Synthesis And Anti-inflammatory Analgesia Activities Of Diclofenac Potassium And Its Derivates

Diclofenac potassium and its derivates belong to Nonsteroidal anti-inflammatory drugs(NSAIDs). NSAIDs is one of the most applied drugs on clinical application . It is drugs of non-steroidal structure which make functions on anti-inflammatory, analgesia, relieving fever .It is mainly applied in the treatment of the inflammation immunologic diseases such as rheumatic arthritis, arthritis deformans, ostarthritis etc.At present, NSAIDs has been developed into an excellent drugs which make functions on anti-inflammatory and anti-rheumatism and it has various kinds. Its outputs is among the top in the world. However, we discovered that most of NSAIDs had toxicity and side-effects more or less, which affected the long term apply of it . The discovery of its side-effects stimulates the pharmaceutical chemists to do deep researches on the inflammatory reaction mechanism and the mechanism of actions of anti-inflammatory drugs continuously to find a new anti-inflammatory drug with better performance and less poisonous effects. As a new medicine, it should have higer biological activity, meanwhile secure to human body. Therefore, although NSAIDs has been developed into a commonly used drugs in our daily life, it is extremely important for our pharmacy workers to study its development, reduce its cost and discuss the mechanism of its adverse effects.Diclofenac potassium is the derivate of Phenylacetic acid, which belongs to the NSAIDs with functions of anti-flammatory, analgesia and pyretolysis. The chemical name of Diclofenac potassiumpotassium is 2-(2-(2,6-dichlorophenyl amino) phenyl) acetate, which is the promotion substitution product of diclofenac sodium, It has stronger effect among the NSAIDs. Its depressant effect to ptostate glanding is stronger than Asp, IMT, etc, and it also has vivid pharmacology characteristic. It can be absorbed quickly, and the absorption rate is also higher. The pharmacokinetics character demonstrated that it can be absorbed quickly and completely for oral use, and the peak time is about one hour, which is two hours faster than sodium salt . Therefore it has better effect on relieving pain than diclofenac sodium. However, diclofenac potassium also has many adverse effects, for example abdomen ache, disgusting, disgorging, diarrhea, abdomen spasm, dyspepsia, gaseous distention, anorexy, gastrointestinal bleeding, haematenesis, dark stools, gastrointestinal tract ulcer, perforation, hemorrhagic, diarrhea, headache, dizziness, efflorescence, cnidosis, SGOT advanced, hepatitis, allergic response, dropsy and so on. Therefore, the world has undertook the massive research on the structure of diclofenac to cut down its poisonous side effect. All these works mainly displays two aspects. On the one hand, diclofenac has been made in the products of inorganic salt and organic salt, however, because the water solubility of inorganic salt is very small, and there are the ingredient of carcinogenesis in the organic salt, so the results are not ideal. On the other hand, people studied and researched the mother nucleus structure of diclofenac, and developed the correlated products of diclofenac choline and the salt of diclofenac lysine. On the base of related literatures, our study also modified the structure of diclofenac, synthesized a derivate of diclofenac, methyl 2-(2-(2,6-dichlorophenylamino)phenyl)acetate. The pharmacodynamics experiments indicate that this compound possess better anti-inflammatory activity than diclofenac potassium.In the technology research aspect, we established the chemical synthesis technology of diclofenac potassium. The raw materials of this technology are amino benzene and dichloro-phenol, through chlorine acylation reaction, etherification reaction and rearrangement reaction, we synthesized the key intermediate—2,6-dichloro diphenylamino, later this key intermediate, through acylation reaction, cyclization reaction, lytic reaction and so on, synthesized diclofenac potassium. The yield of each reaction is about 85% averagely. At present, the synthesis technology of diclofenac sodium has been reported, however there isn't literature report about the synthesis technology of diclofenac potassium, which can be looked up in the item investigation information. This technology possess many characteristics: ordinary raw materials, convenient operation, bland reaction conditions, lower cost, shorter route, fine security, and the yield and purity are also high. Therefore, this technology suits to industrialization production. Besides, we synthesized a derivate of diclofenac, methyl 2-(2-(2,6-dichlorophenylamino)phenyl)acetate. The pharmacodynamics experiments indicate that this compound possess better anti-inflammatory activity than diclofenac potassium.The structures of the key intermediates and the final compound are ensured by the ultraviolet spectrum, the infrared spectrum, the nuclear magnetic resonance hydrogen spectrum and the carbon spectrum. We determined the contents of diclofenac potassium by the method of HPLC, its purity is about 99%. And we has controlled its quality well. We carried out the stability investigation of three batches of crude drug and their prepatation, the results indicate that under the condition of room temperature, the targets of indentification, load difference, the water content, disintegration time, content and hygiene of these crude drugs and their preparations. So the stability of diclofenac potassium conforms to the requirement of the new drug.In brief, the results of this research provide a feasible method and the reliable theory basis for the further study on Diclofenac potassium and its derivates...