Recently, diffusion models have emerged as a promising paradigm for molecular design and optimization. However, most diffusion-based molecular generative models focus on modeling 2D graphs or 3D geometries, with limited research on molecular sequence diffusion models. The International Union of Pure and Applied Chemistry (IUPAC) names are more akin to chemical natural language than the Simplified Molecular Input Line Entry System (SMILES) for organic compounds. In this work, we apply an IUPAC-guided conditional diffusion model to facilitate molecular editing from chemical natural language to chemical language (SMILES) and explore whether the pre-trained generative performance of diffusion models can be transferred to chemical natural language. We propose DiffIUPAC, a controllable molecular editing diffusion model that converts IUPAC names to SMILES strings. Evaluation results demonstrate that our model outperforms existing methods and successfully captures the semantic rules of both chemical languages. Chemical space and scaffold analysis show that the model can generate similar compounds with diverse scaffolds within the specified constraints. Additionally, to illustrate the model's applicability in drug design, we conducted case studies in functional group editing, analogue design and linker design.

Progesterone is currently the first-line drug for clinical treatment and prevention of threatened abortion and habitual abortion. However， due to its special chemical structure， its solubility is low， which limits its clinical application. Therefore， the new technology and new dosage form of progesterone solubilization preparation is an important direction of its research and development. In this paper， the research progress of progesterone solubilization preparation technology in recent years is reviewed. It is found that the water solubility of progesterone can be enhanced by solid dispersion technology， inclusion technology， micronization， nanocrystallization （ including nanosuspensions， polymer micelles， nanoparticles， etc. ）， liposome technology， self- emulsification， cocrystal technology， and 3D printing. Eight technologies are used to increase the solubility of progesterone， improve its bioavailability and reduce its toxic and side effects， to serve the clinic better.

Objective To explore the preventive and therapeutic effects of Caryopteris incana decoction in a rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome.Methods Sixty healthy specific pathogen-free SD female rats were randomly divided into six groups of ten rats each:normal group,model group,ibuprofen group,C.incana high-dose group,C.incana medium-dose group,and C.incana low-dose group.All groups except the normal group were treated with cold stimulation combined with estradiol benzoate and oxytocin to establish a rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome.On the fifth day of modeling,the rats were intragastrically administered the study drugs for 10 days.Their symptoms were observed and recorded.The writhing response and hemorheological indices were measured.The serum levels of TXB2,6-keto-prostaglandin F1α(6-Keto-PGF1α),estradiol(E2),and progesterone(PROG)were measured.Additionally,the levels of prostaglandin F2α(PGF2α),prostaglandin E2(PGE2),nitric oxide(NO),and calcium(Ca2+)in the uterine tissues were measured.The organ indices of the uterus and ovary were calculated,and histopathological changes were observed.Results Compared with the normal group,the rats in the model group showed obvious symptoms of cold coagulation and blood stasis syndrome and writhing reaction.The morphology of uterus and ovary showed obvious hyperplasia,inflammation,edema and other lesions.The plasma viscosity,packed cell volume and whole blood viscosity were significantly increased(P＜0.01).The serum levels of thromboxane B2 and E2 and the E2/PROG ratio were significantly increased(P＜0.01),the levels of 6-Keto-PGF1α and PROG were significantly decreased(P＜0.01).The uterine index and ovarian index were significantly increased(P＜0.01).The levels of PGF2α and Ca2+and the PGF2α/PGE2 ratio in uterine tissue were significantly increased(P＜0.01),while the levels of PGE2 and NO were significantly decreased(P＜0.01).Compared with the model group,Caryopteris incana significantly improved the symptoms of model rats,improved the morphological lesions of the uterus and ovary,prolonged the latency time of the writhing reaction,and reduced the number of writhing episodes(P＜0.01);significantly reduced the plasma viscosity,packed cell volume,and whole blood viscosity(P＜0.01);significantly reduced the serum levels of TXB2 and E2 and the E2/PROG ratio,increased the serum levels of 6-Keto-PGF1αand PROG,and reduced the uterine and ovarian indices(P＜0.01,P＜0.05);significantly reduced the levels of PGF2αand Ca2+and the PGF2α/PGE2 ratio in uterine tissue(P＜0.01,P＜0.05);and significantly increased the levels of PGE2 and NO in the uterine tissue(P＜0.01).Conclusions Caryopteris incana decoction can effectively improve the clinical symptoms of primary dysmenorrhea in rats with cold coagulation and blood stasis syndrome,and it has a good control effect.Its mechanism may be correlated with the levels of TXB2,6-Keto-PGF1α,E2,and PROG in serum and PGF2α,PGE2,NO,and Ca2+in uterine tissue.

OBJECTIVE To prepare progesterone-2-chloro-4-nitroaniline cocrystal （CNA） so as to improve the solubility of progesterone and primarily evaluate the safety of the progesterone cocrystal in vivo. METHODS Using progesterone as the main body and CNA as the ligand， progesterone-CNA cocrystal was prepared with solvent evaporation method. The cocrystal was characterized by X-ray single crystal diffraction， X-ray powder diffraction （XRPD）， differential scanning calorimetry （DSC） and Fourier transform infrared spectroscopy （IR）. The dissolution rate of cocrystal was compared with those of progesterone and physical mixture. Forty-eight female KM mice were randomly divided into normal group （phosphate buffer containing 0.1% dimethyl sulfoxide）， progesterone group （16 mg/kg）， CNA group （9 mg/kg）， progesterone-CNA cocrystal low-dose， medium- dose and high-dose groups （6， 12.5， 25 mg/kg）， with 8 mice in each group. They were given relevant medicine/solvent intramuscularly， once a day， for consecutive 14 d. The safety of cocrystal was evaluated primarily by determining/observing the changes in body weight， organ index， tissue morphology， blood routine indicators， and liver and kidney function indicators. RESULTS The new crystal structure in the X-ray single crystal diffraction results， the new characteristic peak in the XRPD pattern， the change of melting point in the DSC results， and the change of the characteristic peak position in the range of 3 500- 2 750 cm－1 and 1 700-1 250 cm－1 in the infrared spectrum all Δ 基金项目国家重点研发计划项目（No.2022YFC3502100） indicated that progesterone-CNA cocrystal was successfully ＊第一作者 硕士研究生 。研究方向 ：药物制备技术与工艺 。 prepared， and the dissolution rate of cocrystal was more than E-mail：SWB_1221@163.com # 通信作者教授，硕士生导师，博士。研究方向：药物制备技术与 twice that of the progesterone raw material drug. The results of 工艺。E-mail：wuxx-415@126.com in vivo safety experiments showed that the mortality rate of all 中国药房 2023年第34卷第13期 China Pharmacy 2023 Vol. 34 No. 13 · 1567 · groups was zero. Compared with normal group， uterine indexes of mice in progesterone group and progesterone-CNA cocrystal groups were significantly increased （P＞0.05）， and endometrium was also thickened； there was no statistical difference in the changes of body mass， liver and kidney function， liver index， kidney index， the number of leukocyte， lymphocyte and neutrophil in routine blood test among those groups （P＞0.05）， and the morphology of liver and kidney tissue has also no significant difference. However， the number of plasma red blood cells in the progesterone group decreased significantly （P＜0.05）， and there was no statistical significance in the number difference of red blood cells among progesterone-CNA cocrystal groups （P＞0.05）. CONCLUSIONS The progesterone-CNA cocrystal is successfully prepared with good safety in vivo， which significantly improve the solubility of progesterone.

OBJECTIVE：To study the prot ective effects of crocin （CR）against triptolide （TP）-induced visceral organ injury in mice，and to provide reference for the studying TP compatibility and detoxification. METHODS ：Fifty mice were randomly divided into normal group ，TP low-dose and high-dose groups （i.e. TP-L group ，TP-H group ，with 300，600 μg/kg），TP low-dose and high dose combined with CR groups （i.e. TP-L+CR group ，TP-H+CR group ，with 300 μg/kg TP+100 mg/kg CR ，600 μg/kg TP+ 100 mg/kg CR ），with 10 mice in each group. Except for normal group ，other groups were given relevant medicine intragastrically ， once a day ，for consecutive 7 d. The body weight of mice was weighted every day ，and their death was recorded. After last administration，the mice were sacrificed ，and the heart ，liver，kidney and testis were taken ，and the organ index was calculated ； serum levels of ALT ，AST，BUN and Scr ，the activity of T-SOD and the contents of MDA were all determined. The pathological changes of heart ，liver，kidney and testis were observed ；mRNA expression of Bcl- 2，Bax and caspase- 3 in liver tissue were determined. RESULTS ：Three，five，two and three mice in TP-L group ，TP-H group ，TP-L+CR group and TP-H+CR group died respectively，and the survival rates were 70％，50％，80％ and 70％，respectively. Compared with normal group ，the body weight （7th day of experiment ），heart index ，liver index ，kidney index （except for TP-L group ），testicular index ，T-SOD activity and mRNA expression of Bcl- 2 in liver tissue ，serum levels of ALT （except for TP-L group ），AST（except for TP-L group ），BUN and Scr，MDA content and mRNA expression of Bax ，mRNA expression of caspase- 3 in liver tissue were increased significantly （P＜ 0.05 or P＜0.01）. There were obvious pathological changes in heart ，liver，kidney and testis tissue. Compared with the same dose of TP alone group ，the above indexes of TP combined with CR group were improved in varying degrees. Except for the renal index and serum ALT level of TP-L+CR group ，there was statistical significance for all indexes （P＜0.05 or P＜0.01）；the pathological injuries of heart ，liver，kidney and testis were significantly improved. CONCLUSIONS ：CR can relieve the damage of heart ， liver，kidney and testis induced by TP ，which may be related to the antioxidant stress of CR.

The HPLC fingerprint differences ofRadix Platycodonis from different origins were studied to provide references for their quality control and production. The total platycodins were purified by DB101 macroporous resin. HPLC-ELSD fingerprints of the total platycodins for 39 batches ofRadix Platycodonis samples from 9 provinces were performed on an Agilent HC-C8 column (4.6 mm x 250 mm, 5μm) with gradient elution. The mobile phase was acetonitrile-0.5% acetic acid. The injection volume was 6μL. The flow rate was 0.5 mL·min-1. The temperature of drift tube was set at 90℃. And the gas flow (N2) was set at 1.2 mL·min-1. The results showed that there were large differences in the quality ofRadix Platycodonis from different origins with the common fingerprints of 6 batches of samples fromChifeng in Inner Mongolia as references. The quality ofRadix Platycodonis was closely related to the seeds, the ecological environment, the way of drying and storing and so on. It was concluded that it was important to strengthen the provenance base construction, standardization of the seeds, reasonable formulation of the regionalization, and standardization of the production processing for the cultivation and production ofRadix Platycodonis.