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CN115040641B - Preoperative intervention pharmaceutical composition for neurosurgery - Google Patents

Preoperative intervention pharmaceutical composition for neurosurgery Download PDF

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CN115040641B
CN115040641B CN202210745770.3A CN202210745770A CN115040641B CN 115040641 B CN115040641 B CN 115040641B CN 202210745770 A CN202210745770 A CN 202210745770A CN 115040641 B CN115040641 B CN 115040641B
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pharmaceutical composition
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CN115040641A (en
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陈涛
任旭
李云飞
杨理坤
朱洁
王玉海
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904th Hospital of the Joint Logistics Support Force of PLA
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Abstract

本发明涉及神经药物技术领域,尤其涉及神经外科术前干预药物组合物,包括60%~80%的A组分,包括以下成分:肉毒杆菌神经毒素、非蛋白质性质稳定剂、麦冬多糖、pH缓冲剂及纯水;20%~40%的B组分,包括以下成分:西红花、丝瓜络、络石藤、半胱氨酸、右旋糖及焦磷酸钠。本发明在制备的过程中介入运用了麦冬多糖,保证生产制备环境的同时,提高混合物的稳定性,使得最终得到的组合物的应用效果更佳,在提取之后进一步加入焦磷酸钠,并进行浓缩干燥,进而得到药物组合物,药物的主体质量高,使得组合物在应用后可较佳的提高神经传导速度。The present invention relates to the field of neuropharmaceutical technology, and in particular to a preoperative neurosurgery intervention drug composition, comprising 60% to 80% of component A, including the following ingredients: botulinum neurotoxin, non-protein stabilizer, ophiopogon japonicus polysaccharide, pH buffer and pure water; 20% to 40% of component B, including the following ingredients: saffron, luffa, trachelospermum officinale, cysteine, dextrose and sodium pyrophosphate. In the preparation process, the present invention uses ophiopogon japonicus polysaccharide to ensure the production and preparation environment while improving the stability of the mixture, so that the application effect of the final composition is better, and sodium pyrophosphate is further added after extraction, and concentrated and dried to obtain a pharmaceutical composition, the main body of the drug is high in quality, so that the composition can better improve the nerve conduction velocity after application.

Description

神经外科术前干预药物组合物Neurosurgery preoperative intervention drug composition

技术领域Technical Field

本发明涉及神经药物技术领域,尤其涉及神经外科术前干预药物组合物。The present invention relates to the technical field of neurological drugs, and in particular to a preoperative intervention drug composition for neurosurgery.

背景技术Background Art

神经外科,也常称作脑外科,为外科的一个支系,是以外科的方法来诊断与治疗中枢神经系统、周围神经系统和自主神经系统及其支撑结构(颅骨、脊柱等)疾病的医学。神经外科被公认为医学上地位最高的领域,其原因是要完成这样的手术对医生所需要的极其复杂的知识基础,以及获得进行这样的手术的允许所需要经过的严格的筛选。在允许进行神经外科手术前,一个医生至少需要经过六至七年的训练,这也是所有医学专业中最长和要求最高的。Neurosurgery, also often called brain surgery, is a branch of surgery that uses surgical methods to diagnose and treat diseases of the central nervous system, peripheral nervous system, and autonomic nervous system and their supporting structures (skull, spine, etc.). Neurosurgery is recognized as the highest-ranking field in medicine because of the extremely complex knowledge base required of doctors to perform such operations and the strict screening required to obtain permission to perform such operations. Before being allowed to perform neurosurgery, a doctor needs to undergo at least six to seven years of training, which is also the longest and most demanding of all medical specialties.

在神经外科进行手术前需要进行药物的预处理,而现有的神经药物的在使用后的神经传导速度(NCV)未见明显改善。Drug pretreatment is required before neurosurgery, but existing neurological drugs have not shown significant improvement in nerve conduction velocity (NCV) after use.

因此,我们提出了神经外科术前干预药物组合物用于解决上述问题。Therefore, we propose a neurosurgery preoperative intervention pharmaceutical composition to solve the above problems.

发明内容Summary of the invention

本发明的目的是为了解决现有技术中存在的缺点,而提出的神经外科术前干预药物组合物。The purpose of the present invention is to solve the shortcomings of the prior art and to propose a neurosurgery preoperative intervention drug composition.

为了实现上述目的,本发明采用了如下技术方案:In order to achieve the above object, the present invention adopts the following technical solutions:

本发明提出的神经外科术前干预药物组合物,包括:60%~80%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素100~200份、非蛋白质性质稳定剂10~30份、麦冬多糖10~15份、pH缓冲剂3~8份及纯水150~300份;20%~40%的B组分,按重量份计包括以下成分:西红花30~80份、丝瓜络20~50份、络石藤20~70份、半胱氨酸25~40份、右旋糖10~20份及焦磷酸钠15~30份。The neurosurgery preoperative intervention drug composition proposed by the present invention comprises: 60% to 80% of component A, which comprises the following ingredients in parts by weight: 100 to 200 parts of botulinum neurotoxin, 10 to 30 parts of non-protein stabilizer, 10 to 15 parts of ophiopogon polysaccharide, 3 to 8 parts of pH buffer and 150 to 300 parts of pure water; 20% to 40% of component B, which comprises the following ingredients in parts by weight: 30 to 80 parts of saffron, 20 to 50 parts of luffa, 20 to 70 parts of trachelospermum officinale, 25 to 40 parts of cysteine, 10 to 20 parts of dextrose and 15 to 30 parts of sodium pyrophosphate.

优选的,神经外科术前干预药物组合物,包括70%的A组分及30%的B组分。Preferably, the pharmaceutical composition for preoperative intervention in neurosurgery comprises 70% of component A and 30% of component B.

优选的,所述A组分按重量份计包括以下成分:肉毒杆菌神经毒素150份、非蛋白质性质稳定剂20份、麦冬多糖13份、pH缓冲剂5份及纯水220份,所述B组分按重量份计包括以下成分:西红花40份、丝瓜络35份、络石藤45份、半胱氨酸35份、右旋糖15份及焦磷酸钠20份。Preferably, the component A comprises the following ingredients in parts by weight: 150 parts of botulinum neurotoxin, 20 parts of non-protein stabilizer, 13 parts of Ophiopogon japonicus polysaccharide, 5 parts of pH buffer and 220 parts of pure water, and the component B comprises the following ingredients in parts by weight: 40 parts of saffron, 35 parts of Luffa fructus, 45 parts of Trachelospermum jasminoides, 35 parts of cysteine, 15 parts of dextrose and 20 parts of sodium pyrophosphate.

优选的,所述A组分中按重量份计还包括10~15份防冻剂。Preferably, the component A further comprises 10 to 15 parts by weight of antifreeze.

优选的,所述防冻剂为肌醇、甘露醇和山梨醇中的一种或多种。Preferably, the antifreeze agent is one or more of inositol, mannitol and sorbitol.

优选的,所述非蛋白质性质稳定剂为透明质酸,所述pH缓冲剂为醋酸钠。Preferably, the non-proteinaceous stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

本发明的另一方面提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:Another aspect of the present invention provides a method for preparing a neurosurgery preoperative intervention pharmaceutical composition, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置10~15min,而后调节温度至30~35℃,加入麦冬多糖,持续搅拌10~15min至均匀,得到混匀物;S1: Add botulinum neurotoxin to pure water, add non-protein stabilizer at the same time, continue stirring, add pH buffer during stirring, let stand for 10-15 minutes after stirring, then adjust the temperature to 30-35°C, add Ophiopogon japonicus polysaccharide, continue stirring for 10-15 minutes until uniform, and obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌10~15min;S2: Add antifreeze to the mixture and continue stirring for 10 to 15 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,得到药渣及提取液;S3: grinding saffron, luffa and trachelospermum officinale, and then adding cysteine and dextrose to perform warm immersion extraction to obtain medicinal residues and extract;

S4:在提取液中加入焦磷酸钠,持续搅拌10~20min,而后进行回流提取,完成后进行浓缩干燥,得到干燥物;S4: adding sodium pyrophosphate to the extract, stirring continuously for 10 to 20 minutes, and then performing reflux extraction, and after completion, concentrating and drying to obtain a dry product;

S5:将干燥物与S1中的混匀物进行混匀,即得到干预药物组合物。S5: Mix the dried product with the mixed product in S1 to obtain an intervention drug composition.

优选的,所述S1中,搅拌过程中加入pH缓冲剂,搅拌完成后静置12min,而后调节温度至32℃,加入麦冬多糖,持续搅拌12min至均匀,得到混匀物。Preferably, in S1, a pH buffer is added during the stirring process, and after the stirring is completed, the mixture is allowed to stand for 12 minutes, and then the temperature is adjusted to 32° C., Ophiopogon japonicus polysaccharide is added, and stirring is continued for 12 minutes until the mixture is uniform to obtain a mixture.

优选的,所述S3中,温浸提取2~4次,每次提取时间120~180min。Preferably, in S3, the warm immersion extraction is performed 2 to 4 times, and each extraction time is 120 to 180 minutes.

本发明的另一方面提出了一种神经外科术前干预药物组合物的应用,包括上述干预药物组合物。Another aspect of the present invention provides a use of a pre-neurosurgical intervention pharmaceutical composition, including the above-mentioned intervention pharmaceutical composition.

与现有技术相比,本发明的有益效果是:Compared with the prior art, the present invention has the following beneficial effects:

1、本发明将组合物分为两部分进行处理,其中一部分涉及肉毒杆菌神经毒素及非蛋白质性质稳定剂(透明质酸),并在过程中使用了pH缓冲剂,进一步的在制备的过程中介入运用了麦冬多糖,保证生产制备环境的同时,提高混合物的稳定性,使得最终得到的组合物的应用效果更佳。1. The present invention divides the composition into two parts for processing, one of which involves botulinum neurotoxin and a non-protein stabilizer (hyaluronic acid), and a pH buffer is used in the process. Further, Ophiopogon japonicus polysaccharide is used in the preparation process to ensure the production and preparation environment while improving the stability of the mixture, so that the application effect of the final composition is better.

2、本发明在另一部分设置了西红花、丝瓜络及络石藤,并对其进行研磨处理,而后与半胱氨酸、右旋糖进行混合并提取,在提取之后进一步加入焦磷酸钠,并进行浓缩干燥,进而得到药物组合物,药物的主体质量高,使得组合物在应用后可较佳的提高神经传导速度。2. The present invention arranges saffron, loofah and trachelospermum officinale in another part, grinds them, and then mixes and extracts them with cysteine and dextrose. After the extraction, sodium pyrophosphate is further added, and the mixture is concentrated and dried to obtain a pharmaceutical composition. The main body of the drug has high quality, so that the composition can better improve the nerve conduction velocity after application.

具体实施方式DETAILED DESCRIPTION

除非另有限定,本文使用的所有技术以及科学术语具有与本发明所属领域普通技术人员通常理解的相同的含义。当存在矛盾时,以本说明书中的定义为准。“质量、浓度、温度、时间、或者其它值或参数以范围、优选范围、或一系列上限优选值和下限优选值限定的范围表示时,这应当被理解为具体公开了由任何范围上限或优选值与任何范围下限或优选值的任一配对所形成的所有范围,而不论该范围是否单独公开了。例如,1-50的范围应理解为包括选自1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、或50的任何数字、数字的组合、或子范围、以及所有介于上述整数之间的小数值,例如,1.1、1.2、1.3、1.4、1.5、1.6、1.7、1.8、和1.9。关于子范围,具体考虑从范围内的任意端点开始延伸的“嵌套的子范围”。例如,示例性范围1-50的嵌套子范围可以包括一个方向上的1-10、1-20、1-30和1-40,或在另一方向上的50-40、50-30、50-20和50-10。”Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention belongs. In the event of a conflict, the definitions in the specification shall prevail. "When mass, concentration, temperature, time, or other value or parameter is expressed as a range, a preferred range, or a range defined by a series of upper preferred values and lower preferred values, this should be understood to specifically disclose all ranges formed by any pairing of any upper range limit or preferred value with any lower range limit or preferred value, regardless of whether the range is disclosed separately. For example, a range of 1-50 should be understood to include 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91 6, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50, any number, combination of numbers, or subrange, and all decimal values between the above integers, for example, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, and 1.9. With respect to subranges, "nested subranges" extending from any endpoint within the range are specifically contemplated. For example, nested subranges of the exemplary range 1-50 may include 1-10, 1-20, 1-30, and 1-40 in one direction, or 50-40, 50-30, 50-20, and 50-10 in the other direction."

下面结合具体实施例对本发明作进一步解说,在以下实施例中,未详细描述的各种过程和方法是本领域中公知的常规方法。下述实例中所用的材料、试剂、装置、仪器、设备等,如无特殊说明,均可从商业途径获得。The present invention is further explained below in conjunction with specific examples. In the following examples, various processes and methods not described in detail are conventional methods known in the art. The materials, reagents, devices, instruments, equipment, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources.

实施例一Embodiment 1

一种神经外科术前干预药物组合物,包括:A neurosurgery preoperative intervention drug composition comprising:

70%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素100份、非蛋白质性质稳定剂10份、麦冬多糖10份、pH缓冲剂3份及纯水150份、防冻剂10份;70% of component A, comprising the following ingredients by weight: 100 parts of botulinum neurotoxin, 10 parts of non-protein stabilizer, 10 parts of ophiopogon polysaccharide, 3 parts of pH buffer, 150 parts of pure water, and 10 parts of antifreeze;

30%的B组分,按重量份计包括以下成分:西红花30份、丝瓜络20份、络石藤20份、半胱氨酸25份、右旋糖10份及焦磷酸钠15份。30% of component B comprises the following ingredients by weight: 30 parts of saffron, 20 parts of luffa, 20 parts of trachelospermum officinale, 25 parts of cysteine, 10 parts of dextrose and 15 parts of sodium pyrophosphate.

其中,防冻剂为肌醇、甘露醇和山梨醇中的一种或多种,非蛋白质性质稳定剂为透明质酸,pH缓冲剂为醋酸钠。The antifreeze agent is one or more of inositol, mannitol and sorbitol, the non-protein stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

实施例中,还提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:In the embodiment, a method for preparing a neurosurgery preoperative intervention pharmaceutical composition is also proposed, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置10min,而后调节温度至30℃,加入麦冬多糖,持续搅拌10min至均匀,得到混匀物;S1: Add botulinum neurotoxin to pure water, add non-protein stabilizer at the same time, continue stirring, add pH buffer during stirring, let stand for 10 minutes after stirring, then adjust the temperature to 30°C, add Ophiopogon japonicus polysaccharide, continue stirring for 10 minutes until uniform, and obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌10min;S2: Add antifreeze to the mixture and continue stirring for 10 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,提取2次,每次提取时间120min,得到药渣及提取液;S3: Grind saffron, luffa and Trachelospermum officinale, then add cysteine and dextrose, perform warm immersion extraction, extract twice, each extraction time is 120 minutes, and obtain medicinal residues and extract;

S4:在提取液中加入焦磷酸钠,持续搅拌10min,而后进行回流提取,完成后进行浓缩干燥,得到干燥物;S4: adding sodium pyrophosphate to the extract, stirring continuously for 10 minutes, and then performing reflux extraction, and after completion, concentrating and drying to obtain a dry product;

S5:将干燥物与S1中的混匀物进行混匀,即得到干预药物组合物。S5: Mix the dried product with the mixed product in S1 to obtain an intervention drug composition.

实施例二Embodiment 2

一种神经外科术前干预药物组合物,包括:A neurosurgery preoperative intervention drug composition comprising:

70%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素120份、非蛋白质性质稳定剂15份、麦冬多糖12份、pH缓冲剂4份及纯水180份、防冻剂12份;70% of component A, comprising the following ingredients by weight: 120 parts of botulinum neurotoxin, 15 parts of non-protein stabilizer, 12 parts of ophiopogon polysaccharide, 4 parts of pH buffer, 180 parts of pure water, and 12 parts of antifreeze;

30%的B组分,按重量份计包括以下成分:西红花40份、丝瓜络30份、络石藤35份、半胱氨酸30份、右旋糖14份及焦磷酸钠18份。30% of component B comprises the following ingredients by weight: 40 parts of saffron, 30 parts of luffa, 35 parts of trachelospermum officinale, 30 parts of cysteine, 14 parts of dextrose and 18 parts of sodium pyrophosphate.

其中,防冻剂为肌醇、甘露醇和山梨醇中的一种或多种,非蛋白质性质稳定剂为透明质酸,pH缓冲剂为醋酸钠。The antifreeze agent is one or more of inositol, mannitol and sorbitol, the non-protein stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

实施例中,还提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:In the embodiment, a method for preparing a neurosurgery preoperative intervention pharmaceutical composition is also proposed, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置12min,而后调节温度至32℃,加入麦冬多糖,持续搅拌12min至均匀,得到混匀物;S1: Add botulinum neurotoxin to pure water, add non-protein stabilizer at the same time, continue stirring, add pH buffer during stirring, let stand for 12 minutes after stirring, then adjust the temperature to 32°C, add Ophiopogon japonicus polysaccharide, continue stirring for 12 minutes until uniform, and obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌12min;S2: Add antifreeze to the mixture and continue stirring for 12 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,提取3次,每次提取时间150min,得到药渣及提取液;S3: Grind saffron, luffa and Trachelospermum officinale, then add cysteine and dextrose, perform warm immersion extraction, extract for 3 times, each extraction time is 150 minutes, and obtain medicinal residues and extract;

S4:在提取液中加入焦磷酸钠,持续搅拌14min,而后进行回流提取,完成后进行浓缩干燥,得到干燥物;S4: adding sodium pyrophosphate to the extract, stirring continuously for 14 minutes, and then performing reflux extraction, and after completion, concentrating and drying to obtain a dry product;

S5:将干燥物与S1中的混匀物进行混匀,即得到干预药物组合物。S5: Mix the dried product with the mixed product in S1 to obtain an intervention drug composition.

实施例三Embodiment 3

一种神经外科术前干预药物组合物,包括:A neurosurgery preoperative intervention drug composition comprising:

70%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素180份、非蛋白质性质稳定剂25份、麦冬多糖14份、pH缓冲剂7份及纯水250份、防冻剂14份;70% of component A, comprising the following ingredients by weight: 180 parts of botulinum neurotoxin, 25 parts of non-protein stabilizer, 14 parts of ophiopogon polysaccharide, 7 parts of pH buffer, 250 parts of pure water, and 14 parts of antifreeze;

30%的B组分,按重量份计包括以下成分:西红花70份、丝瓜络45份、络石藤65份、半胱氨酸35份、右旋糖18份及焦磷酸钠25份。30% of component B comprises the following ingredients by weight: 70 parts of saffron, 45 parts of luffa, 65 parts of trachelospermum officinale, 35 parts of cysteine, 18 parts of dextrose and 25 parts of sodium pyrophosphate.

其中,防冻剂为肌醇、甘露醇和山梨醇中的一种或多种,非蛋白质性质稳定剂为透明质酸,pH缓冲剂为醋酸钠。The antifreeze agent is one or more of inositol, mannitol and sorbitol, the non-protein stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

实施例中,还提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:In the embodiment, a method for preparing a neurosurgery preoperative intervention pharmaceutical composition is also proposed, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置14min,而后调节温度至34℃,加入麦冬多糖,持续搅拌14min至均匀,得到混匀物;S1: Add botulinum neurotoxin to pure water, add non-protein stabilizer at the same time, continue stirring, add pH buffer during stirring, let stand for 14 minutes after stirring, then adjust the temperature to 34°C, add Ophiopogon japonicus polysaccharide, continue stirring for 14 minutes until uniform, and obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌14min;S2: Add antifreeze to the mixture and continue stirring for 14 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,提取3次,每次提取时间160min,得到药渣及提取液;S3: Grind saffron, luffa and Trachelospermum officinale, then add cysteine and dextrose, perform warm immersion extraction, extract 3 times, each extraction time is 160 minutes, and obtain medicinal residues and extract;

S4:在提取液中加入焦磷酸钠,持续搅拌18min,而后进行回流提取,完成后进行浓缩干燥,得到干燥物;S4: adding sodium pyrophosphate to the extract, stirring continuously for 18 minutes, and then performing reflux extraction, and after completion, concentrating and drying to obtain a dry product;

S5:将干燥物与S1中的混匀物进行混匀,即得到干预药物组合物。S5: Mix the dried product with the mixed product in S1 to obtain an intervention drug composition.

实施例四Embodiment 4

一种神经外科术前干预药物组合物,包括:A neurosurgery preoperative intervention drug composition comprising:

70%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素200份、非蛋白质性质稳定剂30份、麦冬多糖15份、pH缓冲剂8份及纯水300份、防冻剂15份;70% of component A, comprising the following ingredients by weight: 200 parts of botulinum neurotoxin, 30 parts of non-protein stabilizer, 15 parts of ophiopogon polysaccharide, 8 parts of pH buffer, 300 parts of pure water, and 15 parts of antifreeze;

30%的B组分,按重量份计包括以下成分:西红花80份、丝瓜络50份、络石藤70份、半胱氨酸40份、右旋糖20份及焦磷酸钠30份。30% of component B comprises the following ingredients by weight: 80 parts of saffron, 50 parts of luffa, 70 parts of trachelospermum officinale, 40 parts of cysteine, 20 parts of dextrose and 30 parts of sodium pyrophosphate.

其中,防冻剂为肌醇、甘露醇和山梨醇中的一种或多种,非蛋白质性质稳定剂为透明质酸,pH缓冲剂为醋酸钠。The antifreeze agent is one or more of inositol, mannitol and sorbitol, the non-protein stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

实施例中,还提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:In the embodiment, a method for preparing a neurosurgery preoperative intervention pharmaceutical composition is also proposed, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置15min,而后调节温度至35℃,加入麦冬多糖,持续搅拌15min至均匀,得到混匀物;S1: Add botulinum neurotoxin to pure water, add non-protein stabilizer at the same time, continue stirring, add pH buffer during stirring, let stand for 15 minutes after stirring, then adjust the temperature to 35°C, add Ophiopogon japonicus polysaccharide, continue stirring for 15 minutes until uniform, and obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌15min;S2: Add antifreeze to the mixture and continue stirring for 15 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,提取4次,每次提取时间180min,得到药渣及提取液;S3: Grind saffron, luffa and Trachelospermum officinale, then add cysteine and dextrose, perform warm immersion extraction, extract 4 times, each extraction time is 180 minutes, and obtain medicinal residues and extract;

S4:在提取液中加入焦磷酸钠,持续搅拌20min,而后进行回流提取,完成后进行浓缩干燥,得到干燥物;S4: adding sodium pyrophosphate to the extract, stirring continuously for 20 minutes, and then performing reflux extraction, and after completion, concentrating and drying to obtain a dry product;

S5:将干燥物与S1中的混匀物进行混匀,即得到干预药物组合物。S5: Mix the dried product with the mixed product in S1 to obtain an intervention drug composition.

对比例一Comparative Example 1

一种神经外科术前干预药物组合物,包括:A neurosurgery preoperative intervention drug composition comprising:

70%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素200份、非蛋白质性质稳定剂30份、pH缓冲剂8份及纯水300份、防冻剂15份;70% of component A, comprising the following ingredients by weight: 200 parts of botulinum neurotoxin, 30 parts of non-proteinaceous stabilizer, 8 parts of pH buffer, 300 parts of pure water, and 15 parts of antifreeze;

30%的B组分,按重量份计包括以下成分:西红花80份、丝瓜络50份、络石藤70份、半胱氨酸40份、右旋糖20份及焦磷酸钠30份。30% of component B comprises the following ingredients by weight: 80 parts of saffron, 50 parts of luffa, 70 parts of trachelospermum officinale, 40 parts of cysteine, 20 parts of dextrose and 30 parts of sodium pyrophosphate.

其中,防冻剂为肌醇、甘露醇和山梨醇中的一种或多种,非蛋白质性质稳定剂为透明质酸,pH缓冲剂为醋酸钠。The antifreeze agent is one or more of inositol, mannitol and sorbitol, the non-protein stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

对比例中,还提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:In the comparative example, a method for preparing a neurosurgery preoperative intervention drug composition is also proposed, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置15min,得到混匀物;S1: Add botulinum neurotoxin to pure water and a non-protein stabilizer, and continue stirring. Add a pH buffer during the stirring process, and let stand for 15 minutes after the stirring is completed to obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌15min;S2: Add antifreeze to the mixture and continue stirring for 15 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,提取4次,每次提取时间180min,得到药渣及提取液;S3: Grind saffron, luffa and Trachelospermum officinale, then add cysteine and dextrose, perform warm immersion extraction, extract 4 times, each extraction time is 180 minutes, and obtain medicinal residues and extract;

S4:在提取液中加入焦磷酸钠,持续搅拌20min,而后进行回流提取,完成后进行浓缩干燥,得到干燥物;S4: adding sodium pyrophosphate to the extract, stirring continuously for 20 minutes, and then performing reflux extraction, and after completion, concentrating and drying to obtain a dry product;

S5:将干燥物与S1中的混匀物进行混匀,即得到干预药物组合物。S5: Mix the dried product with the mixed product in S1 to obtain an intervention drug composition.

对比例二Comparative Example 2

一种神经外科术前干预药物组合物,包括:A neurosurgery preoperative intervention drug composition comprising:

70%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素200份、非蛋白质性质稳定剂30份、麦冬多糖15份、pH缓冲剂8份及纯水300份、防冻剂15份;70% of component A, comprising the following ingredients by weight: 200 parts of botulinum neurotoxin, 30 parts of non-protein stabilizer, 15 parts of ophiopogon polysaccharide, 8 parts of pH buffer, 300 parts of pure water, and 15 parts of antifreeze;

30%的B组分,按重量份计包括以下成分:西红花80份、丝瓜络50份、络石藤70份、半胱氨酸40份、右旋糖20份。30% of component B comprises the following ingredients by weight: 80 parts of saffron, 50 parts of luffa, 70 parts of trachelospermum officinale, 40 parts of cysteine and 20 parts of dextrose.

其中,防冻剂为肌醇、甘露醇和山梨醇中的一种或多种,非蛋白质性质稳定剂为透明质酸,pH缓冲剂为醋酸钠。The antifreeze agent is one or more of inositol, mannitol and sorbitol, the non-protein stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

对比例中,还提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:In the comparative example, a method for preparing a neurosurgery preoperative intervention drug composition is also proposed, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置15min,而后调节温度至35℃,加入麦冬多糖,持续搅拌15min至均匀,得到混匀物;S1: Add botulinum neurotoxin to pure water, add non-protein stabilizer at the same time, continue stirring, add pH buffer during stirring, let stand for 15 minutes after stirring, then adjust the temperature to 35°C, add Ophiopogon japonicus polysaccharide, continue stirring for 15 minutes until uniform, and obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌15min;S2: Add antifreeze to the mixture and continue stirring for 15 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,提取4次,每次提取时间180min,得到药渣及提取液;S3: Grind saffron, luffa and Trachelospermum officinale, then add cysteine and dextrose, perform warm immersion extraction, extract 4 times, each extraction time is 180 minutes, and obtain medicinal residues and extract;

S4:将提取液与S1中的混匀物进行混匀,即得到干预药物组合物。S4: Mix the extract and the mixture in S1 to obtain an intervention drug composition.

对比例三Comparative Example 3

一种神经外科术前干预药物组合物,包括:A neurosurgery preoperative intervention drug composition comprising:

70%的A组分,按重量份计包括以下成分:肉毒杆菌神经毒素200份、非蛋白质性质稳定剂30份、pH缓冲剂8份及纯水300份、防冻剂15份;70% of component A, comprising the following ingredients by weight: 200 parts of botulinum neurotoxin, 30 parts of non-proteinaceous stabilizer, 8 parts of pH buffer, 300 parts of pure water, and 15 parts of antifreeze;

30%的B组分,按重量份计包括以下成分:西红花80份、丝瓜络50份、络石藤70份、半胱氨酸40份、右旋糖20份。30% of component B comprises the following ingredients by weight: 80 parts of saffron, 50 parts of luffa, 70 parts of trachelospermum officinale, 40 parts of cysteine and 20 parts of dextrose.

其中,防冻剂为肌醇、甘露醇和山梨醇中的一种或多种,非蛋白质性质稳定剂为透明质酸,pH缓冲剂为醋酸钠。The antifreeze agent is one or more of inositol, mannitol and sorbitol, the non-protein stabilizer is hyaluronic acid, and the pH buffer is sodium acetate.

对比例中,还提出了一种神经外科术前干预药物组合物的制备方法,包括以下步骤:In the comparative example, a method for preparing a neurosurgery preoperative intervention drug composition is also proposed, comprising the following steps:

S1:将肉毒杆菌神经毒素加入纯水中,同时加入非蛋白质性质稳定剂,持续进行搅拌,搅拌过程中加入pH缓冲剂,搅拌完成后静置15min,得到混匀物;S1: Add botulinum neurotoxin to pure water and a non-protein stabilizer, and continue stirring. Add a pH buffer during the stirring process, and let stand for 15 minutes after the stirring is completed to obtain a mixture;

S2:在混匀物中加入防冻剂,并持续搅拌15min;S2: Add antifreeze to the mixture and continue stirring for 15 minutes;

S3:将西红花、丝瓜络、络石藤进行研磨,而后加入半胱氨酸及右旋糖,进行温浸提取,提取4次,每次提取时间180min,得到药渣及提取液;S3: Grind saffron, luffa and Trachelospermum officinale, then add cysteine and dextrose, perform warm immersion extraction, extract 4 times, each extraction time is 180 minutes, and obtain medicinal residues and extract;

S4:将提取液与S1中的混匀物进行混匀,即得到干预药物组合物。S4: Mix the extract and the mixture in S1 to obtain an intervention drug composition.

对上述实施例一到实施例四、对比例一到对比例三制备的药物组合物进行检测(每日灌服2ml),结果如下表1:The pharmaceutical compositions prepared in the above-mentioned Examples 1 to 4 and Comparative Examples 1 to 3 were tested (2 ml was administered daily), and the results are shown in Table 1:

表1Table 1

NCV(D/L)NCV (D/L) 红细胞压积(%)Hematocrit (%) 实施例一Embodiment 1 62.91462.914 46.7246.72 实施例二Embodiment 2 63.12763.127 47.3147.31 实施例三Embodiment 3 63.19563.195 47.7847.78 实施例四Embodiment 4 63.27363.273 47.6347.63 对比例一Comparative Example 1 47.86447.864 43.9143.91 对比例二Comparative Example 2 61.29661.296 24.8424.84 对比例三Comparative Example 3 46.46146.461 22.6522.65

其中,检测过程采用雄性大鼠,体重250-300g,10周龄左右。用0.1mol/L柠檬酸缓冲液(pH=4.4)将STZ溶液用0.1mol/L无菌枸橼酸-枸橼酸钠缓冲液新鲜配制成2%溶液,大鼠禁食10h,按45mg/kg尾静脉注射,给药后7d测定空腹血糖(FBG),测得空腹血糖15mmol/L以上者为DPN大鼠,在盐酸氯胺酮(100mg/kg)麻醉下,用两根针灸针分别刺入股骨颈的上下两侧作为坐骨神经上端的刺激电极,无关电极置于大鼠臀部,IL-B电刺激器的刺激参数为:方波脉冲,超强刺激,频率1HZ。在大鼠的外踝上1cm处向内上方刺入腓肠肌肌腹一同心圆电极,心记录电刺激诱发的腓肠肌动作电位,并用SR46型二线示波器观察波形情况,调试仪器,波形稳定后将信号输入微机,用上海医科大学生理教研室研制的SMUP电生理分析软件系统中的AVERAGE程度进行记录、测量、打印。根据刺激坐骨神经两点诱发腓肠肌动作电位的M波潜伏期的差值(L)及两刺激点间的距离(D),得到NCV。Among them, male rats weighing 250-300g and about 10 weeks old were used in the detection process. STZ solution was freshly prepared into 2% solution with 0.1mol/L sterile citric acid-sodium citrate buffer solution using 0.1mol/L citric acid buffer (pH=4.4). The rats were fasted for 10h and injected into the tail vein at 45mg/kg. Fasting blood glucose (FBG) was measured 7 days after administration. Those with fasting blood glucose above 15mmol/L were DPN rats. Under ketamine hydrochloride (100mg/kg) anesthesia, two acupuncture needles were inserted into the upper and lower sides of the femoral neck as stimulation electrodes at the upper end of the sciatic nerve. The irrelevant electrode was placed on the rat's buttocks. The stimulation parameters of the IL-B electrical stimulator were: square wave pulse, super-strong stimulation, and frequency 1HZ. A concentric circle electrode was inserted into the gastrocnemius muscle belly 1 cm inward and upward above the lateral malleolus of the rat, and the gastrocnemius action potential induced by electrical stimulation was recorded. The waveform was observed with a SR46 two-wire oscilloscope, and the instrument was debugged. After the waveform was stable, the signal was input into the microcomputer, and the AVERAGE level in the SMUP electrophysiological analysis software system developed by the Department of Physiology of Shanghai Medical University was used to record, measure, and print. The NCV was obtained based on the difference in the M wave latency (L) of the gastrocnemius action potential induced by stimulating the two points of the sciatic nerve and the distance (D) between the two stimulation points.

通过上述表1,可明显的看到,在实施例一到实施例四中,大鼠的NCV均较高,且红细胞压积在45%左右,药物组合物在使用后可较佳的提高神经传导速度,并对红细胞压积进行改善。From the above Table 1, it can be clearly seen that in Examples 1 to 4, the NCV of rats is relatively high, and the hematocrit is about 45%. After use, the pharmaceutical composition can better increase the nerve conduction velocity and improve the hematocrit.

在其他条件均相同的实施例四与对比例一中,对比例一中未进行麦冬多糖的配套处理,使得最终得到的组合物在使用后,神经传导速度的改善情况降低,而红细胞压积情况未出现较大变动;In Example 4 and Comparative Example 1, where other conditions were the same, the Ophiopogon japonicus polysaccharide was not used in Comparative Example 1, so that after use of the final composition, the improvement in nerve conduction velocity was reduced, while the hematocrit did not change significantly;

在对比例二与实施例四的对比中,对比例二在第二组分的处理中,未进行焦磷酸钠的加入,使得最终得到的组合物在使用后,红细胞压积情况降低,而神经传导速度未有太大的变换;In the comparison between Comparative Example 2 and Example 4, in the treatment of the second component in Comparative Example 2, sodium pyrophosphate was not added, so that the hematocrit of the final composition was reduced after use, while the nerve conduction velocity did not change much;

对比例三中,未进行麦冬多糖的配套处理,在第二组分的处理中,未进行焦磷酸钠的加入,最终得到的组合物在使用后,神经传导速度的改善情况降低,红细胞压积情况降低。In comparative example 3, the supporting treatment of Ophiopogon japonicus polysaccharide was not carried out, and in the treatment of the second component, sodium pyrophosphate was not added. After use of the final composition, the improvement of nerve conduction velocity was reduced and the hematocrit was reduced.

综上,本发明将组合物分为两部分进行处理,其中一部分涉及肉毒杆菌神经毒素及非蛋白质性质稳定剂(透明质酸),并在过程中使用了pH缓冲剂,进一步的在制备的过程中介入运用了麦冬多糖,保证生产制备环境的同时,提高混合物的稳定性,使得最终得到的组合物的应用效果更佳。In summary, the present invention divides the composition into two parts for processing, one of which involves botulinum neurotoxin and a non-protein stabilizer (hyaluronic acid), and a pH buffer is used in the process. Further, Ophiopogon japonicus polysaccharide is used in the preparation process to ensure the production and preparation environment while improving the stability of the mixture, so that the application effect of the final composition is better.

在另一部分设置了西红花、丝瓜络及络石藤,并对其进行研磨处理,而后与半胱氨酸、右旋糖进行混合并提取,在提取之后进一步加入焦磷酸钠,并进行浓缩干燥,进而得到药物组合物,药物的主体质量高,使得组合物在应用后可较佳的提高神经传导速度。In another part, saffron, loofah and trachelospermum officinale are arranged, and they are ground, and then mixed with cysteine and dextrose and extracted. After the extraction, sodium pyrophosphate is further added, and the mixture is concentrated and dried to obtain a pharmaceutical composition. The main body of the drug has high quality, so that the composition can better improve the nerve conduction velocity after application.

以上所述,仅为本发明较佳的具体实施方式,但本发明的保护范围并不局限于此,任何熟悉本技术领域的技术人员在本发明揭露的技术范围内,根据本发明的技术方案及其发明构思加以等同替换或改变,都应涵盖在本发明的保护范围之内。The above description is only a preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can make equivalent replacements or changes according to the technical scheme and inventive concept of the present invention within the technical scope disclosed by the present invention, which should be covered by the protection scope of the present invention.

Claims (10)

1. A pharmaceutical composition for neurosurgical preoperative intervention, the raw materials comprising:
60-80% of A component comprises the following components in parts by weight: 100-200 parts of botulinum neurotoxin, 10-30 parts of non-protein stabilizer, 10-15 parts of ophiopogon polysaccharide, 3-8 parts of pH buffering agent and 150-300 parts of pure water;
20-40% of a component B, which comprises the following components in parts by weight: 30-80 parts of saffron, 20-50 parts of loofah sponge, 20-70 parts of Chinese starjasmine stem, 25-40 parts of cysteine, 10-20 parts of dextrose and 15-30 parts of sodium pyrophosphate;
the non-proteinaceous stabilizing agent is hyaluronic acid.
2. The pre-neurosurgical intervention pharmaceutical composition according to claim 1 comprising 70% of the a component and 30% of the B component.
3. The neurosurgical preoperative intervention pharmaceutical composition according to claim 1, wherein the a component comprises the following components in parts by weight: 150 parts of botulinum neurotoxin, 20 parts of non-protein stabilizer, 13 parts of ophiopogon polysaccharide, 5 parts of pH buffer and 220 parts of pure water, wherein the component B comprises the following components in parts by weight: 40 parts of saffron, 35 parts of loofah, 45 parts of Chinese starjasmine stem, 35 parts of cysteine, 15 parts of dextrose and 20 parts of sodium pyrophosphate.
4. The neurosurgical preoperative intervention pharmaceutical composition according to claim 1, wherein the a component further comprises 10-15 parts by weight of an antifreezing agent.
5. The pre-neurosurgical intervention pharmaceutical composition according to claim 4, wherein the cryoprotectant is one or more of inositol, mannitol and sorbitol.
6. The pre-neurosurgical intervention pharmaceutical composition according to any of the claims 1-5, wherein the pH buffering agent is sodium acetate.
7. A method of preparing a neurosurgical preoperative intervention pharmaceutical composition according to any of claims 1 to 6, comprising the steps of:
s1: adding botulinum neurotoxin into pure water, adding a non-protein stabilizer, continuously stirring, adding a pH buffering agent in the stirring process, standing for 10-15 min after stirring, adjusting the temperature to 30-35 ℃, adding ophiopogon polysaccharide, and continuously stirring for 10-15 min to be uniform to obtain a uniformly mixed substance;
S2: adding an antifreezing agent into the uniformly mixed matter, and continuously stirring for 10-15 min;
s3: grinding stigma croci, retinervus Luffae fructus, and caulis Trachelospermi, adding cysteine and dextrose, and performing warm leaching to obtain residue and extractive solution;
s4: adding sodium pyrophosphate into the extracting solution, continuously stirring for 10-20 min, then carrying out reflux extraction, concentrating and drying after the reflux extraction is completed to obtain a dried product;
S5: and (3) uniformly mixing the dried substance with the uniformly mixed substance in the S1 to obtain the intervention pharmaceutical composition.
8. The method for preparing a pharmaceutical composition for preneurosurgical intervention according to claim 7, wherein in S1, a pH buffer is added during stirring, the mixture is left to stand for 12min after stirring, the temperature is adjusted to 32 ℃, and ophiopogon japonicus polysaccharide is added, and stirring is continued for 12min until uniformity is achieved, so as to obtain a mixture.
9. The method for preparing a pre-neurosurgical intervention pharmaceutical composition according to claim 7, wherein in S3, the extraction is performed 2-4 times with each extraction time being 120-180 min.
10. Use of a pharmaceutical composition for the preparation of a neurosurgical preoperative intervention drug, characterized in that it comprises an intervention pharmaceutical composition according to any of claims 1-9.
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