Attached Pills To Good Traditional Chinese Medicine As A Model Drug Microemulsion Drug Carrier System

The content of this paper is part of a project entitled"The key technology of microemulsion vehicle system of the Traditional Chinese Medicine"sponsored by the State Administration of Traditional Chinese Medicine (No.: 2004BA721A46). In this paper, the integration of microemulsion techniques and techniques for preparing traditional Chinese compound drugs was investigated in order to find out the feasibility of applying microemulsion techniques in preparing traditional Chinese compound drugs. In addition, the safety of microemulsion dosage form of traditional Chinese compound drugs was also evaluated in the paper.1 Objectives1.1 To investigate the microemulsion drug carrier system for traditional Chinese compound drugs by using Liangfu pills as a study model According to the special features of microemulsion and administration of traditional Chinese drugs in clinical practice, this paper took Liangfu Pills as a drug model to study the microemulsion drug carrier system for traditional Chinese compound drugs. In addition, this paper also aimed at the possibility of the application of microemulsion techniques in entire field of traditional Chinese pharmaceutics.1.2 To evaluate the effects of Liangfu Oral Microemulsion To develop Liangfu Oral Microemulsion through a series of pharmaceutical experiments, such as the quality control experiment and pharmacological effect experiment. In the study, the mechanism of the effects of Liangfu Oral Microemulsion was also investigated, with a comparison with Liangfu Pills in the dosage form of water-pasted pill.1.3 To evaluate the safety of Liangfu Oral Microemulsion To carry out acute toxicity and long-term toxicity tests on Liangfu Oral Microemulsion in order to provide experimental data on safety for the application of microemulsion drug carrier system in the traditional Chinese pharmaceutical field.2 Methods2.1 The study of the technology for preparing Liangfu Oral Microemulsion.2.1.1 To extract attar from rhizoma alpiniae officinarum and Rhizoma Cyperi and obtain their water extract liquid. We use the attar as oil phase and use the water fries liquid as water phase of microemulsion to Sift formula of Liangfu Oral Microemulsion. On the basis of principles that Dosages of Tween respond to the full small, proportion of oil and water is proper and formula proportion accords with the proportion of attar and water fries liquid of unit medicine, we select preferential prescription ultimately.2.1.2 Use pseudo-ternary phase diagram and titrimetric method to select Liangfu Oral Microemulsion′s formular and confirm the best roportion of oil phase, water phase, surfactant phase and Cosurfactant phase.... 2.1.3 Research and confirm Liangfu Oral Microemulsion′s fabricating technology according to literatures methods.2.2 Liangfu Oral Microemulsion′s pharmaceutical research We used the methods in Chinese Pharmacopoeia to study characters, relative density, pH Value and microorganism limitation of Liangfu Oral Microemulsion. The content of galangin in Liangfu Oral Microemulsion was determined by HPLC. We used transmission electron microscope and laser particle size analyzer to determine the form and size distribution of Liangfu Oral Microemulsion according to literatures methods. Preliminary study on the stability of Liangfu Oral Microemulsion was done. we established the quality standands for Liangfu Oral Microemulsion.2.3 Experimental Study on Pharmacodynamics of Liangfu Oral Microemulsion According to literatures methods, using the models of dimethylbenzene-induced mouse ear swelling, research the anti inflammatory effects of Liangfu Oral Microemulsion on acute inflammation. Using Cotton Ball Granuloma in Rats experiment,research the anti inflammatory effects of Liangfu Oral Microemulsion on chronic inflammation. analyesis experiment adopted hot-plate procedure and torsion body method to study its analgesiceffect. Use intestine propelling motion test in normal mice and in cold gastric mucosa lesion animal model mice to study effect of Liangfu Oral Microemulsion on intestinal movement. Use experimental stress-induced ulcers in Rats and cold gastric mucosa lesion animal model ulcers to study Liangfu Oral Microemulsion′s anti-ulcer action. Use the secretion experiment of gastric fluid acidity and pepsin of rats to study the effect of Liangfu Oral Microemulsion on gastric secretion function. These effects were compared with traditions dosage forms water - paste pills.2.4 By The experimental observation of Liangfu Oral Microemulsion about acute toxicity and chronic tocicity, its safety was evaluated3 Results3.1 Liangfu Oral Microemulsion′s forming technology3.1.1 Use and titrimetric method screening method and gain Liangfu Oral Microemulsion′s prescription.3.1.2 according to forming technology Obtain Liangfu Oral Microemulsion.3.2 Liangfu Oral Microemulsion′s preparation is stable3.2.1 Liangfu Oral Microemulsion is brown-red clarify and transparent liquid. It is adhibit and greasy. It bitter. The relative density is 1.02686. The Mean Value of pH is 4.537. The mean size diameter of Liangfu Oral Microemulsion is 16.6 nm. The result of Liangfu Oral Microemulsion′s microorganism limitation test accord with Regulationchinese pharmacopoeia standard. The result of determination of bacteria content negative test accord with regulations of Chinese pharmacopoeia standard. Stability property observation results indicated that after it was stored at room temperature for 6 months, Liangfu Oral Microemulsion keeped clarify and transparent condition all the while and there was not stratification, flocculation and demulsification phenomenon. Freezing stability test indicated that Liangfu Oral Microemulsion keeped clarify and transparent condition in 7 days and there was not stratification, flocculation and demulsification phenomenon. Heating-stable test indicated that Liangfu Oral Microemulsion could keep clear and transparent at 40℃and 60℃and there was not stratification, flocculation and demulsification phenomenon. After Liangfu Oral Microemulsion was stored at 80℃for 2 days, there was insignificance turbidness phenomenon. After the sample was placed at room-temperature, stratification phenomenon disappeared. Mechanical stability test indicated the Liangfu Oral Microemulsion could keep clear and transparent after being centrifuged and there was not stratification, flocculation and demulsification phenomenon.3.2.2 Chromatogram column is Diamonsil C18 (4.6 mm×150 mm,5μm). The mobile Phase Is methanol-water(68:32). Flow rate is 1.0mL/min. Detection wavelength is 241 nm. Column temperature is 40℃. These Conditions are suitable for identification qualitatively of cyperas rtundus in Liangfu Oral Microemulsion.3.2.3 Chromatogram column is Diamonsil C18(4.6 mm×150 mm,5μm). mobile Phase is methanol-0.5% H3PO4(58:42). Flow rate is 1.0mL/min. Detection wavelength is 360 nm. Column temperature is 40℃.These conditions are suitable for determination of galangin in Liangfu Oral Microemulsion.3.2.4 Preliminary stability tests indicated that Liangfu Oral Microemulsion was stable in 3 months.3.2.5 To establish the quality standands for Liangfu Oral Microemulsion.3.3 The experimental study results of Liangfu Oral Microemulsion.on pharmacodynamics3.3.1 Liangfu Oral Microemulsion has better anti-inflammatory effect in the models of dimethylbenzene-induced mouse ear swelling and cotton ball granuloma in rats.It′s anti-inflammatory effect was reached dose-dependently.3.3.2 Hot-plate procedure and torsion body method indicated that Liangfu Oral Microemulsion has better analgesiceffect.3.3.3 Liangfu Oral Microemulsion has not influence on intestine propelling motion in normal mice. It can restrain quickening intestinal movement in cold gastric mucosa lesion animal model mice.3.3.4 Liangfu Oral Microemulsion has anti-ulcer action in experimental stress-induced ulcers in rats and cold gastric mucosa lesion animal model mice.3.3.5 Liangfu Oral Microemulsion has inhibiting effects on gastric fluid acidity and pepsin of rats.3.3.6 Liangfu Oral Microemulsion′s optimal dose is 1mL per capit adaily. When the dosage is 1/5 of Liangfu water-paste pills, Liangfu Oral Microemulsion has the drug action equivalent to Liangfu water-paste pills. 3.4 The safety of Liangfu Oral Microemulsion was satisfactory3.4.1 The greatest tolerability experimental study indicated that when the maximum tolerance dose of mice of Liangfu Oral Microemulsion was 840 times of that in human, no toxicity reaction was observed.3.4.2 In long term toxicity test of Liangfu Oral Microemulsion, no toxicity reaction was observed.4 ConclusionLiangfu Oral Microemulsion not only possesses strong points of general microemulsion dosage forms, but also has all pharmaceutical features of a new dosage form of traditional Chinese compound drugs that completely accords with clinical requirements of traditional Chinese medicine. Experimental results have showed that Liangfu Oral Microemulsion has stable physiochemical properties, reliable efficacy, and satisfactory safety. So far, no abnormal reactions have been found in its preclinical research. The results of the present study have also showed that the microemulsion drug carrier system is a very good drug carrier system for renewing traditional Chinese compound drugs, and that the development of Liangfu Oral Microemulsion has set up a new example for developing new dosage forms of traditional Chinese drugs on the nanometer level. The microemulsion techniques still have great potentials in their application in the development of new traditional Chinese compound drugs. It may be said that the microemulsion drug carrier system is of great significance to the modernization of traditional Chinese pharmaceutics.