CN118105459A - 一种用于眼科手术的灌洗液 - Google Patents
一种用于眼科手术的灌洗液 Download PDFInfo
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- CN118105459A CN118105459A CN202410235715.9A CN202410235715A CN118105459A CN 118105459 A CN118105459 A CN 118105459A CN 202410235715 A CN202410235715 A CN 202410235715A CN 118105459 A CN118105459 A CN 118105459A
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/06—Tripeptides
- A61K38/063—Glutathione
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (AREA)
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Abstract
本发明公开了一种用于眼科手术的灌洗液,该灌洗液由谷胱甘肽、赋形剂、稳定剂、等渗调节剂、pH调节剂和注射用水组成。还公开了上述灌洗液的制备方法。本发明提供了一种用于眼科手术的灌洗液及其制备方法,该灌洗液活性成分的稳定性得到增强。通过调整升华干燥过程和解析干燥过程中的工艺参数,采用阶段升温、分段干燥的方式;能进行充分均匀的干燥,得到疏松的药物快活粉末,有效保证了冻干制剂的饱满性和疏松状,增加制剂的稳定性。本发明采用冷冻干燥工艺,在冻干制剂中可以少使用,甚至不使用防腐剂,降低了防腐剂带来的副作用。本发明提供的用于眼科手术的灌洗液在使用时只需要将无菌水溶液加入到制剂中溶解摇匀即可,操作简单便捷。
Description
技术领域
本发明涉及药物制剂技术领域,尤其涉及一种用于眼科手术的灌洗液。
背景技术
还原型谷胱甘肽(glutathione,GSH)是人类细胞质中自然合成的一种肽,由谷氨酸、半胱氨酸和甘氨酸组成,含有巯基(-SH),广泛分布于机体各器官内,为维持细胞生物功能已呈有重要作用。它可通过巯基与体内的自由基结合,可以转化成容易代谢的酸类物质从而加速自由基的排泄,有助于减轻化疗、放疗的毒副作用,对化疗、放疗的疗效无明显影响。
谷胱甘肽有还原型(GSH)和氧化型(GSSG)两种形式,在生理条件下以还原型谷胱甘肽占绝大多数。还原型谷胱甘肽可以高浓度存在于眼组织的水晶体、角膜、视神经、视网膜及睫状体内,能保护角膜上皮细胞,有益于角膜或水晶体透明性的维持以及组织的再生与修复。在角膜疾患的情况下,上皮组织中的谷胱甘肽明显减少,还原型谷胱甘肽对角膜疾患的迅速恢复有作用。对不稳定的眼晶状体蛋白质巯基有抑制作用,可控制进行性白内障及控制角膜、视网膜病变的发展。但是,谷胱甘肽不易透过细胞膜,在水中易氧化,导致产品稳定性不高,影响了产品的质量,给它的应用带来了很大限制。
粘结是结缔组织纤维带与相邻的组织或器官结合在一起而形成的异常结构,术后组织粘连是手术过程造成的最严重的术后并发症之一。目前,在临床治疗过程中,使用亲水性的溶液来包裹由接触干燥和手术致腹膜创伤的组织,在手术前或术中接触组织来防止粘连。但是现有的亲水性溶液功能单一,只能起到防止粘连的作用。
因此,有必要对现有技术中亲水性的溶液加以改进,以解决上述问题。
发明内容
本发明的目的在于公开一种用于眼科手术的灌洗液,既能防止粘连,又有益于角膜或水晶体透明性的维持以及组织的再生与修复,且制备方法简单,活性成分的稳定性能得到增强。
根据本发明的一个方面,提供了一种用于眼科手术的灌洗液,该灌洗液由谷胱甘肽、赋形剂、稳定剂、等渗调节剂、pH调节剂和注射用水组成。
上述灌洗液的制备方法包括以下步骤:
(1)配制药液:称取适量的注射用水于配液罐中,控制温度25℃±5℃,加入谷胱甘肽,搅拌至溶解后,加入谷胱赋形剂、稳定剂、等渗调节剂、pH调节剂,再以喷淋方式加入注射用水至处方量,定容后搅拌10-20min;
(2)除菌过滤:通过两个串联的除菌过滤器对药液进行除菌过滤得药液;
(3)灌装:将制得的药液灌装于清洗、干燥灭菌后的中硼硅玻璃管制注射剂瓶,用清洗、灭菌、干燥后的氯化丁基橡胶塞半加塞;
(4)冻干:将上述样品预冻后,经升华、解析干燥,得冻干制剂,冻干完成后向样品内充氮,干燥,后压紧胶塞,外轧铝盖;
其中,冻干步骤为:
预冻:在120-240min内降温至-45℃,保持2-4h;
一次升华:60-120min升温至-25℃,保持真空度0.15-0.20mbar,保持12-18h;
解析干燥:1h内升温至-10℃,保持真空度0.1-0.2mbar,保持1-2h,3h内升温至30-40℃,保持真空度0.1-0.2mbar,保持5-6h。
在一些实施方式中,赋形剂选自氯化钠、葡萄糖、葡聚糖、山梨醇、乳糖、海藻糖、甘露醇和聚氧乙烯吡咯烷酮等中的一种或几种的任意组合。
在一些实施方式中,稳定剂选自维生素C钠、硼酸、焦亚硫酸钠、亚硫酸氢钠和聚乙二醇6000等中的一种或几种的任意组合。
在一些实施方式中,等渗调节剂选自葡萄糖、甘油、氯化钠、丙三醇、山梨醇、甘露醇和木糖醇等中的一种或几种的任意组合。
在一些实施方式中,pH调节剂选自盐酸、磷酸或其碱金属盐、枸橼酸或其碱金属盐、草酸或其碱金属盐、柠檬酸或其碱金属盐、冰醋酸或其碱金属盐、甘氨酸或其盐、氢氧化钠、氢氧化钾等中的一种或几种的任意组合。
与现有技术相比,本发明具有如下有益效果:
本发明提供了一种用于眼科手术的灌洗液及其制备方法,该灌洗液活性成分的稳定性得到增强。通过调整升华干燥过程和解析干燥过程中的工艺参数,采用阶段升温、分段干燥的方式;能进行充分均匀的干燥,得到疏松的药物快活粉末,有效保证了冻干制剂的饱满性和疏松状,增加制剂的稳定性。
本发明采用冷冻干燥工艺,在冻干制剂中可以少使用,甚至不使用防腐剂,降低了防腐剂带来的副作用。
本发明提供的用于眼科手术的灌洗液在使用时只需要将无菌水溶液加入到制剂中溶解摇匀即可,操作简单便捷。
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。
实施例1
本实施例公开的用于眼科手术的灌洗液,其处方为:
谷胱甘肽 | 100g |
甘露醇 | 20g |
维生素C钠 | 2g |
氯化钠 | 5g |
磷酸二氢钠 | 3g |
注射用水 | 2000mL |
共制成 | 1000支 |
上述灌洗液的制备方法包括以下步骤:
1、配制药液:称取适量的注射用水于配液罐中,控制温度25℃±5℃,加入谷胱甘肽,搅拌至溶解后,加入甘露醇、维生素C钠、氯化钠、磷酸二氢钠,再以喷淋方式加入注射用水至处方量,定容后搅拌10-20min;
2、除菌过滤:通过两个串联0.22μm的除菌过滤器对药液进行除菌过滤得药液;
3、灌装:将制得的药液灌装于清洗、干燥灭菌后的中硼硅玻璃管制注射剂瓶,用清洗、灭菌、干燥后的氯化丁基橡胶塞半加塞;
4、冻干:将上述样品预冻后,经升华、解析干燥,得冻干制剂,冻干完成后向样品内充氮,干燥,后压紧胶塞,外轧铝盖。
步骤4中冷冻干燥参数如下:
实施例2
本实施例公开的用于眼科手术的灌洗液,其处方为:
谷胱甘肽 | 100g |
氯化钠 | 10g |
硼酸 | 2.5g |
葡萄糖 | 6g |
氢氧化钠 | 2g |
注射用水 | 2000mL |
共制成 | 1000支 |
上述灌洗液的制备方法包括以下步骤::
1、配制药液:称取适量的注射用水于配液罐中,控制温度25℃±5℃,加入谷胱甘肽,搅拌至溶解后,加入甘露醇、维生素C钠、氯化钠、磷酸二氢钠,再以喷淋方式加入注射用水至处方量,定容后搅拌10-20min;
2、除菌过滤:通过两个串联0.22μm的除菌过滤器对药液进行除菌过滤得药液;
3、灌装:将制得的药液灌装于清洗、干燥灭菌后的中硼硅玻璃管制注射剂瓶,用清洗、灭菌、干燥后的氯化丁基橡胶塞半加塞;
4、冻干:将上述样品预冻后,经升华、解析干燥,得冻干制剂,冻干完成后向样品内充氮,干燥,后压紧胶塞,外轧铝盖。
步骤4中冷冻干燥参数如下:
实施例3
本实施例公开的用于眼科手术的灌洗液,其处方为:
上述灌洗液的制备方法包括以下步骤:
1、配制药液:称取适量的注射用水于配液罐中,控制温度25℃±5℃,加入谷胱甘肽,搅拌至溶解后,加入甘露醇、维生素C钠、氯化钠、磷酸二氢钠,再以喷淋方式加入注射用水至处方量,定容后搅拌10-20min;
2、除菌过滤:通过两个串联0.22μm的除菌过滤器对药液进行除菌过滤得药液;
3、灌装:将制得的药液灌装于清洗、干燥灭菌后的中硼硅玻璃管制注射剂瓶,用清洗、灭菌、干燥后的氯化丁基橡胶塞半加塞;
4、冻干:将上述样品预冻后,经升华、解析干燥,得冻干制剂,冻干完成后向样品内充氮,干燥,后压紧胶塞,外轧铝盖。
步骤4中冷冻干燥参数如下:
下面通过具体实验验证实施例1-3中制得的用于眼科手术的灌洗液的稳定性研究。
试验例1:采用实施例1-3中制得的用于眼科手术的灌洗液做稳定性研究。
试验条件为:温度30℃±2℃,湿度65%±5%RH,检测样品在放置不同时间后的含量及有关物质。具体数据见下表。结果表明本发明制备的用于眼科手术的灌洗液在考察期内制剂稳定,质量可控。
表1稳定性试验结果
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 (5)
1.一种用于眼科手术的灌洗液,其特征在于,所述灌洗液由谷胱甘肽、赋形剂、稳定剂、等渗调节剂、pH调节剂和注射用水组成;
所述灌洗液的制备方法包括以下步骤:
(1)配制药液:称取适量的注射用水于配液罐中,控制温度25℃±5℃,加入谷胱甘肽,搅拌至溶解后,加入谷胱赋形剂、稳定剂、等渗调节剂、pH调节剂,再以喷淋方式加入注射用水至处方量,定容后搅拌10-20min;
(2)除菌过滤:通过两个串联的除菌过滤器对药液进行除菌过滤得药液;
(3)灌装:将制得的药液灌装于清洗、干燥灭菌后的中硼硅玻璃管制注射剂瓶,用清洗、灭菌、干燥后的氯化丁基橡胶塞半加塞;
(4)冻干:将上述样品预冻后,经升华、解析干燥,得冻干制剂,冻干完成后向样品内充氮,干燥,后压紧胶塞,外轧铝盖;
其中,冻干步骤为:
预冻:在120-240min内降温至-45℃,保持2-4h;
一次升华:60-120min升温至-25℃,保持真空度0.15-0.20mbar,保持12-18h;
解析干燥:1h内升温至-10℃,保持真空度0.1-0.2mbar,保持1-2h,3h内升温至30-40℃,保持真空度0.1-0.2mbar,保持5-6h。
2.根据权利要求1所述的用于眼科手术的灌洗液,其特征在于,所述赋形剂选自氯化钠、葡萄糖、葡聚糖、山梨醇、乳糖、海藻糖、甘露醇和聚氧乙烯吡咯烷酮等中的一种或几种的任意组合。
3.根据权利要求2所述的用于眼科手术的灌洗液,其特征在于,所述稳定剂选自维生素C钠、硼酸、焦亚硫酸钠、亚硫酸氢钠和聚乙二醇6000等中的一种或几种的任意组合。
4.根据权利要求3所述的用于眼科手术的灌洗液,其特征在于,所述等渗调节剂选自葡萄糖、甘油、氯化钠、丙三醇、山梨醇、甘露醇和木糖醇等中的一种或几种的任意组合。
5.根据权利要求4所述的用于眼科手术的灌洗液,其特征在于,所述pH调节剂选自盐酸、磷酸或其碱金属盐、枸橼酸或其碱金属盐、草酸或其碱金属盐、柠檬酸或其碱金属盐、冰醋酸或其碱金属盐、甘氨酸或其盐、氢氧化钠、氢氧化钾等中的一种或几种的任意组合。
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