Review
Some useful pharmazooticals,
now and in the future
Michael Danckwerts, PhD, MBL(Cum laude)
Department of Pharmacy and Pharmacology, Faculty of Health Sciences, University of the Witwatersrand
Correspondence to: Michael Danckwerts, e-mail: [email protected]
Keywords: pharmazooticals, drugs, well-being, medicinal compounds
Abstract
Animals remain an important source of drugs in the search for new medicinal compounds. Drugs from animal sources include insulin,
pituitary hormones, vitamins, and antibiotics and biological agents, such as vaccines and immune serums. Insulin, discovered by
Frederick Banting, was one of the earliest drugs to derive from animals. Today, a new drug called exenatide from the Gila monster’s spit
keeps glucose blood levels steady, as well as ensuring weight loss in many patients. Many drugs, adjuvants and cosmetic substances
derive from domestic animals, as well as wild ones. Premarin and gelatine, obtained from horses, are vital to our being. Hyaluronic acid,
originally found in rooster combs, is a popular skin care ingredient, as well as a medicinal agent for osteoarthritis and eye surgeries.
The venom and toxin from animals, like snakes, spiders, scorpions and insects, is extremely potent because it interacts with specific
macromolecular targets in the body. Thus, it has been used as the lead compound in the development of novel drugs, such as natural
adhesives used in surgeries, and to help to treat strokes, digestive disorders and gastric reflux disease. It may also be useful in treating
and preventing cardiovascular disease. Cytarabine, obtained from the Caribbean sponge, is used in the treatment of acute myeloid
leukaemia. Many new antibiotics are being developed from alligators and frogs which spend their lives in places that are teeming with
infectious microbes.
© Medpharm
S Afr Pharm J 2015;82(1):37-42
Introduction
derived from the pancreas of pigs and cows, has saved the lives of
an estimated 15 million people with diabetes.
The World Health Organization estimates that as many as 80% of
the world’s more than six billion people rely on animal- and plantbased medicines.1 The bulk of time and money invested in research
into new drug entities is in the field of medicines extracted from
plants. This is unsurprising as flora is abundant, and it is easier to
conduct research on plants than on animals. There are very few
ethical restraints concerning research on plants, even though
political negotiations continue on the indigenous ownership of
plants, as well as the indigenous use thereof.2 Do plants belong to
specific societies or governments, or are they there for the use and
enjoyment of all mankind?
What of our four-, six-, and eight-legged friends, as well as the
marine fauna? Animal and marine creatures have resulted in the
production of some of the most potent and life-saving drugs
on the market today. Many potent new drugs that derive from
animals look promising. Conopeptides, obtained from the cone
snail, have analgesic properties which are approximately 200
times more potent than morphine.3
Modern investigation into drugs from animal sources started in
1921 when diabetes was referred to as the “sugar disease”. The
Nobel prize-winning work of Canadian surgeon, Frederick Banting,
and his assistant, Charles Best, led to the discovery of insulin, and
its ability to lower blood sugar. Since that time, insulin, mainly
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Many prominent scientists predicted that new drug discoveries
deriving from nature would become redundant because of the
capabilities of laboratories to synthesise the various molecules
with the help of computer simulation, compounded by the
burgeoning knowledge of combinatorial chemistry. To an extent,
this is true, but achieving this is akin to firing a bullet in the dark
while trying to hit a small target. However, because of research
into the many varied and defence mechanisms of animals, Mother
Nature still has much to offer.
Taggi et al4 have been researching the role of chemistry in insect
interactions, and specifically how they use endogenous chemicals
to mate, in defence and for communication purposes. Some of
these powerful natural chemicals, such as those found in spider
venom, may prove to have important medical applications.
The venom injected by spiders to paralyse prey contains novel
neurotoxins which block certain receptors, so there is potential
in investigating spiders which have not yet been considered to
determine the presence of neuropharmacological agents.
Ingredients sourced from wild plants and animals are used in
traditional medicines, and are also increasingly valued as raw
materials in the preparation of modern medicines and herbal
preparations.5
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The fauna used to extract drugs varies widely. Animals and
insects currently used as sources of important pharmaceuticals
and adjuvants include horses, bees, maggots, leeches, roosters,
reptiles, marine creatures, spiders and scorpions, cone snails and
frogs.
Horses
One of the most widely used and controversial drugs derived from
animals is Premarin®, an oestrogen analogue used for menopausal
hormone therapy. The drug is taken from the urine of pregnant
horses, and the treatment of those animals and their foals on socalled pregnant mares’ urine farms is subject to criticism from many
animal rights groups. Unfortunately, even with today’s modern
synthesising technology, the synthetic forms of oestrogen, which
are considerably more costly to produce, also do not seem to work
as well as the extracted product.
Image courtesy of Tina Phillips at FreeDigitalPhotos.net
A mare and her foal
Gelatine, extracted from the hooves of horses and other hooved
animals, is used to produce capsule shells. It is the material of
choice as its sol-gel properties are ideal for the production of
capsule shells.
Bees
Honey produced by bees has been use medicanally for many
years. It was approved by the US Food and Drug Administration
(FDA) to treat burns and wounds, and many believe that it is an
effective treatment for cataracts. In addition, it tastes good and
is a healthier sweetener than sugar and corn syrup. Propolis, an
extract from beeswax has also been used for its antimicrobial
properties for many years.6
Image courtesy of James Barker at FreeDigitalPhotos.net
A honey bee
Maggots
As repugnant as it may seem, maggots are an FDA-approved
medical treatment. Maggot therapy was really only discovered
in World War I by military surgeons who noted that soldiers with
open wounds crawling with maggots had a better chance of
healing than those with wounds that were covered. Maggots are
used to eat away at the decaying tissue in the wounds of victims
for whom other treatment has not worked. They have saved the
lives and limbs of many, and they obtain a free meal in the process!
Maggot therapy was successfully and routinely performed by
thousands of physicians in the 1930s, but was supplanted by the
new antibiotics and surgical techniques developed after World
War II. Maggot therapy was occasionally used in the 1970s and
1980s, but only when antibiotics, surgery and modern wound care
therapy had failed to control the advancing wound.7
Image courtesy of Steven De Polo, Creativecommons.org/licenses/by/2.5/
Maggots
Leeches
During a study in 2003 on the effect of maggot therapy in treating
diabetic foot ulcers unresponsive to conventional therapy,
Sherman8 found that 33% of the surface of conventionally treated
wounds was still covered with necrotic tissue after five weeks
of therapy, whereas maggot-treated wounds were completely
debrided after only four weeks. Maggot therapy was also
associated with the hastened growth of granulation tissue and
greater wound healing rates.
S Afr Pharm J
The leech is another FDA-approved treatment modality. The use
of leeches (Hirudo medicinalis) in the practice of medicine dates
back to 2 500 years ago, when the Greeks and Indians used
them for blood letting. Leech therapy is explained in ancient
Ayurvedic texts. They were used in ancient times to treat almost
every disease. Today, leeches are used in microsurgeries, such as
plastic and reconstructive surgery, to combat insufficient venous
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The combined effect is to reduce the swelling in the tissue and
to promote healing by allowing fresh, oxygenated blood to
reach the area.9 When leeches attach to their prey, they secrete
a small amount of anaesthetic so that their prey does not detect
their presence. Their saliva also contains an anticoagulant called
hirudin.
Roosters
Hyaluronic acid was discovered in 1934 by Karl Meyer, and
his assistant, John Palmer. They discovered it in the vitreous
of bovine eyes. It is found in skin layers. Rooster combs also
contain a large amount of hyaluronic acid, and were the original
commercial source of hyaluronic acid before it was synthesised.
Image courtesy of Mike Talbot, Creativecommons.org/licenses/by/2.5/
A leech
Hyaluronic acid contains uronic acid and amino sugar which
relate to glucose. It is also a stable substance suitable for beauty
products as it is naturally synthesised in the body. One of its main
roles is to prevent degeneration and dryness of the skin surface.
Binding water and lubricating the movable joints in the body and
the skin’s dermal layers is another biological use of hyaluronic acid
in the body.
It is a popular skin care ingredient because it retains moisture so
well. It can be injected into knees to treat osteoarthritis, and it is
also used in eye surgery to protect delicate eye tissue. It is the
main ingredient in Hylaform®, which is injected into skin to soften
the appearance of wrinkles.10 Newer products, such as Restylane®
and Juvederm®, also contain hyaluronic acid, but it is not derived
from animals, so they are better options.
Reptiles
The use of venomous reptiles is not new in the pharmaceutical
industry. Highly dangerous snakes have been used to produce
drugs that are already in use.
The recently launched drug, exenatide, is a synthetic version of
exendin-4, a hormone found in the saliva of the Gila monster,
found mainly in the south-western parts of the USA and northwestern parts of Mexico.11 The drug is injected twice daily, but
a once-weekly subcutaneous injection of exenatide recently
became available. Exenatide has shown great promise in patients
who struggle to keep their glucose blood levels steady. The drug
also has an important side-effect in type 2 diabetic patients in that
it results in weight loss.12
Image courtesy of Karen Shaw at FreeDigitalPhotos.net
A rooster
Image courtesy of “Walknboston”, Creativecommons.org/licenses/by/2.5/
A Gila monster
drainage. If not cleared up quickly, the blood clots and arteries
become clogged with resultant tissue necrosis. Medicinal leeches
are then applied to a congested flap where they ingest the excess
blood before they fall away. The wound continues to bleed for a
while because of the anticoagulant hirudin in the leeches’ saliva.
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The angiotensin-converting enzyme (ACE) inhibitor, captopril,
used to lower blood pressure, derives from the venom of the
Brazilian arrowhead viper.13 The original extract from the venom
of the viper, which contains a bradykinin-potentiating factor, was
synthesised into captopril, the first ACE inhibitor on the market.
Integrelin® (eptifibatide), is also a new drug which comes from
a protein in the venom of the Southeastern pygmy rattlesnake.
It is used to treat acute coronary syndrome. Eptifibatide is
administered to decrease the threat of acute cardiac ischaemia
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Marine creatures
in patients with unstable angina or myocardial infarction who are
to undergo non-surgical treatment or undertake a percutaneous
coronary intervention.14
Cytarabine (Cytosar-U®) is a synthetic pyrimidine nucleoside
which was developed from spongothymidine, a nucleoside
originally isolated from the Caribbean sponge, Tectitethya
crypta.17 Cytarabine is an antimetabolite cytotoxic agent which
inhibits DNA polymerase and DNA synthesis. Thus, it is used in
the treatment of acute lymphocytic leukaemia, acute myelocytic
leukaemia and the blast crisis phase of chronic myelogenous
leukaemia and meningeal leukaemia.18
Ancrod comes from the venom of the Malayan pit viper, and is
an anticoagulant with the potential to prevent cell damage and
death when someone has a stroke.15
Alligator blood was recently found to contain proteins that can
fight off the “superbug”, methicillin-resistant Staphylococcus
aureus, together with other bacterial and fungal diseases. It may
also even be effective in the treatment of acquired immune
deficiency syndrome. However, this discovery may only be useful
once more information is available and effective clinical trials have
been completed.16
Calcitonin-salmon (Miacalcin®) is a man-made version of the
hormone, calcitonin, that is found in the coho salmon. Calcitonin
is used to treat postmenopausal bone loss, Paget’s disease of bone
and hypercalcaemia.19 Calcitonin is produced by the thyroid gland
in humans. It acts primarily on bone, but the mechanism of its
action is not well understood.
Spiders and scorpions
NPS Pharmaceuticals specialises in researching and developing
drugs based on spider and scorpion venom. A new class of drugs
called “delucemines” (NPS1506), which act to protect brain cells
Image courtesy of SD Beazley, Creativecommons.org/licenses/by/2.5/
A Southeastern pygmy rattlesnake
Image courtesy of “Soggydan”, Creativecommons.org/licenses/by/2.5/
Image courtesy of Frame Angel at FreeDigitalPhotos.net
A coho salmon
A Malayan pit viper
Image courtesy of Michael Elliott at FreeDigitalPhotos.net
Image courtesy of “furryscaly”, Creativecommons.org/licenses/by/2.5/
An alligator
An Israeli yellow scorpion
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and minimise brain cell death in stroke victims until blood flow can
be restored,20 is currently being developed. However, the clinical
trial was stopped in 2005, and NPS Pharmaceuticals is looking at
other uses for delucemines. The drugs might also have potential in
the treatment of depression.
With spiders, as with most species, the goal is to synthesise the
active chemicals, rather than to depend upon animals.21 Spiders’
venom can be milked without killing them, but sufficient quantities
cannot be obtained to meet the potential demand for new drugs.
TM-601 is derived from the Israeli yellow scorpion, and attacks
malignant brain tumours, called glioma tumours, responsible
for two thirds of brain cancer cases, without harming the
healthy cells.22
Cone snail
Image courtesy of “fredthebusker”, Creativecommons.org/licenses/by/2.5/
A cone snail
The vibrant and deadly cone snail has been known to kill
swimmers. The deadly venom contains compounds called
conopeptides which can be used or synthesised to make a number
of pharmacologically active compounds.23 A drug discovery and
development company, Cognetix, is researching applications for
acute and chronic pain, epilepsy, local anaesthesia, heart disease,
strokes, neuromuscular back pain, multiple sclerosis and spinal
cord injury. However, many scientists are demanding protection
of the cone snail as it is on the brink of extinction.
Frogs
Frogs swim in polluted waters which are full of bacteria and yet
they do not acquire infections. Many scientists believe that frogs
have potent antimicrobial agents in their skin which prevent them
from becoming infected. A substance called magainin 2, obtained
from the skin of frogs, looks promising in the search for antibiotics
to which bacteria won’t develop resistance.24
Image courtesy of Christian Meyn at FreeDigitalPhotos.net
A frog
Tebanicline (ABT-594) comes from the skin of the South American
frog. It showed potent analgesic activity against neuropathic pain
in both animal and human trials, but with far less toxicity than its
parent compound, epibatidine, originally derived from the frog.25
Tebanicline reached phase 2 trials in humans, but was dropped
from further development because of the associated unacceptable
incidence of gastrointestinal side-effects.26
Many animals have not been studied as an important source of
drugs in the search for new medicinal compounds. Hopefully, in
the future, a drug will be discovered that will be useful to stroke
victims for the long term, as currently, nothing of the sort exists.
Many unexplored animals, such as bats, still have to be investigated
with regard to the anticoagulant substances in their saliva.
Image courtesy of “jpokele”, Creativecommons.org/licenses/by/2.5/
Conclusion
A poisonous tree frog
The Brazilian rainforest is one of the most biodiverse and
pharmaceutically promising regions of the world, and yet it is
rapidly disappearing, together with an untold number of plant
and animal species. A little section of the forest disappears as more
and more humans encroach upon it. In the last decade or two, the
encroachment has been exponential because of clear cutting for
industrial development. Many countries are no longer willing to
collaborate with foreign researchers in the search for new drugs
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that derive from animals and plants. This is another major obstacle
to such research. This relates to the challenge of how to fairly
reward the supplier of the natural product. Most governments
believe that international pharmaceutical companies exploit
their valuable natural resources and make considerable profits
therefrom without fair compensation to the local inhabitants.
However, financial rewards are only achieved after considerable
cost into research, and only in 10-12 years’ time. Most new drugs
do not reach the market owing to adverse effects and other
problems. An arrangement needs to be established whereby the
relevant parties all benefit, while the development of new drugs
to fight disease is simultaneously facilitated. In addition, the
continuity of resources with respect to plants and animals needs
to be ensured.
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