| Yixinshu tablets are composed of panax ginseng C.A.,Astragalus membranaceus?Fisch.?Bge,Ophiopogon japonicus?L.f.?KerGawl,Crataegus pinnatifida Bge,Salvia miltiorrhiza Bge,Schisandra chinensls?Turcz.?Baill and Ligusticum chuanxiong Hort.With beneficial effects of supplement qi and restore pulse,invigorate the circulation of blood and nourishing yin and generating body fluid.Modern is used to treat coronary heart disease,angina pectoris,chronic heart failure,etc.According to the current national drug standards,Yixinshu tablets can be prepared by two kinds of granulation technology: traditional wet granulation technology and one-step granulation technology.The granulation technology has a significant influence on the quality and curative effect of traditional Chinese medicine tablets,traditional wet granulation process and one-step granulation process have differences in granulation time,granulation temperature and granule drying method,which may lead to different types and contents of chemical components in Yixinshu tablets,and may also affect the dissolution and release of drugs.Therefore,the methods for determining chemical composition content,fingerprint and dissolution of Yixinshu tablets were studied in this paper,with major component content,fingerprint similarity and dissolution similarity factor as indexes of one-step granulation and traditional wet granulation of two kinds of granulating process benefit heart comfortable piece of quality evaluation,from two aspects of chemical composition and in vitro dissolution to explore different granulating process on the influence of Yixinshu tablets.Objective:1 To establish a method for simultaneous determination of schisandrin,cryptotanshinone,tanshinone ?,and tanshinone ?A in Yixinshu tablets.2 To establish HPLC-VWD fingerprints and HPLC-ELSD fingerprints of Yixinshu Tablets.3 To establish a method for determination of salvianolic acid B in Yixinshu tablets.4 The quality differences of Yixinshu tablets prepared by one-step granulation and traditional wet granulation were evaluated by the content of various indexes,similarity of fingerprints and similarity factors of dissolution as indicators.Methods:1 HPLC method was used,chromatographic column: Agilent 5 TC-C18?2??250 mm×4.6 mm,5?m?,mobile phase:acetonitrile-water?gradient elution?,the injection volume was 10 ?L,the flow rate was 1.0 m L/min,the column temperature was 25 and the detection wavelength ? was 260 nm.2 The HPLC fingerprint of Yixinshu tablets was established by dualwavelength method,chromatographic column: Agilent 5 TC-C18?2??250 mm×4.6 mm,5?m?,mobile phase:acetonitrile-0.02% phosphoric acid water?gradient elution?,wavelength: 0?62 min,280 nm;62?125 min,260 nm.With salvianolic acid B as the reference peak,the fingerprints of 9 batches of yixinshu tablets were determined,and the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System?2012 edition?was used for similarity evaluation,to determine the common peak,and the common peak to confirm the medicinal materials belonging.The HPLC-ELSD fingerprint of Yixinshu tablets was established by evaporative light scattering detection,Chromatographic column:Agilent 5 TCC18?2??250 mm×4.6 mm,5?m?,mobile phase: acetonitrile-water?gradient elution?.detector: evaporative light scattering detection.With ginsenoside Rd as the reference peak,the fingerprints of 10 batches of Yixinshu tablets were determined,and the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System?2012 edition?was used for similarity evaluation,to determine the common peak,and the common peak to confirm the medicinal materials belonging.3 Salvianolic acid B was selected as the index of in vitro dissolution of Yixinshu tablets,paddle method was used,the dissolution medium was 500 m L p H = 1 hydrochloric acid solution,the temperature was 37±5? and the speed was 75 r/min,samples were taken at 10,20,40,60,80,100 and 120 min,each with a sampling volume of 4m L and rehydration is conducted,detection by HPLC method,calculate the cumulative dissolution and draw a dissolution curve.4 According to the content determination method established in "Method 1" and the content determination method of Yixinshu tablets in "Chinese Pharmacopoeia"?2015 edition?,the contents of eight index chemical components in Yixinshu tablets obtained by two granulation processes were determined respectively;According to the fingerprint determination method of Yixinshu tablets established in "Method 2",HPLC-VWD fingerprint and HPLC-ELSD fingerprint of the two kinds of granulation technologies were determined respectively;According to the dissolution determination method of Yixinshu tablets established in "Method 3",the dissolution of Yixinshu tablets obtained by the two granulation processes were measured and the cumulative dissolution curves were drawn.The content of index components,fingerprints and drug dissolution of Yixinshu tablets obtained by two granulations were compared to evaluate the quality of the two granulations.Results:1 HPLC method was established for simultaneous determination of schisandrin,cryptotanshinone,tanshinone ? and tanshinone ?A,the precision,repeatability and stability of the method were all in accordance with the regulations,the concentration of schisandrin,cryptotanshinone,tanshinone ?,and tanshinone ?A showed a good linear relationship with the peak area in the ranges of 2.527?40.432,1.937?30.992,1.328?21.24,2.477?39.624 ?g/m L,and the linear range of schisandrin was Y=15612X-12.147?r=0.9998?,the linear range of cryptotanshinone was Y=49121X-28.802?r=0.9998?,the linear range of tanshinone ? was Y=42086X-1.2291?r=0.9996?,the linear range of tanshinone ?A was Y=42655X-31.23?r=0.9998?.2 HPLC-VWD fingerprint and HPLC-ELSD fingerprint of Yixinshu tablets were established.A total of 25 common peaks were identified in 9 batches of HPLC-VWD fingerprint,and the similarity between the sample and control was above 95%.A total of 34 common peaks were identified in 10 batches of HPLC-ELSD fingerprint,and the similarity between the sample and control was above 97%.3 A dissolution method for salvianolic acid B in Yixinshu Tablets was established,and the cumulative dissolution in 120 min was 80.83%.4 The average contents of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,salvianolic acid B,schisandrin,cryptotanshinone,tanshinone ? and tanshinone ?A in one-step granulation Yixinshu tablets were 0.96?0.85?1.15 ? 9.88 ? 0.77 ? 0.40 ? 0.19 ? 0.55mg/g.The average contents of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1,salvianolic acid B,schisandrin,cryptotanshinone,tanshinone ? and tanshinone ?A in traditional wet granulation Yixinshu tablets were 1.03 ?0.93 ? 1.20 ? 10.78 ? 0.52 ?0.25 ? 0.1 ? 0.25mg/g;The similarity value between one-step granulation Yixinshu tablets and traditional wet granulation Yixinshu tablets by HPLC control fingerprint was 0.990,the similarity value of HPLC-ELSD control fingerprint was 0.992,and the similarity value was greater than 0.990;The f2 similarity factor of the average cumulative dissolution of one-step granulated Yixinshu tablets and traditional wet granulated Yixinshu tablets was 74.34>50.Conclusion:1 The established HPLC method for simultaneous determination of schisandrin,cryptotanshinone,tanshinone ? and tanshinone ?A in Yixinshu tablets is suitable for the quality evaluation of Yixinshu tablets.2 The established HPLC-VWD and HPLC-ELSD fingerprints of Yixinshu tablets are suitable for the quality evaluation of Yixinshu tablets.3 The established method for determination of salvianolic acid B in Yixinshu tablets is suitable for the quality evaluation of Yixinshu tablets.4 Yixinshu tablets prepared by two granulation processes have a great influence on the content of the eight index components measured.Compared with the one-step granulation process,the traditional wet granulation process increased the content of ginsenoside Rg1,ginsenoside Re,ginsenoside Rb1 and salvianolic acid B,and decreased the content of schisandrin,cryptotanshinone,tanshinone ? and tanshinone ?A.The fingerprint similarity evaluation,the similarity values of the HPLCVWD control fingerprint and the HPLC-ELSD control fingerprint were greater than 0.990,indicating that different granulation processes did not significantly affect the main chemical composition of the product.Under the established dissolution conditions,salvianolic acid B dissolution,f2 similarity factor is 74.34> 50,indicating that the dissolution profiles of salvianolic acid B in Yixinshu tablets prepared by the two granulation processes are similar and the dissolution characteristics are basically the same. |
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