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ADIMIX®
Sodium ButyrateSodium Butyrate
For animal’s Health & PerformanceFor animal’s Health & Performance
ADIMIX®
Improves Feed Conversion
Stimulates Early Feed Intake
Enhances Intestinal Health
Natural Attractant
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Active substance butyric acid
an organic acid with specific characteristics a short chain fatty acid (SCFA) a viscous liquid miscible with water, ethanol and ether (lipids)
(unlike other SCFA’s, like propionic acid / acetic acid)
the characteristic smell of rancid butter (when it is present as -very volatile- free fatty acid)
CH3 - [CH2]2 - COOH
ADIMIX®
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Physical and Chemical Characteristics of Short Chain Fatty Acids (SCFA)
Chemical formula
Trivial name Mol mass
Boiling point (°C)
Melting point (°C)
pK value
Kp*
CH3- COOH Acetic acid 60.05 118.1 16.7 4.76 0.02
CH3CH2- COOH Propionic acid 74.08 141.1 -22 4.87 0.15
CH3(CH2)2COOH N-Butyric acid 88.11 163.5 -4.7 4.82 0.44
Distribution in chloroform/water. Increasing number indicates higher solubility in lipids Na-n-butyrate: white stable non-volatile powder up till 250°C
Watersoluble
Water & Fatsoluble
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N – Butyric acid sodium salt, or N – Butyrate, sodium salt, or Butanoic acid, sodium salt, or Sodium butanoate, or E 470
Spray-dried white powder
Pure form contains
98% sodium butyrate or 78% butyric acid
What is ADIMIX® ?
CH3 - [CH2]2 - COONa
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Adimix® : dissociation
CH3 - [CH2]2 – COOH CH3 - [CH2]2 – COO¯ + H+
In the undissociated state, butyric acid is strongly lipophilic and can easily cross membranes (both bacterial and cellular membranes) The dissociation rate of organic acids is mainly influenced by the pKa value (pH at which 50% of the acid is in the dissociated state and 50% is in the undissociated state) and the pH of the intestinal liquidThe pKa value of butyric acid is about 1 pH unit higher than ‘traditional’ organic acids like formic and lactic acid (see next slide). As a result, butyric acid has different characteristics with respect to its anti-microbial activity, but also the biological effect of butyric acid is linked with its high pKa value.
n-butyric acid n-butyrate
pH
(Undissociated) (Dissociated)
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Antibacterial effect : G- &
G+
G-bacteria
G+bacteria
Butyric acid
XOrganic Acids
Only at10 X normal dose
More complex membrane( > FAT !! )
Favours / does not harm / even stimulatesLactobacillus
The combination of O
rganic Acids & Adimix
®
Perfo
rms bette
r than single approach (s
ynergy)
Is th
e most e
conomical application
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Bacterial Cell
Antibacterial effect
pH drop
RCOO- H+
pKa
DNA
RCOOH (Organic Acid – Undissociated)
H+ ATP ADP + P
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Antibacterial effect
Stop of DNA transcription (prevents growth and cell multiplication)
Bacterial Cell exhausts
No energy for multiplication
Bacterial Cell collapses
Bacterial Cell
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Dissociation of n-Butyric acid: pH dependent
0
20
40
60
80
100
120
3 3.5 4 4.5 5 5.5 6 6.5 7pH
No
t d
iss
oc
iate
d (
%)
Butyric acid
Formic acid
Lactic acid
At higher pH values (5-6), more butyric acid is present in the undissociated form compared to formic or lactic acid (differences in pKa value)
This means there is a synergy between Butyric acid and Formic/Lactic acid in terms of their anti-microbial effect (this is the basis for the Nutri-Ad acidification program for pigs).
pKa value
4.82
3.75
3.79
Butyric acid travels further
down the digestive tract
pH
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Butyric acid, Acetic acid, Propionic acid
metabolic end-products
of carbohydrate digestion by bacteria
in the rumen or large intestine of pigs, poultry, rabbits and ruminants
Short Chain Fatty Acids: metabolism
Low Fibre-fermentation capacity for young animals
Naturally present, . . . but insuffient ?
1 - 2 % in milk fat
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Metabolism of n-butyrate
Cellulose and/or Starch (from Cellulose and/or Starch (from diet)diet)
Bacterial fermentation pigs, (poultry) colon
multigastrics rumen
n-butyraten-butyrate
Metabolisation by rumen and intestinal eptithelium cells (villi)
Secretion
via respiratory tract, skin, . . .
Blood absorption
70%30%
High levels in human : leaves body via sweat and breath socially unacceptable
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Cell metabolism
Immune system
Selective action on bacterial micro-flora
ADIMIX®
Biological Functions
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1. Cell metabolism
Energy source for intestinal mucosa (brush border) Differentiation of enterocytes +++ Contact surface of intestinal microvilli +++ Calcium aborption +++ Secretion of pancreatic enzymes +++ Secretion of intestinal digestive enzymes ++++
ADIMIX® : Biological Functions
2. Immune system
3. Selective action on bacterial micro-flora
Differs it from any other acid
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1. Cell metabolism
2. Immune system Increased haemoglobin synthesis Stimulation of non-specific immunity (phagocytosis by macrophages)
Stimulation of local immunity in the intestine (Gut Associated Lymphoid Tissue)
Increase in haptoglobine values (indicator for immune stimulation)
Correlation with LPS (liposaccharides) from pathogenic bacteria in a way that it controls the nitric oxide production
3. Selective action on bacterial micro-flora
ADIMIX® : Biological Functions
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1. Cell metabolism
2. Immune system
3. Selective action on bacterial micro-flora
Increase in Bifido-bacteria + Lactobacils
Colonisation resistance against harmful / bad-natured bacteria, like E. Coli, Salmonella
Direct anti-bacterial action (organic acid effect)
ADIMIX® : Biological Functions
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Prevention of inflammatory diseases in the gastro-intestinal tract
Chrone disease Enterocolitis Necrotic enteritis
Regression of colon and rectum cancers
‘A deficiency of butyric acid or other SCFA to the colon causes inflammation’ (Kien et al., 1999)
Butyric acid in human gut pathology
Inhibits growth of
abnormal cells
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New Spray Drying Tower installedFinalized early 2003
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“Power”
in the hindgut
Coated Formic Acid (C1)
Coated Acetic Acid (C2)
Coated Propionic acid (C3)
Coated Butyric Acid (C4)
++
+++++
Trial Veterinary Faculty of the University of Gent – Belgium
Anti-Salmonella / Anti-Dysenterie Effect
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Adimix® C 30 Coated
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LIPASE
1
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LIPASE
2
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LIPASE
3
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Na-Butyrate versus Ca-Butyrate
A small molecule penetrates the bacterial cell more easy
Calcium Butyrate has a lower anti-bacterial effect, as its molecular weight is 2 X higher than Sodium Butyrate ( resp. 216 and 111, resulting in less diffusion capacity)
Sodium Butyrate is perfectly water-soluble (1.0 kg in 1 kg water) Calcium Butyrate’s water-solubility is poor (0.3 kg in 1 kg water)
the higher the solubility, the easier the reaction to salt vice versa ; otherwise it only stays as a crystal
Calcium Butyrates are not spray-dried ( 1 - 2% free, volatile But.-acid) ADIMIX (Na-Butyrate) is spray-dried (< 0.1% free, volatile But.-acid)
ADIMIX : high concentration active ingredient ADIMIX : captured and covered odeur
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Na-Butyrate versus Ca-Butyrate
Calcium Butyrate has a much stronger ‘typical’ odeur/smell than spray-dried Sodium Butyrate (= related to the level of ‘free buteric acid’, which is an extremely volatile molecule)
Calcium Butyrate have lower levels of active ingredients, and often contains a rather high level of (non-nutritional) anti-caking products
Dust level (measured by ITECH) is twice as high in Ca-Butyrate (>4%) compared to ADIMIX (2%)
ADIMIX (spray-dried) has a much more uniform particle size than Ca-Butyrate (dry mix)
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Granulometry and particle size distribution
01234567
0 200 400 600 800 1000 1200 1400 1600
Particle size (µm)
% o
f to
tal v
olu
me
ADIMIX Butyrate 98C
Calciumbutyrate
ADIMIX
More uniform particle size distribution
Significantly less fine particles less dusty product
Fines / dust
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ADIMIX Calcium-butyrate
Spray-dried powder
Uniform particles
Low dust
Dry mix (butyric acid + mineral support)
Variable particle size
High dust
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ADIMIX : superior solubility
Adimix Butyrate
1000 g in 1000 ml of water
Calcium Butyrate:
300 g in 1000 ml of water
Poor water solubility
Risk of complex formation of calcium with other dietary components
Perfectly water soluble, no sedimentation
Higher bio-availability
Preferred source for all in-feed applications
-specifically for milk replacers & liquid applications-
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