Aspirin-its preparation, history and applications Essay

How drugs are discovered and developed Pharmacologist along with chemist focus on a specific disease and unmet patient needs in order to discover new drugs. They search for biological targets within the body that play a role in a given disease. Unique molecules are found or created that some day might be medicines. Lead Compound Selection, is the testing of compounds that might undergo the long expensive drug develop process. Random Screening- uses existing ‘library’ of chemical agents. This is the simplest method but the odds are low and patience is needed. Combinational Chemistry Screening- uses a compound (from existing library) as a base, then randomly adding amino acids or molecule segments of other agents to the base compound in order to enhance the base compounds activity and disease fighting potential. The enhanced compounds are then tested in rapid screening test. However this method is complex and costly but it improves the odds. Target Synthesis- targets the disease for drug intervention. For example High Blood Pressure would be studied in detail. Consequently this method still requires screening of hundreds of compounds and extensive amount of research to understand a particular disease process. Drug Modeling- uses more high technology. This method manipulates chemical structures by computers so that they can attach to, activate or deactivate proteins that interfere with or maintain the body’s normal functioning. The model is used to enhance the properties of the other methods but the cost for designer compounds are significant because of the huge amount of research that is needed to identify biochemical target and establish their molecular structure. How safety of drugs is checked before being used on the public A drug undergoes 3 clinical phases before being used on the public. PHASE 1 This is designed to determine the safety of the new drug, how best to administer it and the correct dosage- (one that will minimize desirable side effects). 20-30 patients (volunteers) are used to find out how the drug behaves in their body, so their blood and urine will be frequently monitored. Even though drugs in this will have been already tested in a laboratory. PHASE 2 After the correct dosage has been determined in phase1 clinical trial, it can enter phase2. This trial consists of determining the drug’s effectiveness in treating a specific disease. Phase2 involves more patients (volunteers) and they are tested for the number of platelets in their blood and take frequent blood samples. If the drug being tested brings a positive change in at least 1/5 of the patients then it can be tested in phase3. However if the drug shows very positive effects in-patients, the Food and Drug Administration also have the option of approving the drug for general use at this point. PHASE 3 This trial involves hundreds of patients and is divided into two groups. The control group receives a standard treatment (placebo) and the treatment groups are given the new drug. Results are then compared from the two groups. Blinded studies are used to prevent biased study results. If the new successfully passes a phase3 trial the FDA will approve the drug for marketing to the general public. . Purification -The acetylsalicylic acid is washed with distilled water until all the acetic acid is removed. -It is pressed to be as dry as possible and then dried more by a current of warm air at 60-70 degrees Celsius. The yield of pure acetylsalicylic acid is between 1780-1795kg per batch using this reaction process. * History of Aspirin and its modern development * How aspirin is prepared on the large scale Main reactor for the process- a glass lined 1500 gallon fitted with a water-cooled reflux condenser, thermometers with automatic temperature register and an efficient agitator. The Mother Liquor- 1532kg of acetic anhydride in 1200kg of toluene (this does not get used up. ). The reactor is charged up with the mother liquor. 1382kg of salicylic acid is added to the mother liquor. The reaction mixture is heated to between 85-92 degrees Celsius and kept at this temperature for 20 hours. The reaction mixture is transferred into an aluminum-cooling tank and is allowed to cool for 3-4 days. By the end the cool mixture will have reached room temperature 15-25 degrees Celsius. At this point the acetylsalicylic acid has precipitated as large regular crystals. Mother liquor is removed by filtration or centrifuging. Filtrate solution- 180-270kg of UN-precipitated acetyl acid, 510kg of acetic anhydride, 600kg of acetic acid and 1200kg of toluene. The acetic acid is obtained as a by-product of the acetylation step of the process. An well-agitated reactor using a diffusion plate will introduce Ketene gas, to be passed through the recycled filtrate at a temperature between 15-25 degrees Celsius. When a weight increase of 420. 5kg of the Ketene gas is observed, the mother liquor contains 180-270kg of UN-precipitated acetyl acid and 1532kg of acetic anhydride in 1200kg of toluene. The Mother liquor is recycled and 1382kg of Salicylic acid is added to continue the reaction cycle. BC- the first and most influential physician wrote about the bitter powder extracted from the willow bark that could ease aches and pains and reduce fever. 1700- The scientist Reverend Edmund Stone found out that the part of the willow tree bark that was bitter and good for fever and pain is a chemical known as Salicin. This converts into another chemical called Salicylic acid when eaten. 1829- A pharmacist known as Leroux showed that Salicin is the active willow ingredient and for the first time an Italian chemist Piria used Salicylic acid to treat pain and swelling in diseases such as Arthritis and to treat fever in illnesses like Influenza. The problem was that these chemicals was causing the users upset stomachs. Some people had bleeding in their digestive tracts from high doses needed to control swelling and pain. It was thought that the reason of stomach upsets were because of the acid in the chemical, therefore the compound Salicylic acid went through a couple of chemical reactions that covered up one of the acidic parts with an ACETYL group, converting it to ACETYLSALICYLIC ACID (ASA). It was found that ASA reduced fever and relieve of pain and swelling but also it was much better for the stomach and worked better than Salicylic Acid. 1899- ASA was given the name ASPIRIN- that comes from the plant relative of a rose that makes SALICYLIC ACID (several plants makes this compound not just willow). Â  How drugs such as aspirin work Prostaglandin is a chemical that is released to make the nerve ending register an even stronger pain to the brain. It is made in working cells of the damaged tissues by using an enzyme called CYCLOOXYGENASE 2 (COX-2). Prostaglandin makes you feel the pain of the damaged area and causes it to swell up (inflammation), to bathe the tissues in fluid from the blood so that it will protect it and help it heal. Pain serves the purpose here to remind you that the damaged area cannot be used, as it is not healed. However sometimes we endure pain when there is no real reason to. For example Period Pains and Arthritis. It can make people feel really uncomfortable and arthritis can damage joints permanently. ASPIRIN works by locking itself to the enzyme that makes the chemical Prostaglandin. The enzyme C0X-2 that is found in normal tissues but mostly in tissues that have been damaged in some way, can no longer convert floating chemicals into Prostaglandin because they are unable to move with the aspirin lock on. Aspirin does not treat the cause of the pain; it just lowers the pain signals getting through your nerves to the brain. How effective aspirin is New researches suggest that an aspirin a day is a preventive measure against Heart Attacks. However the effectiveness of aspirin has differential effects depending on genetics.