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Hyaluronan

Basic Biology
Hyaluronan is a polysaccharide
Repeating disaccharide which contains Glucuronic

acid and N-acetylglucosamine.


Bonding of monosaccharides is 1-4 glycosidic bond
Bonding of disaccharides is 1-3 glycosidic bond.
It is one of the most anionic (negatively charged)
molecules produced by animal cells.

Hyaluronan
NATURE OF PRODUCT
BY ANISAH BINT ISMAIL, ALGHALIAH ALRUJAIB, SARA
GREEN

Products
Beauty
products
Knee
osteoarthritis
injection

Skin
wounds
healing

Products of
Hyaluronan

Applications
1.

Injection for knee osteoarthritis

Hyaluronan is a naturally occurring macromolecule that is an essential part of


synovial fluid and is thought to contribute to its viscoelastic properties.

Hyaluronan helps to lubricate the joints by upgrading the concentration of


synovial fluid, contributing to increase of joint mobility.

ADVANTAGE : The side effects are mild such as temporary pain and swelling
after injection.

DISADVANTAGE : Some people might have a slight allergic reaction and the
injections have to be taken frequently as the pain relief is only temporary.

Applications
2. Beauty product
Hyaluronan is able to absorb up to 1000 times of its weight in H2O, therefore it

is suitable to hydrate and firm up skin cells.


Found in various cosmetic products such as lotions, serums, shampoos,

conditioners, bath oils, foundations, lipsticks or lip balms. Example : Estee


Lauder
3. Skin wound healing
Hyaluronan is one of the first components synthesized at the point of injury.
It creates moist environment in wound to support synthesis of other parts of

connective tissues and cell reproduction.

Applications
Injury results in hyaluronan fragmentation in hyaluronan of very low molecular

weight. These small fragments activate the immune cells and thus support the first
process of healing which is inflammation.
Hyaluronan is able to eliminate scar formation during the wound healing process.

This is similar with embryo tissue, which is rich in hyaluronan.

http://www.hyiodine.com/patients-hyaluronan-in-wound-healing

Hyaluronan
PROCESS OF PRODUCT
BY ASIF HASSAN, ANAND SUBASH,WAJAHAT NASEEM,
JUNIOR AGBOOLA

Production by extraction from animal tissue


Extracted from most tissues of vertebrates.
Most accessible sources include rooster combs which

undergoes mechanical slicing to smaller pieces prior to


production.
Raw material is full of contaminants and requires proteolytic
enzymes to isolate them from the natural complexes
Washed with ethanol and then undergoes chloroform
extraction and centrifugation.
Purified by several intermediate stages of precipitations.
Sterile filtration, alcohol precipitation drying and
conditioning to eradicate remaining microbial cells.

Production using bacteria


Streptococci strains are normally fermented in a batch process

under aerobic conditions with unlimited supply of glucose.


Overall synthesis of 1 mol of HA- five moles of nucleosides
triphosphates, two moles of glucose and one mole of acetyl
coenzyme A.
ATP levels and reducing equivalents in the cell play a key role in
biosynthesis, these substances are consumed and generated in the
production of HA.
Process takes place at 37C and pH7.
The process can yield 6-7 grams per litre.
Streptococci C strains are preferred due to its relatively high
production of Hyaluronan but also importantly due the C groups
strains being non-pathogenic to humans.

Hyaluronan
SAFETY ISSUES
BY ATHANASIE MUNYANEZA, HARRY WILKINSON,
CALLUM DYKES, ALEXANDER CHILVERS

Safety Issues regarding the Uses

Hyaluronan assists with the metastasis of cancer cells, which

means it aids the spread from one part of the body to other
parts. It does this by protecting the cell from physical
damage.
Another use is in injections aimed to help people suffering

from osteoarthritis in knee joints. It has been concluded that


the injections are deemed a safe and efficient way of reducing
the patients pain. The main adverse effect of concern is joint
infection which can be easily overcome if administered
correctly.

Examples of Safety Issues


In a clinical study patients were injected with

hyaluronic acid as a facial intradermal implant. The


worst cases were swelling of the implant, thought to
be caused by the hydrophilic properties of hyaluronic
acid.
Other cases included bruising, swelling, tenderness
and erythema but these occurred at the injection site
so are not directly linked to the hyaluronic acid but
the use itself.

Hyaluronan
ENVIRONMENTAL ISSUES
BY GIORGIO DE MITRI, SILVIA LUNGU,
NADHIRAH MUHAMMAD FITHRI

Hyaluronic acid is safe for most people.


Some of the uses:

Osteoarthritis

Ageing skin
Cataracts

No environmental issues associated with HA.


Produced by our body naturally.
Large molecule, therefore too large to pass
through skin.

HA injection side effects

https://www.hsc.com.my/ort_arthroscopic.php

http://www.wisegeek.org/what-ishyaluronic-acid.htm

Anti-ageing treatment:
In general, the side effects are

mild: bruising, redness, swelling,


pain, tenderness, allergy reaction.
In some cases, serious

hyaluronic acid side effects


happened for those received more
than one injection.

Injection into a joint


Increased pain after injection
Side effects: redness and tenderness

at the site of the injection, increased


stiffness, swelling or warmth,
inflammation
Less common side effects: Allergy,

joint may become severely inflamed


after injection, headache, muscle
pain, nausea.

Other side effects


Use in pregnancy and breastfeeding

Hyaluronic acid has not been tested in pregnant women or women who are
breastfeeding. It is important to tell your doctor if you are, or intend to
become pregnant or if you are breastfeeding.

Use with other medicines


Tell the doctor about all medicines you are
taking or plan to take.
Mention treatment
when seeing other health professionals.
http://images.iherb.com/l/WHE-03548-1.jpg

Hyaluronan
COMMERCIAL AND ECONOMIC
ISSUES
BY MONIKA ROWCZENIO, DINESH SELVANATHAN,
JIULIO LAFONTANT

Scope
Hyluronan has a world market value of US$500M and
is sold for up to US$100K per kg (Heinz T.J. 2013).
Production is based on two methods:
o Extraction from animal tissues
o Microbial Fermentation using bacteria strains

Pharmaceutical Value
Hyaluronan has a pharmaceutical value of $US170m (Novozymes 2012).
Below are the figures for the Hyaluronan Division of Lifecore, one
company which is extensively involved in its usage .
6,000,000.00

5,000,000.00

4,000,000.00

2007
2006

3,000,000.00

2,000,000.00

1,000,000.00

0.00
Net sales

Cost of goods sold

Gross Profit

Commercial and Economic Issues


Extraction from animal Tissues:
Advantages

Disadvantages

Well-established technology

Due to uncontrolled degradation during


extraction and low concentration of
Hyaluronan in the waste, the process has a
low yield.

Available raw material at low costs

Risk of polymer degradation

Natural product

Risk of contamination with protein, nucleic


acids, and viruses
Low yield
Extensive purification needed

As you can see, there are currently more issues than benefits in extracting
hyaluronan from animal tissues.

Commercial and Economic Issues


Microbial Fermentation using bacteria strains:
Due to hyaluronans high viscosity in the fermentation broth, there is a
practical (physical) limit of mass transfer during the reaction process.
(heinz 2014).
High risk of contamination of culture with bacteria endotoxins, proteins, nuclei
acids and heavy metals.
Carbon source for this process is glucose which is more expensive than starch
and lactose.

Hyaluronan
COMPETING TECHNOLOGY
BY TAYLOR OSBORNE, JOSHUA STEEL, BEN FOWLER,
CHIBUIKEM NWAYO

Competition
Treatment of osteoarthritis of the knee

Painkillers e.g Paraceutamol


Non-steriod Anti-Inflammatory Drugs (NSAIDS0 e.g ibuprofen
Transcutaneous Electrical Nerve Stimulation (TENS)
[Arthritis Research UK]

Diagnose cancer, check and predict response treatment

CA15-3/CA27.29 (used to assess of breast cancer treatment is working)


Carcinoembryonic antigen (CEA) (used to check for recurrence and assess
respose treatment)
Prostate-specific antigen (PSA) (help diagnose, assess response and check for
recurrence)
[National Cancer Institute, 2011]

Competition
Post-operation induced tissue healing, notably after

cataract surgery

Laser treatment
Stem cells
[Berthiaume, 2009]

Treatment of atopic dermatitis (eczema)

Phototherapy
Barrier repair moisturiser
Coal tar
Vitamin B6
[EczemaNet, 2007]

Hyaluronan
FUTURE OF PRODUCT

Future perspectives
Intra-articular hyaluronic acid viscosupplementation is becoming popular as nonoperative treatment for patients with
osteoarthritis.
It enhances the lubricating ability of synovial fluid
after injury. Helping to prevent osteoarthritis.
It contributes to the viscosity of synovial fluid and
so can act as a cushion.

http://huntsvillesportsdoc.squarespace.com/storage/Visco
supplementation2.jpg?__SQUARESPACE_CACHEVERSION=13408091
23371

Intra-articular injections of hyaluronic acid are


currently approved for the treatment of knee
osteoarthritis but presents potential for other
joints.

http://www.trixsyn.com/images/1254_canin
e_02.jpg

Future perspectives
Extensive experimental evidence in cell and animal tumor models have shown that
Hyalurana acts a drug carrier.
Hyluranan attaches to the drug which allows the drug to directly attach onto the
tumours cells. This is because Hyluranan can selectively attach onto tumours cells
via a marker called CD44. This allows the drugs to be more effective as it will not
effect the surrounding healthy cells.
It is an increasingly investigated area for applications to anticancer
chemotherapeutics.

http://www.mdpi.com/ijms/ijms-12-01009/article_deploy/html/images/ij
ms-12-01009f3-1024.png

References
Australian Rheumatology Association . (2011). PATIENT INFORMATION ON HYALURONIC

ACID . Available: http://www.rheumatology.org.au/downloads/HyaluronicAcid230811.pdf


Arthritis Research UK What treatments are there for osteoarthritis of the knee [online]. Available at:
http://www.arthritisresearchuk.org/arthritis-information/conditions/osteoarthritis-of-the-knee/treat
ments.aspx
(Accessed: 13 November 2014)
Berthiaume, F (2009) Stem cells for skin tissue engineering and wound healing [online]. Available at:
http://www.ncbi.nlm.nih.gov/pubmed/20528733 (Accessed: 13 November 2014)
EczemaNet (2007) Medications and other therapies for eczema [online]. Available at:
www.skincarephysicians.com/eczemanet/medications.html (Accessed: 20 November 2014)
JASON R. LUPTON, MD AND TINA S. ALSTER, MD. (2000). Cutaneous Hypersensitivity Reaction to
Injectable Hyaluronic Acid Gel. Available:
https://www.skinlaser.com/wp-content/uploads/2011/06/Cutaneous-Hypersensitivity-Reaction-to-Inj
ectable-Hyaluronic-Acid-Gel.pdf
.
Zhang W, Moskovitz R, Nuki G et al. OARSI recommendations for the management of hip and knee
osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines. Osteoarthritis & Cartilage
2008; Available: https://www.myjointpain.org.au/media/injections1.pdf
WebMd. HYALURONIC ACID. Available:
http://www.webmd.com/vitamins-supplements/ingredientmono-1062-hyaluronic%20acid.aspx?active
ingredientid=1062&activeingredientname=hyaluronic%20acid

References
Chiara Schiraldi, Annalisa La Gatta and Mario De Rosa (2010). Biotechnological Production

and Application of Hyaluronan, Biopolymers, Magdy Elnashar (Ed.), ISBN: 978-953-307-1091, InTech, Available from: http://www.intechopen.com/books/biopolymers/biotechnologicalproduction-characterization-and-application- of-hyaluronan
Carmen G. Boeriu, Jan Springer, Floor K. Kooy, Lambertus A. M. van den Broek, Gerrit Eggink.
(2013). International Journal of Carbohydrate Chemistry Volume 2013. Available:
http://www.hindawi.com/journals/ijcc/2013/624967/. Last accessed 20th Nov 2014.
Gary. H. G., Hales C.A., (2004) Chemistry and biology of hyaluronan. [online] Google scholar.
Page 1 available from: books.google.co.uk [accessed 14 October 2014]
Heinz. T.J., (2013) International Journal of Carbohydrate Chemistry. Production Methods for
Hyaluronan [online] Volume 2013 pages 3-6. Available from
www.hindawl.com/journals/iju/2013/624967/ [accessed 19 October 2014
Wikipedia (2014) Glycosaminoglycan [online] Available from:
http://en.wikipedia.org/wiki/glycosaminoglycan [accessed 19 October 2014]
Wikipedia (2014) Hyaluronan [online] available from:
http://en.wikipedia.org/wiki/hyaluronan [accessed 19 October 2014]
(Wikipedia used for background knowledge)

References
Spyros S. Skandalis*, Chrisostomi Gialeli*, , Achilleas D. Theocharis*, Nikos K.

Karamanos. (29 July 2014). Advances in Cancer Research.Available:


http://www.sciencedirect.com/science/article/pii/B9780128000922000113. Last
accessed 10th Nov 2014.
http://onlinelibrary.wiley.com/doi/10.1111/j.1524-4725.1998.tb00007.x/full#leftBo
rder
, Date article first published online: 8 May 2014, Dermatologic Surgery, Volume 24,
Issue 12, Pages 1317-1325, December 1998, Authors: Fabrizio Duranti, Giovanni
Salti, Bruno Bovani, Mario Calandra and Maria Laura Rosati
Baradwaj AG, et al. Spontaneous metastasis of prostate cancer is promoted by
excess hyaluornan synthesis and processing. Am J Path. 2009;174:10271036
Drug Safety, August 2000, Volume 23, Issue 2, pp 115-130, Date: 21 Nov 2012,
Dr Mark E. Adams, Andre J. Lussier, Jacques G. Peyron
Microbial hyaluronic acid production, Barrie Fong Chong . Lars M. Blank . Richard
Mclaughlin . Lars K. Nielsen Received: 14 April 2004 / Revised: 13 September
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Springer-Verlag 2004