| In this paper,a new type of flexible liposomal granule was prepared by using the extract of the effective parts of the high altitude Tibetan medicine(Russian flavonoids,ESTF).Due to the poor stability,poor solubility of ESTF,low bioavailability,and poor skin permeability,it cannot be applied directly to the skin for treatment of diabetes.The purpose of this project is to use the flexible liposome technology to make the ESTF transfersome to solve and improve the stability,solubility and skin permeability of the drug simultaneously.In order to develop a new type of safe,effective,high bioavailability of the percutaneous medicine for hypoglycemic agents.In this paper,the ESTF flexible liposome preparation process,quality control,initial stability and in vitro transdermal properties are studied,success was reasonable and feasible,the quality is stable and controllable ESTF transfersome.The details are as follows: 1.Establishment of ESTF in vitro analysis method.The method of determination of ESTF by high performance liquid chromatograpHy(HPLC)was studied.The results of methodological verification showed that the established method was accurate and feasible and met the relevant requirements.Selecting glucan column chromatography separation ESTF transfersome and coating of the drug,particle size SepHadexG-50 of 100 ~ 200(including m column chromatography separation ESTF transfersome and coating of the drug,HPLC method to determine content of ESTF,high performance liquid chromatography determination of ESTF content.A short and convenient method for determining the encapsulation rate of ESTF transfersome was established.2.Preparation of ESTF transfersome.The ESTF flexible liposome preparation technology research,the film-ultrasound prepared ESTF transfersome,transfersome encapsulating rate as the index,by single factor experiment and orthogonal experiment design,identified the best prescription of the preparation of ESTF transfersome and the process parameters.Best preparation prescription for lecithin: cholesterol 4:1(w/w),lecithin,ESTF 7:1(w/w),phosphate buffer 15 mL,20 mg,sodium deoxycholic acid in accordance with the prescriptions of said the ESTF lecithin and cholesterol and use a moderate amount of chloroform dissolve and eggplant shaped bottle,in the rotary evaporation apparatus general organic solvent to remove,in tomato shaped bottle bottle walls form a layer of uniform film,using dissolve 20 mg deoxycholic acid sodium phosphate buffer 15 mL will wash the bottle wall film,indirect ultrasonic processing 10 min,a quick.The obtained ESTF transfersome are the equipollent suspension with a pale yellow color.3.Study on the quality evaluation of ESTF transfersome.In the quality evaluation study of the ESTF transfer body,the transfer body morphology identification,particle size and Zeta potential measurement,and the transfer body deformability and acid value were examined.Under the electron microscope,they were spherical or spheroid-like,with a medium size,a particle size distribution of(162.1±6.3)nm,a Zeta potential of(-32.8±7.3)mV,and an ESTF content determination result of three batches of the ESTF transfer body.The average value of the assay was 2.512 mg/mL.An examination of the deformability of the ESTF transfer body was performed,and the results showed that the ESTF transfer body was more deformable than the ordinary liposome.The acid value of the ESTF transfersome was studied.The acid value of the ESTF transferor was measured after storage for 1,5,10,and 20 days at 4℃,25℃,and 40℃.The results showed that the ESTF was at 4℃.The transfer body has no obvious oxidation and has good properties.4.Study on freeze-drying of ESTF transfersome.The ESTF transfersome of freeze drying has carried on the preliminary investigation,investigates the three kinds of different concentrations of sugars,mannitol,glucose,sucrose)protectant for ESTF transfersome freeze-dried samples of different effects,and by comparing before and after the appearance of freeze drying and the envelopment rate after dissolving rate,particle size change rate and PDI group,the rate of change of the minimum sample rate reach 6% mannitol,freeze-dried protective effect is relatively good.Therefore,6% mannitol as the ESTF flexible liposome freeze-dried protectant as freeze-dried protectant can make ESTF transfersome to be well preserved.5.Study on the stability of ESTF transfersome.The stability of ESTF transfersome was studied.Will of ESTF transfersome in 4 ℃low temperature test high temperature 40 ℃,25 ℃at room temperature experiment,experiment and 4000 lx glare.The stability of ESTF transfersome under different temperature conditions and strong illumination ESTF transfersome was investigated.Results showed that the ESTF transfersome in 4 and 25 under the ℃ ℃experimental conditions has good stability within six months,but under the condition of strong light can appear unstable phenomenon of coagulation.6.ESTF transfersome in vitro transdermal and skin irritation experiments.The ESTF transfersome in vitro transdermal experiments,using the rat in vitro transdermal experiment compares the ESTF transfersome with ordinary liposomes in different period the difference between drug osmotic quantity and hold up the skin.Results showed that the ESTF transfersome,compared to the ordinary liposome ESTF transfersome in the osmotic quantity of drugs and the skin hold up all has the obvious advantage,and with the increase of drug delivery time,lipid ESTF flexible advantages are more obvious and illustrate ESTF flexible nano liposome promote ESTF through the skin effect is better than ordinary liposome.Therefore,it is an important foundation to promote the development of ESTF flexible lipid percutaneous systemic administration.In the skin irritant experiment,the ESTF transfersome were applied evenly to the skin of the back of the mouse.After 2,4 and 6 hours,the drug site was observed and no red swelling was observed.It is indicated that the composition of ESTF transfersome does not stimulate or induce allergic reaction to the skin of rats. |
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