Trend of phytogenic feed additives (bioactives) market

Source: https://www.marketsandmarkets.com/Market-Reports/feed-phytogenic-market-162036047.html

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Trend of phytogenic feed additives (bioactives) market

Bioactives (and particularly essential oils)

have gained the trust of feed operators
and farmers as a potential strategy for de-
medication with health and performances
promotion.

For this reason, different market insights

experts agree with a marked increase
projected to 2027, that could range from
865 mil. USD to 1098 mil. USD.

EU Countries would represent approx 25%

of this market value projection

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Global dynamics driving high quality bioactives’growth

Regulatory Authorities Growing of poultry Pressure for antibiotic-

pushing for reduction of market – animal protein free food from large-
antibiotic treatment in at affordable cost – at scale distribution
feed/water; ban of ZnO global level (internal, stringent
pharma in EU (5,7% in 2021 – 2026) guidelines)

Workers/farmers safety Increasing pressure on Many companies selling

concerns: developing vets, due to strong herbal extracts and/or
technologies that can limitation of mass essential oils, without
allow a safe production treatment, but also to scientific data,quality
and distribution/ process new EU regulations on certifications and “Black
of feed veterinary prescription Box” formula

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Value proposition to Customers of Phytosolutions

• Phytosolutions brings the experience and professionality of

ALIVIRA, a globally-established pharma Group, into the new
scenarios open from rational use of antibiotics

• Our value proposition is:

✓ Supporting customers and their growth with high-quality,

consistant products, solid data, and a skilled internal Team
✓ Generating trust (quality, support) and satisfaction (safety,
problem-solving, predictability) through our experience in
production and marketing of bioactives
✓ Establishing a strong relationship both with animal health and
feed production decision-makers. Sustainability and rational use
of antibiotics doesn’t go against optimization of productive
performances
✓ Building and delivering an image of “science-based Brand”.
Strenghtening our presence in the scientific arena (technicaland
scientific events, peer-reviewed publications, co-operation with
University, Research Centers and KOLs)
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What makes Phytosolutions products unique?
Thanks to the support of a world-wide pharma
Group, producing and marketing bioactive-based
product with GMP rules in compliance with FAMI-
QS code
• Quality Control procedures
• Qualification of suppliers (FAMI-QS certified)
• Validated process and analytical methods
• Total batch traceability
• Certificación
In de Calidad FAMI QStechnology, aimed
house microencapsulation
both to facilitate handling and distribution of spicy
phytogenics and to obtain slow-release of active
ingredients in the gut

Production of liquid solutions and powder products,

targeting both feed producers and veterinarian
segment (problem-solving nutraceuticals)

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Value propostion: products’ quality
Following strict process and controls (accordingly with GMP and FAMI-QS rules) make us able to place in
the market nutritional products with a pharmacological quality

Our quality Routinary analysis of ingredients with HPLC and GC before being released
standard Validated quality control of finished product (for active ingredients)
Stability trials performed (liquid solutions and powders)
GMP guidelines are routinarily followed

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Value proposition: multi-level positiong. Feed and water use

Powders Oral solutions

(solid feed) (drinking water)
High concentration and consistancy of Use of EU-approved emulsifiers to improve
active ingredients solubility of concentrated essential oils

High homogeneity and uniformity of Tests on homogeneity and stability of

the finished product (selected carriers) the finished formulation

Very tight particle size range (from 200 Low dosage in drinking water and
µm to 300 µm). solubility tests

Homogeneus water
emulsion
Essential oil
Essential oil

Water
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Value proposition: technologies for problem-solving

Advantages of SLOW-RELEASE EFFECT (monogastrics)

microencapsulation
+/- 20% gastric release
Homogeneity of particle size (average +/- 80% intestinal release
600 µm to 1mm). (after digestion of fat coating from pancreatic lypase)
Uniformity of the concentration of active
ingredients (precise dosing)

Slow-release/Taste-masking effect

Safe handling
(corrosive/hygroscopic/spicy ingredients)
Drastic reduction of “active” dusts in
feedmill and farm

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 Products’ segmentation (functional & galenic)

Coxsan Phytmax Acid

Bioactives Licorol Phytobutyrin
(drinking Phytmax M Phytobutyrin plus Synergistic
water and Phytmax Cox Gastroherb Plus conditioners (organic
feed) Liversan Galenic
acids + bioactives)
“multiplicator”
(powder and
liquid forms)

Wide-spectrum Protigen (SR urea) Slow-release feed

additives/safety-
detoxifiers Phytmax Detox Phytmax M powder (enc.)
enhanced
Phtymax capsicum enc. bioactives

All the Phytosolutions products are designed to fall into the «complementary feed»
category, as per EU feed regulation: so, they can be used by all feed operators
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Products’segmentation (Company’s focus)

• Coxsan (Naturcox)* • Protigen

• Licorol • Phytobutyrin
• Gastroherb Plus • Phytobutyrin plus
• Phytmax capsicum • Phytmax Detox
encaps

Strategic Entry
products products
* Spain and Italy
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GUT HEALTH MANAGEMENT: integrating pharma and
nutrition to improve animal welfare
GUT HEALTH MANAGEMENT is a new brand concept, aimed to offer to a wider range of Customers
nutritional and pharma strategic products, in order to protect gastro-intestinal health and welfare, still the
most frequent challenge in animal farming

• Phytmax • Halofusol
Monogastrics

Ruminants

Pharma products Karizoo

• Coxsan liquid
• Coxsan capsicum 0,5mg/ml
powder encaps (Halofungino
• Phytobutyrin • Coxsan liquid ne)
plus • Coxsan • Toltra-K
• Gastroherb powder 25mg/ml
plus (Toltrazuril)

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Strategic products

COXSAN
COMPOSITION
CATEGORY • Oregano oil PROPERTIES
Complementary feed (tipified on • Wide-spectrum
carvacrol and antimicrobial
timol) • Antioxidant
• Garlic oil • Protection of
PRESENTATION (tipified in gastro-intestinal
Oral solution/powder for feed allildisuldide and mucosa
(25kg bag) alliltrisulfide)

AVERAGE INCLUSION RATE

150–250ml/ 1,000L drinking water
RECOMMENDATION FOR USE
250–500g/T of feed
Non pharma management of digestive disorders of various nature
(wet litters in poultry), recover of digestive stress during feeding
TARGET SPECIES changes, reduction in antibiotic treatments of bacterial enteritis
Poultry, pigs, calves, beef (until (e.g. Clostridium perfringes in poultry or E. Coli in calves)
180-200 kg l.w.), rabbits

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Strategic products: summary of Coxsan trials (1)
PLACE AND DATE OF TARGET SPECIES PRESENTATION PROTOCOL
TRIAL
Mexico, 2018 Broilers Powder (alone and in 250g/t, alone and in
association with Licorol) association with Licorol at
250ml/1,000l for 4 weeks. 2
control groups (negative
and Bacitracine)
Mexico, 2020 Broilers Liquid 3 groups: 150 ml/ 1,000 l
for 35 days; 250 ml/1,000 l
for 7 days (dd.24-30); 250
ml/1,000 l for 35 days.
Negative control and
coccidia challenge
Mexico, 2018 Shrimps Liquid 17-34-51ml/25kg of
biomass (equal to 1L/Ton
of feed)
Portugal, 2015 Broiler breeders Liquid 250 ml/1,000 l for 2 days
per week (total 18 days).
Positive control:
competitor oregano
product
Spain, 2014 Broilers LIquid 3 groups at 250ml/1,000 L
for 2 days per 7 weeks.
Licorol was added in 2 of
the 3 test groups for 3
days at 250ml/1.000L
RESULTS
Final weight improvement
in Coxsan-Licorol group;
homogeneity comparable
to bacitracine group;
lower coccidia count in
Coxsan groups
Lower oocystis count,
lower intestinal lesions in
all the Coxsan groups
Weight improvement in
the starter period
Reduction of digestive
problems/lower mortality
The test groups performed
better than control (treated
with enrofloxacin) in terms
of weight, FCR and
mortality 14
Strategic products: summary of Coxsan trials (2)

PLACE AND DATE OF TARGET SPECIES PRESENTATION PROTOCOL RESULTS

TRIAL

Spain, 2016 Lambs Powder High dosage: 2kg/T for 4 FCR improved. Oocystis
weeks. Controls negative excertion comparable to
and positive (decoquinate) decoquinate group

Italy, 2019 Piglets Powder 500-300g/T for 70 days. Better weight tendence in
Compared to positive the last part of trial.
(antibiotics/anticoccidic) Significant reduction of
and negative control treatment for enteric
diseases

Italy, 2020 Calves Liquid/powder Calves reared for 200 days Weight performance
approx. First month: 2 improved. Better health in
ml/head/day; then 500g/T). the first phase and
Negative control reduction of individual
treatments for enteritis

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Coxsan liquid: broiler trial 2014 (Spain)

Groups Initial Final No. of FCR % Mortality Feed Intake

Weight Weight animals (kg)
No. animals
Control 1 46 g/ u 2642 g 71.400 2.075 6.82% 4.873 5.482
Control 2 48 g/ u 2740 g 71.400 2.095 3.76% 2.688 5.740
PHYTO 1 49 g/ u 2871 g 74.766 1.991 3.65% 2.734 5.716
PHYTO 2 48 g/ u 3001 g 75.174 1.972 2.60% 1.958 5.917
PHYTO 3 47 g/ u 2774 g 72.114 1.889 3.53% 2.550 5.240

The trial (Valladolid, broilers Ross 308) lasted 47 days. Control (negative) groups had to be treated with
Enrofloxacin for 5 days (starting from day 25 of life) for a severe E. coli enteritis. Phyto 1 received Coxsan
liquid at 250ml/1.000 L of water at day 1 and then for 2 days/week. Phyto 2 and 3 same, together with Licorol
liquid, administered for 3 days at 250ml/1.000 L (from day 20 of life).
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Coxsan powder: pig trial, 2019 (Italy)
Birth weight Weaning Weight at 49 Weight at 70 ADG ADG ADG
weight (d28) days days (0-28 days) (49-70 (0-70 days)
days)

Medicated 7,440a 14,331 32,950 0,220ª 0,411 0,229x

group*
“White” 1,729 6,916b 13,712ª 32,617b 0,189b 0,398ª 0,218b
control
Coxsan 6,942b 14,959b 33.793a 0,198b 0,437b 0,240ay
group

*Medicated group received toltrazuril at day 1, injective treatments at castration, marking, weaning and amoxicillin via water

Mortality Total Individual Individual Total

before mortality at treatment for treatment for treatments
weaning* the end diarroea** meningitis **** * No infectious diseases
*** **caused by strains of E.Coli
***caused by Straptococus suis
Medicated 7,35% 8,82% 46,03% 0,00% 6,15 ****sum of number of treatments per animals
group (individual plus mass treatment) both oral and
injective
“White” 12,28% 14,04% 40,0% 4,00% 0,37
control
Coxsan 16,67% 18,06% 22,95% 2,78% 0,19
group
p ns ns <0,1 <0,1 <0,1

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Coxsan liquid/powder: calves trial, 2020 (Italy)

N. animals Weight at start Age at start Days in feed Weight at the ADG
(kg) end of trial

“White” control 248 47,6 24,1 202,8 287,0 1,180

Coxsan group* 266 47,8 22,8 200,9 294,8 1,229

p ns ns ns <0,05 <0,05

*Coxsan was administered at 2ml/head/day per 30days, then at 500g/T for approx 6 months

Mortality % Morbidity % (nº) Incidence of enteritis % Incidence of respiratory

(nº) symptoms

“White” control** 3,6 38,9% (96) 22,7% (56) 16,2% (40)

Coxsan group** 3,7 27,9% (74) 11,7% (31) 16,2% (43)

p n <0,05 <0,05 ns

** To avoid high mortality both groups were put under mass tratments, both for enteric and respiratory diseases

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Coxsan: dosage recommendation
❖ Poultry: liquid product at 250ml/1,000 l of
water. Treatment period: 2 days/week during
stress period. See table on the left side. The use
can be extended up to 3-5 days, accordingly
with the sanitary status
❖ Pigs: powder product. Dosage 300-500g/T
from weaning period up to 30-35kg. Liquid
product can be used in piglet at the rate of 0,3-
0,5ml/day per 1-3 days (coccidiosis control)
❖ Veal calves: liquid version at 2 ml/head/day for
cycles of 3 days/week for the first 2-3 weeks, or
2ml/head/day for 15 days continuosly
(accordingly with sanitary status).
❖ Small ruminants/ beef. Powder version at
500g/T. In lambs it has to be administered unti
18kg of weight. In beef cattle at arrival in
fattening farms (approx. 180-200kg), administer
for 7-10 days
❖ Rabbits. Liquid version at 250 ml/1,000 l of
water for 3-5 days at weaning and in any case
of enteric disorder
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Strategic products

LICOROL
COMPOSITION
CATEGORY • Eucalyptol oil (1- PROPERTIES
Complementary feed 8 cineol) • Antibacterial
• Menthol oil • Expectorant
• Gaultheria P. • Mucolytic
AVERAGE INCLUSION RATE (Wintergreen, • Inflammation
200–250ml/ 1,000L water source of natural modulator
250–350g/T feed salicylates)

PRESENTATION
Oral solution/powder for feed RECOMMENDATION FOR USE
(25kg)
Non pharma management of non-infective respiratory problems (dustiness,
ammonia, etc), heat stress or management stress (female separation in broilers) ,
post-vaccination respiratory fatigue, synergistic effects (antimicrobial, anti-
TARGET SPECIES inflammatory) with Coxsan, support to respiratory mass therapy (rotation with
Poultry, pigs, calves, rabbits antibiotics)
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Licorol: a successful development

✓ The oldest product of Phytosolutions, still in the

flagship group and within the sale leaders

Gaulteria procumbens, source of natural salicylates

✓ Recently re-formulated to boost menthol and
eucalyptol oils with a natural antinflammatory
action (unique product in the market)
✓ Tested succesfully in different Countries:
Philippines (2011, broiler, as antibiotic treatment
replacer), Portugal (2014 and 2015: laying hens,
breeders, piglets after weaning), Rumania
(2014, weaning piglets and growing pigs) and
others

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Mode of action of Licorol

Increase
oxygen
uptake

Mint and Wintergreen : expectorant/anti-

inflammatory effect, clearing the airways
Purification of respiratory tract
metabolism

from small particles and

disinfection effect on the bronchial
surface Better efficiency
and
performance

Eucalyptus: Myorelaxant on bronchial

muscles: it facilitate the excretion of
mucus, recovering normal permeability of
respiratory tract

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Licorol: dosage recommendation (poultry)

Poultry program A: Licorol liquid at 200-

250ml/1.000l for 2-3 days, to reduce
respiratory stress after vaccination

Poultry program B: Licorol liquid at 250

ml/1.000l for 3-4 days max., to reduce
stress and treatments during stressful
periods

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Licorol: dosage recommendation (other species)

❑ Rabbits: Licorol liquid at 200-250ml/1.000l for 3-4 days, to reduce respiratory stress in growing
rabbits
❑ Pigs: Licorol premix at 350g/T of feed (from weaning to growing period for at least 2-3 weeks).
Shorter administration periods can be done with liquid version (0,2 ml/piglet for 4 days)
❑ Veal Calves: Licorol liquid at 2 ml/head day for 4 days (after 2 weeks of age). Repeat after a
pause of 3-4 days.

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Strategic products

PHYTMAX CAPSICUM ENCAPS

CATEGORY
Complementary feed
PROPERTIES
COMPOSITION • Feed behaviour
AVERAGE INCLUSION RATE • Capsicum modifier
Beef cattle: 250–300mg/head/day oleoresin (1,2% • Stimulation of
Sows: 100mg/head/day (heat stress capsaicinoides) fats/protein
management) digestion

PRESENTATION
Microcapsules containing Capsicum
oleoresin at high concentration
RECOMMENDATION FOR USE
Feed and water intake control, regulation of ruminal pH (management of
TARGET SPECIES acidosis in heat stress), digestion enhancer
Beef cattle, pigs (sows)

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 Phytmax Capsicum encaps: focus on ruminants
❑ The effects on production and health status of Capsicum extract
in vitro and in ruminant diets have been elucidated by many
Authors, but also by property literature (Compiani, Sgoifo Rossi
et al., Administration of Essential Oils Cinnamaldehyde, Eugenol,
and Capsicum to Beef Cattle: Effects on Health Status and
Growth performance, in Trends in Veterinary Science, pp. 177-
180, 2013)
Scoville heat units Chemical
❑ Capsicum extracts at high concentration should be 16,000,000,000 Resiniferatoxin
microencapsulated in order to avoid irritation problems (high 5,300,000,000 Tinyatoxin
spiciness) in mixing and feeding plants Capsaicin,
❑ For this reason, a property microencasulation process has been
16,000,000
Dihydrocapsaicin

put in place 9,200,000 Nonivamide

9,100,000 Nordihydrocapsaicin

Homocapsaicin,
8,600,000
Homodihydrocapsaicin
160,000 Shogaol
100,000 Piperine
60,000 Gingerol
16,000 Capsiate

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Effects and consequences of heat stress in beef cattle

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Controlling acidosis through feed behaviour modification

❖ Severe acidosis
represents the most
negative risk for
ruminants during heat
stess
❖ The «soft» spicy effects
of protected Capsicum
modify feeding pattern,
increasing the number of
meals during the day
(chewing = buffering
effect of saliva)
❖ Fractionating feed intake
and improving water
intake (dilution effect of
Adapted from Cardillo, 2011 rumen fluid) contribute to
reduce the risk of
acidosis

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Strategic products
GASTROHERB PLUS
COMPOSITION PROPERTIES
CATEGORY
• Carvacrol • Antibacterial
Complementary feed
• Chestnut tannins • Astringent
• Medium Chain • Gut mucosa
Fatty Acids protection
AVERAGE INCLUSION RATE (MCFA) • Inflammation
1–1,5kg/T feed • Licorice extracts modulation

PRESENTATION
powder for feed (20kg) RECOMMENDATION FOR USE
Indicated for piglets at weaning, to counteract with a non-pharma effect the
symptoms of Post Weaning Diarroea and their effects on production and normal
animal welfare. Replacement of ZnO at pharma level. Possible use as astringent in
TARGET SPECIES grower periods during feeding /management stress periods (not in presence of
Pigs infective enteritis like Swine Disentery).
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The building blocks of Gastroherb plus: MCFA

❖ E.coli has shown a suceptibility to caprilic (C8)

and capric (C10), that gave a bactericidal
effect (Marounek., 2017)

❖ Lauric acid is known to have activity mostly

on Gram +, even if many new trials and
evidences suggest that a remarkable role of
its activity can be linked to antinflammatory
and immunomodulatory activity (Framelco
commercial literature)

❖ Synergism between essential oil compounds

and MCFA has been widely put into evidence
(Omonjio et al., 2017) Suggested activity of MCFA on bacterial cell membrane (from Yoon et al. 2017)

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Carvacrol: in vitro cell effects against E.coli

E. coli cells treated with carvacrol,

E. coli cells with fragella
flagella not developed

E. coli control:
Intact cells

E. coli with carvacrol

(damaged cells)

E. coli treated in vitro with carvacrol (from Burt and Rijnders, 2003) E. coli treated in vitro with carvacrol (from Burt et al. 2007)

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GASTROHERB PLUS: field monitored trial in Italy (Dec. 2021)

Gastroherb plus has been recently tested in Italy in field conditions, with an experimental design
developed and monitored by the DIVAS Department, of the Faculty of Veterinary Medicine of the
University of Milan.

❖ Farm with good management standard in the province of Brescia

❖ 210 post-weaning piglets divided in two groups, Control (CTR): “white”, with basal diet;
Treatment (T): addition of Gastroherb Plus at a dosage of 1,5kg/T
❖ Each group divided into 7 replicates (pens) of 15 piglets each
❖ Trial duration: 35 days from weaning day (average 26 days)
❖ Parameters monitored: Individual weights, pen weights, feed consumption and feed efficiency
per pen, mortality/culling, general health status (individual treatment incidence and fecal
score), adverse events
Effects of Gastroherb Plus on intestinal morphology, integrity of tight junctions,
microbiome, TAC (total antioxidant capacity)

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GASTROHERB PLUS: preliminary results (single piglets)

Parameters CTR T p-value

BW (kg)
Day 0 7.65 7.74
Day 14 9.03 9.23
Day 35 15.82 16.67 p<0.05
ADG (kg/d)
Days 0-14 0.10 0.11
Days 14-35 0.32 0.35
Days 0-35 0.23 0.25 p<0.03

Growth performance parameters of post-weaning piglets fed a basal diet alone

(CTR) or supplemented with Gastroherb plus (T) for 35 days.

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GASTROHERB PLUS: preliminary results (pen)

Parameters CTR T p-value

N. piglets/pen 14.57 14.43
BW (kg)
Day 0 111.52 111.62
Growth Day 14 131.64 133.17
performance
Day 35 228.28 240.54 p<0.10
parameters of
ADGI (kg)
replicates (pen)
fed a basal diet Days 0-14 1.44 1.54
alone (CTR) or Days 14-35 4.60 5.11
supplemented Days 0-35 3.34 3.68
with Gastroherb ADFI (kg)
plus (T) for 35
Days 0-14 2.71 2.81
days.
Days 14-35 7.67 7.88
Days 0-35 5.69 5.85
FCR
Days 0-14 1.95 1.86
Days 14-35 1.70 1.56
Days 0-35 1.74 1.61 p<0.10

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GASTROHERB PLUS: sanitary parameters

Parameters CTR T
Single injection with Enrofloxacin
6 1
100mg/ml
Culling (abdominal hernial) 3 4

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GASTROHERB PLUS: earlier recover of FAECAL SCORE

Fecal score
CTR T

3 1=liquid faeces
2=intermediate
3=normal

2
In the first 2 weeks after
weaning (the most
critical for PWD) the
1 piglets in GP group
could reach more quickly
a 2-3 score than the C
group
0
0 1 3 7 14 21 28 35

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GASTROHERB PLUS: dosage recommendation

✓ 1.5kg/T in prestarter-starter feed. In prestarter feed, the dosage can be

increased up to 2kg/ton. Gastroherb plus can be used together with
medicated feed
✓ Growing pigs (30-50kg) 1kg/T for 15-21 days (management of dietary, non
infective diarroea)

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“ENTRY” PRODUCTS
PROTIGEN

• Complementary feed for ruminants with functioning rumen.

• Composition: Encapsulated urea (+ curcuma) in a slow-release matrix. Info available on request

PHYTMAX ACID

• Complementary feed for mongastrics

• Composition: synergic combination of Cinnamaldehyde, Carvacrol, Lactic acid, Malic acid y Citric acid.
• Powder and liquid presentation

PHYTOBUTYRIN and PHYTOBUTYRIN PLUS

• Complementary feeds for monograstric (poultry, calves, pigs, rabbits)

• Composition: Mono-di-and triglycerides of butiric acid, Cinnamaldehyde, Carvacrol.
• Phytobutyrin Plus: Mono-di-and triglycerides of butiric acid, Cinnamaldehyde, Carvacrol + MCFA (lauric, capric,
caprilic acid). Can be used in synergistic program with Gastroherb Plus (e.g. gestating sows) or Coxsan (enteric
problems in poultry)
• Powder and liquid presentation

PHYTMAX DETOX

• Complementary feed for monogastric and ruminants. Wide-spectrum toxin binders

• Composition: alluminumsilicates (HSCAS), MOS, Beta-glucans, diatomeous earth, montmorillonite, calcium propionate

38
Thanks for your
attention