Research on the World’s Most Valuable Antihypertensive Drugs Based on Patent Analysis

Objective To find out several patented technologies of antihypertensive drugs with the most market value through analysis,and provide a reference for the research and development of enterprises.Methods The most valuable patented technologies of antihypertensive drugs from 2009 to 2019 were analyzed to explore the patent layout and technical characteristics of the main patent applicants,and then the key directions of their research and development were gotten.Results and Conclusion Based on the method of patent analysis,five patents with the most market value are extracted to provide important technical support and market value reference for the research and development of generic drugs or new drugs.

Clinical evidence and potential mechanisms of Chinese medicines for the treatment of diabetic retinopathy

Diabetic retinopathy is one of the main causes of visual impairment and blindness on a global scale. At present, thelimitations of anti-vascular endothelial growth factor agents, steroids, laser photocoagulation, and vitreous surgery haveled to a growing awareness of the role of Chinese medicines in the treatment of diabetic retinopathy. This review firstdescribes the ingredients and characteristics of the formulae including Chinese herbal formulaes, Chinese patent drugsand ancient processed drugs and summarizes the application of Chinese medicines and their mechanisms of action in thetreatment of diabetic retinopathy. Due to the complexity of Chinese medicines, in-depth mechanisms, side effects of herb,and drug interactions need to be elaborated in future research. Chinese medicines have the potencial to protect theresidual eyesight and delay the progression of disease, thereby offering a beneficial, exploitable option in thetreatment/prevention of diabetic retinopathy.

Development of the generic drug industry in the US after the Hatch-Waxman Act of 1984

The key events in the development of the US generic drug industry after the Hatch-Waxman Act of 1984 are systematically reviewed,including the process of approval for generic drugs,bioequivalence issues including“switchability”,bioequivalence for complicated dosage forms,patent extension,generic drug safety,generic substitution and low-cost generics.The backlog in generic review,generic drug user fees,and“quality by design”for generic drugs is also discussed.The evolution of the US generic drug industry after the Hatch-Waxman Act in 1984 has afforded several lessons of great benefit to other countries wishing to establish or re-establish a domestic generic drug industry.

Simultaneous and interference-free determination of eleven nonsteroidal anti-inflammatory drugs illegally added into Chinese patent drugs using chemometrics-assisted HPLC-DAD strategy

In this work, a smart strategy that combines three-way high performance liquid chromatography-diode array detection(HPLCDAD) data with second-order calibration method based on alternating trilinear decomposition(ATLD) algorithm was proposed for simultaneous determination of eleven non-steroidal anti-inflammatory drugs(NSAIDs) illegally added into Chinese patent drugs and health products. All target analytes were rapidly eluted out within 14.5 min under a simple gradient elution. With the aid of the prominent "second-order advantage" of the ATLD algorithm, three HPLC problems, i.e. peak overlaps, unknown interferences and baseline drift, could be mathematically calibrated, and pure signals of target analytes could be extracted out from heavy-interference but information-rich HPLC-DAD data. The average spiked recoveries for all target analytes were in the range of 95.9%–106.4% with standard deviations lower than 7.5%. Validation parameters including sensitivity(SEN), selectivity(SEL), limit of detection(LOD), limit of quantitation(LOQ) and precisions of intra-day and inter-day were calculated to validate the accuracy of the proposed method, quantitative results were further confirmed by the classic HPLC method, which proved that chemometrics-assisted HPLC-DAD analytical strategy was highly efficient, accurate and green for drug-abuse monitoring of NSAIDs in Chinese patent drugs and health products.

Selection of characteristic spectral bands for the analysis by the NIR correlation coefficient method

We analyzed the infrared 0R）-near infrared （NIR） 2D correlation spectra of drugs perturbed by temperature. By identification of functional groups by IR spectrum and by the correlation analysis of IR-NIR spectrum, we identified the characteristic spectral bands that were closely related to the structure of a drug substance of interest. These characteristic spectral bands were relatively less interfered by other ingredients for analysis by the NIR correlation coefficient method. With these characteristic spectral bands, the accuracy of screening illegally added Sildenafil citrate, Tadalafil and Metforrnin hydrochloride in Chinese patent drugs and healthcare products reached about 90%, which met the requirements of rapid screening.

Application of UHPLCMS/ MS method in determining the content of multiingredient in hospital preparations

In the present study, we established an ultra-high pressure liquid chromatography-tandem mass spectrometry （UHPLC-MS/MS） method to simultaneously determine 11 compounds in two hospital preparations （Shegan mixture and Gandi capsules）, including ephedrine, caffeic acid, ferulic acid, rutin, scutellarin, belamcandin, baicalin, baicalein, astragaloside IV, irisflorentin and wogonin. The chromatographic separation was conducted on ZORBAX SB-C18 （2.1 mm×50 mm, 1.8 μm）. Eleven analytes and IS were detected using ESI and MRM combined with positive and negative scanning switch. Caffeic acid, ferulic acid, scutellarin and belamcandin were detected using negative ion mode detection, whereas ephedrine, rutin, baicalin, baicalein, astragaloside IV, irisflorentin and wogonin were detected using positive ion mode detection. The quantification limits of ephedrine, caffeic acid, scutellarin, belamcandin, baicalin, baicalein, irisfiorentin and wogonin were 4.90×10^-3 ng/mL, 7.80 ng/mL, 6.8 ng/mL, 5.3×10^-2 ng/mL, 4.20×10^-3 ng/mL, 4.6×10^-2 ng/mL, 1.44×10^-4 ng/mL, 4.85 ng/mL, 0.23 ng/mL, 3.18× 10^-4 ng/mL and 2.95× 10^-4 ng/mL, respectively. The detection limits of these components were 2.90× 10^-4 ng/mL, 0.77 ng/mL, 2.0 ng/mL, 0.016 ng/mL, 1.3×10^-3 ng/mL, 3.33×10^-4 ng/mL, 4.32×10^-5 ng/mL, 1.46 ng/mL, 0.07 ng/mL, 9.5×10^-5 ng/mL and 8.84× 10^-5 ng/mL, respectively. All calibration curves showed good linearity （R^2〉0.99） within the test range. The RSD values of intra-day and inter-day precision were less than 5%, and the average recovery rates of the 11 components ranged fi＇om 80% to 120%. In conclusion, our newly developed method was simple, rapid, sensitive and accurate. It could be used to determine ephedrine, caffeic acid, ferulic acid, rutin, scutellarin, belamcandin, baicalin, baicalein, astragaloside IV, irisflorentin and wogonin in Shegan mixture and Gandi capsules, which was helpful for the quality control of drugs.