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The acetylsalicylic acid (Name international non-proprietary of the acid 2 (acétyloxy) benzoic ) is a chemical Composé used like Médicament Analgésique and more known Antipyrétique under the name of aspirine , coming from “Aspirin”, mark created in 1899 by the German company Bayer.

It is a derivative of the Salicylic acid . The salicylic term comes from the Latin name of the Saule, which one used the bark for his curative properties.

The name of Aspirine mark was formed of the Greek privative prefix has, of the scientific Latin radical Spiraea (ulmaria) , denomination erudite of the Queen-of-meadows, and the German erudite suffix - in , clean with the chemical and medical term: literally “which is made without Spiraea (ulmaria) ”. This term was forged to distinguish the natural acetylsalicylic acid, extracted the flowers of the Spiraea ulmaria , of the acid obtained by synthesis, introduced into therapeutic in 1899 thanks to work of the German chemist Adolf von Baeyer (1835-1917).

History

The bark of Saule is known since the Antiquité for its healing virtues. One found the trace of decoction of sheets of willow in an Egyptian papyrus going back to 1550 av. J.C Hippocrates (460 - 377 av. J. - C.), Greek doctor, advised already a preparation starting from the bark of the white willow to relieve the pains and the fevers. The Romans knew also its properties, the Latin name of the willow is salix .

In 1763, Edward Stone presents a report in front of Royal Medicine Society on the therapeutic use of the bark of the white Saule against the fever. In 1829, Pierre-Joseph Leroux, a French pharmacist, after having made boil powder of bark of white willow in water, tries to concentrate its preparation; it results from it from the soluble crystals that it baptizes salicylic acid ( salix ).

Then German scientists purify this active substance, initially called salicylic acid Salicyline then.

Other natural sources are found as the Queen-of-meadows whose scientific denomination of the time Spirea ulmaria will give rise to the name aspirine. Very quickly, one will realize that the acids spiric and salicylic do only one. One uses this preparation to make fall the fever, relieve the pains and the rheumatoid arthritis, but it causes heartburn.

In 1853, the chemist Strasbourg eois Charles Frederic Gerhardt tries out the synthesis of the acetylsalicylic acid and deposits a patent. He dies three years later and its work falls into the lapse of memory.

In 1859, Kolbe makes a success of the chemical synthesis of the salicylic acid, but it is Felix Hoffmann, German chemist entered to the service of the laboratories Bayer in 1894, which, in October 1897, resuming former work of Gerhardt, finds the means of obtaining pure acetylsalicylic acid and carries out its industrial production. It makes use of it initially to look after his father, who suffered from chronic rheumatism. According to searchs for Walter Sneader of the University of Strathclyde to Glasgow, it was however the superior of Hoffmann, Arthur Eichengrün, which had the idea to synthesize the salicylic acid.

Finally, the patent and the mark of aspirine are deposited by the company Bayer in 1899, under the denomination “ Aspirin ”. The preparation arrives to France in 1908 and is marketed by the chemical Company of the factories of the Rhone. However, after the First World War, the Traité of Versailles stipulates that the mark and the manufactoring process fall into the Public domain in a certain number of countries (France, the United States… but they perdurent in other countries like Canada).

Today, one still produces each year more 12  000 tons of this drug throughout the world, and one does not cease discovering new properties to him, to see therapeutic Indications and preventions.

Pharmacological properties

Aspirine has the pharmacological properties following:

Mechanism of action

In 1971, John R. Vane, at the time of research which was worth the Nobel Prize to him medicine in 1982, discovered that aspirine inhibits the production of Prostaglandine S and of Thromboxane S. aspirine by a chemical reaction of Acétylation inhibits in an irreversible way the Enzymes Cyclo-oxygénase (COX 1 AND COX 2), enzymes participating in the production of prostaglandins and thromboxanes. Aspirine is different from the other anti-inflammatory drugs not stéroïdiens (AINS) which inhibit in a reversible way this enzyme.

Aspirine cause a drop in the Fièvre (Antipyrétique), by reducing the production of Prostaglandine S in the Hypothalamus, thermostat of the body temperature.

It reduces the pain (Analgésique) by blocking the production of the Hormone S persons in charge of the messages transmitted to the receivers of the Douleur in the Cerveau, from where its effectiveness on the Migraine S and the pains of various origins. By the same mode of action, it reduces the ignitions (AINS) resulting from a vascular dilation, like the heat strokes, which are not accompanied inevitably by sunstrokes.

Aspirine acts on the blood plates, by inhibiting the Cyclo-oxygénase, an enzyme having a big role in the aggregation of the plates, and this, in a permanent way, i.e. during all the lifespan of the plate (between 7 and 15 days). It supports by this skew circulation and can be used for to prevent the heart attacks, by avoiding the formation of clots (Thrombose).

Pharmacokinetic

Aspirine is absorbed on the level of the Estomac and the Duodénum. The rate of absorption depends on the amount: from 60 for less than 500 Mg with 90% per 1 gr. or more by saturation of the hepatic hydrolysis.

For the immediate dosage forms, the peak of concentration is reached from 25 to 60 minutes after the catch. Several clinical trials show that small amounts of aspirine decrease, modestly, the recurrence of the intestinal polyps and occurred of the cancers of the colon, primarily if the latter express the enzyme Cyclo-oxygénase of the type 2 (either, approximately 2/3 of known as cancers). However the amounts indicated are likely to cause bleedings gastric or intestinal and the use of aspirine is currently not recommended for the cancer prevention.

Fecundation

According to a study (2004) of the hospital of Shelly sand (Sweden), the catch of aspirine with 75  mg/j would increase the effectiveness of the In vitro fertilization by improving vascularization of the Utérus.

Counter-indications and precautions

Its side effects are gastric disorders (example: gastrite to see digestive hemorrhage in the event of amount raised at long the court.

Aspirine is disadvised to the infants and to the children, because in the event of overdose (50  Mg per kg and day), it is neurotoxic. Moreover, it can involve the appearance of the Syndrome of Reye in the event of Varicelle or of Grippe.

The Cardiac S, under treatment the long course with small amounts because of its effect Antiagrégant, can be exposed with these side effects. The benefit of the treatment remains higher than the risk however by far, which justifies its regulation.

At the people suffering from a gastric Ulcer, aspirine can cause a digestive Hémorragie.

At the time of a Pregnancy, it can be taken on a purely specific basis during the first two quarters, then the use of aspirine is contra-indicated with the third quarters: on the Fetus as from the sixth month, this type of drug exerts vasoconstricteurs effects on the level them kidneys and can lead to an impaired renal function or to disorders of the cardiopulmonary apparatus.

This drug is also contra-indicated during the Allaitement (the molecule passes in milk).

In the event of risk of Dengue, the use of drugs containing aspirine, is strongly disapproved considering the risk of appearance of the hemorrhagic form of the disease. This opinion must accompany, with the Brésil, any publicity of the product.

In a general way, aspirine fluxes blood because it inhibits plate aggregation. Consequently, the risk of hemorrhage is to be taken into account, especially if there is already regulation of anticoagulants.

Chemical properties

The acid acetylsalycilic is the Name international non-proprietary acid 2 (acétyloxy) benzoic (according to the standards IUPAC).

During years, it was also called acid 2-acétyloxybenzoïque, acid 2-acétoxybenzoïque, acétylsalicylate, acid ortho-acetylsalicylic, acid ortho-acétyloxybenzoïque or acetosal.

The Pharmacopeia S European (pH. Eur.), American (USP) and Japanese woman describe methods of identification and analyzes of the acetylsalicylic acid intended for the drugs.

Synthesis

The initial synthesis of Gerhardt described in 1853 was improved in 1975. It is rather simple and consists of the esterification of the function alcohol of the Salicylic acid with the acetic Anhydride the whole in condition Acide. One obtains the acetylsalicylic acid and of the acetic acid as under product. (For the synthesis of the Salicylic acid , to refer to Salicylic acid or Reaction of Kolbe).

The purification can be made two ways: by recrystallization in the Acetone (according to a patent of Monsanto of 1959), by recrystallization in a mixed solvent ethanol/water 1:2.5 or by a process implementing a distillation (patent of Norwich pharm of 1966). The purified product is appeared as crystals white in the shape of needle.

A test with iron chloride (III) could be useful to determine the possible presence of salicylic acid not having reacted. The iron chloride (III) will react with group OH of the acid and will give place to a red coloring of the product.

Conclusion

This old product preserves the favors of the public, as an investigation of the Sofres shows it realized in 2003. It is competed with by the Paracétamol, other Analgésique and Antipyrétique, but is deprived of effects in the gastric plan (aspirine supports the ulcer like the others anti-inflammatory drugs not stéroïdiens). On the other hand, paracetamol has irreversible harmful effects on the liver with very strong amounts.

Today, self medication by aspirine, from its effects on the stomach and the blood (antiagrégant plate, which involves a reduction in the capacities of the blood to be coagulated) in fact a drug which requires a delicate and precise handling, that one advantageously replaces by paracetamol if it is a question of fighting against light or average pains. It remains on the other hand very useful for the prevention of the cardiovascular risks within the limit of 84  Mg per day like previously mentioned.

References

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