CN101507747B - Preparation method of astragalus total-saponin sodium chloride injector - Google Patents
Preparation method of astragalus total-saponin sodium chloride injector Download PDFInfo
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- CN101507747B CN101507747B CN2009100740024A CN200910074002A CN101507747B CN 101507747 B CN101507747 B CN 101507747B CN 2009100740024 A CN2009100740024 A CN 2009100740024A CN 200910074002 A CN200910074002 A CN 200910074002A CN 101507747 B CN101507747 B CN 101507747B
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- radix astragali
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Abstract
The invention relates to a radix astragali pharmaceutical preparation, in particular to a method for preparing a radix astragali total saponin sodium chloride injection. The method solves the problems existing in the prior art that an effective ingredient of the radix astragali total saponin sodium chloride injection has small solubility, and poor stability during the storage and the like. The method comprises the steps of: adding polyethylene glycol-12-hydroxystearate into water for injection, stirring the mixture to prepare a solution with mass proportion of between 2 and 5 percent; adding total saponins from radix astragali and sodium chloride into the polyethylene glycol-12-hydroxystearate solution, stirring, and dissolving; filtering and decarburizing; and encapsulating and sterilizing. The method for preparing the radix astragali total saponin sodium chloride injection can greatly improve the solubility of the total saponins from radix astragali in water, improve the stability of the total saponins from radix astragali in the water, does not produce a precipitate when placed for a long time at temperature of 60 DEG C, between 18 and 26 DEG C, and between 0 and 4 DEG C under light conditions, and has steady quality as well as convenient and safe clinical use.
Description
Technical field
The present invention relates to a kind of Radix Astragali pharmaceutical preparation, be specially a kind of preparation method of astragalus total-saponin sodium chloride injector.
Background technology
The Radix Astragali is the conventional Chinese medicine material, have support unit, strengthening vital QI to eliminate pathogenic factors, nourish heart promote blood circulation, the effect of invigorating spleen to remove dampness.The modern clinical hepatitis that is widely used in the motive is deficient, blood vessels become silted up resistance viral myocarditis, cardiac insufficiency and stagnation of dampness due to deficiency of the spleen etc.
Radix Astragali injection is at the clinical treatment that is used for obstruction of qi in the chest and cardialgia disease in a large number, determined curative effect.After deliberation, the main effective ingredient of its cardiovascular system activity is the Radix Astragali saponin class, pharmacological evaluation proof it and Radix Astragali injection therapeutic equivalence.That the Radix Astragali injection of present clinical use remains is not high at content, lack the reliable quality standard, wayward, the clinical use of drug effect can cause reactions such as patient allergy, the not high deficiency of safety in utilization.
Be that feedstock production becomes injection directly, can improve the content of Radix Astragali total saponins, increase quality controllability, make more effective, the safety of formulation of astragalus root with Radix Astragali total saponins through extracting purification.But Radix Astragali total glycosides is insoluble in water, and need seek suitable method when it is prepared into injection increases its dissolubility.Polyethylene Glycol ten dihydroxystearic acid fat are American-European a kind of novel adjuvants of exploitation in recent years, are used for solubilizing agents for drugs, have recorded in European Pharmacopoeia (EP5.5) and British Pharmacopoeia version in 2005.The pharmacological toxicology experimental data of bibliographical information shows, polyethyleneglycol-12-hydroxy stearin after intravenous injection in the animal body histamine levels utmost point significance ground be lower than polyoxyethylene sorbitan monoleate, illustrating that polyethyleneglycol-12-hydroxy stearin has low hemolytic and better physiological tolerance, is a kind of hypotoxic nonionic solubilizing agent.At present do not find that also this solubilizing agent is used for the preparation of Radix Astragali total saponins injection.
Summary of the invention
The present invention is problem such as the Radix Astragali total saponins injection effective ingredient dissolubility that exists in the prior art is little, lay up period poor stability and a kind of preparation method of astragalus total-saponin sodium chloride injector is provided in order to solve.
The present invention realizes that by following technical scheme a kind of preparation method of astragalus total-saponin sodium chloride injector comprises the following steps:
(1), in water for injection, add polyethyleneglycol-12-hydroxy stearin, stir, be configured to the solution that mass ratio is a 2-5% concentration;
(2), the ratio according to the 0.24-0.30 mg/ml in polyethyleneglycol-12-hydroxy stearin solution adds Radix Astragali total saponins, the ratio adding sodium chloride that 0.9 gram is/100 milliliters, stirring, dissolving;
(3), add charcoal treatment, filtering decarbonization;
(4), fine straining, embedding, sterilization.
The present invention finds through experiment, adopts polyethyleneglycol-12-hydroxy stearin as solubilizing agent, can significantly improve the dissolubility of Radix Astragali total glycosides in water.With the astragaloside that content is the highest in Radix Astragali total glycosides is example, and under the room temperature, its dissolubility in water is very little, has only 22.2ug/ml, but in 4% polyethyleneglycol-12-hydroxy stearin solution, its dissolubility can reach 109.7ug/ml, gained solution clear.This provides a kind of new method for Radix Astragali total saponins is mixed with injection.Among the present invention, polyethyleneglycol-12-hydroxy stearin is as solubilizing agent, and its working concentration is 2%-5% or 20mg/ml-50mg/ml.
Clear liquid with the astragalus total-saponin sodium chloride injector that adopts the inventive method to make, placed 6 months under 4-8 ℃, room temperature and 60 ℃ of temperature conditions, significant change does not take place in the solution character, and Radix Astragali total glycosides content is surveyed in sampling, do not change, medicinal liquid is stable, reliable.
The selection of polyethyleneglycol-12-hydroxy stearin and Radix Astragali total saponins rate of charge:
With the polyethyleneglycol-12-hydroxy stearin of variable concentrations as solvent, adopt above-mentioned preparation method to prepare astragalus total-saponin sodium chloride injector, with polyethyleneglycol-12-hydroxy stearin concentration is 0.1%, 0.5%, 1%, 2%, 5%, 10%, 20% preparation astragalus total-saponin sodium chloride injector, the content of survey Radix Astragali total saponins and astragaloside, the result is more suitable with the concentration preparation of 2%-5%, the concentration preparation of 0.1%-1%, it is lower to record content, illustrates that dissolving is not exclusively, concentration preparation and the 2%-5% of 10%-20% compare, content differs and is not clearly, illustrates that the preparation of 2%-5% concentration can reach best solute effect, and changes of contents is not obvious along with the increase of concentration, the declaratives polyethyleneglycol-12-hydroxy stearin is excessive for feeding intake, have neither part nor lot in preparation, invalid composition, so we have determined that the best compound concentration of Radix Astragali total saponins and polyethyleneglycol-12-hydroxy stearin is 2%-5%.The content of Radix Astragali total saponins and astragaloside is as shown in the table in the astragalus total-saponin sodium chloride injector of variable concentrations preparation.
The amount of Radix Astragali total glycosides and first glycosides in the astragalus total-saponin sodium chloride injector of table 1 variable concentrations preparation
Adopt the safety research of the astragalus total-saponin sodium chloride injector of polyethyleneglycol-12-hydroxy stearin preparation:
Injection is the highest to security requirement in multiple dosage form, therefore we make injection with above-mentioned preparation method and have carried out zoopery, by various dose, different way of administration is a laboratory animal with mice, rat, and maximum dose level intraperitoneal and intravenously administrable have reached 10.0g/kg, the behavior of observation animal, dietary habit, nephrotoxicity etc. after the administration, all have no adverse effect, vital sign is normal, illustrates that the injection that this product makes is safe.Its experimental result is as shown in the table.
Table 2 zoopery result
Adopt the stability study of the astragalus total-saponin sodium chloride injector of polyethyleneglycol-12-hydroxy stearin preparation
In order to verify the stability of the prepared injection of the present invention, we select to test under 60 ℃, 18-26 ℃, 0-4 ℃, 4576lx illumination condition with a collection of astragalus total-saponin sodium chloride injection.Result such as following table:
Table 3 injection stability test result
| Condition | Time (my god) | Clarity | Differentiate | The content of Radix Astragali total saponins (mg/ml) | The content of astragaloside (mg/ml) |
| 60℃ | 0 30 90 180 | Clarification clarification clarification clarification | Positive | 0.2742 0.2739 0.2737 0.2737 | 0.0931 0.0921 0.0918 0.0917 |
| 18-26℃ | 0 30 90 180 | Clarification clarification clarification clarification | Positive | 0.2744 0.2740 0.2738 0.2737 | 0.0933 0.0927 0.0919 0.0915 |
| 0-4℃ | 0 30 90 180 | Clarification clarification clarification clarification | Positive | 0.2738 0.2739 0.2735 0.2731 | 0.0929 0.0925 0.0916 0.0918 |
| 4576lx | 0 30 90 180 | Clarification clarification clarification clarification | Positive | 0.2743 0.2739 0.2731 0.2727 | 0.0934 0.0927 0.0916 0.0909 |
Through experimental results show that repeatedly: the method for the astragalus total-saponin sodium chloride injector of the present invention's preparation, can increase the dissolubility of Radix Astragali total saponins in water greatly, the stability of raising in water, long-term placement does not produce precipitate under 60 ℃, 18-26 ℃, 0-4 ℃ and illumination condition, steady quality, clinical safety easy to use.
The specific embodiment
Embodiment 1
Preparation prescription:
Radix Astragali total saponins 2.7g (wherein containing astragaloside 0.9g)
Polyethyleneglycol-12-hydroxy stearin 200g
Sodium chloride 90g
Water for injection adds to 10000ml
Preparation method:
1) accurately takes by weighing the polyethyleneglycol-12-hydroxy stearin of recipe quantity, join in the water for injection, stir, dissolving;
2) accurately take by weighing Radix Astragali total saponins, the sodium chloride of recipe quantity, join in the polyethyleneglycol-12-hydroxy stearin solution for preparing, stir, dissolving;
3) add 0.1% activated carbon adsorption, filtering decarbonization;
4) fine straining, embedding, the sterilization of pressurizeing of 100ml/ bottle, 30min, check, packing, promptly.
The astragalus total-saponin sodium chloride injector that embodiment 1 makes is measured through HPLC, and Radix Astragali total glycosides content is 0.2830mg/ml, and Astragaloside content is 0.0928mg/ml.
This injection is removed outer package, place under 60 ℃, 0-4 ℃, frozen process experiment and the 4576lx strong illumination, continuous ten days, and, observe clarity in sampling in 0,5,10 day, and measure Radix Astragali total glycosides and Astragaloside content, the results are shown in following table.
| Time (my god) | Clarity | Differentiate | The content of Radix Astragali total saponins (mg/ml) | The content of astragaloside (mg/ml) | |
| 60℃ | 0 5 10 | Clarification clarification clarification | Positive positive | 0.2830 0.2912 0.2814 | 0.0928 0.0935 0.0914 |
| 0-4℃ | 0 5 10 | Clarification clarification clarification | Positive positive | 0.2830 0.2871 0.2904 | 0.0928 0.0927 0.0912 |
| 0 | Clarification | Positive | 0.2830 | 0.0928 | |
| 4576lx | 5 10 | The clarification clarification | Positive | 0.2984 0.2837 | 0.0925 0.0919 |
| Freezing-thawing test | 0 5 10 | Clarification clarification clarification | Positive positive | 0.2830 0.2936 0.2793 | 0.0928 0.0909 0.0921 |
As can be seen from the above table, the astragalus total-saponin sodium chloride injector that the inventive method makes is stable under 60 ℃, 0-4 ℃, frozen process experiment and 4576lx strong illumination.
Embodiment 2
Preparation prescription:
Radix Astragali total saponins 6g (wherein containing astragaloside 2g)
Polyethyleneglycol-12-hydroxy stearin 500g
Sodium chloride 90g
Water for injection adds to 10000ml
Preparation method:
1) accurately takes by weighing the polyethyleneglycol-12-hydroxy stearin of recipe quantity, join in the water for injection, stir, dissolving;
2) accurately take by weighing Radix Astragali total saponins, the sodium chloride of recipe quantity, join in the polyethyleneglycol-12-hydroxy stearin solution for preparing, stir, dissolving;
3) add 0.1% activated carbon adsorption, filtering decarbonization;
4) fine straining, embedding, the sterilization of pressurizeing of 100ml/ bottle, 30min, check, packing, promptly.
The astragalus total-saponin sodium chloride injector that embodiment 2 makes is measured through HPLC, and Radix Astragali total glycosides content is 0.6014mg/ml, and Astragaloside content is 0.2024mg/ml.
This injection is removed outer package, place under 60 ℃, 0-4 ℃, frozen process experiment and the 4576lx strong illumination, continuous ten days, and, observe clarity in sampling in 0,5,10 day, and measure Radix Astragali total glycosides and Astragaloside content, the results are shown in following table.
| Time (my god) | Clarity | Differentiate | The content of Radix Astragali total saponins (mg/ml) | The content of astragaloside (mg/ml) | |
| 60℃ | 0 5 10 | Clarification clarification clarification | Positive positive | 0.6014 0.6102 0.6019 | 0.2024 0.2084 0.2045 |
| 0-4℃ | 0 5 10 | Clarification clarification clarification | Positive positive | 0.6014 0.6022 0.6024 | 0.2024 0.2076 0.2078 |
| 4576lx | 0 5 10 | Clarification clarification clarification | Positive positive | 0.6014 0.6114 0.6058 | 0.2024 0.2035 0.2047 |
| Freezing-thawing test | 0 5 10 | Clarification clarification clarification | Positive positive | 0.6014 0.6032 0.6047 | 0.2024 0.2051 0.2015 |
As can be seen from the above table, the astragalus total-saponin sodium chloride injector that the inventive method makes is stable under 60 ℃, 0-4 ℃, frozen process experiment and 4576lx strong illumination.
The method of the astragalus total-saponin sodium chloride injector of the present invention's preparation, simple to operate, the injection clarity of preparation is good, stable performance.
Embodiment 3
Preparation prescription:
Radix Astragali total saponins 4.35g (wherein containing astragaloside 1.45g)
Polyethyleneglycol-12-hydroxy stearin 350g
Sodium chloride 90g
Water for injection adds to 10000ml
Preparation method is with embodiment 2.
Claims (2)
1. the preparation method of an astragalus total-saponin sodium chloride injector is characterized in that: comprise the following steps:
(1), in water for injection, add polyethyleneglycol-12-hydroxy stearin, stir, be configured to the solution that mass ratio is a 2-5% concentration;
(2), the ratio according to the 0.24-0.30 mg/ml in polyethyleneglycol-12-hydroxy stearin solution adds Radix Astragali total saponins, the ratio adding sodium chloride that 0.9 gram is/100 milliliters, stirring, dissolving;
(3), add charcoal treatment, filtering decarbonization;
(4), fine straining, embedding, sterilization.
2. the preparation method of astragalus total-saponin sodium chloride injector according to claim 1, it is characterized in that: polyethyleneglycol-12-hydroxy stearin is configured to the solution that mass ratio is 4% concentration.
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| CN104116749A (en) * | 2013-04-26 | 2014-10-29 | 成都力思特制药股份有限公司 | Polyoxyethylene-660-12-hydroxy stearate containing breviscapine injection preparation and preparation method thereof |
| CN104116777A (en) * | 2013-04-26 | 2014-10-29 | 成都力思特制药股份有限公司 | Polyoxyethylene-660-12-hydroxy stearate containing astragalus membranaceus injection drug preparation and preparation method thereof |
| CN105560173B (en) * | 2015-12-29 | 2019-02-05 | 江苏九旭药业有限公司 | A kind of high stability astragalus injection and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1481806A (en) * | 2003-07-29 | 2004-03-17 | 上海博泰医药科技有限公司 | Injection formulation of astragalus root saponin and its preparation mehod |
| CN1543976A (en) * | 2003-11-27 | 2004-11-10 | 上海博泰医药科技有限公司 | Astragaloside injection preparation and its preparing process |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1481806A (en) * | 2003-07-29 | 2004-03-17 | 上海博泰医药科技有限公司 | Injection formulation of astragalus root saponin and its preparation mehod |
| CN1543976A (en) * | 2003-11-27 | 2004-11-10 | 上海博泰医药科技有限公司 | Astragaloside injection preparation and its preparing process |
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