Studies On Colon-specific Osmotic Pump Capsules Of Compound Danshen

Coronary heart disease is a clinically common serious cardiovascular disease,often showing different types,such as angina,myocardial infarction,sudden death and so on,and it had gradually become a common diseases and frequently-occurring disease which was serious threat to the health of the elderly.Compound Danshen prescription are composed of three medicinal herbs,namely Radix Salviae Miltiorrhizae,Radix Notoginseng and Borneolum which have the effects of promoting blood circulation and removing blood stasis and regulate the flow of vital energy and remove obstruction toit and relieving pain,the Compund Danshen commonly used to treat coronary heart disease as traditional Chinese medicine preparations for in our country,after years of clinical trials,the curative effect is remarkable.The current commercial Compound Danshen preparation generally have disadvantage,such as poor compliance,poor synchronization between the active ingredients,some of the active ingredients low bioavailability.Therefore,this aims to develop a new dosage form to improve these shortcomings.Objective:To developing a compound Danshen colon-specific osmotic pump capsule which can improve patient compliance,achieve long-term controlled release and simultaneous release of the active ingredients in the compound Danshen,and improve oral bioavailability of Radix Notoginseng.Methods:（1）A UPLC method for the determination of compound Danshen colon-specific osmotic pump capsule in vitro were established,which were determine simultaneously salvianolic acid B,tanshinone IIA and notoginsenoside R₁,ginsenoside Rg₁,Rb₁,Re,Rd,（2）Taking the cumulative release and similar factors as indexes,the dosage of Na Cl,the type and dosage of PEO and the dosage of HP-β-CD in the capsule core of osmotic pump were investigated.（3）Investigate the release characteristics of self-made compound Danshen colon-specific osmotic pump capsules and study the influence of release conditions on drug release,explore drug release regularity and drug release mechanism.（4）A UPLC-MS/MS method for the quantitative analysis of compound Danshen in vivo were established and study the pharmacokinetics of the compound danshen colon-specific osmotic pump capsule in Beagle dogs.Results:（1）The in vitro method of quantitative analysis of compound Danshen by UPLC was simple,accurate and reliable.Under the selected chromatographic conditions,the seven main components of compound danshen prescription had good resolution and good peak shape.（2）In the single factor study,the colon-specific osmotic pump capsule optimal prescription process is as follows:the capsule shell is pre-laboratory self-made,capsule core prescription:Radix Salviae Miltiorrhizae extract 174 mg,notoginseng extract 32mg,borneol 8 mg,Na Cl 100 mg,PEO wsr-N10 20 mg,and HP-β-CD 20 mg.The colon-specific osmotic pump capsules were prepared,and the capsules achieve the effect of colonic colonization,multi-component simultaneous release and controlled release.（3）The obtained compound Danshen colon-specific osmotic pump capsule basically free from the impact of speed and release device in vitro release,the release mechanism is through the release of small holes uniform speed drug release by the capsule osmotic pressure difference within and outside the capsule shell,and drug release behavior consistent with the zero-order equation,with better positioning controlled release effect.（4）Pharmacokinetic study in Beagle dogs showed that the plasma concentration of seven index components of the compound Danshen in the colon-specific osmotic pump capsules were relatively stable compared with that of common capsules and colonic capsules.And the T_maxand MRT were prolonged to different extents,showing obvious controlled release effect.At the same time,the bioavailability of effective components in the prescription was also increased.Conclusion:The compound Danshen colon-specific osmotic pump capsules improve the patient’s compliance,achieve a variety of active ingredients in the side of the release and improve the oral bioavailability,and it laid out a solid foundation in the aspect of the preparation of osmotic pump formulations for chinese herbal medicine compound preparation,while promoting the modernization of traditional Chinese medicine preparations.