Nhom 001 nhom 08-sv
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Transcript of Nhom 001 nhom 08-sv
PRODUCINGCEPHALOSPORIN
In 1929,Alexander Fleming had discovered Peniciline
SETTING PROBLEM
CONTENTSIII. Producing Cephalosporin C
IV. Application.
II. About C
ephalosporin.
I. G
ener
al v
iew a
bout A
ntibio
tics.
PART I: GENERAL VIEW ABOUT ANTIBIOTICS.
To inhibit the growth of or to destroy bacteria
Have a specific
Low concentration
Secreted by microoganism
synthetic or semi-synthetic chemical compound
AntibioticsAnti
biotics
I.DEFINITION
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
………………..
II.CLASSIFICATION TABLE
PENICILINES
CEPHALOSPORIN
MONOBACTAMS
CARBAPENEMS
III.β- LACTAM GROUP
-lactams Group
-lactamsrings
Antibiotic resistance -lactams group
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
CEPHALOSPORIN ’S GENERAL
CEPHALOSPORIN’S GENERATIONS
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-lactamaseinhibit, Repress Pseudomoas
+Cefepime+Cefozopran
5th gener.
β-lactamaseinhibit,Repress MRSA
+Ceftobiprole+Ceftaroline
Cep
hal
osp
orin
cl
assi
fica
tion
Name
PART III: PRODUCING CEPHALOSPORIN C BY
MICRORGANIC FERMENTATION METHOD
I.CEPHALOSPORIN C (CPC) BIOSYNTHESIS
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:
1.3. Growth condition:
Nutrition
Microquantity
pH
Water
Sacharose 36gGlucose 27g(NH4)2SO4 7.5gOleic acid 1.5gMethionin 3.0g
K, Fe, Mn, Mg, Zn, Cu,…
7.3
(Adequate add 1liter)
1.4 Fermentation condition:
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.
1.5 Prepare for fermentation:
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
Step 1. Subdeviding and selecting race
5.Transplant bacteria into Mueller-Hinton agar disk
6. Put in antibiotic paper
7. Measure absolute sterility ring
8.Analyse and answer result
1.Subdevidingrace
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
Step 3: Produced Ferment
YBS environment ( growth environment) Two phases fermentFirst phase (get biomass): 2-3 days, at 28 – 30oC, pH 6.5-6.8Last phase (get product) : 5 -7 days, at 22-25oC, pH lower than frist phase
Step 4: Frationate and Purify
Fermentation method:
Ferment in batch-reactor
Using stirrer blades
Aerating air by power pump
Producing CEPHALOSPORIN fermentation figure
Submerged fermentation
Foam breaking
Partition
Heat transfer
Flat turbine
Aseptic air
EQUIPMENT FACTOR
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
Ferment equipment inside laboratory
Pilot
Industrial Fermentation
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
Reaction scheme
= 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 =
Calculating data
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
0 1 2 3 4 5 60
1
2
3
4
5
6
7
8
9
f(x) = 1.41996987793073 x + 0.142586087819977R² = 0.921047635800439
1/CA 0.59 0.83 1.25 3.3 5
Cc/rc 1 1.57 2.22 3.7 8
Reaction rate
We have this from the chart above:K= 7 day-1
Cm= 9.94 (g/l)
Volume of equipment
Antibiotics concentration: 1.6 g/l.Weekly yeild: 30 kgAnually yeild: 1560 kgVolume of equipment 18.75 m3
Need 5 serial reactors
With this ouput, about 150.000600.000 Cefpodoxime tablet will be produced per week.
Part IV: Appication
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 609015252. Phạm Thị Hồng Nhật 609018443. Thiều Nguyễn Trường Giang 609006804. Vũ Viết Văn Thưởng 608021995. Phạm Như Quốc Khánh 609011926. Hứa Tiến Đức 609006257. Trần Ngọc Hưng 609011198. Nguyễn Văn Nguyên 609017649. Trần Ngọc Kiều Khanh 60901164
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INSTRUCTOR :Doctor. Lê Thị Kim Phụng
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