ANALGESIC
ASPIRIN
D
ES PITE BEING ONE OF T H E
ASPIRIN and significant role in the prevention and treatment of heart attacks and strokes. NSAIDs can have serious side effects when taken regularly or in large doses, most notably gastrointestinal symp toms, including ulcers and stomOs^ ach bleeding. Not only do the Π acidic molecules irritate the gas trointestinal tract, but cyclooxygenase enzymes are found in abundance in the stomach lining, where the prostaglandins they release play a pro tective role for the stomach mucosa. As pirin has also been linked to Reye's syn drome, a deadly illness associated with viral infections, which is why aspirin is no longer used to treat flulike symptoms in children. Since the development of aspirin at
Name: 2-(Acetyloxy)benzoic acid CAS Registry: 50-78-2 Other names: Acetylsalicylic acid, ASA, Aspergum, Empirin, Ecotrin, Measurin Did you know that pharmacist Harold J. DeMonaco, author of "How Drugs Work" and senior editor for Harvard Health Publications, believes that if aspirin had been launched recently, it would not be sold over the counter because of its side effects?
world's oldest and most com mon drugs—perhaps the oldest drug used solely for therapeutic reasons —aspirin has been reluctant to give up its se crets. For more than four mil lennia, people have been using aspirin or naturally occurring analogs to treat pain and inflam mation, but it was only in the 1970s that scientists finally cracked the medicine's aspirin, has also become quite popular as biochemical mode of action. an analgesic, in part because it causes litWith understanding has come a second tle irritation to the stomach lining. But renaissance for aspirin, whose storied his even though scientists have found that tory has come full circle from ancient paracetamol also affects cyclooxygenase painkiller to legal leper, through adven enzymes, it is not properly an NSAID: It tures on the Napoleonic high seas and in works in a different manner and has no interbellum Europe, and finally to m anti-inflammatory or clot-reducing a still-burgeoning set of new and ^ properties. UNITED STATES PATENT OFFICE* preventative uses. It accompanied S Aspirin's new role in circulatory astronauts to the moon and has 2 health has cemented its place as one FEUX HOFFMANN, OF ELBBRFELO, GERMANY, ASSIGNOR TO THE FARlîEKbeen mentioned in the "Guinness < of the world's most popular drugs. FABRÎKEN OF BLBKRFELD COMPANY, OF S B W YORK. Book of World Records," and the Ξ Studies have even hinted at addiACETYL SALICYLIC ACID. 20th century was even dubbed "the S tional preventative uses for aspirin— SPfiCXFICATIOX fonateg part of Lett*» FaUnt Kb. M4,OT7, dated Tefarwy 37,1900. age of aspirin" by Spanish philoso irr".:*wi*i^il*rMtMtw. ?»*»: Kt. UÎ.MS. cfjwf·*·^ 2 though they have yet to be properly pher Jose Ortega y Gasset. Ta uU tehom it i»v*y concern • eanae Kraut does not giro the woUiRff-point 3 substantiated. Be it known lhatl.FKMX liOFfHAXK,doc- of ht» eompesod. It follow* front these detor of philosophy, chemist, (assignor to the tail* that the two eoopcand* are absolutely $ In 1971, Sir J o h n Vane, then It's been a strange journey for the FARBKSVAUSJXEN OP EMIKKFCLD CODWXM, different. 5 of New Ywk,) residing acElberfekl,U«rm»ny, la producing my new compound I can proworking at the Royal College of have invented a new and tuefal Improvement ceed M follows, fwithont limiting mymt to wonder drug. People have been us la the Manufacture Of Production of Aeetyl the particular» given:) A mixta» prepared Salicylic Acid; and ! hereby declare the fol· from fifty parte of salicylic ««id Mad seventy • * Surgeons of England, uncovered ing salicylic acid, found naturally in lowing to be a clear A»d exact description of ftve part» of acetic ««hydride is heated for to my invention. about two hoar· at about 150* centigrade in the mode of action of aspirin and willow and myrtle, for almost as long la the AnnaUniUr Chemin and Phormacit-, a vessel provided with a reflex condenser. VoL 150,-page* « and 12,Kraaiha»de#ribed Tau* a «ear liquid U obtained, from which 1 hat-he obtained by the action of acetyl cblorid «β cooling a cryKtalline roas» i» separated, é related compounds, known as as civilization has been around. An on salicylic acid a body which lie thotgbt to which b the acetyl «aKcylle acid. It i* freed 1$ be *cetyl salicylic acid. I have aow found fro» the acetic anhydride by prating and N S A I D s (nonsteroidal anti-in cient Sumerian clay tablets mention that on heating salknlic acid with acetic an- then recrystaUiMd from dry chloroform. The hydride a body i* obtained the properties of acid « t h u s obtained in the «hap* of glitterflammatory drugs). This achieve using willow leaves to treat rheuma which are perfectly different fro» those of the ing white needles «totting at about. ISA*TOE- 7 body described î>y Kraut. According to my tigrade, wbieh are «wily soluble in benzene, JO rceearcfaea the bodyobtaiacd by ntCADS of my alcohol, glacial aceuc acid, and chloroform,· ment ultimately garnered the sci toid arthritis, and the Ebers papyrus, new proceed in eudoubtcdlv the real acetyl but difficultly aotahle ia «old water. It has the form via salicylic acid entist b o t h the Nobel Prize in one of the world's oldest preserved •OCO.CII ^OOOCH, C.H, Physiology or Medicine (1982) medical texts, indicates that the *> Xrooii. *NCOOH Therefore the eotaponad deeeribed by Kraut and exhibit* Uterapenlical properties. and a knighthood. The drugs, he Egyptians knew of the analgesic prop cannot be the real acetyl salicylic acid, bnt Having aow described my Invention and in i taanothcrcompoend. in the following I point what ntaaner the same Is to be performed, found, inhibit the synthesis of erties of dried myrtle leaves from at 50 oat «peciAeally the principal differences be- what I claim as new, and desire to secure by tween my new eocuponnd ami the body de letters Patent, is— aeribod by Kraut Aa a new article of masafactare the acetyl a group of hormonelike sub least the middle of the second mil ί If the Hrant product is boiled even for a salicyllQ acid having the formula. Ions while with water, (according to KraotS stances known as prostaglandins. lennium B.C. The Greek physician >0.C0CI1, i$ Maternent, > acetic acid iaaot produced,while ' '^COOH my new body when boiled with water is readAspirin and most other NSAIDs Hippocrates wrote in the 5th centu ily split up, acetic and salicylic acid being ] being when crystallised from dry chloroform Î produced. Tbe watery solution of the Knutt intheshapeof white «littering aeedlee, easily body »how
part of reparations mandated by the 1919 Recently, though, the exact nature of Treaty of Versailles. The company estiacetylsalicylic acid's discovery has become a source of controversy In 1949, Arthur mates that its total sales in 1919 were onEichengriin, Hoffman's sometime-boss at ly two-thirds of those of 1913. Bayer, claimed that it was his idea to acetylate salicylic acid and that he was never given credit for this work. And it turns out that acetylsalicylic acid had already been invented decades previously: French chemist Charles Gerhardt made an impure version in 1853, and German chemist Karl J. Kraut made a more pure version shortly thereafter. But neither scientist picked up on the medicinal potential of his work. Heinrich Dreser, the head of Bayer's pharmacology division at the time, was unimpressed with acetylsalicylic acid at first, dismissing the compound. But eventually clinical trials in animals and then humans were conducted, and their success quickly inspired Bayer to market its new drug; they dubbed it aspirin: "a" for acetyl; "spir" for the spiraea flower, another natural source of salicin; and "in," a common drug ending at the time. In 1899, Bayer sent infor- OLD MEDICINE Since ancient times, people mation on aspirin to nearly have been using willow to treat pain and 30,000 doctors. Soon, it was inflammation. Willow and myrtle trees contain the world's best-selling drug, salicylic acid, a close analog of modern aspirin. and Bayer began branching out its production to capitalize on its sucIn the U.S. and Canada, Sterling Drug cess, including a plant in New York. But won the auction for Bayer's assets, including the right to its name and its famous aspirin would once again have a fateful cross-shaped logo, for about $5 million. encounter with world war. W h e n generic competitors flooded the In 1914, the assassimarket soon thereafter, aspirin also benation of Austrian came a generic and unprotected name in Archduke Franz Ferdithe U.S. and some other countries. Bayer nand triggered a tanmanaged to retain its trademark in more gled web of alliances than 70 other nations, where acetylsalithat pulled almost all cylic acid is used to refer to the generic of Europe into conform, but the war auctions forced it to sell flict. The guns of Auits own aspirin under a different name for gust shattered contidozens of years in the U.S., the world's nental tranquility in a largest market. Finally in 1994, SmithKline war that soon balBeecham, the new owners of Sterling looned to encompass Winthrop, sold Bayer's over-the-counter Africa, Asia, and the line back to the company through Bayer's Americas. Bayer found itself the unfortuwholly owned Miles subsidiary— for $ 1 bilnate victim of its location; its foreign assets lion. It was a steep price for Bayer to pay (including patents and trademarks) were to once again secure worldwide rights to its seized by the victorious Allied powers— own name and logo.—AAL0K MEHTA Britain, France, the U.S., and Russia—as
People have been using salicylic acid, found naturally in willow and myrtle trees, for almost as long as civilization has been around.
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