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Hippocrates, a Greek physician, wrote in the 5th century BC about a bitter powder extracted from willow bark that could ease aches and pains and reduce fevers. This remedy is also mentioned in texts from ancient Sumer, Lebanon, and Assyria. The Cherokee and other Native Americans used an infusion of the bark for fever and other medicinal purposes for centuries. The medicinal part of the plant is the inner bark and was used as a pain reliever for a variety of ailments. The Reverend Edward Stone, a vicar from Chipping Norton, Oxfordshire, England, noted in 1763 that the bark of the willow was effective in reducing a fever.
The active extract of the bark, called salicin, after the Latin name for the white willow (Salix alba), was isolated to its crystalline form in 1828 by Henri Leroux, a French pharmacist, and Raffaele Piria, an Italian chemist. Piria was able to convert the substance into a sugar and a second component, which on oxidation becomes salicylic acid.
Salicylic acid was also isolated from the herb meadowsweet (Filipendula ulmaria, formerly classified as Spiraea ulmaria) by German researchers in 1839. While their extract was somewhat effective, it also caused digestive problems such as gastric irritation and bleeding and diarrhea, and even death when consumed in high doses. In 1853, a French chemist named Charles Frederic Gerhardt neutralized salicylic acid by buffering it with sodium (sodium salicylate) and acetyl chloride, creating acetosalicylic anhydride. Gerhardt's product worked, but he had no desire to market it and abandoned his discovery. In 1897, researcher Arthur Eichengru"n and Felix Hoffmann, a research assistant at Friedrich Bayer & Co. in Germany, derived one of the hydroxyl functional groups in salicylic acid with an acetyl group (forming acetylsalicylic acid, an acetyl ester). This thereby greatly reduced the negative effects caused by the free phenolic group of salicylic acid. When in the body, the ester (aspirin) is hydrolyzed to free the active drug. This was the first synthetic drug, not a copy of something that existed in nature, and the start of the pharmaceuticals industry.
Hoffmann made some of the formula and gave it to his father, who was suffering from the pain of arthritis and could not stand the side-effects of salicylic acid. With good results, he then convinced Bayer to market the new wonder drug. 'Aspirin' was patented on March 6, 1899. It was marketed alongside another of Hoffmann's products, an acetylated synthetic of morphine called 'Heroin' that he invented 11 days after aspirin. Heroin was initially the more successful of the two painkillers and it was common belief that it was healthier than aspirin. But, as heroin's shortcoming of addictiveness became more obvious, aspirin stepped to the forefront. Aspirin was originally sold as a powder (still the preferred form in many European countries) and was an instant success; in 1915, Bayer introduced aspirin tablets.
Several claims to invention of acetylsalicylic acid have arisen. Acetylsalicylic acid was already being manufactured by the Chemische Fabrik von Heyden Company in 1897, although without a brand name. Arthur Eichengru"n claimed in 1949 that he planned and directed the synthesis of aspirin while Hoffmann's role was restricted to the initial lab synthesis using Eichengru"n's process. In 1999, Walter Sneader of the Department of Pharmaceutical Sciences at the University of Strathclyde in Glasgow reexamined the case and agreed with Eichengru"n's account. Bayer continues to recognize Felix Hoffmann as aspirin's official inventor. Despite its argued origin, Bayer's marketing was responsible for bringing it to the world.
It was not until the 1970s that the mechanism of action of aspirin and similar drugs called NSAIDs was elucidated (see below).
Aspirin
Aspirin is commercially synthesized using a two-step process. First, phenol (generally extracted from coal tar) is treated with a sodium base which generates sodium phenoxide, which is then reacted with carbon dioxide under high temperature and pressure to yield salicylate, which is acidified, yielding salicylic acid. This process is known as the Kolbe-Schmitt reaction.
Salicylic acid is then acetylated using acetic anhydride, yielding aspirin and acetic acid as a byproduct. It is a common experiment performed in undergraduate organic chemistry practicals, and generally tends to produce low yields due to the relative difficulty of its extraction from an aqueous state. The trick to getting the reaction to work is to acidify with phosphoric acid and heat the reagents under reflux with a boiling water bath for between 40 to 60 minutes.
The original synthesis of aspirin from salicylic acid involved acetylation with acetyl chloride. Unfortunately, the byproduct from this is hydrochloric acid, which is corrosive and environmentally hazardous. As described above, it was then later found that acetic anhydride was a better acylating agent, with the byproduct acetic acid formed, which does not have the unwanted properties of hydrochloric acid and can also be recycled. The salicylic acid/acetic anhydride method is commonly employed in undergraduate teaching labs.
Formulations containing high concentrations of aspirin often smell like vinegar. This is because aspirin can undergo autocatalytic degradation to salicylic acid in moist conditions, yielding salicylic acid and acetic acid.
The acid dissociation constant (pKa) for Acetylsalicylic acid is 3.5 at 25 °C. ASA, being a weak acid, dissociates as shown by the following reaction equation:
• Heart Problems - Aspirin...
• Heart Problems - Aspirin as Genericized Trademark...
• Heart Problems - Discovery...
• Heart Problems - Synthesis...
• Heart Problems - Mechanism of Action...
• Heart Problems - Indications...
• Heart Problems - Toxicity of Low-dose Aspirin...
• Heart Problems - Contraindications and Warnings...
• Heart Problems - Common Side-effects...
• Heart Problems - Interactions...
• Heart Problems - Overdose...
• Heart Problems - Research Into Cancer Prevention...
• Heart Problems - Aspirin in Pets...
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Important notice:
The content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other
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