58 • April 2013 Chemical Engineering World

CEW Features

Green technology is quickly gaining favour in many industries across the globe. In this article, Dr Shankar M Singh, (PhD), General Manager, Biotech Center, Kumar Organic Products Ltd, discusses how some of the products can be produced using green technology.

Microbial Polysaccharide: Green Technology Prospects for India

India can take up the mantle of green technology because it is an emerging market and several specific technologies

do not require large scale investments. The focus from both a public policy as well as private investment should be on identifying and providing investment capital as well as ensuring that requisite technical and intellectual resources are available in these areas in the years to come. In the case of a developing country like India, with a highly populated educated class as well as a vibrant and entrepreneurial private sector, this can serve as a great opportunity and help kick start several sectors in the economy. Several of these specific areas and products are discussed in the article with specific focus on Hyaluronic Acid, Pullulan and Xanthan Gum.

Microorganisms under proper media culture conditions secrete mucoid products which have high molecular weight substances. Most of the extracellular substances secreted by microorganism are called polysaccharides. These polysaccharides have been of a great interest because of their role as virulence factors in bacteria that cause invasive infections. Green Technology processes for producing the majority of these exopolysaccharides have a wide range of applications in pharmaceutical, nutraceutical and cosmeceutical industries. Hyaluronic Acid, Pullulan and Xanthan Gum, which are produced by green technology, have found applications in health, food and cosmetic field and its applications

keep increasing every year. This article will briefly focus on the industrialisation and applications of three polysaccharides.

Hyaluronic Acid (HA) is a naturally occurring biopolymer, which has important biological functions in bacteria, animals, and human. It is found in most connective tissues particularly in synovial fluid, skin, and vitreous fluid of eye, umbilical cords and chicken combs. Hyaluronic acid was discovered in 1934 by Karl Meyer and John Palmer at Columbia University, New York. The first commercial application of HA was a few years later, in 1942, when Endre Balazs applied for a patent to use it as a substitute for egg whites in bakery products. Since then, in the past three decades, the therapeutic and aesthetic uses of hyaluronic acid have been extended to three main categories ie, anti-aging, nutritional supplements and in medical applications.

Animal sources provide higher molecular weight (1.2-12 MDa) Hyaluronic Acid. However, HA from the rooster comb-based extraction process is facing growing criticism due to the use of animal-derived products for biomedical and pharmaceutical applications. Hence, microbial fermentation has emerged as a new green technology for the production of HA which gives molecular weight (1MDa - 3.5 MDa). The bacterial production of HA involving a Streptococcus zooepidemicus strain was first described in 1989, giving rise to the first commercialisation of

fermented HA. Nowadays, hyaluronic acid (HA) production from the green bacterial technology is the main source of HA in the market. Recently, the availability of Hyaluronic form recombinant bacterial strain technology has also provided hyaluronic acid for medical uses.

The current worldwide market for HA for the treatment of joint pain is estimated to be over USD 1 billion USD. With the population of patients with knee osteoarthritis increasing by 26 per cent from 15 million USD in 2000 to 19 million USD in 2010, the demand for viscosupplements is expected to escalate. In the US, the first single-injection HA viscosupplementation product, Synvisc, was approved in 1997 after which other viscosupplements, Supartz, Orthovis, Hyalgan and Euflexxa also gained rapid acceptance by patients and physicians because of their convenience and safety profiles. The European HA viscosupplementation market is shifting toward shorter treatment regimens, and the convenience of undergoing this procedure will continue to attract more patients through 2013. In the Asia Pacific, the HA viscosupplementation market will be favourably affected by both the aging and physically active demographics, as well as rising awareness of the treatmentÊs benefits among physicians and patients. Cross-linked Hyaluronic acids as viscosupplements are gaining more preference over hyaluronic acid due to their better bio-compatibility.

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April 2013 • 59Chemical Engineering World

CEWFeatures

clinical, and health care uses. Pullulan can be used in pharmaceutical coatings, including sustained-release formulations. As binder and agglomerator, it is widely used is cosmetic industry. Oral care products based on pullulan films have recently been commercialised. In addition, pullulan and its derivatives have photographic, lithographic, and electronic applications. Another emerging market for pullulan may be in the formulation of capsules for dietary supplements and pharmaceuticals. Increased demand for pullulan could justify expanded production, resulting in new viable market niches for this unique biopolymer.

Although pullulan is efficiently produced by fermentation of relatively inexpensive substrates, it currently sells for approximately three times the price of other microbial gums produced by fermentation such as dextran or xanthan. Technical improvements in pullulan production, such as engineering innovations, could further

bacterium Xanthomonas campestris and has been extensively studied due to its properties which would allow it to supplement other known natural and synthetic water-soluble gums. Substantial commercial production of this product began in the early 1964. Today, there are a number of companies which are producing this Gum.

The toxicological and safety properties of xanthan gum for food and pharmaceutical applications have been extensively studied. Xanthan is non-toxic and does not inhibit growth. It is non-sensitising and does not cause skin or eye irritation. On this basis, Xanthan has been approved by the FDA as generally recognised as safe (GRAS) product for use in food as an additive without any specific quantity limitations. In 1980, the European Economic Community also approved Xanthan Gum to the food emulsifier/stabiliser list.

Xanthan gum has been used in a wide variety of foods for a number of important reasons, including emulsion stabilisation, temperature stability, compatibility with food ingredients, and its pseudo-plastic rheological properties. Because of its properties in thickening aqueous solutions, as a dispersing agent, and stabiliser of emulsions and suspensions, xanthan gum is used in pharmaceutical formulations, cosmetics, and agricultural products. It is used in textile printing pastes, ceramic glazes, slurry explosive formulations, and rust removers. High viscosity of solutions and water solubility of the polymer have created important applications for Xanthan Gum in the petroleum industry where it is commonly used in drilling fluids and in enhanced oil recovery processes.

Ever-growing and emerging trends for the production of chemical/bio-products using the green engineering technologies via the use bacteria and substances available in nature are becoming the technologies of future. Biotechnology still has a lot to offer to the public and there is a great need to help the public understand its benefits. Not only do these technologies have the potential to improve human health, cosmetic, and food products, they also have significant potential to reduce environmental pollution and contamination in the earth soil and can also contribute to an overall reduction in global warming.

The global market for dermal fillers is also booming, at people spending approximately 759 million USD during 2009. Nowadays, there are almost 100 different dermal fillers on the market, and about half of them are based on HA. American Society for Aesthetic Plastic Surgery reports that about 23,000 dermatologists, plastic surgeons, and cosmetic surgeons in the US performed more than 11.8 million surgical and non-surgical cosmetic surgery procedures in 2004, generating USD 12.5 billion USD in fees. In the US, the dermal filler market is expanding at an annual rate of more than 25 per cent through 2011 and 20 per cent throughout the rest of the world, reaching USD 1.5 billion in global sales. The launch of Restylane, with NASHA technology (non-animal cross-linked HA) has ushered in a new era in dermal enhancement. This filler addresses many of the issues with traditional bovine collagen fillers, namely shelf life, skin testing, and its animal origin. There are number of cross-lined HA, available in market. The unique viscoelastic nature of HA along with its biocompatibility and non-immunogenicity has led to its use in a number of clinical applications, such as a surgical aid in eye surgery and facilitation in healing and regeneration of surgical wounds.Pullulan is a natural polysaccharide produced extracellularly by the fungal species and is commercially prepared by a non-pathogenic and non-toxigenic strain of organism via a green technology. Molecular

Hyaluronic Acid (HA) is a naturally occurring biopolymer, which hasimportant biological functions in bacteria, animals, and human. It isfound in most connective tissues particularly in synovial fluid, skin,and vitreous fluid of eye, umbilical cords and chicken combs.

weight of Pullulan ranges from 50KDa to 500KDa. Pullulan is generally recognised as safe (GRAS) for use in food by Food and Drug Administration (FDA). Commercial production of pullulan began in 1976 in Japan however, now many countries are manufacturing it using green technology.

Pullulan has unique properties and is highly water soluble. It is non-toxic, non-immunogenic, bio-compatible and inert in nature and has found application in pharmaceutical, food and cosmetic industries. Pullulan and its derivatives have many potential pharmaceutical,

reduce the cost of production. Costs may also be high due in large extent to the modest production scale of pullulan. Production levels have been fairly stable for a number of years, with specialty food applications as a major market. The recent commercialisation of pullulan-based oral, pharma and cosmetic care products is very encouraging for the future of pullulan.

Xanthan gum is a natural polysaccharide and an important industrial biopolymer. It was discovered in the 1950s at the Northern Regional Research Laboratories in the USA. The polysaccharide is produced by the

2 5 0 b i l l i o n USD by 2016.

Growing environmental concerns and increasing demands f rom end-use sectors are expected to increase the global market for microbial products to about

16.

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