Synthesis of 5-methyl-2-(2,4,4,7-tetramethylchroman-2-yl) Phenol as an Impurity in Thymol

[Objectives] To optimize the preparation process of 5-methyl-2-(2,4,4,7-tetramethylchromanyl) phenol(impurity C) and the liquid phase determination method of the impurity, and to provide an important basis for the establishment of material methods and quality control of thymol. [Methods] The 4,7-dimethylcoumarin as the starting material was hydrolyzed by potassium hydroxide to obtain the substance II 5-methyl-2-(1-propylene-2-yl) phenol, and then purified and treated with hydrochloric acid to obtain a pale yellow solid. High-purity main peak was obtained by high-performance liquid phase method, and it was identified as impurity C by ~1H-NMR measurement and spectrum analysis. [Results] After the method was optimized, the synthesis route to the impurity C was simple, and the purity of impurity C was high. The obtained impurity C was confirmed by ~1H-NMR to be a compound 5-methyl-2-(2,4,4,7-tetramethylchromanyl) phenol. The liquid phase detection method was successfully established to identify the compound. [Conclusions] The optimized method is easy to control and the impurity C has high purity and it is expected to provide quality assurance for the study of related substances in the quality control of thymol.

Trends of consumption and expenditure of antibacterial traditional Chinese medicine in secondary and tertiary hospitals in China:an analysis of pharmaceutical sales data,2011–2015

Traditional Chinese medicines(TCMs)are commonly used in China,and some of them have been proved to be effective against infection caused by certain pathogenic bacteria.In the present study,we aimed to describe the trends of antibacterial-effect traditional Chinese medicine(AeTCM)consumption and expenditure in secondary and tertiary hospitals in China using pharmaceutical sales data from January 2011 to December 2015.Aggregated monthly surveillance data on AeTCM sales in China’s hospitals were retrospectively analyzed.Population weighted daily define doses,which are the recommended daily amounts based on dosage regimen recommended in the manufacturers’instructions,were adopted.The AeTCM consumption was expressed in DDD per 1000 inhabitants per day(DID).The AeTCM expenditure was expressed in US dollars.A compound annual growth rate(CAGR)was used to describe the growth of AeTCM consumption and expenditure.A total of 1293 AeTCMs were matched and analyzed from 468 tertiary hospitals and 114 secondary hospitals from 28 provinces.The total AeTCM consumption and expenditure demonstrated a significant upward trend during the study period from 4.07 DID to 6.82 DID with a CAGR of 13.75%,and 839.75 million US dollars to 1276.82 million US dollars with a CAGR of 11.04%,respectively.Compared with eastern provinces,the consumption of AeTCMs was higher in the central and western provinces.Parenteral AeTCMs accounted for 7.20%of the total Ae TCM consumption,but nearly 45%of the total AeTCM expenditure.The AeTCM use in China demonstrated a rapid growth,which could be the result of the substitutional effect from antimicrobial stewardship and brought a potential risk of overuse.More studies are needed to further explore the potential efficacy of AeTCMs as an alternative approach towards infection treatment and to help confine antimicrobial resistance.

Engineered Spindles of Little Molecules Around Electrospun Nanofbers for Biphasic Drug Release

Biphasic drug release is a popular advanced drug controlled release profle that has been drawing increasing attention from many felds.Electrospun nanofbers and their derivatives can be act as a strong platform for developing biphasic release dosage forms.In this study,a modifed coaxial electrospinning was implemented,in which little molecule solutions that contain a drug ibuprofen(IBU)and polyethylene glycol(PEG)were exploited as a sheath fuid to surround the core solutions composed of polymer ethyl cellulose(EC)and IBU.The prepared nanofber-based structural hybrids,i.e.,engineered spindles-on-astring(SOS)products,were successfully created and subjected to a series of characterizations.Scanning electron microscopy and transmission electron microscopy results showed the engineered SOS structures.IBU and the carriers EC and PEG had good compatibility,as suggested by X-ray difraction and Fourier transform infrared spectroscopy assessments.In vitro dissolution tests verifed that the SOS products were able to provide a typical biphasic release profle,releasing 40%of the loaded IBU within 1 h in an immediate manner in the frst phase,and the rest of the IBU in a sustained manner in the second phase.A combined mechanism of erosion and difusion is proposed for manipulating the IBU molecule release behaviors.