摘要：【中文】本发明涉及达格列净的氨基酸共晶物及其制备方法。包括达格列净与共晶配体L脯氨酸。达格列净与L脯氨酸形成共晶物I或II：共晶物I是达格列净‑L脯氨酸1:1共晶，共晶物II是达格列净‑L脯氨酸1:2共晶。在20～80℃温度下，分别配制无定形达格列净和L脯氨酸的有机溶液，然后将无定形达格列净和L脯氨酸的有机溶液加热至40～80℃，搅拌2h～48h，共晶形成，将所得悬浮液分离、常压干燥，得到的固体就是达格列净与L脯氨酸形成的共晶物。熔点高于无定形达格列净和达格列净‑1水·(S)‑丙二醇合物，提高了药物的热稳定性，同时共晶组分不含有毒物质，有利于达格列净生产、储存、运输过程的顺利进行。 【EN】The invention relates to an amino acid eutectic compound of dapagliflozin and a preparation method thereof. Comprises dapagliflozin and a eutectic ligand L proline. Dapagliflozin forms a co-crystal I or II with L proline: the eutectic compound I is a dapagliflozin-L proline 1:1 eutectic, and the eutectic compound II is a dapagliflozin-L proline 1:2 eutectic. Respectively preparing organic solutions of amorphous dapagliflozin and L proline at the temperature of 20-80 ℃, heating the organic solutions of amorphous dapagliflozin and L proline to 40-80 ℃, stirring for 2-48 h, forming an eutectic crystal, separating the obtained suspension, and drying at normal pressure to obtain a solid, namely the eutectic crystal formed by dapagliflozin and L proline. The melting point of the compound is higher than that of amorphous dapagliflozin and dapagliflozin-1 water- (S) -propylene glycol compound, the thermal stability of the medicine is improved, and meanwhile, the eutectic component does not contain toxic substances, so that the smooth production, storage and transportation processes of dapagliflozin are facilitated.

摘要：【中文】本发明公开的回收提纯头孢氨苄结晶母液中7‑氨基去乙酰氧基头孢烷酸和苯甘氨酸的方法，15‑40℃搅拌下，碱性调节剂加入到头孢氨苄结晶母液中，保持pH值7‑8，加入裂解酶进行头孢氨苄裂解反应，固液分离，将酸性调节剂加入到清液中，调pH值至6‑7，并加入醇类溶剂，使苯甘氨酸结晶析出，固液分离，将酸性调节剂加入到清液中，调pH值至3‑4，获得7‑氨基去乙酰氧基头孢烷酸结晶产品。本发明采用溶析结晶方式，将裂解液中的苯甘氨酸优先结晶分离，其纯度>99％，收率>20％，得到的7‑氨基去乙酰氧基头孢烷酸的纯度>99％，回收率90％左右。本发明方法环境友好，经济实用，分离回收效率高。 【EN】The invention discloses a method for recovering and purifying 7-aminodesacetoxycephalosporanic acid and phenylglycine in cefalexin crystallization mother liquor, which comprises the steps of adding an alkaline regulator into the cefalexin crystallization mother liquor under stirring at 15-40 ℃, keeping the pH value at 7-8, adding a lyase for cefalexin cracking reaction, carrying out solid-liquid separation, adding an acidic regulator into clear liquid, regulating the pH value to 6-7, adding an alcohol solvent to crystallize and separate the phenylglycine, carrying out solid-liquid separation, adding the acidic regulator into the clear liquid, regulating the pH value to 3-4, and obtaining a 7-aminodesacetoxycephalosporanic acid crystallization product. The method adopts a elution crystallization mode to preferentially crystallize and separate phenylglycine in the lysate, the purity of the phenylglycine is more than 99%, the yield of the phenylglycine is more than 20%, the purity of the obtained 7-aminodesacetoxycephalosporanic acid is more than 99%, and the recovery rate of the obtained 7-aminodesacetoxycephalosporanic acid is about 90%. The method is environment-friendly, economical and practical, and has high separation and recovery efficiency.

摘要：【中文】本发明公开一种头孢氨苄结晶母液回收方法，15‑40℃搅拌下，碱性调节剂加入到头孢氨苄结晶母液中，保持pH值7‑8，加入裂解酶进行头孢氨苄裂解反应，固液分离，将酸性调节剂加入到清液中，调pH值至6‑7，并降温至5‑10℃，使苯甘氨酸沉淀析出，固液分离，将酸性调节剂加入到清液中，调pH值至3‑4并升温至20‑40℃，获得7‑氨基去乙酰氧基头孢烷酸结晶产品。本发明通过冷却结晶，将裂解液中的苯甘氨酸优先结晶分离，其纯度>99％，收率5％左右，得到的7‑氨基去乙酰氧基头孢烷酸纯度>99％，回收率90％以上。本发明未引入水和VOC物质，对环境无污染，实现了结晶母液的清洁化回收，分离回收效率高。 【EN】The invention discloses a method for recovering cefalexin crystallization mother liquor, which comprises the steps of adding an alkaline regulator into cefalexin crystallization mother liquor under stirring at 15-40 ℃, keeping the pH value to be 7-8, adding lyase to carry out cefalexin cracking reaction, carrying out solid-liquid separation, adding an acidic regulator into clear liquid, regulating the pH value to be 6-7, cooling to 5-10 ℃, precipitating phenylglycine, carrying out solid-liquid separation, adding the acidic regulator into the clear liquid, regulating the pH value to be 3-4, heating to 20-40 ℃, and obtaining a 7-aminodeacetoxy cephalosporanic acid crystallization product. According to the invention, phenylglycine in the lysate is preferentially crystallized and separated through cooling crystallization, the purity is more than 99%, the yield is about 5%, the purity of the obtained 7-aminodesacetoxycephalosporanic acid is more than 99%, and the recovery rate is more than 90%. The invention does not introduce water and VOC substances, has no pollution to the environment, realizes clean recovery of the crystallization mother liquor and has high separation and recovery efficiency.

摘要：【中文】本发明涉及一种通过单固桥测量颗粒材料的结块强度参数的方法及装置，通过装置固定两个颗粒，控温控湿使两个颗粒之间生成单个固桥，通过显微镜测定固桥半径，并用外力破坏固桥，从而采用公式σ＝C/πb²或σ＝G/πb_c²计算获得该材料的结块强度参数。其中，σ为颗粒材料的结块强度参数，b为固桥半径，C为破碎半径为b的固桥所需要的力，即结块强度；G为颗粒重量，b_c为临界固桥半径。装置由控温控湿箱，固定颗粒装置和显微镜组成。固定颗粒装置可为双机械臂压力传感、提拉、平台下降、震动等形式。该方法具有更准确的物理意义和可信度，精度高，可重复性强，测量周期短，样品消耗少，和高通量等优势。 【EN】The invention relates to a method and a device for measuring caking strength parameters of a granular material by a single solid bridge²Or σ ═ G/π b_c²Calculating to obtain the caking strength parameter of the material. Wherein, sigma is the caking strength parameter of the particle material, b is the bridge fixing radius, and C is the force required by the bridge fixing with the crushing radius b, namely the caking strength; g is the weight of the particles, b_cIs the critical solid bridge radius. The device consists of a temperature and humidity control box, a particle fixing device and a microscope. The particle fixing device can be in the forms of pressure sensing, lifting, platform descending, vibration and the like of the double mechanical arms. The method has the advantages of more accurate physical significance and reliability, high precision, strong repeatability, short measurement period, less sample consumption, high flux and the like.

摘要：【中文】本发明公开一种针对颗粒聚结成球技术的三元溶剂体系筛选方法，所筛选得到的三元溶剂体系能够实现颗粒在该体系中聚结并形成类球形二次颗粒。利用有序排列组合法列出全部的三元溶剂组合，通过溶剂的溶解度、互溶性、粘附能力和润湿能力筛选符合条件的组合。随后基于被留下的组合的润湿能力差别进行降序排列并进行快速成球实验验证，以确定最终能够成球的溶剂组合。本发明方法显著提高溶剂筛选的正确率，普适性强，效率大幅提高，工作量少，测量难度低，满足测量要求的设备和方法多，可实现大量物系和溶剂的批量筛选。 【EN】The invention discloses a ternary solvent system screening method aiming at a particle coalescence balling technology, wherein the screened ternary solvent system can realize the coalescence of particles in the system and form sphere-like secondary particles. All ternary solvent combinations are listed by an ordered arrangement combination method, and combinations meeting the conditions are screened according to the solubility, intersolubility, adhesive capacity and wetting capacity of the solvents. Then, based on the difference in wetting ability of the remaining combinations, descending order arrangement and verification of a rapid balling experiment are carried out to determine the combination of solvents that can be balling finally. The method provided by the invention has the advantages that the accuracy of solvent screening is obviously improved, the universality is strong, the efficiency is greatly improved, the workload is low, the measurement difficulty is low, more devices and methods meeting the measurement requirements are provided, and the batch screening of a large number of systems and solvents can be realized.