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

用于控制疼痛的非口服型缓释制剂的开发

• 批准号: 13672328
• 负责人: WATANABE Jun
• 金额: $ 2.18万
• 依托单位: College of Pharmacy, Nihon University.
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672328/
• 关键词: Calcium phosphate cement; Hydroxyapatite; Sustained release preparation; dissolution test; pharmacokinetics; Analgesic; Pentazocine; Rat

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

本研究的目的是开发适合患者病情和疾病状态的癌症疼痛治疗缓释镇痛剂，我们使用最近注意到的非口服型羟基磷灰石生产了自凝羟基磷灰石水泥药物制剂。缓释制剂中含有喷他佐辛，对癌症相关疼痛具有优异的作用，我们得到了以下结果。（1）为了防止 PTZ 从药物制剂中洗脱，我们检测了喷他佐辛的抗压强度羟基磷灰石水泥药物配方及PTZ从羟基磷灰石水泥中的洗脱以羟基磷灰石水泥为晶种，添加20-40%的晶体羟基磷灰石，制备负载PTZ的羟基磷灰石水泥药物的抗压强度。增加羟基磷灰石作为晶种的用量，我们发现抗压强度有所提高。负载PTZ的药物制剂从4.24Mpa降低至1.58Mpa，此外，从这些结果发现，通过增加作为晶种的羟基磷灰石的剂量，PTZ从该药物制剂的溶出速率增加299.71ng/mL/hr至197.47ng/mL/hr。 ，可以清楚地控制自凝羟基磷灰石水泥药物制剂中 PTZ 的溶出速率。（2）我们研究了这种关系向大鼠皮下植入自凝羟基磷灰石水泥药物制剂后，血液和脑浓度与 PTZ 的镇痛效果之间的关系在本研究中负载 PTZ 的药物制剂中，证实血液浓度持续 96。负载PTZ的药物制剂的药代动力学参数中，当通过羟基磷灰石水泥药物制剂施用相同量的PTZ和皮下注射时的小时数。皮下注射PTZ溶液的1.8倍我们发现，与皮下注射相比，施用载有PTZ的药物制剂后PTZ的麸皮浓度增加，阐明了植入后PTZ的镇痛效果的持续时间。载有 PTZ 的药物制剂保持皮下注射时间的 8 倍以上。

项目成果

Jun Watanabe et al.: "Investigation of Transport Mechanism of Pentazocine across The Blood Brain Bariier Using the In Situ Rat Brain Perfusion Technique"JOURNAL OF PHARMACEUTICAL SCIENCES. 91(11). 2346-2353 (2002)

Jun Watanabe 等人：“使用原位大鼠脑灌注技术研究喷他佐辛跨血脑屏障的转运机制”《药物科学杂志》。

Jun Watanabe et al.: "Investigation of Transport Mechanism of Pentazacine across The Blood Brain Barrier Using the In Situ Rat Brain Perfusion Technique"JORNAL OF PHARMACEUTICAL SCIENCES. 91(11). 2346-2353 (2002)

Jun Watanabe 等人：“使用原位大鼠脑灌注技术研究喷他辛穿过血脑屏障的转运机制”《药物科学杂志》。