布比卡因

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Microspheres containing bupivacaine loaded to about 75 percent by weight with bupivacaine are prepared, in a percent loading of about 0.05 percent, by weight, using the methods described in EXAMPLES 1-3 or EXAMPLES 4-9, above. In addition, microspheres containing added epinephrine, in a percent loadings of 0.001 percent, 0.05 percent and 1 percent, without bupivacaine, are also prepared according to EXAMPLES 1-3 or EXAMPLES 4-9, above. are prepared, in a percent loading of about 0.05 percent, by weight In addition, microspheres containing

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Microspheres containing bupivacaine loaded to about 75 percent by weight with bupivacaine are prepared, in a percent loading of about 0.05 percent, by weight, using the methods described in EXAMPLES 1-3 or EXAMPLES 4-9, above. In addition, microspheres containing added epinephrine, in a percent loadings of 0.001 percent, 0.05 percent and 1 percent, without bupivacaine, are also prepared according to EXAMPLES 1-3 or EXAMPLES 4-9, above. are prepared, in a percent loading of about 0.05 percent, by weight In addition, microspheres containing

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Microspheres containing bupivacaine loaded to about 75 percent by weight with bupivacaine are prepared, in a percent loading of about 0.05 percent, by weight, using the methods described in EXAMPLES 1-3 or EXAMPLES 4-9, above. In addition, microspheres containing added epinephrine, in a percent loadings of 0.001 percent, 0.05 percent and 1 percent, without bupivacaine, are also prepared according to EXAMPLES 1-3 or EXAMPLES 4-9, above. are prepared, in a percent loading of about 0.05 percent, by weight In addition, microspheres containing

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Microspheres containing bupivacaine loaded to about 75 percent by weight with bupivacaine are prepared, in a percent loading of about 0.05 percent, by weight, using the methods described in EXAMPLES 1-3 or EXAMPLES 4-9, above. In addition, microspheres containing added epinephrine, in a percent loadings of 0.001 percent, 0.05 percent and 1 percent, without bupivacaine, are also prepared according to EXAMPLES 1-3 or EXAMPLES 4-9, above. are prepared, in a percent loading of about 0.05 percent, by weight In addition, microspheres containing

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A uniform mixture of DMS and bupivacaine was formed by combining DMS dissolved in 95% ethanol with bupivacaine dissolved in 95% ethanol. The solution was air-dried under the hood at room temperature until the ethanol evaporated and left behind a well-dispersed mixture of dry crystalline DMS and bupivacaine. The crystalline mixture was pulverized under mortar and pestle and combined with copolymer. The rest of the procedures followed those described for CHP PLAMs. All DMS/bupivacaine PLAMs were synthesized using large bore Teflon® tubing. The solution was air-dried under the hood at room temperature until the ethanol evaporated left behind a well-dispersed mixture of dry crystalline DMS and bupivacaine

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A composition suitable for administration in vaginal suppository form 1a prepared by weighing 2 mg of finely divided polynucleotide medicinal substance into a tared container, adding 10 ml of 0.5% bupivacaine HCl in purified water, to make a total of 10 g, and dissolving or mixing depending on the solubility of the medicinal substance; 70 g of glycerin is added and mixed; 20 g of granular gelatin is then added and the composition heated carefully on a steam bath until the gelatin is dissolved. The melted mixture is poured into chilled molds to yield 20 vaginal suppositories of 6 grams each containing 100 mcg of polynucleotide medicinal substance in admixture with 2.5 mg bupivacaine. dissolving mixing mixed 20 g of granular gelatin is then added the composition heated carefully on a steam bath until the gelatin is dissolved The melted mixture is poured into chilled molds

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A uniform mixture of DMS and bupivacaine was formed by combining DMS dissolved in 95% ethanol with bupivacaine dissolved in 95% ethanol. The solution was air-dried under the hood at room temperature until the ethanol evaporated and left behind a well-dispersed mixture of dry crystalline DMS and bupivacaine. The crystalline mixture was pulverized under mortar and pestle and combined with copolymer. The rest of the procedures followed those described for CHP PLAMs. All DMS/bupivacaine PLAMs were synthesized using large bore Teflon® tubing. The solution was air-dried under the hood at room temperature until the ethanol evaporated left behind a well-dispersed mixture of dry crystalline DMS and bupivacaine

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A composition suitable for administration in vaginal suppository form 1a prepared by weighing 2 mg of finely divided polynucleotide medicinal substance into a tared container, adding 10 ml of 0.5% bupivacaine HCl in purified water, to make a total of 10 g, and dissolving or mixing depending on the solubility of the medicinal substance; 70 g of glycerin is added and mixed; 20 g of granular gelatin is then added and the composition heated carefully on a steam bath until the gelatin is dissolved. The melted mixture is poured into chilled molds to yield 20 vaginal suppositories of 6 grams each containing 100 mcg of polynucleotide medicinal substance in admixture with 2.5 mg bupivacaine. dissolving mixing mixed 20 g of granular gelatin is then added the composition heated carefully on a steam bath until the gelatin is dissolved The melted mixture is poured into chilled molds

实验步骤: 投料: 游离：取原料（4.89mg，1.0eq），用100ml水溶解，滴加饱和碳酸氢钠溶液5ml，有大量白色固体析出，加入EA溶解，萃取，收集有机相，干燥浓缩，得到白色固体（3.57g）。 将得到的白色固体（3.57g，1.0eq），加入到250ml单口瓶中，用65mlDCM溶解，加入85%mcpba(3.02g,1.2eq),室温搅拌过夜，\n后处理: 往反应液中加入饱和亚硫酸钠溶液洗两遍，后用2M氢氧化钠溶液洗一遍，再用饱和食盐水洗一遍，干燥浓缩得到黄色油状物 \n监测: LCMS监测，TLC监测，DCM：MEOH=40：1，原料基本反应完全， \n纯化: 产物性状不好，冲一遍柱子，DCM：MEOH=20:1,迅速冲出产物，旋干，还是得到黄色油状物。 将产物用少量甲叔醚超声溶解，后放入-20°冰箱过夜析晶，第二天来过滤固体，滤液用干冰乙醇浴冰冻，反复析晶，反复过滤，最终得到白色固体2.6g。送LCMS和HNMR确认结构正确。

实验步骤: 03-10 16:19: 往100ml单口瓶中加入原料（324mg，1.0eq），5mlDCM溶解，加入mcpba（208mg，1.2eq），室温搅拌2h，LCMS监测，原料基本没反应，少量产物生成， 判断：有可能是买回来是盐酸盐，成盐位置在N上，成季铵盐，影响反应。 往反应中加入三乙胺（417mml，3.0eq），继续搅拌过夜，LCMS监测，原料基本没有变化。

实验步骤: 03-10 16:22: 游离：取原料（974mg，1.0eq），用15ml水溶解，滴加饱和碳酸氢钠溶液5ml，有大量白色固体析出，加入EA溶解，萃取，收集有机相，干燥浓缩，得到白色固体（865mg）。 将得到的白色固体（865mg，1.0eq），加入到100ml单口瓶中，用15mlDCM溶解，加入mcpba(621mg,1.2eq),室温搅拌2h，LCMS监测，原料基本反应完全，将反应液旋干，后用10mlDCM溶解，加入氢氧化钠溶液搅拌1h，LCMS监测，mcpba的副产物已除去，分液，收集有机相，干燥浓缩，得到无色油状物

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Bupivacaine hydrochloride (Sigma-Aldrich Corporation, St. Louis, Mo.) was dissolved in deionized (DI) water at a concentration of 40 mg/ml (saturation). A calculated amount of sodium hydroxide (in the form of 1 N solution) was added to the solution and the pH of the final mixture was adjusted to 10 to precipitate the Bupivacaine base. The precipitated product was filtered, and further washed with DI water at least three times. The precipitated product was dried at ca. 40° C. in vacuum for 24 hours. to precipitate the Bupivacaine base The precipitated product was filtered further washed with DI water at least three times The precipitated product was dried at ca. 40° C. in vacuum for 24 hours