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Singh Neelam et al
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irjponline
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C, Maurya Krishna, Khatoon Ruqsana, Paswan Shravan
Institute of Pharmaceutical Research, GLA University, Mathura-281406 India
Article Received on: 01/04/12 Revised on: 30/04/12 Approved for publication: 10/05/12

*Email: neelamsingh151989@gmail
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Artificial blood is supposed to fulfil some functions of biological blood, especially in humans
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There is additional longer range research on true artificial RBCs and WBCs which could
theoretically compose a blood substitute with higher fidelity to human blood
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There are
two basic approaches to construct oxygen therapeutic: perflurocarbons (PFCs), a chemical compound which can carry and release oxygen
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Perfluorochemicals will not mix with blood; therefore emulsions must be made by dispersing small drops of PFC in water
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This can benefit damaged, blood-starved tissue, which conventional RBC cannot reach
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By providing a PFC solution we can maintain the circulating blood
volume as well as the need of the patients
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Keywords- Blood, Perflurocarbons, Antibiotics, WBC, RBC

INTRODUCTION
It is very amazing, that an artificial substance could replace
something that is so central to human life
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Blood has two main components -- plasma and formed
elements
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Formed elements, which are cells and parts of
cells, also float in the plasma
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Red blood cells
(RBCs) are responsible for one of the blood's most important
tasks -- carrying oxygen and carbon dioxide
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They make up more than 90 percent of
the formed elements in the blood
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A RBC is
shaped like a disc that's concave on both sides, so it has lots
of surface area for oxygen absorption and release
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A red blood cells
lack of nucleus also gives it more room for haemoglobin
(Hb), a complex molecule that carries oxygen
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The hemes use iron to bond to oxygen
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If you lose a lot of blood, you lose a lot of your oxygen
delivery system
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In an emergency situation, doctors will often give
patients volume expanders, like saline, to make up for lost
blood volume
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Sometimes, this is enough to keep the body going until it can
produce new blood cells and other blood elements
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Blood transfusions are also fairly common
during some surgical procedures
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1 A scanning electron microscope image from normal circulating
human blood

This process works pretty well, but there are several
challenges that can make it difficult or impossible to get
patients the blood they need:
· Human blood has to be kept cool, and it has a shelf life of
42 days
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Volume expanders alone may not be
enough to keep a badly bleeding patient alive until he
reaches the hospital
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If a person
receives the wrong type of blood, a deadly reaction can
result
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· Viruses like HIV and hepatitis can contaminate the blood
supply, although improved testing methods have made
contamination less likely in most developed countries
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Sometimes, it can't even replace lost blood volume
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IRJP 2012, 3 (5)
carries oxygen in situations where a person's red blood cells
can't do it on their own
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Unlike real blood, artificial
blood can be sterilized to kill bacteria and viruses
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Many
current types have a shelf life of more than a year and don't
need to be refrigerated, making them ideal for use in
emergency and battlefield situations
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1
ARTIFICIAL BLOOD CELLS
Artificial blood or blood surrogates is a substance used to
mimic and fulfil some functions of biological blood, usually
in the oxygen-carrying sense
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2
Unfortunately, oxygen transport has proven very difficult to
achieve artificially, and all efforts as of 2011 have failed to
overcome the challenges
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4 Artificial blood can be produced in
different ways using synthetic production, chemical isolation,
or recombinant biochemical technology
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While HBOCs utilize
haemoglobin, an actual component of red blood cells, PFCs
rely solely on synthetic chemical processes
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None of the
products perform all the functions of blood; neither do they
persist in the circulation as long as human red blood cells
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In the short term, the prospective benefits of a
blood substitute overshadow the shortcomings
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[6]
COMPOSITION OF ARTIFICIAL BLOOD
Perfluoro-octyl bromide
28%
FO-9982
12%
Yolk lecithin
2
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12%
DSPE-50 H
Distilled water
57
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2 Both HBOCs and PFCs are considerably smaller than red blood
cells
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PFBOCs achieve oxygen delivery by using
organic chemicals with high gas solubility
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One of the
problems with perfluorocarbons is that they are an oil-like
fluid that does not mix well with water and cannot carry
water-soluble salts and metabolic substrates
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Emulsifying agents are substances that
help stabilize two seemingly unbendable things
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Green Cross Corp
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The product was
called Fluosol-DA
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It could only
deliver 0
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In order to meet metabolic
oxygen demand, the patients would have had to breathe in
gas that was 100% oxygen which would lead to adverse
effects due to oxygen toxicity
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Oxygent, their
product, could deliver up to 1
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The advantage of
Oxygent over Fluosal-DA is that it has a longer circulation
time, and it can be excreted from the body in 4 days
compared to Fluosal –DA which could take months
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Ø PFCs allow easy transportation of the oxygen to the body
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Ø PFCs minimize the effects of factors like pH and
temperature in blood circulation
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Ø This is often caused by phagocytosis of the
perfluorocarbons emulsion by the recipient organism’s
immune system
Ø Unable to remain mixed as aqueous solutions – thus, they
must be prepared as emulsions for use in patients
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Ø PFC products cannot be used by the human body, and
must be discarded
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Ø PFCs absorb oxygen passively, patients must breathe at a
linear rate to ensure oxygenation of tissues
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The first major clinical study
with purified haemoglobin resulted in nephrotoxicites,
poisonous effects on the kidney
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To side-step these problems, stromafree haemoglobin were developed that also was free of
endotoxins and it did reduce nephrotoxicity but new
problems arose
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IRJP 2012, 3 (5)
have too high of an affinity for oxygen which affected
oxygen being delivered to tissue
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7 In 1898
haemoglobim solution was firstly used for the treatment of
anaemia
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Currently, HBOCs represent an
interesting class of blood substitutes, which are undergoing
advanced clinical trials
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The main advantages of artificial blood include
availability in large volumes, storage for prolonged periods,
rapid administration (without typing and cross matching) and
sterilisation by pasteurisation
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10
Synthetic haemoglobin based products are produced from
haemoglobin harvested from an E
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The
haemoglobin is grown in a seed tank and then fermented
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Ø Can be stored for long durations
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Ø Can be sterilized via pasteurization
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Ø They release free radicals into the body
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Safe to use
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Compatible in human body
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Able to transport and release oxygen where needed
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Storable and durable for longer time periods
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Is free of pathogens and toxins which would produce an
immune system response in the human body
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Donations are increasing by about 2–3% annually in the
United States, but demand is climbing by between 6–
8% as an aging population requires more operations that
often involve blood transfusion
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The blood supply in many countries is very safe but
this is not the case for all regions of the world
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In certain regions of southern
Africa, it is believed that as much as 40% of the
population has HIV/AIDS, although testing is not
financially feasible
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3
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Medical care in the
armed services would benefit from a safe, easy way to
manage blood supply
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Great benefit could be derived from the rapid treatment
of patients in trauma situations
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5
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For
example, the cost of blood substitutes may fall as
manufacturing becomes refined
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Artificial Blood can be stored for much longer period
than transfusable blood, and can be kept at room
temperature
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7
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Also, in comparison, natural replenishment of
lost red blood cells usually takes months, so an oxygencarrying blood substitute can perform this function until
blood is naturally replenished
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Oxygen carrying blood substitutes also would become
an alternative for those patients that refuse blood
transfusions for religious or cultural reasons, such as
Jehovah's Witnesses
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[11] Analysis showed that an
artificial blood substitute increased risk for mortality more
than usual care in patients who had surgery, trauma, or
stroke
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This liquid is then mixed with antibiotics, vitamins,
nutrients and salts, producing a mixture that contains about
80 different components, and performs many of the vital
functions of natural blood
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This small size
can enable PFC particles to traverse capillaries through which
no RBCs are flowing
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PFC solutions can carry oxygen so well in mammals,
including humans, can survive breathing liquid PFC solution,
called liquid breathing
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3 PFC-based artificial blood made by Oxygent

Perfluorocarbons-based blood substitutes are completely
man-made; this provides advantages over blood substitutes
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Singh Neelam et al
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PFCs in solution act as an intravascular oxygen carrier to
temporarily augment oxygen delivery to tissues
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PFC particles in solution can
carry several times more oxygen per cubic centimetre (cc)
than blood, while being 40 to 50 times smaller than
haemoglobin
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It is developed to reduce the need for donor blood
during surgery
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The lecithin is digested
intracellularly
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Oxycyte is currently approved for Phase II-b Trials in the United States
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[13]
In research
Approved for Russian clinical application in 1996
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Status: Approved an authorized blood substitute in Mexico in 2005
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Its infusion alleviates symptoms of ischemia at different types of occlusion vessels disease, improves grafting
in plastic surgery, diminishes inflammation and prevents rejection of transplants, activates detoxication functions of liver,
inhibits retro-virus infection development
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[15]

Haemoglobin based
Haemoglobin is the main component of red blood cells, comprising about 33% of the cell mass
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However, pure haemoglobin separated from red cells cannot be used,
since it causes renal toxicity
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Various other steps are needed to form haemoglobin into useful and safe oxygen therapeutic
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These are needed because the red cell is not a simple container
for haemoglobin, but a complex entity with many biomolecular features
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It is
Biopure’s first-in-class product for human use, and is a HBOC solution
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Many safety measures are taken to render free of pathogens, including herd
control and monitoring
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[16]
Oxyglobin is currently approved for veterinary use in US and Europe
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It consists of chemically stabilized
bovine haemoglobin in a balanced salt solution and contains no red blood cells
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Introduced to veterinary
clinics and hospitals in March 1998 and nationally distributed by October 1998, Oxyglobin has been used primarily for
blood transfusions and for treatment of anaemia in dogs
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PolyHeme is a unique human hemoglobin-based oxygen-carrying blood substitute in development for the treatment of
urgent, large volume blood loss in trauma and surgical settings, with a particular focus on settings where blood is not
immediately available
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It represents the leading technology
in this field
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It uses human haemoglobin as the oxygen-carrying molecule in solution, and the extraction and
filtration of this haemoglobin from red blood cells is the first step in production
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The polymerization of
the haemoglobin represents the critical step in this process because, as demonstrated by failed attempts at blood substitutes,
when haemoglobin remains disassociated, it tends to take up nitric oxide, causing vasoconstriction
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[17]
Hemospan is currently in Phase II trials in the United States
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Robert M
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It is produced in powder form, which can then be mixed into liquid form and transfused
immediately, regardless of a patient’s blood type
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According to researchers haemospan can be stored for a year
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In the past
four years, Hemospan has shown promise as a possible commercial product, yielding positive results in both Phase Ib/II and
Phase II clinical trials
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It is created by the Dexto-Sang Corporation
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The safety of dextran has already been established, due to its wide use
as a plasma volume expander
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Hemotech is currently approved for Phase I trials
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It has been able to identify and nullify the source of toxicity issues associated with previous blood
substitute candidates
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Hemotech's lack of toxicity is due to Hemobiotech's proprietary chemical modification of
haemoglobin
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Limited tests have shown it to be clear of the vasoconstriction and inflammatory toxicity issues
that have hampered competitors
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IRJP 2012, 3 (5)
ARTIFICIAL BLOOD vs
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No working artificial blood has been created in the
status quo

Blood Substitutes
The main purpose of a blood substitute is to provide temporary support to the circulatory
system when necessary
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Blood substitutes are generally simpler since they are only focused on one of the several
functions of real blood
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[9]

Hence we can conclude that the artificial blood is a good tool
for the survival of patients at the time of surgery when blood
loss is higher
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The blood substitutes carry and transport oxygen
to tissues and can support life temporarily until patients can
either regenerate their own red cells or can be transfused with
banked blood
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In addition to carrying
oxygen, such compounds can be sterilized against infectious
diseases and used in patients whose religious beliefs prevent
them from accepting blood transfusions
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REFERENCES
1
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howstuffworks
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htm Date 03-12-2011
2
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wikipedia
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Cherkas David, Facep MD Traumatic haemorrhagic shock: Advances in
fluid management
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Schimmeyer S Illumin article:The search for blood substitute
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Sarkar Suman Artificial Blood
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6
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Section Review: Cardiovascular & Renal: Blood
substitutes in development
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8
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10
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12
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14
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16
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18
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Experimental studies on artificial blood usage for hemodilution
during cardiopulmonary bypass
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Beauchesne Pascal The Design of Blood Substitutes: Oxygen Carriers
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ucdavis
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pdf
Date 07/12/2011
Goorha Brig YK, Deb Maj Prabal, Chatterjee T, Dhot PS, Prasad Brig
RS Artificial blood
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http://abcnews
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com/Health/Healthday/Story?id=4741269&page=1
Date 03-12-2011
Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM Cell-free
hemoglobin-based blood substitutes and risk of myocardial infarction
and death: a meta-analysis
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Yoffee Lynn Oxycyte is on track as oxygen carrier, not as faux blood
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Henkel-Hanke Artificial oxygen carriers
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Maevsky Eugene, Ivanitsky Genrih, Bogdanova Ludmila, Axenova
Olga, Karmen Natalia, Zhiburt Eugene et al
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Artificial cells Blood
Substitutes and Biotechnology 2005; 33(1): 37-46
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C, Uys R, and Wessela G Hemopure transfusion in a child with
severe anemia
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Karla F
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Holloway Accidental Communities: Race, Emergency
Medicine, and The Problem of PolyHeme
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Mcleod Maria Persues Human- Blood Substitute
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1951; 1: 1-3

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