Development of Non-Oral Type Sustained Release Formulation for Pain Control

本研究的目的是研制适合患者病情和病情的癌痛缓释止痛剂。我们利用新近发现的羟基磷灰石制备了自固化羟基磷灰石-骨水泥药物配方。非口服型缓释制剂中含有对癌性疼痛有良好作用的五唑类药物，我们获得了以下结果：(1)为了保持PTZ从药物制剂中的洗脱，我们考察了羟基磷灰石-骨水泥制剂的抗压强度和PTZ从羟基磷灰石水泥中的洗脱情况。在以羟基磷灰石水泥为晶种的配方下，加入晶态羟基磷灰石的量为20~40%，制备了PTZ负载羟基磷灰石水泥药剂的抗压强度。增加羟基磷灰石作为晶种的用量，我们发现压缩的…负载PTZ的药物配方的强度从4.24 Mpa下降到1.58 Mpa。此外，还发现随着羟基磷灰石晶种用量的增加，该制剂的溶出度提高了299.71，达到197.47 ng/mL/hr。研究了自固化羟基磷灰石-骨水泥制剂大鼠皮下埋植后的血药浓度与脑内药物浓度的关系及PTZ的镇痛作用。在本研究中的PTZ载药制剂中，证实了相同剂量的PTZ分别以羟基磷灰石-骨水泥制剂和皮下注射给药时，血药浓度持续96h。载药制剂的药代动力学参数MRT是皮下注射PTZ溶液的1.8倍。结果发现，与皮下注射相比，PTZ皮下注射后，PTZ的麸皮浓度增加，说明PTZ植入后的镇痛作用持续时间是皮下注射的8倍以上。较少

The purpose of this study was the development to formulate the sustained release analgesia to cancer pain management, which is suitable to condition and disease state of the patient. We produced self-setting hydroxyapatite-cement pharmaceutical formulation using hydroxyapatite noticed recently. Non-oral type sustained release formulation contained the pentazocine with the action of being excellent for cancer related pain, and we obtained following results.(1) In order to keep the elution of PTZ from the pharmaceutical formulation, we examined the compressive strength of the hydroxyapatite-cement pharmaceutical formulation and the elution of PTZ from hydroxyapatite cement. Under prescription of the hydroxyapatite cement as a seed crystal, the quantity of crystal hydroxyapatite was added 20-40 % to prepare the compressive strength of the PTZ-loaded hydroxyapatite-cement pharmaceutical formulation. Increasing the dosage of the hydroxyapatite as seed crystal, we found that the compressive … More strength of the PTZ-loaded pharmaceutical formulation decreased from 4.24 to 1.58 Mpa. Moreover, it was found that the dissolution rate of PTZ from this pharmaceutical formulation increased 299.71 to 197.47 ng/mL/hr by increasing the dosage of the hydroxyapatite as seed crystal. From these results, the dissolution rate of PTZ from the self-setting hydroxyapatite-cement pharmaceutical formulation could be controlled clearly.(2) We investigated the relationship between blood and brain concentration and the analgesic effect of PTZ after the subcutaneous implantation of the self-setting hydroxyapatite-cement pharmaceutical formulation to the rat. In the PTZ-loaded pharmaceutical formulation in this study, it was confirmed that the blood concentration continued by 96 hours, when PTZ of the same quantity was administered by the hydroxyapatite-cement pharmaceutical formulation and subcutaneous injection. MRT in the pharmacokinetic parameter of the PTZ-loaded pharmaceutical formulation, was 1.8-times of the subcutaneous injection of PTZ solution. We found out that the bran concentration of PTZ increased after the administration of the PTZ-loaded pharmaceutical formulation comparing the subcutaneous injection, It was clarified that the duration of analgesic effect of PTZ after the implantation of the PTZ-loaded pharmaceutical formulation was kept over 8-folds hours of the subcutaneous injection. Less