Degradation Mechanism And Mateiral Behaviors Analysis Of The Inclusion Complexes Of Sinomenine To Cyclodextrins

Sinomenine(SN) is the main active ingredients separated from the traditionalChinese herb Sinomenium acutum. Modern medical research showed that it is effectiveto anti-inflammatory, analgesic. It is widely used and achieved good effect in thetreatment of rheumatoid arthritis and arrhythmia. In recently, with the development ofresearch on SN, the disadvantages of itself gradually be found such as instability andeasy decomposition under alkaline, light or heat, make the production process ofpreparation complicated, easy to deteriorate and the validity turns to short. It presentesskin rash, stomach discomfort and other clinical side-effects with the factor of histaminerelease. With these reasons it is seriously hindered further application of SN in clinic.Cyclodextrins (CDs) are the products of starch degradation by Glucosyltransferase,and they have special cavity structure. They can form inclusion complexes by bindingguest molecules selectively. According their special cavity structure and in this way,many properties of the inclusion complexes are greatly improved such as solubility,diffusion performance, chemical and optical properties compared to guest compounds.CDs have been widely used in pharmaceutical, foodstuff, and other chemical industriesto increase the solubility and stability of guest molecules, control the volatile andsublimation, improve the flavor and eliminate the odor, slow release drugs andfragrance.In this paper the changes of SN under different conditions were system withdetailed reseached in solution. UV spectrophotometry was applied to determine spectralchange of SN with change of pH in solution to calculate the dissociation constants ofSN. The inclusion complexes of SN with CDs were prepared successfully throughmixed solution method in order to improve the stability and bioactivity on condition thatprotecting the structure of SN. Then the crystalline morphology of the inclusioncomplexes were characterized and analyzed by stereomicroscope after purification andrecrystallization. Other material behaviors of the inclusion complexes of SN with CDswere characterized through ultraviolet spectrum (UV), X-ray diffraction(XRD), infraredspectrography(IR), differential scanning caborimetry(DSC) and nuclear magneticresonance(HNMR). The invitro transdermal characteristics and bioavailability wereinvestigated both on mouses and domestic rabbits, and their anti-inflammatory andanalgesi effects were studied. The results presented that the inclusion complexes ofsinomenine with CDs could be formed from the solution and the inclusion complexeswere new physical form. CDs can sharply increase the solubility of SN. The inclusioncomplexes have excellent invitro transdermal characteristics and bioavailability, theeffects on anti-inflammation and analgesi effects of inclusion complexes were the sameas SN and the inclusion complexes provide longer effective drug duration.