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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.
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BACKGROUND: At present, there are many types of bone defect repair scaffolds, but a single type of material is difficult to meet the requirements of bone tissue engineering scaffold materials. Several suitable materials can be combined into a composite material by appropriate methods, taking into account the advantages and disadvantages of various materials. It is the focus of scholars in recent years. OBJECTIVE: To construct nano-hydroxyapatite/chitosan/polycaprolactone composite scaffolds and analyze characterization of composite scaffolds. METHODS: Nano-hydroxyapatite/chitosan/polycaprolactone porous ternary composite scaffold material was prepared by 3D printing and molding technology. The characterization of scaffold material was studied from X-ray diffraction analysis, stent water absorption rate, stent compressive strength, stent degradation performance in vitro, stent aperture analysis, scanning electron microscope analysis and other dimensions. RESULTS AND CONCLUSION: (1) X-ray diffraction analysis showed that the crystal-shaped peak map of nano-hydroxyapatite/chitosan/ polycaprolactone scaffold materials was similar to the hydroxyapatite powder diffraction standard card, suggesting that the scaffold materials were integrated with each other through physical interaction, and did not affect the biological function of hydroxyapatite. (2) The average water absorption rate of the scaffold was 18.28%, and the hydrophilicity was good. The maximum pressure that the scaffold could withstand was 1 415 N, and the degradation rate was similar to the osteogenic rate. (3) Under a microscope, a ternary scaffold material with an aperture of 250 µm was successfully produced. The pore size was uniform and distributed regularly. (4) Scanning electron microscope demonstrated that the fibers composed of chitosan and polycaprolactone were arranged orderly and grid like, hydroxyapatite was distributed uniformly on the fiber surface in granular form, and the ternary composite material presented uniform and loose microporous structure. (5) Nano-hydroxyapatite/chitosan/polycaprolactone ternary composite scaffold material can be successfully prepared through 3D printing and molding technology, which has moderate compressive strength, certain porosity, appropriate degradation rate and water absorption rate, and can lay a foundation for repairing bone defects.
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According to the structure and effect differences of Panax notoginseng saponin components(PNSC), subcomponent division and network pharmacological characterization were conducted to provide a research basis for the medicinal properties of P.notoginseng saponin subcomponents and the technical design of unit preparations. PNSC were screened by the TCMSP database and subcomponents were classified according to systematic clustering. Then the subcomponents obtained were subjected to target prediction and attribution analysis by PharmMapper server, GeneCards, DisGeNET and HOME-NCBI-GENE database. A subcomponent target interaction network was constructed by using the STRING database. KEGG and GO enrichment analysis were performed on each subcomponent target using the DAVID database. The subcomponents-targets-pathways visualization network was constructed by Cytoscape. The subcomponent targets and pathways involved were compared to analyze the differences in anti-myocardial ischemic drug mechanisms and the rationality of subcomponent division. Eighteen compounds of PNSC were screened out, and classified into three subcomponents A, B, and C according to their properties, involving 67 targets and 17 common anti-myocardial ischemic pathways directly or indirectly related to myocardial ischemia. Subcomponent A had the highest number of targets and the target interaction was dense, possibly indicating its key role in the mechanism of pharmacodynamics. Subcomponents A, B, and C had similar basic structures, and KEGG and GO analysis showed that they all can enhance the heart function and protection of cardiomyocytes by inhibiting apoptosis, promoting angiogenesis and regulating inflammatory response to play the effect on myocardial ischemia. This study fully reflected the differences in the efficacy of various subcomponents in preventing and treating myocardial ischemia due to the different physical properties of P. notoginseng saponin subcomponents. To some extent, the differences in the efficacy of each subcomponent in the prevention and treatment of myocardial ischemia could verify the rationality of the division of P. notoginseng saponin subcomponents according to the structural properties, realizing the characterization of P. notoginseng saponin subcomponents based on structure and effect differences.
Subject(s)
Humans , Apoptosis , Coronary Artery Disease , Myocardial Ischemia , Panax notoginseng , SaponinsABSTRACT
The sequence of Neurospora crassa(XP_322380)and Gibberella zeae PH-1(EAA76971)ribosomal protein gene were subjected to local tBlastn searching against the Chaetomium globosum ESTs datebase.The 765 bp full length cDNA encoding 60S ribosomal protein L10a gene was obtained.The open reading frame was 654 bp and encoded 217 amino acids.The protein molecular mass was 23.9 kD.The BlastP analysis revealed that amino acids sequence of ribosomal protein L10a gene from C.globosum shared 89% high similarity with N.crassa and 78% low similarty with Ustilago maydis.The cDNA and deduced amino acid sequence of 60S ribosomal protein L10a gene were accepted by GenBank(accession numbers: AY669070,AAT74578).