[Structure-activity relationship of coptis alkaloid bitterness inhibited by mPEG-PLLA].

Inhibition of bitterness is a significant measure to improve the compliance and clinical efficacy of traditional Chinese medicine(TCM) decoction. According to the characteristics of TCM decoction, such as high dispersion of bitterness components, multi-component bitterness superposition and strong instantaneous stimulation, the research group put forward a new strategy to inhibit bitterness in the early stage based on the self-assembly characteristics of amphiphilic substances in aqueous solution, in order to reduce the distribution of bitterness components in real solution and achieve the purpose of bitter-masking. It was found that the bitter-masking effect of amphiphilic substances was different on the bitter compounds of various structures. Therefore, it was speculated that there might be a certain relationship between the bitter inhibition effect and the substrate structure. In this paper, the interaction between mPEG-PLLA and five bitter alkaloids(bamatine, jatrorrhizine, berberine, epiberberine and coptisine) in Coptidis Rhizoma was studied to explore the effect of substrate structure on the inhibition of bitterness. The sensory test of volunteers was used to determine the bitter-masking effect of mPEG-PLLA on the decoction of Coptidis Rhizoma and its main bitter alkaloids. The molecular docking and molecular force field were applied to locate the bitter groups and the bitter-masking parts. The relationship between the bitter strength and the structure was analyzed by the surface electrostatic potential of the bitter alkaloids, and the correlation between the bitter-masking effect and the structural parameters of the bitter components was explored by factor analysis, so as to clarify the structure-activity relationship of mPEG-PLLA in masking the bitterness of coptis alkaloids. It was found that mPEG-PLLA had significant taste masking effect on the decoction of Coptidis Rhizoma and five alkaloids. The masking effect was obviously related to the structure of different alkaloids: the effect increased with the increase of the number of hydrogen donors, rotatable bonds, molecular weight, and hydrophobicity, and decreased with the increase of surface electrostatic potential, electrophilicity and binding energy with bitter receptors. In this study, the influence of alkaloid structure of Coptidis Rhizoma on the butter-masking effect of mPEG-PLLA was preliminarily elucidated, providing a scientific basis for better exerting the bitter-masking effect of amphiphilic block copolymers.

Amphiphilic Block Copolymers: A Novel Substance for Bitter-Masking in Aqueous Solutions.

It is a challenging task to suppress the bitterness of liquid preparations, especially for children. Bitter molecules are highly dispersible in liquids, leading to a strong and instant stimulation of the bitter receptors. At present, there is no effective way to correct this issue except for adding sweeteners, resulting in an unsatisfying taste. Based on the three-point contact theory, which is a universally accepted mechanism of bitterness formation, a new idea and application of amphiphilic block copolymers (ABCs) for bitterness suppression was proposed for the first time. We found that ABCs could widely inhibit the bitterness of four typical bitter substances. The mechanism is that ABCs self-assemble to form association colloids, which attract bitter components and reduce their distribution in the molecular form in solution. The bitter components were demonstrated to automatically embed in the spiral hydrophobic cavity of the hydrophobic chain of the ABCs, and their special interaction dispersed the positive electrostatic potential of bitter groups. The combination did not affect the pharmacokinetic parameters and pharmacodynamics of bitter drugs. These findings highlight the novel application of ABCs for the inhibition of bitterness and illuminate the underlying inhibition mechanisms.

[Optimized model for formulation prescription of traditional Chinese medicine buccal tablets based on temporal dominant description of sensations combined with multivariate statistical analysis:an example of Compound Caoshanhu Buccal Tablets].

The taste is the key to the research and design for formulation prescription of traditional Chinese medicine buccal tablets( TCMBTs). TCMBTs are dissolved in the oral cavity in parallel with the release of the drug,providing a sufficient " time window" for the perception of various basic taste,tactile and retention. The overall taste is the result of competitive inhibition,comprehensive superposition and dynamic change of multiple tastes. Traditional evaluation methods rely mostly on recalled experience score,difficult to reflect the dynamic changes of taste for buccal tablets. Therefore,it is urgent to establish a new optimized model for taste evaluation and formulation prescription according to the formulation characteristics of TCMBTs. To this end,this paper proposed for the first time to construct a research method for the optimal formulation of TCMBTs based on temporal dominant description of sensations combined with multivariate statistical analysis: the sensory test of volunteers was carried out by temporal dominant description analysis method,and elements separation was conducted for the time and taste in the process of inclusion to form a temporal dominant descriptive score of multi-time points and multi-sensory attributes. Finally,the optimal formulation was obtained by multivariate statistical analysis. Taking the formulation prescription of Compound Caoshanhu Buccal Tablets as an example,the research ideas of this method were explained,and the optimal formulation prescription was obtained as follows,Glabrous Sarcandra Extract of 20. 0 g,mannitol of 24. 0 g,microcrystalline cellulose of 12. 0 g,aspartame of 1. 0%,menthol of 0. 7%,and menthol oil of 0. 7%. This study provides a new method for the taste evaluation and formulation research of TCMBTs,providing a new idea for the fine manufacturing and innovative development of TCM buccal tablets in the new era.

Study on the stability control strategy of Triphala solution based on the balance of physical stability and chemical stabilities.

Triphala is a well-known prescription in Indian Ayurveda and TCM medicine for its great effect on gingivitis and hyperlipidemia. However, its solution is unstable for the containing of excessive polyphenol, leading to the production of sediment in the short term and the decrease of efficacy. Based on the analysis of sediment formation, a novel control strategy is proposed. To conduct the analysis, the sediment formation was recorded for a consecutive five days. The changes in the composition of the supernatant and the sediment were studied by the HPLC profile analysis. The main components of the sediment were identified as corilagin, ellagic acid and gallic acid, and the amount of ellagic acid sediment increased with the storage time. Then, with a series of pH status adjustments of the Triphala solution, the physical and chemical stabilities were acquired by Turbiscan and HPLC respectively. The results showed that as the pH value increased, so did the physical stability, but the particle size and TSI of the association decreased. While the fingerprint of chemical profile similarity decreased, so did the chemical stability. Combining physical and chemical stability parameters, an equilibrium point was found out. When the pH value was adjusted to 5.0, both the physical and chemical stabilities were better: the verification test showed that the sedimentation inhibition rates on the 3rd, 5th,10th and15th days were 41%, 55%, 41%, and 23%, respectively. This manuscript provided a new control strategy that will pique pharmaceutical and food development engineers' interest and trigger research ideas controlling the quality of decoction.

Screening for the anti-inflammation quality markers of Xiaojin Pills based on HPLC-MS/MS method, COX-2 inhibition test and protein interaction network.

Nowadays, breast disorders seriously affect women's health in an increasing number. In China, Xiaojin Pills are commonly used in the treatment of breast diseases. Doctors have concluded that the combined use of Xiaojin Pills with conventional therapy can significantly improve the efficacy with fewer side effects. However, the prescription of Xiaojin Pills is complicated and their quality control methods cannot completely ensure the quality of Xiaojin Pills. On the basis of its mechanism, our study combined chemical evaluation and biological evaluation to identify the anti-inflammatory markers of Xiaojin Pills. In this manuscript, 13 compounds in Xiaojin Pills were quantified. At the same time, the cyclooxygenase-2 inhibition rates of different Xiaojin Pills were measured and the possible markers were screened by spectrum-effect relationship. Further, anti-inflammatory activities of markers were verified and protein interaction network was analyzed, identifying the components of Protocatechuate, Beta-Boswellic acid and Levistilide A as the anti-inflammatory quality markers of Xiaojin Pills. We hope our studies can provide a scientific theoretical basis for accurately quality control of Xiaojin Pills and reasonable suggestions for pharmaceutical companies and new ideas for the quality control of other medicines.