The Technics And Equipment Study Of Producing Of Ultrafine CoQ₁₀ Partieles By RESS

Coenzyme Q₁₀ is a kind of vitamin-like substances,it has important physiology function and clinical value.Currently,it has been widely used in many aspects,such as cosmetics, medicine and chemical industry and health products.In Europe and the United States and other developed countries,coenzyme Q₁₀ is one of few substances added to health products that need not to be tested,and the market prospect is broad.Coenzyme Q₁₀ is fat-soluble compound, bioavailability is low,and is not propitious to absorb and utilize in human,the formulations are also been restricted.Supercritical fluid technology is a new method for preparation of ultra-fine powder materials in recent years.Rapid expansion of supercritical solution technology(RESS) and Supercritical anti-solvent crystallization technology(SAS) are two methods researched more in-depth.RESS and SAS technology are two complementary methods,the former need good solubility in the supercritical fluid for solute,and the later requires insoluble or small solubility in the supercritical fluid.The history of the rapid expansion of supercritical solution technology research has been several decades,the condition is mild and green,and especially it can be well used in the materials which are temperature-sensitive and have strong biological activity,it has a wide application prospect in application of chemical,biological engineering,medical, pharmaceutical,and other fields.However,it needs improvement in its equipment yet.In this paper,by the preparation of coenzyme Q₁₀ ultra-fine particles used RESS technology,each part of the equipment was optimized.The parameters such as temperature, pressure,nozzle diameter in the process of coenzyme Q₁₀ RESS were examined,micro-devices of the rapid expansion of supercritical solution technology was optimized,and the rules of the influence on particle shape,size and size distribution for each parameters were mastered.In respect of equipment alteration:1.Material canister for entire membrane sample dissolved was adopted.Compared with traditional dissolved material canister,on the one hand,the new material canister was helpful for the dissolution of samples.The dissolution process was also the diffusion process.First of all,the solute was contacted with solvent,and the solute dissolved in the solvent.And then,the solvent contained solute or with higher concentration diffused to other solvent which non-solute or with lower concentration.Because of the new material canister was porous,the diffusion was easier,and the dissolution speed was increased,the dissolution time with pressure and temperature retained was reduced.On the other hand,during the process of injecting operation,supercritical fluid brought along the solute to the nozzle through the filtrate membrane,and injecting crystallization was taken place in the kettle.In general,this process was a quantitative process,i.e.the quantity of the supercritical fluid should be a certain value which passed the filtrate membrane within unit time.For the whole of the new material canister,it was filtrate membrane,however,the traditional material canister only for a part of bottom.Within unit time,fix quantified supercritical fluid passed through the new material canister was faster than through the traditional material canister,the reduction of the effect of cutting was conducive to control the temperature.2.An automatically vacuum injection and two dissolved system which with continuous injection were designed and manufactured.In the process of production,operation with vacuum relatively had higher security,which was the precondition for the use of negative pressure in this design.Using automatic vacuum injection,higher demands of GMP could be achieved,contact with the powder for human body was reduced and the dust losses on human were reduced,especially for the production of the material that had a negative effect on human body.The utilization of two crystallization kettle made the production continuous,the removal of the device reduced and the wastage of the equipment reduced.3.Utilization of cyclone collector in reception part.Cyclone collector was independently designed in accordance with principles of fluid dynamics.After injection expansion,the supercritical fluid changed into a gaseous state,samples and gas separated automatically through the cyclone collector,samples collection were more complete,the collection process was easy,simple and little-polluted.Cyclone collection bottles could be replaced during interim of pressure retained operation process and did not affect the continuous process.1.The conditions of rapid expansion of supercritical solution for coenzyme Q₁₀ were optimized by an orthogonal test,according to the main factors of rapid expansion technology and physical and chemical properties of coenzyme Q₁₀,16 times tests of 4 factors and 5 levels were carried out,eventually the particles that the minimum was 700 nm were obtained.The chromatography showed that its functional structure had not changed and the physiological functions had not been affected.2.The results of range analysis showed that among the effect conditions,pressure of dissolved kettle was the most important factors,the second was nozzle diameter,the temperature of crystallization kettle almost had no effect on the change of particle size.3.With analyzing from each parameter,the results were obtained:the pressure which was the main factor changed greatly at the beginning,and then slowed down,dissolved pressure at the range of 18～23 MPa could be selected;the trend of the effect of nozzle diameter was more evident than pressure,nozzle diameter could be selected at the range of 200～150μm.At the same time,it could be further optimized,such as structure changed and more head nozzles created,and so on.The search in this paper provided necessary data for the preparation of ultra-fine powder with the rapid expansion of supercritical solution technology for Coenzyme Q₁₀,and provided a model for production and application with the rapid expansion of supercritical solution technology.