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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5424_Библиотеки_им_академика_М_И_Перельмана
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CHAPTER 2
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EXTRACTION OF NATURAL
COMPOUNDS FROM PLANTS
CONTENTS
2.1. Introduction ...................................................................................... 50
2.2. Cultivation ........................................................................................ 56
2.3. Extraction .........................................................................................59
2.4. Extraction Techniques ....................................................................... 65
2.5. Purification .......................................................................................68
References ...............................................................................................76
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Natural Compounds: An Introduction
2.1. INTRODUCTION
The natural products were extracted even in Egyptian and Mesopotamian
times, where they were mainly used for the production of pharmaceutically
active oils, perfumes, and waxes. From about 3500 BC, extraction pots were
found in archeological excavations near Baghdad (250 km south) (Levey,
1959). These pots were made from sandy, hard material (probably was
air-dried brick earth). Soxhlet-like procedure extracted solid feed, with oil
or water, was in the circular channel. At the cap, the solvent vapors were
condensed, wet rags possibly cool them. The leaching is then performed by
the condensate and through holes, it is fed back to the bottom of the channel
(del Valle, 2015; Li et al., 2017).
The existence of sophisticated chemical and pharmaceutical technology
is also conrmed by several Sumerian texts. As shown in Figure 2.2, in the
clay tablets of 2100 BC, found near Baghdad (400 km south), the description
of a batch extraction is shown, which states:
“Pulverize and purify the skin of a water snake. The water should be
poured over the root of myrtle, the amashdubkasal plant, pulverize barley,
alkali, and powered pine tree resin, let water be decanted; the ailing organ
should be washed with the liquid; and then, rub tree oil upon it, and add
saki” — (Thomson, 1990).
Basic knowledge in chemistry and chemical engineering is shown by
the pulverization, admixture of alkali (potash), NaCl, or KNO
obtaining perfumes and creams are also well documented, which dates back
to 1120 BC in the reign of the Assyrian king Tukulti-Ninurta I (Ebeling,
1949; Blass et al., 1997). In a mortar, the natural feedstock was rst crushed,
and then in boiled water, it was leached for one day. Later, a news feed was
added so that higher concentrations can be gained. After percolation, while
increasing the temperature, oil was added. After cooling, the top (oil) layer
is extracted. Also, the use of demisters is reported (Davison et al., 1996;
Multer et al., 2017).
Beer and wine, in 1600 BC, aside from being a beverage, were also used
as an alcoholic solvent. They are advantageous for a solute because they
help achieve higher solubilities when producing perfumes. Otherwise, for
getting a high yield, about 40 repetitive extraction procedures were carried
out. Until medieval times, development was not that rapid then, in 900
AD, pure ethanol, was introduced as a solvent and increased the rate of the
development process (Figures 2.1 and 2.2) (Mahmood, 1996; Casas et al.,
2009).
. Recipes for
3
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Figure 2.1: Ancient extraction pot.
51
Source: https://application.wiley-vch.de/books/sample/3527325042_c01.pdf.
Figure 2.2: Sumerian text (2100 BC).
Source: https://en.wikipedia.org/wiki/Sumerian_language.
As we have discussed the short historical review, now we will consider
the language used. “Natural plant extraction” in German is regarded as
“phytoextraction,” and it is referred to as extraction (the process of extracting
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Natural Compounds: An Introduction
metal ions from the soil) by plants. The term “natural products” may also not
be suitable (Cannell, 1998). A living organism produces a chemical substance
or compound that is termed a natural product. We can extract them from a
microorganism or marine organism fermentation, tissues of terrestrial plants
(Bick and Lange, 2003). Considering this, we can say that all biological
molecules are natural products, though, this term is generally used for secondary
metabolites produced by an organism (metabolites such as phytosterols,
carotenoids, glycosinates, saponins, terpenes, phenolic compounds, alkaloids,
etc.). They are not necessary for reproduction or development, normal growth,
and survival (Huang et al., 2013; Duan et al., 2016).
Besides antibiotic peptides, toxins, and venoms from animals
(snakes, spiders, frogs, etc.), nowadays, the marine world is a new focus.
The use of microorganisms in industrial fermentation is already wellestablished (Bishopp et al., 2006). Alternately, for pharmaceutical or
nutraceutical applications, extracts from plant tissue can serve as a source
of lead compounds (Keller et al., 2003; Laule et al., 2003). For nutritional
supplements, the market alone for herbs, for example, blueberry, melissa,
green tea, in Europe is almost 6.7 billion euros and all over the world is
around 17.5 billion. In regards to this, according to FAO, the medicinal plant
raw materials average trading volume in 1997 was US $440 million in the
USA and now is at US $1 billion. The industrial product extraction derived
annual growth rates for pharmaceuticals and nutraceuticals is about 6 to 8%
(as shown in Table 2.1). According to Figure 2.3, the highest growth rate
is for triterpenes. For pharmaceuticals (extracted from natural plants) the
world market in 2002 was estimated to be US$ 30.7 billion, and in Figure
2.4, the share of triterpenes is depicted, while Figure 2.5 depicts the market
in Europe (Kassing et al., 2010, 2012).
Table 2.1: Annual Market Growth for Natural Products as Projected
Annual Growth Reference
Natural product’s
demand*
Plant extracts** 2020 93.6 B 2026 137.6 B 6.63%
Polymers and gels*** 2016 38 B 2024 55 B 6.0%
Essential oils**** 2019 17.2 B 2027 33.3 B 7.5%
Note: B: Billion; * www.packworld.com; ** www.researchandmarkets.
com; *** www.gminsights.com; **** www.grandviewresearch.com.
Value
Year
2019 166 B 2022 252 B 9.5%
(US$)
Forecast
End
Value
(US$)
CAGR
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Table 2.1 presents the most recent projections on natural products based
on the respective forecast years. It can be deduced that an attractive 6.0%
average annual growth rate is expected by the years 2016 to 2027, with the
overall demand growing at 9.5% from 2019 to 2022. The demand on plant
extracts was seen to be the highest by the year 2026 amounting to $136
billion from the 2020’s $93.6 B. Phenomenal increases is also expected
in terms of polymer gels which was at $38 billion in 2016 and expected
to reach $55 billion by 2024, while essential oils market valued at $17.2
billion in 2019 is expected to be at $33.3 billion in 2027. With this market
industry growth, there is a pressing need for further developments of the unit
processes for natural products.
For extracting the natural products from plants, the feed material can be
branches, roots, owers, rhizomes, seed, leaves, fruits, and barks, and the
API content, active pharmaceutical ingredient, is in between 0.3 and 3%
with seasonal uctuations in producing area and period.
Figure 2.3: Annual growth rates (1997–2002).
Source: https://application.wiley-vch.de/books/sample/3527325042_c01.pdf.
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Figure 2.4: Active pharmaceutical ingredient’s market share.
Source: https://onlinelibrary.wiley.com/doi/book/10.1002/9783527635122.
Natural Compounds: An Introduction
Figure 2.5: Natural plant extracts in Europe (2002).
Source: https://onlinelibrary.wiley.com/doi/book/10.1002/9783527635122.
An overview of the parts where the API is present in the plant materials is
given in Table 2.2. Figure 2.6 depicts the recovery of secondary metabolites.
Mainly for oily constituents, the economically best route is through
pressing. We can remove volatile compounds either by hydrodistillation or
conventional (vacuum) distillation. By condensing the vapors from steam, a
two-phase distillate (water and oil) is obtained. This practically immiscible
mixture of oil and water has a boiling point below 100° C. As vapor pressure
by both constituents is exerted independently, we can prepare high boiling
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55
thermosensitive oils (such as lavender oil). For generating a primary crude
extract, we will be concentrating on solids extraction in the following section
(Kučinskaitė et al., 2007; Bart and Pilz, 2011).
Table 2.2: API in Plants
Leaves Bark Roots Seed/Fruits
Belladonna Chinchona Licorice Senna
Digitalis Berberis Sabal
Duboisia Ipecac Horse chestnut
Hyoscyamus Rauwola Oenothera
Senna Ginseng
Catharanthus
Hawthorn
Cimicifuga
Echinacea purpurea
Ginkgo
Valerian
Figure 2.6: Secondary metabolites recovery methods.
Source: https://www.slideshare.net/rahulbs89/extraction-of-plant-contituents.
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Natural Compounds: An Introduction
2.2. CULTIVATION
There are three major parts of the production chain with natural products that
should be considered. The first one is agricultural, then comes extraction,
i.e., for a concentrated raw extract, and finally, a purification step is essential
in pharmaceutical applications so that an ultrapure product can be obtained.
These all steps collectively determine the final economics and play a part in
the overall yield (Davranov et al., 2000).
To highlight and better understand the importance of including the whole
process of the production chain, a crop of the plant that contains oleanolic
acid can be considered. It is present in many plants (privet, almond hulls,
olive, clove, rosemary, hawthorn, periwinkle, lavender, thyme, etc.), with
the content below 1% in dry mass. By using a different kind of sage, higher
values were observed. The value depends on local climate and location (for
example, Greece versus Germany), soil type (sandy), the distance between
the cultivar and growing rows. With the latter, in comparison to the plants
from sowing (S. lavendulifolia), higher content is present in the ones from
scions obtained by the means of vegetative reproduction (Salvia ofcinalis).
Planting with scions requires more labor; hence it is labor-intensive, which
affects the cost. For the sage, optimal conditions are with wind-protected and
warm sites having light soil that contains water and compost (Khoshnevisan
et al., 2014; Chovanová and Zámocký, 2016). For the plant, dry periods do
not cause a problem, and they should grow in rows at a distance between 20
to 50 cm, as shown in Figure 2.7 (Bart and Pilz, 2011). Almost, 4 to 5 years
are considered as useful life, and after that, according to recommendations,
a 4-year interval is necessary for soil recovery. If plants are being used
for gaining pharmaceutical extracts, it is necessary to document all the
cultivation steps (manuring, sowing, etc.), and as far as pest management is
concerned, any pesticide (dosage, date, etc.), has to be registered. Herbicide
usage with sage is forbidden and as recommended, two cuts per year are
better. The leaves are dried after air classication and only 2% impurities,
according to the Deutsches Arzneibuch are allowed (Galambosi et al., 2007;
Uhlenbrock et al., 2018).
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Figure 2.7: Sage cultivation tests at DLR Rheinpfalz.
Source: https://wikifarmer.com/how-to-grow-common-sage-for-prot-commercial-common-sage-production/.
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Table 2.3 gives a yield of test cultivation (8-year) in Saxony (Zöphel
and Kreuter, 2001). D LR (Dienstleistungszentrum Lä n dlicher Raum)
Rheinpfalz, TU Kaiserslautern, the local pharmaceutical industry, in a 3-year
project, investigated the extraction and cultivation of sage corresponding to
the API’s recovery, like oleanoic acid and urosolic. Since they are position
isomers, they possess a similar structure (Figure 2.8). For obtaining ultrapure
products, the nal separation becomes difcult (Rafter, 1981; Adesina,
1992).
In Saxony, general trends for the harvested plants can be observed. After
the rst year, the overall yield for all plants remained almost constant, but
on the triterpene content, there is a strong dependency. In June, the rst cut
contains mainly monoterpenes, which can be processed further for spice,
tea, etc. An increased triterpene content is observed in September at the
time of the second cut (at max 6% for both acids) and if the plant is kept
under a polytunnel, even better results are possible as the local temperature
is higher. Figure 2.9 depicts the comparison between triterpene content for
S. lavendulifolia and S. Ofcinalis (Taft, 1983; de Morais et al., 2018).
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Natural Compounds: An Introduction
Table 2.3: Yield and Quality in Salvia ofcinalis
Dried leaves
(a)
• year: 1–3 t/ha
• year: 2–4.5 t/ha
Fresh leaves
(a)
• year: 4–12 t/ha
• year: 8–24 t/ha
Essential oil 1.2–2.5%
Rosmarin acid 0.4–3.4%
Camphor 12–21% in essence
Flavonoids 0.5–1.1%
Carnosine derivates 2.3–3.4%
α-thujone 25–42% in essence
(a)
second cut resulted in 1/3 yield of the first cut.
Figure 2.8: Ursolic (a); and oleanoic acid (b).
Source: https://www.researchgate.net/gure/Structures-of-ursolic-acid-A-andoleanolic-acid-B_g1_6954984.
Figure 2.9: In S. ofcinalis, triterpene content is shown (A, B) and S. lavendu-
lifolia; (C, D) after each cut. First (A, C), second (B, D).
Source: https://application.wiley-vch.de/books/sample/3527325042_c01.pdf.
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