CN1332664C - 鼻粉剂 - Google Patents
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Abstract
司琼类药物的鼻粉剂，其包括选自昂丹司琼，托烷司琼和格拉司琼的药物及选自葡萄糖，甘露醇，乳糖，山梨醇，微晶纤维素或β-环糊精的药用载体。
Description
发明领域
本发明涉及通过鼻腔给予司琼类止吐药物的鼻粉剂。司琼类药物包括昂丹司琼Ondansetron(又称枢复宁，奥丹西龙，Iofran)，托烷司琼Tropisetron(托普西龙，呕必停，Navoban)和格拉司琼Granisetron(格雷西龙，康泉，Kytril)。进一步讲，司琼类药物的鼻粉剂包括选自昂丹司琼，托烷司琼和格拉司琼的药物及药用载体。
背景技术
司琼类止吐药物是强效高选择性外周和中枢神经系统5-HT3受体拮抗剂，通过对上端小肠腹部向心神经纤维和孤束或呕吐化学感受区的5-HT3受体的阻断作用，达到预防或治疗肿瘤病人化疗和放疗引起的恶心和呕吐。与其它传统药物相比，具有高效、低毒、安全可靠的特点，已成为当今首选的抗呕吐药物，在世界各地广泛应用。该类药物在临床上应用的剂型有注射液和片剂。注射液静注药物需特定环境，局限在医院使用，而且病人要承受一定的痛苦和较高的经济负担且使用不方便；口服片剂由于起效慢，病人治疗前需提前一定时间服用，且生物利用度低。
发明目的
本发明的目的是提供一种克服目前司琼类药物制剂不足，同时具有吸收快、生物利用度高、使用方便的新的含司琼类药物的制剂。
发明人经研究现已发现司琼类药物可与选择性的药用载体组成新的鼻腔给药的鼻粉剂，该鼻粉剂与已知司琼类药物制剂相比，具有吸收快，生物利用度高，无胃肠副作用及刺激性的特点，本发明基于上述发现已完成。
发明概述
本发明提供了一种含司琼类药物的通过鼻腔给药的鼻粉剂，其包括选自昂丹司琼，托烷司琼和格拉司琼的司琼类药物及药用载体。
本发明提供了一种含司琼类药物的通过鼻腔给药的鼻粉剂，其包括选自昂丹司琼，托烷司琼和格拉司琼的司琼类药物及选自葡萄糖，甘露醇，乳糖，山梨醇，微晶纤维素或β-环糊精的药用载体。
本发明进一步提供了含盐酸格拉司琼及乳糖的鼻粉剂。
本发明还提供了制备含司琼类药物的鼻粉剂的方法，其包括将选自昂丹司琼，托烷司琼和格拉司琼的司琼类药物与选自葡萄糖，甘露醇，乳糖，山梨醇，微晶纤维素或β-环糊精的药用载体混合。
根据本发明，以鼻粉剂重量计，本发明鼻粉剂中司琼类药物的含量为2.0-20.0％；药用载体含量为98.0-80.0％，根据本发明，本发明鼻粉剂的粒径为10-200/μm。
根据本发明，以盐酸格拉司琼鼻腔鼻粉剂为例，其刺激性试验表明对家兔鼻粘膜基本无刺激性和纤毛毒性。比格犬体内药代动力学及生物利用度研究证明，上述鼻粉剂吸收速度平均Tmax(达到血药浓度峰值时间)为0.1-0.7小时，比市售片剂快3倍左右，Cmax(峰浓度)比片剂高1-2倍，相对生物利用度为139.09±17.64％。
根据本发明，本发明的喷雾剂可以单剂量或多剂量形式使用，且每次喷雾给药的剂为30-150μl。
发明详述
下面实施例是对本发明的进一步说明，其不意味着本发明限于此。
实施例1：含盐酸格拉司琼的鼻粉剂的制备：
称取已粉碎过120目筛的盐酸格拉司琼细粉11.2g(以格拉司琼计10.0g)，备用。另将精密称取且粉碎过100目筛的乳糖388.8g，备用。将上述盐酸格拉司琼与乳糖以等量递升法混合均匀，再次筛3次得含盐酸格拉司琼的鼻粉剂。
实施例2.本发明鼻粉剂与片剂给药后在血药浓度峰浓度时间(Tmax)及峰浓度(Cmax)的比较
按实施例1方法制备含2mg格拉司琼的鼻粉剂(下面简称制剂A)；另外采用含2mg格拉司琼片剂。将8条比格犬分别两组，每组4只比格犬。将上述格拉司琼鼻粉剂和格拉司琼片剂分别给予上述两组动物，测量给予上述药物后出现最大血药浓度的时间(Tmax)和相应最大血药浓度Cmax，结果见下面表1。
表1
格拉司琼鼻粉剂和片剂给药后的血药浓度的比较
| 参数 | 制剂A | 片剂 | P值 |
| Tmax(h) | 0.56±0.31 | 1.5±0.41 | 0.0358 |
| Cmax(ng·ml-1) | 11.854±1.588 | 6.451±1.150 | 0.0057 |
由表1中数据可看到，本发明的格拉司琼鼻粉剂在药物的吸收和起效上明显优于格拉司琼片剂。
Claims (6)
1.司琼类药物的鼻粉剂，其由选自昂丹司琼，托烷司琼和格拉司琼的药物及选自乳糖的药用载体组成。
2.权利要求1的鼻粉剂，其中所述司琼类药物为司琼类药物的盐。
3.权利要求2的鼻粉剂，其中司琼类药物的盐为格拉司琼盐酸盐。
4.权利要求3的鼻粉剂，其中所述制剂含2.0-20.0％格拉司琼盐酸盐及80.0-98.0％乳糖。
5.权利要求1-4任一要求的鼻粉剂，其中所述鼻粉剂含2mg盐酸格拉司琼/单位剂量。
6.权利要求1-4任一要求的鼻粉剂，其中所述鼻粉剂颗粒为10-200μm。
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021167176A CN1332664C (zh) | 2002-04-26 | 2002-04-26 | 鼻粉剂 |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021167176A CN1332664C (zh) | 2002-04-26 | 2002-04-26 | 鼻粉剂 |
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| Publication Number | Publication Date |
|---|---|
| CN1452965A CN1452965A (zh) | 2003-11-05 |
| CN1332664C true CN1332664C (zh) | 2007-08-22 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB021167176A Expired - Fee Related CN1332664C (zh) | 2002-04-26 | 2002-04-26 | 鼻粉剂 |
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| Country | Link |
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| CN (1) | CN1332664C (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0328186D0 (en) | 2003-12-05 | 2004-01-07 | West Pharm Serv Drug Res Ltd | Intranasal compositions |
| CN118787601B (zh) * | 2023-11-30 | 2025-03-04 | 福安药业集团宁波天衡制药有限公司 | 一种均匀度好的盐酸格拉司琼片的制备方法 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997018801A1 (en) * | 1995-11-17 | 1997-05-29 | Euro-Celtique S.A. | Pharmaceutical formulation |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997018801A1 (en) * | 1995-11-17 | 1997-05-29 | Euro-Celtique S.A. | Pharmaceutical formulation |
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