CN104116777A - Polyoxyethylene-660-12-hydroxy stearate containing astragalus membranaceus injection drug preparation and preparation method thereof - Google Patents

Abstract

The invention provides an astragalus membranaceus injection drug preparation with higher security and a preparation method thereof, the astragalus membranaceus injection drug preparation is an injection drug mainly prepared by together dissolving an astragalus membranaceus extract and polyoxyethylene-660-12-hydroxy stearate (solutol-HS15) as a solubilizer into injection water, and the use amount of the used polyoxyethylene-660-12-hydroxy stearate (solutol-HS15) is 1g / 100ml. The literature research in the prior art confirms that the security of the polyoxyethylene-660-12-hydroxy stearate (solutol-HS15) used in the preparation is far better than that of polysorbate-80; moreover, safety experiment shows that the security of an astragalus membranaceus injection liquid using the polyoxyethylene-660-12-hydroxy stearate (solutol-HS15) as the solubilizer is obviously better than that of an astragalus membranaceus injection liquid using the polysorbate-80 as a solubilizer.

Description

A kind of Radix Astragali drug injection preparation containing polyethyleneglycol-12-hydroxy stearin and preparation method thereof

Technical field

The present invention relates to field of medicine preparations, relate to particularly a kind of Radix Astragali drug injection preparation containing polyethyleneglycol-12-hydroxy stearin and preparation method thereof.

background technology

[Radix Astragali injection standard is recorded in health drug standard promulgated by the ministries or commissions of the Central Government (WS3-B-3335-98, the 17 of Traditional Chinese medicine historical preparation), is the sterile water solution through being processed into by Milkvetch Root.Get Radix Astragali 2000g, decoct with water three times, each 1.5 hours, collecting decoction, filter, filtrate is concentrated into every 1ml and is equivalent to crude drug 1～2g, with ethanol precipitation process secondary, in solution, be 75% containing amount of alcohol for the first time, be 85% for the second time, each all cold preservation is placed, reclaim ethanol and be concentrated into every 1ml and be equivalent to crude drug 10g, be diluted to every 1ml with water for injection and be equivalent to crude drug 0.75～1g, cold preservation is placed 12 hours, filter, filtrate is concentrated into every 1ml and is equivalent to crude drug 5～6g, let cool, with 20% sodium hydroxide solution adjusting pH value to 7.5, boil, add 0.125% active carbon, boil 5 minutes, filter while hot, inject water and make into 1000ml, filter, regulate pH value to 7.5 with 20% sodium hydroxide solution again, filter, embedding, sterilizing, obtain.Primary standard does not embody in injection has added Tween-80, still in the publicity of Radix Astragali injection standard, has added again 1% Tween-80.And in requiring, the Radix Astragali injection description revision of the up-to-date announcement of State Food and Drug Administration on April 16 in 2013 clearly writes " this product also has Tween-80, to containing Tween-80 class allergy sufferers forbidding " exactly.

Radix Astragali injection has Yiqiyangyuan, and strengthening vital QI to eliminate pathogenic factors nourishes heart and promotes blood circulation, effect of invigorating spleen to remove dampness.The hepatitis of viral myocarditis, cardiac insufficiency and the stagnation of dampness due to deficiency of the spleen of clinical, blood-vessel obstructive deficient for the motive.Usage and dosage is intramuscular injection, a 2～4ml, 1～2 time on the one.Intravenous drip, a 10～20ml, 1 time on the one, or follow the doctor's advice.

The Radix Astragali extract obtaining according to method for making in Radix Astragali injection quality standard, its main component comprises the functional component such as calycosin and glycoside and multiple Radix Astragali saponin.Therefore make Radix Astragali injection easily occur the problems such as precipitation and solution muddiness in high temperature sterilize and long-term storage process.Current Radix Astragali injection all uses Tween-80 as solubilizing agent, but Tween-80 easily becomes sour in high temperature sterilize and long-term storage process, causes impurity content to rise; And Tween-80 itself just has stronger hemolytic and causes anaphylaxis, can increase the occurrence probability of the untoward reaction of injection.And add Tween-80 and in the process of long-term storage, still there will be the problem such as a small amount of precipitation and solution muddiness as the product of solubilizing agent, thereby increased the risk of clinical application.

For addressing the above problem, the invention provides a kind of Radix Astragali drug injection, this injection adopts HS15 (also referred to as " HS15 ", polyoxyethylene-660-12-hydroxy stearate, trade name Solutol HS15) do solubilizing agent.First, verified its of the literature research of prior art has the safety that is much better than Tween-80; Experiment also proves that Pregnant Rabbits intravenous injection contains Tween-80 187.5mg/kg and can cause obvious maternal toxicity, and intravenous injection gives HS15 215mg/kg and has no significant effect; And safety experiment of the present invention also shows to adopt polyethyleneglycol-12-hydroxy stearin to be obviously better than adopting the Radix Astragali injection of Tween-80 as solubilizing agent as the Radix Astragali injection safety of solubilizing agent.

Summary of the invention

The present invention, in order to solve multiple security risk and the preparation defect that in prior art, Radix Astragali drug injection preparation exists, provides a kind of Radix Astragali drug injection preparation of HS15 (hereinafter to be referred as HS15) as solubilizing agent that adopt.

HS15 is a kind of nonionic surfactant, has good biological tolerance and applied range, and is proved to be outstanding solubilizing agent, and the present invention adopts HS15 as solubilizing agent, has following advantages:

Low histamine release---preoperative without using hydryllin and corticoid;

Low haemolysis;

Higher human body safety in utilization, verified its of the literature research of prior art has the safety that is much better than Tween-80;

Higher physiological tolerance;

High solubilising power-make the injection of low capacity high dose become possibility;

Low viscosity, even in the time of high concentration, 30% concentration solution also can painless administration;

Record in Deutscher Arzneibucs, British Pharmacopoeia and European Pharmacopoeia;

In the present invention, concrete HS15 consumption is 1g/100ml.

In above-mentioned Radix Astragali drug injection preparation, the consumption of Radix Astragali extract is that every 100ml solution is containing being equivalent to 200g Milkvetch Root through extracting the Radix Astragali extract of preparing with process for refining.

A preparation method for the above-mentioned Radix Astragali drug injection preparation containing polyethyleneglycol-12-hydroxy stearin, comprises the steps:

(1) get Radix Astragali 2000g, polyethyleneglycol-12-hydroxy stearin 10g;

(2) get Radix Astragali 2000g, decoct with water three times, each 1.5 hours, collecting decoction, filtered, filtrate is concentrated into every 1ml and is equivalent to crude drug 2g, with ethanol precipitation process secondary, in solution, be 63% containing amount of alcohol for the first time, be 86% for the second time, each all cold preservation is placed, and reclaims ethanol and is concentrated into without alcohol taste

(3) be diluted to every 1ml with water for injection and be equivalent to crude drug 2.5g, cold preservation is placed more than 12 hours, filter, filtrate is boiled 5 minutes, add 10g polyethyleneglycol-12-hydroxy stearin, be stirred to dissolve, with sodium hydroxide solution adjusting pH value to 7.5 ~ 8.0 of debita spissitudo, inject water and make into 1000ml, mix;

(4) solution is through filtering with microporous membrane, fill, and sterilizing, to obtain final product.

The present invention studies and shows by experiment, and the Radix Astragali drug injection preparation security that adopts polyethyleneglycol-12-hydroxy stearin to make as solubilizing agent is all better than the Radix Astragali drug injection preparation that adopts Tween-80 to make.

In sum, beneficial effect of the present invention is: the solubilizing agent Tween-80 that provides the higher solubilizing agent of a kind of safety (polyethyleneglycol-12-hydroxy stearin) to be used for replacing to have potential safety hazard in existing commercially available Radix Astragali injection and affected product quality, can predict and can avoid numerous clinical application untoward reaction of causing due to Tween-80, thereby greatly improve the safety of Radix Astragali drug injection preparation clinical application.

Detailed description of the invention

embodiment 1(HS15 consumption is 1g/100ml)

Radix Astragali 2000g

HS15 10g

Get Radix Astragali 2000g, decoct with water three times, each 1.5 hours, collecting decoction, filtered, and filtrate is concentrated into every 1ml and is equivalent to crude drug 2g; With ethanol precipitation process secondary, in solution, be 63% containing amount of alcohol for the first time, be 86% for the second time, each all cold preservation is placed, and reclaims ethanol and is concentrated into without alcohol taste; Be diluted to every 1ml with water for injection and be equivalent to crude drug 2.5g, cold preservation is placed more than 12 hours, filter, filtrate is boiled 5 minutes, add 10g polyethyleneglycol-12-hydroxy stearin, be stirred to dissolve, with sodium hydroxide solution adjusting pH value to 7.5 ~ 8.0 of debita spissitudo, inject water and make into 1000ml, mix.Through filtering with microporous membrane, fill, sterilizing, to obtain final product.

reference examples 1(Tween-80 consumption is 1g/100ml) (according to existing Radix Astragali injection quality standard prescription and preparation technology's preparation)

Radix Astragali 2000g

Tween-80 10g

Get Radix Astragali 2000g, decoct with water three times, each 1.5 hours, collecting decoction, filtered, and filtrate is concentrated into every 1ml and is equivalent to crude drug 2g; With ethanol precipitation process secondary, in solution, be 63% containing amount of alcohol for the first time, be 86% for the second time, each all cold preservation is placed, and reclaims ethanol and is concentrated into without alcohol taste; Be diluted to every 1ml with water for injection and be equivalent to crude drug 2.5g, cold preservation is placed more than 12 hours, filters, filtrate is boiled 5 minutes, adds 10g Tween-80, is stirred to dissolve, with sodium hydroxide solution adjusting pH value to 7.5 ~ 8.0 of debita spissitudo, inject water and make into 1000ml, mix.Through filtering with microporous membrane, fill, sterilizing, to obtain final product.

embodiment 1 and reference examples 1 safety contrast

Safety judgment basis: the different prescription products according to the present invention ( embodiment 1 and reference examples 1) produce immunoreactive difference and degree and different prescription products and animal is produced to difference and the degree of hemolytic carry out its safety of comparison.

The immunoreation that result: embodiment 1 produces and hemolytic reaction are all lower than reference examples 1.

Conclusion: the safety of Radix Astragali drug injection preparation of the present invention (adopting polyethyleneglycol-12-hydroxy stearin as solubilizing agent) is obviously better than adopting existing commercially available Radix Astragali drug injection preparation (adopting Tween-80 as solubilizing agent).Can expect in the middle of clinical practice in the future, can reduce largely the generation due to untoward reaction such as the caused allergy of Tween-80 and haemolysis, can guarantee to greatest extent the safety of clinical application, reduce clinical application risk.

Claims (3)

1. the Radix Astragali drug injection preparation containing polyethyleneglycol-12-hydroxy stearin, it is characterized in that mainly comprising principal agent Radix Astragali extract, solubilizer polyethylene glycol 12-hydroxy stearic acid ester and water for injection, the consumption of described polyethyleneglycol-12-hydroxy stearin is 1g/100ml.

2. Radix Astragali drug injection preparation according to claim 1, is characterized in that, preparation method comprises the steps:

(1) get Radix Astragali 2000g, polyethyleneglycol-12-hydroxy stearin 10g, for subsequent use;

(2) get Radix Astragali 2000g, decoct with water three times, each 1.5 hours, collecting decoction, filtered, filtrate is concentrated into every 1ml and is equivalent to crude drug 2g, with ethanol precipitation process secondary, in solution, be 63% containing amount of alcohol for the first time, be 86% for the second time, each all cold preservation is placed, and reclaims ethanol and is concentrated into without alcohol taste;

(3) be diluted to every 1ml with water for injection and be equivalent to crude drug 2.5g, cold preservation is placed more than 12 hours, filter, filtrate is boiled 5 minutes, adds 10g polyethyleneglycol-12-hydroxy stearin, is stirred to dissolve, with sodium hydroxide solution adjusting pH value to 7.5 ~ 8.0 of debita spissitudo, inject water and make into 1000ml, mix;

(4) solution is through filtering with microporous membrane, fill, and sterilizing, to obtain final product.

3. the application in the medicine of the hepatitis of viral myocarditis, cardiac insufficiency and the stagnation of dampness due to deficiency of the spleen of Radix Astragali drug injection preparation according to claim 1, blood-vessel obstructive deficient in the preparation treatment motive.