaclor +Cepoxitin 3rd gener. β-lactamase inhibit. +Cefotaxime +Ceftriaxone 4th gener. β-lactamase inhibit, Repress Pseudomoas +Cefepime +Cefozopran 5th gener. β-lactamase inhibit, Repress MRSA +Ceftobiprole +Ceftaroline
  • 14. Name
  • 15. PART III: PRODUCING CEPHALOSPORIN C BY MICRORGANIC FERMENTATION METHOD 1. Race. - Cephalosporium acremonium (Acremonium chrysogenum) - Low antibiotics active, doesn’t have super-synthetic race. - Doesn’t have acyltransferase enzyme so can’t use precursor substance to contribute new product
  • 18. Ingredient: Nutrition Microquantity pH Water Sacharose 36g Glucose 27g (NH4)2SO4 7.5g Oleic acid 1.5g Methionin 3.0g K, Fe, Mn, Mg, Zn, Cu,… 7.3 (Adequate add 1liter)
  • 19. pH condition from 6,8 to 7,4. Temp. pH Oxigen CO2 . T = 25-300C, maintain during fermentation process Concentration of dissolved oxygen = 30% concentration of saturated one. Too high concentration of CO2 will resist the adsorbtion and metabolization of substrate ‘s races.
  • 20.  Conserve races and multiplicate races:  Extremely cold storage at -700C or liquid nitrogen shielding.  Races from preservation condition are transplanting to agar to active and growth to get spore.  Finally, the multiplicating equipment will produce the amount of races whose the density in initial ferment solution is about 1 - 5.109 spores / m3.
  • 21. • Ferment equipment: Must be in absolute sterility before using, either to all of the equipments. Sterile in overheated steam at 2,5 – 3,0 at for 3 hr. Manage to maitain the excess pressure in the equipment during the ferment process to limit contaminant. • The air is usually been antiseptic by adiabatic compresion, then get through ultrafiltration. • Surfaced fermentation engineering: Fermenting on solid materials (corn mash, wheat mash added lactose)
  • 23. 4. Fractionate, purify 6.Mass produce 1.Subdividing, Selecting race 2.Preserving, activating race 3. Produced ferment PROCESS 3.Producing Process: 5. Collecting product
  • 24. 5.Transplant bacteria into Mueller-Hinton agar disk 6. Put in antibiotic paper 7. Measure absolute sterility ring 8.Analyse and answer result 1.Subdeviding race 2. Transplant into environment without selection 3. Creating bacteria sap in normal saline (108cell/ml) 4.Adjusting opacity of bacteria (106cell/ml) Cephalosporin acremonium
  • 25. UI  YBS environment ( growth environment)  Two phases ferment  First phase (get biomass): 2-3 days, at 28 – 30oC, pH 6.5-6.8  Last phase (get product) : 5 -7 days, at 22-25oC, pH lower than frist phase
  • 26.
  • 27. Ferment in batch-reactor Using stirrer blades Aerating air by power pump
  • 29.  Volume : 5 m3  Filled coefficient : 0.75  Steel component: X18H10T and X17H13M2T  Stir speed: 110-200 rpm  Antiseptic at: 130- 140ºC  Working pressure : 50 kPa – 0.25 Mpa  Working temprature: 0 – 34ºC  Blow rate : 12 m/s
  • 31.
  • 32.
  • 33.
  • 34. PLEASE KEEP TRACK OF THIS FOLLOWING VIDEO Visit website: http://www.biocon.com/bioconvirtualtour_v1/submergedfermentation.htm
  • 36. Bacterial growth curve in the batch reactor
  • 37.
  • 38. = k . = max. CC- Bacterial concentration (biomass)(g/l) µ particular day growth speed (day-1) µmax maximun particular day growth speed(day-1) CA sucrose concentration (g/l) CM Monod coefficient (g/l). Monod equation for batch reactor: rC = = µCC =
  • 39. CA (g/l) 3 2.9 1.7 1.2 0.8 0.3 0.2 CC (g/l) 0 0 0.2 0.33 1 1.4 1.6 t 0 1 2 3 4 5 6
  • 40. y = 1.42x + 0.142 0 1 2 3 4 5 6 7 8 9 0 1 2 3 4 5 6 1/CA 0.59 0.83 1.25 3.3 5 Cc/rc 1 1.57 2.22 3.7 8
  • 41. We have this from the chart above: K= 7 day-1 Cm= 9.94 (g/l)
  • 42. Antibiotics concentration: 1.6 g/l. Weekly yeild: 30 kg Anually yeild: 1560 kg Volume of equipment 18.75 m3 Need 5 serial reactors With this ouput, about 150.000600.000 Cefpodoxime tablet will be produced per week.
  • 43.  Nowadays, Cephalosporin is the most important antibiotic drug. Cephalosporin use to treat a lot of disease, what resisted another antibiotics such as: penicilin, amoxicilin, ampicilin…  Ranking 7th / 10 antibiotics to treat infections, it is caused by staphylococus aureus and typhoid fever in humans.  Semi-synthetic CPC have antibacterial effect with both β- lactamase bacteria, gram (-) bacteria and have low toxicity.
  • 44. ›CPC second generation antibiotics is very specially effect when we use infections of incision after operation. ›Advantage of CPC third generation antibiotics is the most broad spectrum antibacterial for both bacteria gram (-) and gram (+),including strains of streptococcus . ›It used to treat severely infections in bronchus and lung, sepsis, bacterial contamination of bone, urinaly tract, gonorrhoeae resisted by another antibiotics…
  • 45. 1. Nguyễn Thị Mai 60901525 2. Phạm Thị Hồng Nhật 60901844 3. Thiều Nguyễn Trường Giang 60900680 4. Vũ Viết Văn Thưởng 60802199 5. Phạm Như Quốc Khánh 60901192 6. Hứa Tiến Đức 60900625 7. Trần Ngọc Hưng 60901119 8. Nguyễn Văn Nguyên 60901764 9. Trần Ngọc Kiều Khanh 60901164 INSTRUCTOR :Doctor. Lê Thị Kim Phụng