| In the ventral operation, celiac adherence occurred frequently. So, how to prevent it is a urgent question. Celiac adherence is an inevitable course to restore the peritoneum after the operation. No adherence, no restoring. When it has a disorder or the fibre decompound incompletion, adherence will be the foundation of the mechanical enteric block. The surgery follows this law all along, and we should focus on guiding to obey this rule. At present, the treatment consists celiac douche therapy, improving on surgical ways, exterior and physical treatment. But there are some shortcomings more or less. Now, treatment with traditional Chinese medicine and macromolecule polymer is the hotspot of the research foreland. A study validated that chuanxiong, a herbal medicine classified with promoting blood circulation, can increase the amount of opened tiny blood vessel, speed up the blood circulation, resist blood platelet congregation, restrain the smooth muscle constriction and anti-inflammatory. And it also can resist the celiac adherence. Microemulsion prolong the releasing time, facilitate the absorbtion of sebaceous soluble medicine, debase the toxicity and enhance the biology using degree. Meanwhile, the W/O microemulsion form a physical barrier and it has a wide foreground in the biological technology area. Based on the previous investigation, insuffiation with the W/O microemulsion preparation of traditional Chinese medicine will introduce the traditional therapy into the abdomen. We will focus on mitigating the pathological adherence and supplying basement research to prevent the mechanical enteric block.Large numbers of literatures have retrieved on the prevention development of postoperative abdominal adhesion with Chinese and western integrative medicine and drug microemulsion technique. The genesis and preventive methods of the abdominal adhesion was reviewed in this paper. At present, the prevention and treatment of the abdominal adhesion was concentrated on the intraperitoneal perfusion of drugs, the treatment with chinese traditional medicine, the improvement of operative technique, physical treatment and so on. Nowadays more attention has been focused on the dialectically application of Chinese traditional medicine and macromolecular isolation. In the present study, we combined the Chinese traditional medicine with modern microemulsion technique to prepare a kind of microemulsion with chinese medicine which has sustained release and membrane formation characteristics and examined if intraperitoneal perfusion of this microemulaion has the preventive effect on the postoperative abdominal adhesion.. There are some parts in our study: the W/O microemulsion preformulation, Ligustrazine microemulsion preparation, the biodegradation and compatibility of microemulsion and microemulsion efficacy validation.Drug screen PA model rats were randomly divide into 5 different groups treated with normal saline,TanshinoneⅡA,ligustrazine hydrochloride,urine kinase and aspirin respectively for 15 days,PA grade was assessed by pathology HE dye, Masson dye and immunohistochemical（SABC） observation and analysis, conclusion: ligustrazine hydrochloride and urine kinase prevent and cure PA better.W/O microemulsion preformulation: HLB value was used as index for selecting emulsifier. Emulsifier was selected from Span-80, OP and Span-80 combining with Tween-80. Coemulsifier was selected from glycerol and 1,2-glycol. Oil phase was selected from IPM and ethyl oleate. The prescription which could form stable blank microemulsion was: Km=1:1, OP/glycerol/ethyl oleate/water; Km=2:1, OP/glycerol/IPM/water; Km=2:1, OP/glycerol/ethyl oleate/water. Temary phase diagrams were drawed, and microemulsion area was used as index: the prescription of Km=1:1, OP/glycerol/ethyl oleate/water could form stable microemulsion, and also carry the most water.Preparation of Ligustrazine Hydrochloride microemulsion: Based on the blank microemulsion preparation, we used Ligustrazine Hydrochloride solutions of different concentration instead of water to select the prescription. Based on the drug-carried microemulsion prescription OP/glycerol/ethyl oleate/water, we investigated the effect of Ligustrazine Hydrochloride concentration on the stability of the emulsion. The best prescription has the highest drug content. From the temary phase diagram and the stability investigation, we knew that the most proper concentration was 50mg/mL.Quality evaluation of Ligustrazine Hydrochloride microemulsion: We centrifuged the microemulsion for 10 min (1500rad·min-1), the system was clear and transparence. When the conductivity was 1～10μs/cm, we consider it as W/O microemulsion. The average diameter of the drug-carried microemulsion was 79.5nm, 54% of which＜58.2nm and 89.5% of which＜89.0nm. The particle distribution is narrow and the particle size is homogeneous. The average drug content was 8.0417mg/mL. Drug release investigation in vitro showed that Ligustrazine Hydrochloride microemulsion released stably within the first 4 hours with good linear relationship（r=0.9975）, which was consistent with Higuichi equation.Study on the pharmacodynamics of Ligustrazine Hydrochloride microemulsion: 48 SD model rats were randomly divided into four groups: Sodium Chloride group, Ligustrazine Hydrochloride group, blank microemulsion group and Ligustrazine Hydrochloride microemulsion groups （high dosage, moderate dosage and low dosage）. The drug was administrated intraperitoneally during operation. The rats were put to death on the 22th day after operation. Abdominal adhesion was evaluated according to the Nair five-class standard. HE stain, Masson stain and immunohistochemistry methods was used to semiquantitatively evaluated the grade of the abdominal adhesion. The results showed Ligustrazine Hydrochloride microemulsion with low dosage was the best one.Conclusions: The best Ligustrazine Hydrochloride microemulsion is prepared using OP as emulsifier, glycerol as coemulsifier, ethyl oleate as oil phase and 50mg/mL Ligustrazine Hydrochloride solusion, which is the most stablethe with the proportion 4:4:2:0.95. The average drug content is 8.0417mg/ml. The animal experiments show Ligustrazine Hydrochloride microemulsion of the optimal dosage has the best efficacy and the supplementary component play a part in the prevention of the abdominal adhesion. The results suggest the low dosage is better than the high and moderate dosage. It proved the efficacy of Ligustrazine Hydrochloride microemulsion in the prevention and treatment of abdominal adhesion. |
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