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Theophylline is a main drug used for therapy of asthma.It is a derivative of Purine.Since this compound has so many effects such as smooth muscle relaxation, diuretic effect and cardiac pharmacological and so on,it is usually used for treatment of bronchial asthma,bronchitis and chronic obstructive pneumonia disease(COPD) in the medicine field.Theophylline is considered as the upstream product while synthesizing caffine in chemistry industry.It is synthsized by cyanoacetic acid through steps of condensation,cycclization,deoxidization and so on..Theophylline from this production process is characterized by the long needle-like crystals,which is difficulty crushed.Microtheophylline is regarded as a kind of specifications of theophylline,which has been obtained through a number steps of micropulverization.Importantally,_it is urgent exportations for many foreign countries.The current production of microtheophylline difficultly meet fully the demands of customer.Therefore,the establishment of this subject is very meaningful.Microtheophylline is presently produced through micropulverization.This method has many deficiencies,for example,it’s production capacity is low,quality control of products and the packaging are very difficult,it is labour-intensive and the products are easily polluted,so the failure rate and costs are very high.The subject has made sure that the crystallization is the best method for production of microtheophylline.We find the optimal process through inspecting conditions such as original concentration,PH, temperature,cooling mode and mill speed and so on.The product can meet the demands of different customers now.Through improved technology,the spectrogram of microtheophylline is fully meet European Pharmacopoeia by the IR,UR detection and its other qualities ae aslo meet USP/BP/EP/CP standard,and the particle sizes are more focused:The median size D (0.5)=30～45μm,100%of them can pass 120μm,more than 98%can pass 100μm and there are no obvious needle-like crystals.There are three significances of the study:First,find reliable process of producting microtheophylline,which avoides the many shortcomings from the machinery crush. Second,it won profit,social effects,economic benefits and reduce costs for enterprises. Third,the crystallization process of microtheophylline can promote research on other products.The innovations:Firstly,the theophylline crystallization process is systemly studyed for first time,which inspect the solubility,ultra-solubility,metastable zone, identified the optimal process conditions:original concentration is about 15%;filtrated; refining oxidation is about 4～6,temperature is 90～95℃for 30min by Hydrogen peroxide;refining decolorization PH is about 13～14,temperature is 95～100℃for 30min and the PH is adjusted at 6～7 in 83～60℃metastable region,outer-circle cooling, Compressed air stirring,fast mill,mixing crystal for 4 hours below30℃.Secondly it not only provide some reference for enlarging the experiment but aslo produce the better products compared with mechanical crushed.Lastly it provides lots of reference data.The above study on theophylline crystal technology has not been reported.
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