Studies On Release System Of Zedoary Turmeric Oil Submicron-emulsions

Zedoary Turmeric oil is distilled from Cumuma Wenyujin Y.H.chen et C. Ling, Cumuma phaeocaulis Valeton and Curcuma kwangsiensis S.G. Lee et C. F. Liang .It's light-brown or nigger-brown clear liquid with special smell and bitter sapor. Its main component is triterpenoid and its pharmacologic actions are anti-virus, anti-tumor, anti-inflammatory, anti-internal clot, accentuating immunifaction, exciting smooth muscle and so on. Especially on anti-tumor and anti-virus, Zedoary Turmeric oil has evident inhibitory action on Influenza virus, Influenza A, parainfluenza virus, chimpanzee coryza agent and Staphylococcus aureus. Recently researches indicate that Zedoary Turmeric oil can interfere the synthesis of tumor cell DNA, and achieve the aim of anti-tumor by blocking up tumor cell going into S stage. At present, the chief dosage form of Zedoary Turmeric oil is Zedoary Turmeric oil and Glucose Injection, but it has poor stability and many side effects such as local irritation, haemolytic action,ect. To increase the stability of Zedoary Turmeric oil, diminish its adverse reactions and increase its target ability, we develop Zedoary Turmeric oil submicron emulsion(ZTOSE).The basic formulation of ZTOSE was determined using single factor investigation;the formulation and the preparation process were optimized by orthogonal design test. Using the diameter distribution of emulsion and the stability parameter as the index, the effect of formulation variable formulations such as the kind of phospholipids, the amount of F68 and VE, pH of the ultimate emulsion and also the effect of process variable processes such as emulsifying temperature of colostrums, the pressure, frequency and temperature of the homogen process on emulsionpreparation were investigated. The best formulation of ZTOSE contains Zedoary Turmeric oil 2%, lecithin 1.2% , soybean oil 7.5%, medium chain oil 7.5%, F68 2%, VE 0.03%, glycerol 2.25%, pH6.75. The best preparation technology is first emulsifying temperature 75 °C, pressure of emulsifying lOOOOpsi, number of emulsifying times 3, temperature of emulsifying50°C.The ZTOSE is a white emulsion with blue lactic light. Tt's mean particle diameter size is 200nm, pH range is 5.5-7.5, zeta potential is -50—70mV.Relationship between the stability of the ZTOSE and the factors such as temperature, illumination, zeta potential, pH and so on were investigated, the acceleration experiment were conducted. Results showed there was no significant change of the appearance, content of the drug of ZTOSE at the condition of 30°C after 6 months. Zedoary Turmeric oil was stable in emulsion prepared.Pharmacokinetics of ZTOSE in rabbit and distribution in rat wtere studied in this paper. The high performance liquid chromatographic (HPLC) method using a reverse-phase column and UV detector was adopted for the determination of germacrone in plasma to study the pharmacokinetics of ZTOSE in rabbit. The concentration-time curve of rabbits after iv ZTOSE can be fitted to two-compartment model with the main pharmacokinetic parameters as follows: A=816.67ng.ml"1, a=3.04h1, B=138.32ng.ml1, B=0.076h\ V(c)=0.2207ng.Kg\ Tl/2a=0.408h,Tl/2B=11.576h, K21=0.4461h \ K10 = 0.492b1 , K12=2.176h\ ACU=1986.1ng.ml1.h, Cl(s)=90.83ngKg1h, MRT=14.875h.Its half life is longer than Zedoary Turmeric oil injection. All of these showed sustained release of ZTOSE. The result of distribution study in the rats showed that ZTOSE mainly distributed in liver, lung, spleen and nephridial tissue.Compared with Zedoary Turmeric oil injection, the safety of ZTOSE were investigated;LD50 of ZTOSE and Zedoary Turmeric oil were 810mg/ml and 280mg/ml,respectively. Topical irritation test, haemolysis test were conducted. The result indicated that the side effects of ZTOSE were almost diminished. The research of subacute toxicity indicated that ZTOSE had no harmful effect on the blood^ hearts lung> live^ spleen . Blood index and thymus index number indicated that ZTOSE had some extent of immunologic enhancement effect. All of these showed ZTOSE is a safe dosage form.Anti-tumor pharmacodynamics of ZTOSE was evaluated through establishing tumor model using mice. The effect of anti-tumor of ZTOSE lOOmg/kg is similar to 20mg/kg cyclophosphamide. All of this showed that ZTOSE had a good performance in a safe scale.This paper indicated that ZTOSE can efficiently elevate the stability of Zedoary Turmeric oil, eliminate the stimulus, haemolysis and the other side effect after iv of Zedoary Turmeric oil, increase the safety of Zedoary Turmeric oil vein injection . It was a safe and effective dosage form of Zedoary Turmeric oil. This paper also provided a safe and effective dosage form of Chinese traditional essential oil drug.