CN114177140A - 一种硫酸奈替米星气雾剂 - Google Patents
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- 229960004832 netilmicin sulfate Drugs 0.000 title claims abstract description 29
- 239000000654 additive Substances 0.000 claims abstract description 15
- 230000000996 additive effect Effects 0.000 claims abstract description 14
- 239000002904 solvent Substances 0.000 claims abstract description 11
- 239000003380 propellant Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 16
- 238000003756 stirring Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- 229940101006 anhydrous sodium sulfite Drugs 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 4
- 229940001584 sodium metabisulfite Drugs 0.000 claims description 4
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 238000009472 formulation Methods 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 238000003825 pressing Methods 0.000 claims description 3
- 238000005086 pumping Methods 0.000 claims description 3
- 239000003963 antioxidant agent Substances 0.000 claims description 2
- 230000003078 antioxidant effect Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 9
- 230000000694 effects Effects 0.000 abstract description 7
- 230000009471 action Effects 0.000 abstract description 6
- 206010029155 Nephropathy toxic Diseases 0.000 abstract description 4
- 206010033109 Ototoxicity Diseases 0.000 abstract description 4
- 231100000417 nephrotoxicity Toxicity 0.000 abstract description 4
- 230000007694 nephrotoxicity Effects 0.000 abstract description 4
- 231100000262 ototoxicity Toxicity 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000035622 drinking Effects 0.000 abstract 1
- 239000002245 particle Substances 0.000 description 5
- 239000007921 spray Substances 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
- 201000004813 Bronchopneumonia Diseases 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 206010014568 Empyema Diseases 0.000 description 1
- 208000032376 Lung infection Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229940126574 aminoglycoside antibiotic Drugs 0.000 description 1
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003651 drinking water Substances 0.000 description 1
- 235000020188 drinking water Nutrition 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 208000008423 pleurisy Diseases 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
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- A61K9/0012—Galenical forms characterised by the site of application
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- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
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Abstract
本发明提供了一种硫酸奈替米星气雾剂,该气雾剂包括以下原料:硫酸奈替米星5‑10g、溶剂100‑200ml、抛射剂、附加剂0.05‑0.5g。本发明提供的硫酸奈替米星气雾剂,使药物直接到达作用部位,分布均匀,奏效快,使用方便,无需饮水,一揿即可,老少皆宜,有助于提高患者的用药顺应性。另一方面,也因为是用于局部作用的药物,给药剂量明显降低,降低了耳毒性、肾毒性等副作用的发生率。
Description
技术领域
本发明涉及药物制剂技术领域,尤其涉及一种硫酸奈替米星气雾剂。
背景技术
硫酸奈替米星是由先灵葆雅上市的氨基糖苷类抗生素,可用于胸膜肺部感染:支气管炎,支气管肺炎,胸膜炎,脓胸。肺部感染为继发感染中最常见的感染之一,其发生率最高(64.7%),并成为病人死亡的主要原因之一。因此,正确、及时选用有效抗生素显得尤为重要。
硫酸奈替米星因为水溶性大,口服后几乎不吸收。目前临床使用的有注射和冻干制剂剂型,肌肉注射后吸收迅速而完全。但是,注射剂制备过程复杂,给药剂量较大,患者顺应性差,且用于局部治疗时不可避免全身发挥作用的问题,耳毒性、肾毒性等副作用较大。
发明内容
本发明的目的在于公开一种硫酸奈替米星气雾剂,使药物直接到达作用部位,分布均匀,奏效快,使用方便,无需饮水,一揿即可,老少皆宜,有助于提高患者的用药顺应性。另一方面,也因为是用于局部作用的药物,给药剂量明显降低,降低了耳毒性、肾毒性等副作用的发生率。
为实现上述目的,本发明提供了一种硫酸奈替米星气雾剂,该气雾剂包括以下原料:硫酸奈替米星5-10g、溶剂100-200ml、抛射剂、附加剂0.05-0.5g。
上述气雾剂的制备方法包括以下步骤:
a、取处方量60%-70%的溶剂,加入附加剂,搅拌溶解;冰浴使制剂温度降到25℃以下;加入硫酸萘替米星,搅拌溶解;加入25℃以下溶剂至全量,搅拌均匀;制剂pH值保持在5.0-6.5;
b、将步骤a制得的制剂灌装到气雾瓶,先抽去气雾瓶内的空气,使气雾瓶内残氧量在0.5-1.5%之间,将抛射剂定量压入气雾瓶,即得硫酸奈替米星气雾剂。
进一步地,溶剂为水。
进一步地,抛射剂为氮气。
进一步地,附加剂为抗氧剂,所述抗氧剂为无水亚硫酸钠和焦亚硫酸钠的组合物。
与现有技术相比,本发明的有益效果是:解决了硫酸奈替米星水溶性大,口服不吸收的问题。同时由于是用于局部作用的药物,给药剂量明显降低,降低了耳毒性、肾毒性等副作用的发生率。气雾剂使药物直接到达作用部位,分布均匀,奏效快,使用方便,无需饮水,一揿即可,老少皆宜,有助于提高患者的用药顺应性。
具体实施方式
下面结合各实施方式对本发明进行详细说明,但应当说明的是,这些实施方式并非对本发明的限制,本领域普通技术人员根据这些实施方式所作的功能、方法、或者结构上的等效变换或替代,均属于本发明的保护范围之内。
本发明提供了一种硫酸奈替米星气雾剂,该气雾剂包括以下原料:硫酸奈替米星5-10g、溶剂100-200ml、抛射剂、附加剂0.05-0.5g。溶剂为水,抛射剂为氮气,附加剂为无水亚硫酸钠和焦亚硫酸钠的组合物。
以下通过具体的实施例进行详细阐述本发明的技术方案。
实施例1:
本实施例是以100ml的药物制剂处方为准,其中硫酸萘替米星10g,附加剂中的两种组合物用量不同,具体见下表。
制备方法:a、取处方量60%-70%的水,加入序号1中附加剂的量,搅拌溶解;冰浴使制剂温度降到25℃以下;加入处方量的硫酸萘替米星,搅拌溶解;加入25℃以下水至全量,搅拌均匀;制剂pH值保持在5.0-6.5。
b、将步骤a制得的制剂灌装到气雾瓶,先抽去气雾瓶内的空气,使气雾瓶内残氧量在0.5-1.5%之间,将氮气定量压入气雾瓶,即得硫酸奈替米星气雾剂(实施例1-1)。
上述表格序号2-6中附加剂的量,均可以根据上述制备方法的步骤进行制备硫酸奈替米星气雾剂,分别为实施例1-2至1-6。
实施例2
本实施例是以100ml的药物制剂处方为准,其中硫酸萘替米星5g,附加剂中的两种组合物用量不同,具体见下表。
制备方法同实施例1的制备方法,在此不再赘述。根据上述表格序号1-6中附加剂的量,制备的硫酸奈替米星气雾剂,分别为实施例2-1至2-6。
两个实施例中,附加剂选择无水亚硫酸钠、焦亚硫酸钠的组合物,其用量要能使硫酸奈替米星气雾剂PH为5.0-6.5,以保证制剂的稳定性。
喷雾粒径试验:
将实施例1和实施例2得到的硫酸奈替米星气雾剂,采用BI公司的喷雾装置-能倍乐进行喷雾,采用德国SYMPATEC激光粒度仪检测喷雾液滴粒径。
检测方式是:硫酸奈替米星气雾剂进行10揿喷雾,测定平均喷雾液滴粒径。按影响因素条件(高温60℃;高湿92.5%)放置5天后,再进行10揿喷雾,测定平均喷雾液滴粒径。
从以上考察结果可知:实施例1和例2得到的药物组合物喷雾液滴粒径D50在3.7μm-5.2μm之间,D90在8.2μm-8.9μm之间,且高温高湿条件下喷雾液滴粒径几乎没变化。
上文所列出的一系列的详细说明仅仅是针对本发明的可行性实施方式的具体说明,它们并非用以限制本发明的保护范围,凡未脱离本发明技艺精神所作的等效实施方式或变更均应包含在本发明的保护范围之内。
此外,应当理解,虽然本说明书按照实施方式加以描述,但并非每个实施方式仅包含一个独立的技术方案,说明书的这种叙述方式仅仅是为清楚起见,本领域技术人员应当将说明书作为一个整体,各实施例中的技术方案也可以经适当组合,形成本领域技术人员可以理解的其他实施方式。
Claims (4)
1.一种硫酸奈替米星气雾剂,其特征在于,所述气雾剂包括以下原料:硫酸奈替米星5-10g、溶剂100-200ml、抛射剂、附加剂0.05-0.5g;
所述气雾剂的制备方法包括以下步骤:
a、取处方量60%-70%的溶剂,加入附加剂,搅拌溶解;冰浴使制剂温度降到25℃以下;加入硫酸萘替米星,搅拌溶解;加入25℃以下溶剂至全量,搅拌均匀;制剂pH值保持在5.0-6.5;
b、将步骤a制得的制剂灌装到气雾瓶,先抽去气雾瓶内的空气,使气雾瓶内残氧量在0.5-1.5%之间,将抛射剂定量压入气雾瓶,即得硫酸奈替米星气雾剂。
2.根据权利要求1所述的硫酸奈替米星气雾剂,其特征在于,所述溶剂为水。
3.根据权利要求2所述的硫酸奈替米星气雾剂,其特征在于,所述抛射剂为氮气。
4.根据权利要求3所述的硫酸奈替米星气雾剂,其特征在于,所述附加剂为抗氧剂,所述抗氧剂为无水亚硫酸钠和焦亚硫酸钠的组合物。
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EP1598059A1 (en) * | 2001-05-18 | 2005-11-23 | Chiron Corporation | Methods and unit dose formulations for the inhalation administration of aminoglycoside antibiotics |
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韦超: "《药剂学》", 30 August 2012, 河南科学技术出版社 * |
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