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Bioprospecting, Active Compounds from Marine

Since 100 years ago, application of chemical engineering supported by the success of recombinant bioassay (bioassay) in vitro shifts the method of bioprospecting in developing pharmaceutical products. Interpreted as a simplification of bioprospecting in the exploration of new chemical compounds from living things in nature to the next through the screening proposed as a candidate biological akitivitas pharmaceutical ingredients.

With a chemical engineering recombinant, dozens of pharmaceutical products released to the market each year. This recombinant chemical products synthesized by modifying the random molecule from a chemical compound that has been successful role as a drug. Examples of chemical products includes several types of recombinant semisynthetic antibiotics such as penicillin, cephalosporin, kanamycin, rifamycin, lincomycin, etc..

Pharmaceutical companies rely heavily on chemical engineering recombinant, for various strategic reasons. Among other things, first, in an effort to develop new drugs, companies do not rely on natural ingredients. Second, capital invested in chemical engineering for a recombinant of new drug candidates is not as spectacularly as bioprospecting. Third, freedom from conflict with the supplier of natural raw materials such as bioprospecting.

Fully recombinant product is a result of chemical chemical engineering laboratory work on messing about with a carbon-carbon bond or other constituent elements, as well as modify its stereochemistry to mengkreasi a group of molecules that have different bioactive compounds with molecular origin before experienced recombination.

However, products of chemical engineering of recombinant pharmaceutical results was not spared from criticism of natural materials experts. Fenical (expert natural ingredients from the sea) commented recombinant chemical products is an example of an artificial product that has no roots in the function nature. The reason is, because it is chemically recombinant product innovation solely chemical engineers, assisted by molecular model design, guided by bioinformatics, which the expert molecular and fragment clusters mengkreasi new non-natural clusters that have biological activity, to be developed as new drug. The molecular structure results in general recombinant techniques taklah complicated chemical molecular structure of natural materials.

The uniqueness of Marine Habitat
There is a tendency of resistance of some bacterial pathogens to antibiotics is now commonly applied, coupled with the emergence of new diseases such as HIV-AIDS world's leading pharmaceutical to find new alternative sources of drugs, apart from the application of chemical engineering and quarrying recombinant sources of natural materials which gradually began to terrestrial worn.

With a unique marine ecosystem is believed to save seabrek potential source of new pharmaceuticals with new molecular structure (the novel) and also a new pharmacological mechanism. Skeptical whether these expectations? Presumably not, given the following facts that distinguish biotic marine ecosystems with terrestrial ecosystems.

First, in the marine ecosystem is the largest part of wandering biosphere on earth. Consequently the sea remains a habitat for creatures ranging from the most primitive and the ecosystem with the greatest biodiversity. Second, a unique marine ecosystem because of the communication, signal delivery, food processing, and defense of marine living beings, all of which took place in a column of water. Third, the variety and complexity of the macro-and micro-organisms is greater than other ecosystems. In other words represent the genetic diversity of sea creatures (phylogenetic) and the diversity of complex chemical constituents as well. Fourth, life at sea was dominated by microorganisms such as nanoplankton, mikroalgae, bacteria, archaea, and fungi that control more than 90% of chemical cycles in the ocean. Fifth, marine microorganisms has not been much studied compared to terrestrial microorganisms residents.

Approximately 40-50% drug in the market of chemical products derived from natural materials. Even a tenth of the 25 top selling pharmaceutical products derived from natural ingredients. Some chemistry of natural substances that have been converted to this drug is extracted from microorganisms, plants, and makroorganisme sea. Chemical uniqueness of marine natural products have been known since the 14th century in the traditional medicine of China and Japan. In both these countries have applied to extract sea horses for the treatment of various diseases including: treatment of impotence, respiratory diseases, kidney, liver and so on. But if dikomparasikan with a history of ethnobotany (traditional medicinal plants) in terrestrial ecosystems, is the use of natural ingredients from the sea for traditional medicine is very little.

Secondary Metabolites
Therefore, without guided by tracing the story of ethnobotany, collecting samples of sea creatures to be explored bioaktif compounds that effort really random and somewhat speculative, is solely motivated by the physical disability that sea creatures escape from predators. Instead, these sea creatures secrete secondary metabolites that can be paralysis for predators, or to make predators and competitors do not stand to be around, or just a camouflage.

Prospect isolation of secondary metabolites with new chemical structures which have bioactivity in sea creatures, both living in the vicinity, bersimbiose, or with coral reefs berasosisi probability reaches 300 to 400 times more likely, compared with mainland residents creatures. Until now, marine taxonomic experts, the new successfully identified 10% of residents living biodiversity of coral reefs (Bruckner, 2002).

Can it be imagined such a mega-chemical potential of natural materials which can be extracted from the sea! In coral reef ecosystems have still not fully revealed its contents. Marine abiotic characters differ not only spatially (horizontally) between coastal and offshore areas, but also vary vertically (water column). For coral reefs, Indo Pacific region (Indonesia, Philippines, northern Australia, Papua New Guinea, Fiji, etc.) menghabitati more species of coral and other creatures than the inhabitants of coral reef ecosystems of coral reef ecosystems in other regions of the earth

Moreover, if reviewed, other marine-specific ecological niches, such as hydrothermal vents, deep-sea, hypersaline lagoons, methane gas sparger seabed, Antarctica and Artika sea, mangrove forest, etc, will increasingly make us transfixed on the chemical potential of natural materials and extreme characters to remember specific abiotic be adapted by the inhabitants of the sea creatures niche (niche) is a unique ecology in order to maintain its existence.

Marine Natural Products Chemistry bioprospecting
Conscious of these huge marine potentials, the two countries economic giant, the United States and Japan, are competing to invest in extracting natural materials from the sea (marine natural products / MNP). Japan to spend U.S. $ 1 billion per year (80% came from industry). Japanese experts of natural ingredients that extract 100 species of coral reef sponge residents found 20% of the sponge contains a unique new bioactive compounds. United States who invest smaller in the MNP has also been some success with as many as 170 dipatenkannya new bioactive compound since 1983.

Cephalosporin, an antibiotic that was originally isolated from the fungus Cephalosphorium sp. derived from sea water samples collected in Cagliari, Italy in the 40s, Ara-A (Vidarabin, Vidarabin Thilo) and anti-viral drug Ara-C (Cytarabin, Alexandria, Udicil) anti-cancer drug developed analog synthesis of compounds pilot (lead structure) arabinose-e nucleosid Cryptotethya crypta isolated from sponges collected in the Caribbean Sea in the year 50's are some examples of drugs developed from natural ingredients the sea and has successfully developed commercially (Faulkner 2002).

Ziconotide, agents, pain killers (pain killer) that was isolated from Conus magnus (cone snail) has undergone phase III clinical trials (late phase) was developed by Elan Pharmaceuticals, and Ecteinascidin 743 (anti-cancer), which is extracted from Ecteinascidia turbinata (tunicate) also currently undergoing phase III clinical trials, coupled with dozens of other bioactive compounds that are either in clinical trials phase I and II and are still in preclinical evaluation stage, and the isolation of hundreds of new bioactive compounds from the sea each year to add a long story and the uniqueness of the potential magnitude of natural materials sea as drug candidates.

Biodiversity vs. Intellectual Proper Right
The trend shift in extracting medicines from chemical engineering recombinant to bioprospecting in recent decades of intrigue and raises new conflicts between pharmaceutical companies with third world countries where most of the world's biodiversity resources originated. Intensive efforts livelihoods of natural materials by the pharmaceutical industry was shadowed by the reluctance of developing countries supplying the raw material.

Especially after the ratification of the Convention on Biological Diversity (Biological Diversity) by 140 countries at the Earth Summit in Rio de Janeiro (1992), which gave the concept of holding nations on their property rights to indigenous species. This concept is a powerful sword for politicians biodiversity countries in negotiating with the owner of the pharmaceutical industry of developed countries in terms of chemical utilization of natural materials.

The concept of this reason, a little more guts loosen the pharmaceutical industry and chemists of natural ingredients developed countries in building collaboration with the owner of the country's biodiversity, given the expectations of the country's biodiversity will be royalty owners and revenue that will be obtained.

While bioprospecting is a risky business, and no guarantee of the return of capital was invested. However, developed countries, is not less ingenious concept of biological diversity to compensate for this by proposing the concept of intellectual property rights (intellectual property).

No less than U.S. $ 350 million to be spent and about 10 years old should be taken to transform the new bioactive compounds from natural materials into commercial drugs. So it must be formulated with the ideal model of benefit sharing that can be pocketed by the owners of pharmaceutical companies and the country's biodiversity, so that excesses that arise from bioprospecting can be minimized, so this mega-biodiversity can be explored together to kemashlahatan dedicated to the human race!
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Gelatin, a versatile protein

Gelatin is a protein substance derived from collagen, a natural protein present in the tendons, ligaments, and tissues of mammals. It is produced by boiling the connective tissues, bones and skins of animals, usually cows and pigs. Gelatin's ability to form strong, transparent gels and flexible films that are easily digested, soluble in hot water, and capable of forming a positive binding action have made it a valuable commodity in food processing, pharmaceuticals, photography, and paper production.

As a foodstuff, gelatin is the basis for jellied desserts; used in the preservation of fruit and meat, and to make powdered milk, merinque, taffy, marshmallow, and fondant. It is also used to clarify beer and wine. Gelatin's industrial applications include medicine capsules, photographic plate coatings, and dying and tanning supplies.

Until the mid-nineteenth century, making gelatin was a laborious task. Calves' feet were loaded into a large kettle that was then placed over a fire. The feet were boiled for several hours after which the liquid was strained and the bones were discarded. After setting for 24 hours, a layer of fat would rise to the top. This was skimmed off and discarded. Sweeteners and or flavorings were added to the liquid and it was poured into molds and allowed again to set.

By the 1840s, however, some producers were grinding the set gelatin into a fine powder or cutting it into sheets. One of them was Charles B. Knox, a salesman from Johnston, New York, who hit on the idea of making gelatin more convenient after watching his wife Rose make it in their kitchen. Knox packaged dried sheets of gelatin and then hired salesmen to travel door-to-door to show women how to add liquid to the sheets and use it to make aspics, molds, and desserts. In 1896, Rose Knox published Dainty Desserts, a book of recipes using Knox gelatin.

The first patent for a gelatin dessert was issued in 1845 to industrialist and inventor Peter Cooper. Cooper had already made a name for himself as the inventor of the Tom Thumb steam engine. He had also made a fortune in the manufacture of glue, a process similar to that for making gelatin.

In 1897, Pearl B. Wait, a carpenter and cough medicine manufacturer, developed a fruit-flavored gelatin. His wife, May Davis Wait, named his product Jell-O. The new product was not immediately popular and Wait sold the rights to the process to Orator Francis Woodward, owner of the Genesee Food Company, for $450. Sales continued to limp along until 1902 when an aggressive advertising campaign in Ladies Home Journal magazine generated enormous interest. Sales jumped to $250,000.

The use of gelatin in food preparation increased six-fold in the 40-year period from 1936-1976. Today, 400 million packages of Jello-O are produced each year. Over a million packages are purchased or eaten each day.

In the field of photography, gelatin was introduced in the late 1870s as a substitute for wet collodion. It was used to coat dry photographic plates, marking the beginning of modern photographic methods. Gelatin's use in the manufacture of medicinal capsules occurred in the twentieth century.

Raw Materials
Animal bones, skins, and tissue are obtained from slaughterhouses. Gelatin processing plants are usually located nearby so that these animal byproducts can be quickly processed.

Acids and alkalines such as caustic lime or sodium carbonate are used to extract minerals and bacteria from the animal parts. They are either produced in the food processing plant or purchased from outside vendors.

Sweeteners, flavorings, and colorings are added in the preparation of food gelatin. These can be in liquid or powdered forms and are purchased from outside vendors.

The Manufacturing Process
  • Inspection and cutting 
  • When the animal parts arrive at the food processing plant, they are inspected for quality. Rotted parts are discarded. Then, the bones, tissues, and skins are loaded into chopping machines that cut the parts into small pieces of about Sin (12.7cm) in diameter. 
  • Degreasing and roasting 
  • The animal parts are passed under high-pressure water sprays to wash away debris. They are then degreased by soaking them in hot water to reduce the fat content to about 2%. A conveyer belt moves the degreased bones and skins to an industrial dryer where they are roasted for approximately 30 minutes at about 200° F (100° C). 
  • Acid and akaline treatment 
  • The animal parts are soaked in vats of lime or some other type of acid or akali for approximately five days. This process removes most of the minerals and bacteria and facilitates the release of collagen. The acid wash is typically a 4% hydrochloric acid with a pH of less than 1.5. The alkaline wash is a potassium or sodium carbonate with a pH above 7. 
  • Boiling 
  • The pieces of bone, tissue, and skin are loaded into large aluminum extractors and boiled in distilled water. A tube running from the extractor allows workers to draw off the liquid that now contains gelatin. The liquid is sterilized by flash-heating it to about 375° F (140° C) for approximately four seconds. 
  • Evaporating and grinding 
  • From the extractor, the liquid is piped through filters to separate out bits of bone, tissue or skin that are still attached. From the filters, the liquid is piped into evaporators, machines that separate the liquid from the solid gelatin. The liquid is piped out and discarded. The gelatin is passed through machines that press it into sheets. Depending on its final application, the gelatin sheets are passed through a grinder that reduces them to a fine powder.  
  • Flavoring and coloring 
  • If the gelatin is to be used by the food industry, sweeteners, flavorings, and colorings may be added at this point. Pre-set amounts of these additives are thoroughly mixed into the powdered gelatin.
The packaging process is automated, with preset amounts of gelatin poured into overhead funnels through which the gelatin flows down into bags made of either polypropylene or multi-ply paper. The bags are then vacuumed sealed.

Quality Control
Gelatin manufacturers must adhere to stringent national and international food processing requirements. These regulations include but are not limited to cleanliness of the plant, equipment and employees; and allowable percentages of additives, flavorings, and colorings.

Automated and computerized technologies allow the processors to preset and monitor ingredient amounts, time and temperature, acidity and alkalinity, and flow levels. Valves are installed along pipelines to allow for continuous sampling of the product.

Gelatin is processed to varying "bloom" values that measure the gel strength or firmness. The desired strength corresponds to the manner in which the gelatin will be used. The bloom value is technically measured and monitored throughout the production process.

The Future
Since 1986 when the presence of bovine spongiform encephalopathy (BSE), also known as mad cow disease, was reported in Great Britain, there has been much concern about the processing of beef bones for the production of gelatin. In 1989, the United States Food and Drug Administration (FDA) banned the importation of cattle from the Department of Agriculture's list of of BSE-designated countries. However, a 1994 FDA ruling allowed the continued importation of bones and tissues for the production of pharmaceutical grade gelatin.

By 1997, however, the FDA held hearings to reconsider its decision. After interviewing gelatin processors, the agency found that while gelatin has not been implicated in the spread of BSE, officials are not convinced that the manufacturing processing is extracting all possible agents that are responsible for the disease. It was generally agreed that beef sources carry more of a risk than those from pork, that bones carry a higher risk than skins, and that alkaline processing is more effective than the acid-extraction method. These findings will certainly affect the gelatin-processing industry in the next century.
Source: Harvey Lang, Jenifer, ed. Larousse Gastronomique. New York: Crown Publishers, 1988, reprinted 1998.
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