| ObjectiveUltrafine granular powder of herbal medicine(UGPHM)refers to a series of Chinese medicine,which is pulverized from decoction pieces into ultrafine powder(UP),and made into dry granular without adding any solid agents.UGPHM is more and more popular in China and comes up with a significant economic value due to its convenient intake and reliable therapeutic efficacy.UGPHM of Astragali Radix(RA)is one of the most popular varieties.Astragali Radix(RA),which is a well-known traditional Chinese herbal medicine,also called Huang Qi in Chinese,is derived from the roots of Astragalus membranaceus(Fisch.)Bge.or Astragalus membranaceus(Fisch.)Bge.var.mongholicus(Bge.)Hsiao.It is a crude drug widely used in China,Japan and Korea.Pharmacological studies and clinical practices demonstrated that Astragali Radix possesses various biological functions,such as anti-inflammatory.The existing research data showed that UGPHM of RA has the same material basis as Decoction Pieces(DP)of RA,and it is effective and safe for clinical use.However,some basic issues such as bioavailability and stability of UGPHM of RA remainds unclear,which hampers it from further development.Therefore,we aim to solve five basic problems of UGPHM of RA,including particle size selection,homogeneity,dissolution,bioavailability,stability in this article,so as to provide basic research data for UGPHM of RA.What’s more,DP of RA was used as a reference material so that we can evaluate the quality and characteristics of UGPHM of RA more secientifically.Also,we hope that it can provide some reference for other varieties of UGPHM to carry out some related research.Method1.Different patical diameters of UP were produced by using jet mill.Then their powder characteristics such as particle diameters,powder morphology,liquidity,hygroscopicity and contents of active ingredients were investigated.2.Ten samples were taken from different locations of bulk DP and UGPHM of RA(the DP used for making UGPHM was the same batch as the bulk DP used in this research),whose active ingredients were determinationed.Also,ten parts of small packages DP of RA were tested.3.Regarding exterior,contents of water,Calycosin-7-O-β-D-glucoside,Astragaloside IV as research indexes,experimental study on influencing factors,accelerated stability test,long term stability test were carried out to evaluate the stability of UGPHM,UP and DP of RA.4.Orthogonal test was used to optimize the solid-liquid ratio,cooking time and cooking times of UGPHM and DP,the solid-liquid ratio,soaking times and soaking temprature of UGPHM was also tested,base on that,the determination of five compositions including astragaloside IV,calycoin-7-O-β-D-glucoside,ononin,calycosin,formononetin from UGPHM and DP of RA at different points in time were studied.Furthermore,the dissolution curves were obtained.The dissolution characteristics of the two Astragali radix forms were also compared in this study.5.The rats were treated with 2.3 g/kg,4.6 g/kg and 7.0 g/kg of UGPHM of RA and DP of RA,and a sensitive UPLC-QQQ-MS method was carried out to detect the blood concentration of astragaloside IV,calycoin-7-O-β-D-glucoside,ononin,calycosin,formononetin.The pharmacokinetic parameters were calculated by the DAS 3.2.6 software.And the relative bioavailability of UGPHM of RA was calculated using the DP of RA as reference reagent.Results1.With the decreasing of particle diameters of Astragali radix ultrsafine powder,both the specific surface area and the moisture increased while the liquidity and yield decreased slightly.Also,the concentrations of the active ingredients increased overall.2.Determination of traditional herbs in bulk ratio of maximum to minimum between 1.59-4.60 times,and the RSD values are between 12.44%-62.69%;the radio of maximum to minimum of small package traditional herbs is between 1.24-2.60 times,and the RSD values are between 8.46%-20.14%;the radio of maximum to minimumbroken of UGPHM is between 1.07-1.13 times,and the RSD values are between 2.55%-3.45%.3.The result of experimental study on influencing factors showed that the high temperature and high humidity have a big influence on moisture and calycoin-7-O-ββ-D-glucoside,and the content of the calycoin-7-O-β-D-glucoside of UP declined the most among the three sorts of slices,the stability of three sorts of slices was DP≈UGPHM>UP.The result of accelerated stability test showed that the moisture of the PE bag packaged UP and DP rose while the content of the calycoin-7-O-β-D-glucoside declined from month to month,and the composite aluminum foil bag packaged UGPHM was stable under the accelerated stability test,the stability of three sorts of slices was UGPHM>DP>UP.The result of long term stability test showed the three sorts of slices was stable,but the moisture of UP and DP still rose more than the UGPHM,the stability of three sorts of slices was UGPHM>DP>UP.4.According to the results,at the decoction conditions of decocted 2 times with solid-liquid ratiol:50 and do not soak before decocting,the dissolution of the five active ingredients from UGPHM at 5-10 min were equal to the DP at 30 min,which were at the decoction condition of decocted 3 times with solid-liquid ratiol:50 and soak 30 min before decocting.But the soaking dissolution of UGPHM can be only 80%-90%equal to the boiling dissolution of DP.5.Using the DP of RA as reference product,the relative bioavailability of astragaloside IV,calycoin-7-O-β-D-glucoside,ononin,calycosin,formononetin of UGPHM of RA has increased 56%,81%,14%,78%,94%respectively in high doses;167%,79%,46%,141%,78%respectively in medium doses;and the relative bioavailability of astragaloside IV,calycoin-7-o-β-D-glucoside,ononin has increased 120%,23%,26%respectively in low doses.Conclusions1.An appropriate degree of superfine grinding can promote the dissolution of active ingredients of Astragali radix,but a smaller particle diameters will lead to a lower yield,which is impractical for production.Therefore,a comprehensive survey is needed for the choose of the best particle diameters in production.2.The uniformity of UGPHM of RA is significantly better than the DP of RA,which is good for the clinical efficacy.3.In order to ensure the quality stability,the DP of RA which was packaging by PE needs to provide for its validity under the condition of room temperatrue.Meanwhile,the stability of UP of RA was not so good whatever the condition is,therefore,the suitable package,storage conditions and time was needed to find out for the stable storage.On the other hand,making UP into UGPHM can solve the problem of appearance instability which was caused by the large specific surface area.What’s more,the use of composite aluminum foil bag can successfully cut the air and moisture off and avoid the moisture absorption and oxidation.As a result,the UGPHM is stable under the condition of accelerated and long-term tests(12 months).Therefore,a longer term tests is needed to confirm the period of validity of UGPHM of RA.4.The micronization of RA can reduce the soaked time before decocting,the decoction time and decoction times,makes a great contribution to the dissolution of effective components.On the other hand,soaking can dissolve most of the active components of the UGPHM,which shows that after cell broken,the utilizaton of herbs can improve greatly.Also,it provides a more convinient way for clinical application.5.The bioavailability of the active components of UGPHM of RA could be significantly better than DP of RA. |
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