A Study On The Placebo Of Huolin Shengji Granules Used In Clinical Trials

Since 2007,placebo control was gradually introduced into clinical trials of traditional Chinese medicine(TCM)compound formulation with the aim of evaluating superiority for test formulation.At present,because of being difficult to be prepared,evaluated,and quality control and different from chemical drug placebo,there are few studies on TCM placebo.Therefore,in the study,the Huolingshengji(HLSJ)granules were used as a model to explore the technical problems of the TCM placebo during the development.Purpose: According to the Criterions for the Quality Control of Clinical Trial of Drugs and the General principles of clinical research on new drugs,the requirements of the relevant based on the four basic principles about the safety,similarity,applicability,and controllability.For a TCM formula of HLSJ granules,which was used to treat Amyotrophic lateral sclerosis(ALS).And,the study was to conduct the research of HLSJ granules placebo on clinical trials.Methods: Firstly,the prescription of HLSJ granules was analyzed that included the Prescription information,preparation technology,solid and liquid states of the characteristic attributes by classical scoring evaluation to conduct sensory description.Secondly,in aspect of the dosage form attributes,the visual feature attributes,flavor and taste attributes,the methods of Malvern Laser Particle Size Analyzer?infrared moisture analyzer,Powder comprehensive characteristic tester,color card,electronic tongue,and scoring evaluation combined with the angle cosine algorithm were used to establish similarity evaluation methods for placebo and HLSJ granules.Based on the prescription of HLSJ granules,physical properties of accessory,appearance,flavor and taste,the filler accessory,pigment,and flavor substances were screened,respectively.Besides,the preparation molding process of placebo was investigated.Finally,the quality standard study and preliminary safety evaluation of placebo were conducted under the guidance of the principles of the safety,similarity,applicability,and controllability.Results: The Huolingshengji formula is a kind of brown granules with slight smell of traditional Chinese medicine.And,taking the three kinds of attributes of the test preparation as a reference,the similarity of the related attributes between placebo and HLSJ granules was evaluated by means of scoring evaluation and objective evaluation.After system screening,the prescription of Huolingshengji granule placebo was as follows: Huolingshengji extract,dextrin,maltodextrin,caramel color,?-carotene,sunset yellow,gardenia Yellow,sucrose octaacetate,orange peel extract,mume fructus extract,mint essence,chrysanthemum essence,and traditional Chinese medicine essence.All the accessory were colored and shaped by the dry granulation.In the quality standard study about the applicability research,the quantitative results of Epimedii Folium and Corni Fructus of placebo was determined by the high performance liquid chromatography did not exceed the 10% the test formulation,and the Astragali Radix,Atractylodis Macrocephalae Rhizoma,and Poria had no obvious correspounding spots in the thin-layer chromatography.The establishment of the scoring evaluation similarity result between the HLSJ granules and placebo was0.9936.And,the objective evaluation results of the characteristic attributes of dosage form and taste were 1.000 and 0.8616,respectively.The RGB,HSV,and gray scale values were used as the evaluation indexes for the visual feature attributes and the corresponding similarity evaluation results for the placebo granules and solutions were all close to 1.According to the relevant standards,the daily dosage of accessory that of ?-carotene,sunset yellow,gardenia Yellow,sucrose octaacetate used in the study was 8mg,2mg,1.2mg and 1.5mg,respectively,meeting the safety standard limit.Therefore,a draft quality standard for Huolingshengji granule placebo in clinical trials was formulated.Conclusions: In this study,the Huolingshengji granules placebo and the test preparation had high similarity in appearance,color,smell,and taste.The prepared placebo was reasonable prescription composition,feasible preparation technology,and controllable quality,which could be used for the clinical trial of HLSJ granules.