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Preparation of Transdermal Danshensu Ultradeformable Nanoliposomes Matrix Diffusion Controlled Delivery Systems

Author: WuHuanLin
Tutor: ZhangYangDe
School: Central South University
Course: Biomedical Engineering
Keywords: Coronary heart disease(CHD) Danshensu ultratlexible nanoliposomes System of administration percutem
CLC: R283
Type: PhD thesis
Year: 2008
Downloads: 423
Quote: 2
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Abstract


Danshensu is the major water-solubility compound in Salvia miltiorriza Bunge,which is included in Chinese medicinal herbs of labiatae plant.The modern researchs prove that,it has many pharmacological functions such as protecting cardiac muscle cells, expanding aeteria coronaria,restraining thrombogenesis and resisting artherosclerosis.It is beneficial to heart,and can be clinically used to cure coronary heart disease(CHD)and angina pectoris(AP).Nanometer lipid body(LB)technique is a kind of medicinal trager technique,has so many fine characteristics,such as fitting degradation in vivo,degradation,no immunogenicity,and it could wrap up the two kinds of medicines that conclude water solubility and liposolubility,it also could protect the enveloped medicines and reduce the dosage of medicine, modify to produce the initiative targets.Meanwhile,the construction features of lipid bimolecular leaflet in lipid body determine the fine osmolarity anti the lipid barrier in osmolarity.The new generation lipid body-ultratlexible nanoliposomes,because of its deformability,it profits to pass epidermis barricade,so it could enter the further deep layer of skin, the osmolarity is better.So that we apply the ultratlexible nanoliposomes to the percutem dministration system,then we manufacture the carrying drugs ultratlexible nanoliposomes that possesses fine characteristics of penetrating skin,it would be able to enlarge the medicine scope which is percutem administration overwhelmingly.This research manufactures the carrying drugs ultratlexible nanoliposomes that possesses fine characteristics of penetrating skin through optimization of different membrane materials,prescriptions and tecniques.And also,we put the preparation of the skin tabellae adhaesivus Danshinol of carrying drugs ultratlexible nanoliposomes that possesses fine characteristics of penetrating skin of the type of controlled release that is treated coronary heart disease and angina pectoris as the research cut-in point.We make the skin tabellae adhaesivus Danshino of controlled release of the stable dosage form,the rate of envelop,the degree of release and the fine function of percutaneous absorption.At last,we hope to form the new methods of manufacturing praeparatum that the active component in traditional Chinese medicine administering percutem,and it make the important foundation of promoting the manufacturing praeparatum that the active component in traditional Chinese medicine administering per cutem.The primary part of essay applys the single factor experiments,puts the rate of envelop as index,we investigate in the process of preparation, the effect of the density of phospholipid,the dosis of accessories in long circulation,the dosis of flexibility accessories on preparation of Ultraflexible Nanoliposomes of Danshensu.According to the results,we investigating three main influential factors,including the volume ratio of soybean lecithin and cholesterin(A),the volume ratio of cholesterin and surface acting agents(B),the dosage ratio of lecithin and surface acting agents(C).Each factor is taken three levels,through the orthogonal design experiments,we make the screening of the crafts and prescriptions of preparation on Ultraflexible Nanoliposomes of Danshensu.Combination of considering all round of factors,we eventually defined the best prescription is the dosis ratio of the lecithin of soya bean and cholesterin is 5:1,the dosage ratio of cholesterin and surface acting agents is 1:1,the dosage ratio of lecithin and surface acting agents is 1:1.In the prepared with optimized crafts of Ultraflexible Nanoliposomes of Danshensu,the particle diameter is distributed uniformity,the mean diameter is 121.07nm,the average envelop ratio is(45.35±3.49)%.The second part of essay is put the acrylic resins as the principal agent, add amber as cross linking agent in acrylic resins,add citric acid tri-ethyl ester as elasticizer,we make sure the fundamental compositions of Ultraflexible Nanoliposomes of Danshensu are①0.4g acrylic resins,②0.11-0.33g citric acid tri-ethyl ester;③0.04-0.062g succinic acid;④5%Laurocapram;⑤10%Suspension of Ultraflexible Nanoliposomes of Danshensu.We fix the weight of acrylic resins in prescription,and divide the weight scope of tri-ethyl ester and succinum to 12 levels,then prepare the patch each.At the same time,we make the quality evaluation through putting the medicine content,initial viscous force,keeping viscous force and constancy of patch as index.And in this foundation,we investigate the dosage of tri-ethyl ester and succinic acid the two main influencing factors through putting the viscous force and the keeping viscous force as index,and each factor is get two levels,we optimize the prescription of patch with the experiment of orthogonal design.At last, the results indicate that,the best prescription of patch is 0.4g acrylic resins,0.23g citric acid tri-ethyl ester,0.054g succinic acid,the contents of suspension of Ultraflexible Nanoliposomes of Danshensu and Laurocapram are 10%and 5%respectively.The third part of essay is through the high efficiency liquid chromatography,we make the experiments of extraorgan penetrating skin and releasing drugs and determine the degree of releasing in extraorgan.It is to investigate the skin permeation rate and the performance of releasing drugs in extraorgan.The results of experiments in extraorgan penetrating skin and releasing drugs show the quantity of accumulated penetrating skin of drugs in 24 hours is 206±20μg·cm~2,and the experiments of vitro releasing with the patch of Ultraflexible Nanoliposomes of Danshensu indicates that the curve of vitro releasing meets Higuchi equation within 24 hours with a significant slow-release effect.In the fourth part of essay,we utilize intravenous injection of hypophysin to cause the animal model that rats have the acute myocardial ischemia(AMI),and make model in applying to ligate the left anterior descending coronary artery of rats to cause heart muscle ischemical reperfusion injury.We observe the patch of penetrating skin in Ultraflexible Nanoliposomes of Danshensu protecting cardiac muscles of ischemia and postischemic reperfusion damage.The experimental results of the ischemia myocardial preservation with this patch indicate that.we observe the cardiac muscle cell membrane complete in the group of drugs patch with the electron microscope,the structure of mitochondria is essential clear and slightly swelling,glyc-element particles increase obviously.The experimental results of the postischemic reperfusion damage in cardiac muscles of preservation with this patch indicate that, the group of patch has no obvious improvement arrhythmia of irrigatation again,but coold significantly contract the scope of myocardial infarct caused of ischemia long time afterward.

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CLC: > Medicine, health > Chinese Medicine > Of Pharmacy > Chinese medicine processing,preparation
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