459 DELIVERING SUSTAINABLE SOLUTIONS TO IMPROVE WELLBEING
As illustrated with the example of S rebaudiana extract, the subcritical water extraction
technology provides a clean, sustainable, and efficient extraction of phytochemicals.
Additionally, the spent biomass is readily compostable as it is not contaminated with
chemical solvents. Because of the efficient extraction, raw material usage is also minimized,
which leads to minimizing our footprint and maximizing our handprint.
In the case of biotechnology, the processes can also be considered clean due to the
raw materials and the simplicity of conditions used to grow microorganisms that just
need bioreactor warming and aeration to support microbial growth and production of
metabolites. Moreover, purification methods are mainly based on physical processes such
as centrifugation, filtration, dialysis, and mechanical cell disruption, when applicable. An
example is found in the THW biotech ingredient that is recovered from the bacterial
intracellular milieu with mechanical disruption and purified using physical methods such
as centrifugation and filtration without the need for chemical reagents or solvents other
than water.
Referring to the peptide synthesis, the manufacturing process of tetrapeptide-1 has
been refined to achieve a higher sustainability by implementing the principles of green
chemistry.4 Industrial peptide manufacturing is mainly based on solid phase peptide
chemistry, a technology that was awarded a Nobel Prize (Robert Bruce Merrifield, 1984)
for the efficiency of the process as peptides can be obtained at a high purity without any
intermediate purification steps, which considerably speeds up the manufacture process and
allows for automatization. However, this technology uses traditional twentieth century
organic chemistry reagents with room for improvement given the use of hazardous reagents
and wastes. Improvements achieved in the synthesis of tetrapeptide-1 have been toward a less
hazardous chemical synthesis (reduced 70% of the amount of hazardous acids, avoided the
use of thiols, and replaced explosive reagents), waste prevention (reduced the consumption
of organic solvents during the synthetic process by 11%), and reduced derivatives (25%
reduction in the number of protection and deprotection steps during the synthesis, which
reduced the amount of organic solvents).
Figure 4. Comparison of the caffeoylquinic acid derivatives extracted from S rebaudiana.
460 JOURNAL OF COSMETIC SCIENCE
SUSTAINABLE SOURCING
Stevia leaves are sustainably harvested from an organic certified stevia crop in France.
The supplier monitors environmental factors and ensures only a few harvests per year.
Additionally, full traceability of the supply chain is provided through blockchain technology
through which the entire process is verified from the time of harvest to processing to
shipping the raw material to produce the stevia subcritical water extract and blend it with
non-palm derived, nongenetically modified organism (GMO) glycerin.
PERFORMANCE OF THW BIOTECH INGREDIENT
Inspired by the use of thermal waters to relieve sensitive skin and soothe and prevent
inflammation, and inspired by the fact that the bioactivity is mainly linked to their mineral
composition and microbiota (hydrobiome),5–7 a new hydrobiome-derived ingredient from a
thermal spring in Italy was developed, and its ability to reduce stressorins (molecules that
contribute to extracellular stress signaling and are upregulated in case of sensitive skin)
has been demonstrated.8–12 Moreover, the ingredient also reduces AGEs, which originate
from reactions between sugar molecules and proteins or lipids and nucleic acids and induce
oxidative stress and inflammation. Additionally, the ingredient also reduces lipofuscin
accumulation and endogenous garbage resulting from damaged and/or dead cells and
organelles, which are major sources of inflammatory stimuli. Finally, the anti-inflammatory
capacity of the ingredient was further confirmed by measuring IL1alpha release inhibition.
As shown in Figure 5, treatment with THW biotech ingredient concentrate (without
glycerin) significantly inhibited HMGB1 stressorin release in vitro by 18.5% with respect to
the control as well as a 31.5% reduction when induced by metabolic stress, which suggests
a reduced inflammatory response.
Figure 5. Percentage of inhibition of HMGB1 stressorin release in HEKa cell culture after incubation during
24 hours with THW biotech ingredient concentrate with or without the metabolic stress (consists of adding
20 mM glucose and 0.1 mM palmitic acid to simulate in cell culture an unhealthy diet high in fat and sugar).
Data shown as MEAN ± SEM of the mean of three independent experiments. Statistical significance: versus
control (***p 0.001), versus metabolic stress (****p 0.0001), calculated using an unpaired student’s t test.
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Extracted Text (may have errors)

459 DELIVERING SUSTAINABLE SOLUTIONS TO IMPROVE WELLBEING
As illustrated with the example of S rebaudiana extract, the subcritical water extraction
technology provides a clean, sustainable, and efficient extraction of phytochemicals.
Additionally, the spent biomass is readily compostable as it is not contaminated with
chemical solvents. Because of the efficient extraction, raw material usage is also minimized,
which leads to minimizing our footprint and maximizing our handprint.
In the case of biotechnology, the processes can also be considered clean due to the
raw materials and the simplicity of conditions used to grow microorganisms that just
need bioreactor warming and aeration to support microbial growth and production of
metabolites. Moreover, purification methods are mainly based on physical processes such
as centrifugation, filtration, dialysis, and mechanical cell disruption, when applicable. An
example is found in the THW biotech ingredient that is recovered from the bacterial
intracellular milieu with mechanical disruption and purified using physical methods such
as centrifugation and filtration without the need for chemical reagents or solvents other
than water.
Referring to the peptide synthesis, the manufacturing process of tetrapeptide-1 has
been refined to achieve a higher sustainability by implementing the principles of green
chemistry.4 Industrial peptide manufacturing is mainly based on solid phase peptide
chemistry, a technology that was awarded a Nobel Prize (Robert Bruce Merrifield, 1984)
for the efficiency of the process as peptides can be obtained at a high purity without any
intermediate purification steps, which considerably speeds up the manufacture process and
allows for automatization. However, this technology uses traditional twentieth century
organic chemistry reagents with room for improvement given the use of hazardous reagents
and wastes. Improvements achieved in the synthesis of tetrapeptide-1 have been toward a less
hazardous chemical synthesis (reduced 70% of the amount of hazardous acids, avoided the
use of thiols, and replaced explosive reagents), waste prevention (reduced the consumption
of organic solvents during the synthetic process by 11%), and reduced derivatives (25%
reduction in the number of protection and deprotection steps during the synthesis, which
reduced the amount of organic solvents).
Figure 4. Comparison of the caffeoylquinic acid derivatives extracted from S rebaudiana.
460 JOURNAL OF COSMETIC SCIENCE
SUSTAINABLE SOURCING
Stevia leaves are sustainably harvested from an organic certified stevia crop in France.
The supplier monitors environmental factors and ensures only a few harvests per year.
Additionally, full traceability of the supply chain is provided through blockchain technology
through which the entire process is verified from the time of harvest to processing to
shipping the raw material to produce the stevia subcritical water extract and blend it with
non-palm derived, nongenetically modified organism (GMO) glycerin.
PERFORMANCE OF THW BIOTECH INGREDIENT
Inspired by the use of thermal waters to relieve sensitive skin and soothe and prevent
inflammation, and inspired by the fact that the bioactivity is mainly linked to their mineral
composition and microbiota (hydrobiome),5–7 a new hydrobiome-derived ingredient from a
thermal spring in Italy was developed, and its ability to reduce stressorins (molecules that
contribute to extracellular stress signaling and are upregulated in case of sensitive skin)
has been demonstrated.8–12 Moreover, the ingredient also reduces AGEs, which originate
from reactions between sugar molecules and proteins or lipids and nucleic acids and induce
oxidative stress and inflammation. Additionally, the ingredient also reduces lipofuscin
accumulation and endogenous garbage resulting from damaged and/or dead cells and
organelles, which are major sources of inflammatory stimuli. Finally, the anti-inflammatory
capacity of the ingredient was further confirmed by measuring IL1alpha release inhibition.
As shown in Figure 5, treatment with THW biotech ingredient concentrate (without
glycerin) significantly inhibited HMGB1 stressorin release in vitro by 18.5% with respect to
the control as well as a 31.5% reduction when induced by metabolic stress, which suggests
a reduced inflammatory response.
Figure 5. Percentage of inhibition of HMGB1 stressorin release in HEKa cell culture after incubation during
24 hours with THW biotech ingredient concentrate with or without the metabolic stress (consists of adding
20 mM glucose and 0.1 mM palmitic acid to simulate in cell culture an unhealthy diet high in fat and sugar).
Data shown as MEAN ± SEM of the mean of three independent experiments. Statistical significance: versus
control (***p 0.001), versus metabolic stress (****p 0.0001), calculated using an unpaired student’s t test.

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