CN104306417B - A kind of Radix Et Caulis Acanthopanacis Senticosi injection of low toxicity and preparation method thereof - Google Patents
A kind of Radix Et Caulis Acanthopanacis Senticosi injection of low toxicity and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to a kind of Radix Et Caulis Acanthopanacis Senticosi injection of low toxicity and preparation method thereof.Wherein Radix Et Caulis Acanthopanacis Senticosi injection contains following active component：Containing the 5.5mg/ml of general flavone 1.8, the 0.70mg/ml of Syringin 0.13 and the 0.34mg/ml of eleutheroside E 0.06, the μ g/ml of the quantity of potassium ion≤800.The Radix Et Caulis Acanthopanacis Senticosi injection potassium content that the present invention is provided is low, and the potassium content of said preparation controls in national standard≤1000 μ g/ml, is down to 800 μ g/ml (or being calculated as 800 μ g/5mg general flavones) below；Undue toxicity is small, safe.Shown by zoopery, study subject tolerable concentration reaches 18mg/ml by the 5mg/ml in national standard, raising.The Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided, abnormal toxicity test result is better than existing commercially available prod.
Description
Technical field
The present invention relates to Radix Et Caulis Acanthopanacis Senticosi injection, and in particular to a kind of Radix Et Caulis Acanthopanacis Senticosi injection of low toxicity.
Background technology
Wilsonii is Araliaceae wilsonii Acanthopanax senticosus (Rupr.et Maxim.) Harms
Dry root and rhizome or stem.With replenishing qi to invigorate the spleen, the effect tonified the kidney to relieve mental strain.Property pungent, slight bitter, temperature.Radix Et Caulis Acanthopanacis Senticosi injection is thorn
The extracted sterile water solution being processed into of slender acanthopanax, effect is flat filling liver kidney, strengthening the essence zhuanggu.Caused by for treating kidney deficiency and liver
Transient ischemic attack, cerebral arteriovenous malformation, cerebral thrombosis, cerebral embolism etc..Also it is used to treat coronary heart disease, angina pectoris merges god
Through weak and climacteric metancholia etc..
Traditional Chinese medicine including Radix Et Caulis Acanthopanacis Senticosi injection, the new agent of Chinese medicine produced as development of modern scientific technology
Type, overcomes the shortcomings of traditional Chinese medicine bioavilability is low, action is slow, is gradually favored by many patients.However, clinic makes
During, the report of traditional Chinese medicine injection adverse reaction is increasing, and its security is also all the more taken seriously.
Clinical research shows：During medicine of the drip-feed containing potassium ion, potassium concentration in blood can be increased, be can result in
Cardiac enlargement and powerless, even results in death.Potassium ion reducing heart rate and can prevent beating of the heart from atrium to ventricle,
Its reason is that extracellular high potassium concentration ion reduces the resting membrane electric potential of cardiac muscle fibre, causes action potential to reduce, heart
Shrink powerless.If extracellular potassium concentration is too high, resting membrane electric potential will be eliminated, and cardiac muscle cell cannot produce and fight
It is dynamic, so that cardiac arrest.
Therefore, during medicine of the drip-feed containing potassium ion, the general concentration of potassium ion is no more than 0.3%, and with regard to existing Chinese medicine
For injection, day maximum dosage it is general in below 100ml, such as：XUESAITONG ZHUSHEYE 4-16ml, Shu Xuening injection
20ml, astragalus injection 20ml, Shuanhuanglian injection 60ml；And Radix Et Caulis Acanthopanacis Senticosi injection 20ml specifications 200ml (contains general flavone
1000mg) with Radix Et Caulis Acanthopanacis Senticosi injection 250ml specifications 500ml (containing general flavone 1000mg) day maximum dosage special circumstances,
For the safety of the civilian medicine of guarantor, it is necessary to carry out regulation and accurate measure to quantity of the Radix Et Caulis Acanthopanacis Senticosi injection containing potassium ion.
And existing Chinese patent, such as CN201210049755.1 (hereinafter referred to as patent in 2012) disclose a kind of wilsonii
Composition contains its preparation and its detection method, the problem of not mentioning potassium content in control medicine.
For problem present in existing Radix Et Caulis Acanthopanacis Senticosi injection, inventor passes through substantial amounts of research, finally proposes this hair
It is bright.
The content of the invention
It is an object of the invention to provide a kind of Radix Et Caulis Acanthopanacis Senticosi injection of low toxicity.
Another object of the present invention is to there is provided the preparation method of the injection.A kind of wilsonii note that the present invention is provided
Liquid is penetrated, contains following active component：1.8-5.5mg/ml containing general flavone, Syringin 0.13-0.70mg/ml and eleutheroside
E0.06-0.34mg/ml, the μ g/ml of the quantity of potassium ion≤800.Preferably, the Radix Et Caulis Acanthopanacis Senticosi injection contain it is following activity into
Point, divided by existing specification：
Every 20ml, general flavone 4.5-5.5mg/ml, Syringin 0.32-0.70mg/ml and eleutheroside E 0.15-
0.34mg/ml, the μ g/ml of the quantity of potassium ion≤800；
Every 100ml, 2.7-3.3mg/ml containing general flavone, Syringin 0.19-0.42mg/ml and eleutheroside E
0.09-0.20mg/ml, the μ g/ml of the quantity of potassium ion≤500；
Every 250ml, 1.8-2.2mg/ml containing general flavone, Syringin 0.13-0.28mg/ml and eleutheroside E 0.06-
0.14mg/ml, the μ g/ml of the quantity of potassium ion≤300.
Further preferably, the Radix Et Caulis Acanthopanacis Senticosi injection contains following active component, is divided by existing specification：
Every 20ml, 4.5-5.5mg/ml containing general flavone, Syringin 0.32-0.70mg/ml and eleutheroside E 0.15-
0.34mg/ml, the μ g/ml of the quantity of potassium ion≤550；
Every 100ml, 2.7-3.3mg/ml containing general flavone, Syringin 0.19-0.42mg/ml and eleutheroside E
0.09-0.20mg/ml, the μ g/ml of the quantity of potassium ion≤360；
Every 250ml, 1.8-2.2mg/ml containing general flavone, Syringin 0.13-0.28mg/ml and eleutheroside E 0.06-
0.14mg/ml, the μ g/ml of the quantity of potassium ion≤240.
Still more preferably, the Radix Et Caulis Acanthopanacis Senticosi injection contains following active component, is divided by existing specification：
Every 20ml, general flavone 5.14-5.23mg/ml, Syringin 0.36-0.5mg/ml and eleutheroside E 0.17-
0.25mg/ml, the μ g/ml of the quantity of potassium ion≤550.
A kind of preparation method for Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided, this method comprises the following steps：Extracted and pierced with water
Slender acanthopanax medicinal material, obtained wilsonii herbal decoction is after alcohol precipitation, after being handled through stone sulphur method, crosses macroreticular resin and is adsorbed, eluted,
Alcohol precipitation again after eluent is concentrated, then passes through hot pressing and ultrafiltration, obtains siberian Ginseng P.E again；Through ingredients, embedding, go out
Bacterium, produces Radix Et Caulis Acanthopanacis Senticosi injection.
In the above method：
The siberian Ginseng P.E is prepared by following methods：
(1) extract：The water measured again with 6~12 volumes extracts wilsonii medicinal material 2~3 times, extracts 1~2 hour every time, merges
Extract solution, concentration, obtains wilsonii herbal decoction, standby；
(2) first time alcohol precipitation：Under agitation, concentration is added in the wilsonii herbal decoction obtained to step (1) is
More than 93% ethanol causes alcohol content to be 74-86%, is sufficiently stirred for, and stands more than 6 hours, filtering, and filtrate recycling ethanol is extremely
Without alcohol taste, and when being concentrated into 80 DEG C, relative density is 1.10~1.18, obtains an alcohol precipitation cream of siberian Ginseng P.E, standby；
(3) stone sulphur method is handled：Alcohol precipitation cream of the siberian Ginseng P.E that step (2) is obtained is mixed with water, and stirring is equal
After even, filtered, during 40 DEG C~50 DEG C of liquid temperature degree to be filtered, pH value is adjusted to 10.0~12.0 with 20% milk of lime, stirring,
Again with 20% sulphur acid for adjusting pH value to 5.0~6.0, continue to stir, stand, leaching supernatant simultaneously reclaims and is concentrated into 80 DEG C of phases
It is 1.14~1.19 to density, obtains condensed cream；
(4) macroporous resin adsorption：The wilsonii condensed cream for taking step (3) to obtain, is diluted to general flavone with water for injection and contains
Measure as 7.5~10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 4.0~5.5, stirs, refrigeration 12 hours with
On；After decoction after refrigeration is clarified through filtering with microporous membrane, pH value 2.0 ± 0.5 is adjusted, filtrate is with macropore on 1.5~2BV/h flow velocitys
Resin column, is then rinsed, 50% then measured again with 3~6 volumes with same flow velocity with 0.3~0.5 times of column volume purified water
Ethanol elution, collect eluent, adjust pH be 5.0~6.5, when 50% eluent is concentrated into 80 DEG C relative density be 1.13~
1.20, condensed cream is obtained, it is standby；
(5) secondary alcohol precipitation：Under agitation, it is more than 93% second that concentration is added in the condensed cream obtained to step (4)
Alcohol makes its alcohol content be 80~86%, is sufficiently stirred for, and stands more than 12 hours, leaching supernatant, and filtrate recycling ethanol is to without alcohol
Taste, and relative density is 1.11~1.20 when being concentrated into 80 DEG C, obtains the secondary alcohol precipitation cream of siberian Ginseng P.E；
(6) hot pressing and ultrafiltration：Hot pressing and ultrafiltration：The secondary alcohol precipitation cream of siberian Ginseng P.E for taking step (5) to obtain, with injection
General flavone content is diluted with water to for 7.5~10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 4.0~5.0, stirring
Uniformly, 115~121 DEG C sterilize 30~40 minutes, refrigerate more than 12 hours；Decoction after refrigeration is clarified through filtering with microporous membrane
Afterwards, pH value 5.5 ± 0.5 is adjusted, after decoction is clarified through filtering with microporous membrane, successively progress 100,000,30,000 grades of two-stage ultrafiltering, filtrate
It is 1.11~1.20 to be concentrated into relative density, that is, obtains siberian Ginseng P.E.
In the siberian Ginseng P.E：
The first time alcohol precipitation, comprises the following steps：Under agitation, the wilsonii herbal decoction obtained to step (1)
Ethanol that concentration is more than 93% is added so that alcohol content is 74.5-75.5%, is sufficiently stirred for, stands 6-18 hour, filtering is filtered
Liquid reclaims ethanol to relative density is 1.11~1.15 without alcohol taste, and when being concentrated into 80 DEG C, obtains siberian Ginseng P.E once
Alcohol precipitation cream.
The stone sulphur method processing comprises the following steps：Alcohol precipitation cream of the siberian Ginseng P.E that step (2) is obtained with
The mixing of water that 8-12 times of alcohol precipitation paste volume is measured, is filtered after stirring, during 40 DEG C~50 DEG C of liquid temperature degree to be filtered, with 20% lime
Breast regulation pH value is to 10.5~11.5, stirring, then with 20% sulphur acid for adjusting pH value to 5.1~5.5, continue to stir, stand, filter
It is 1.16~1.19 to take supernatant and reclaim relative density when being concentrated into 80 DEG C, obtains condensed cream.
The macroporous resin adsorption comprises the following steps：The wilsonii condensed cream that step (3) is obtained is dilute with water for injection
It is 8.0~10.0mg/ml to release to general flavone content, after stirring, and filtering, filtrate adjusts pH value 5.0~5.4, stirs, cold
Hide 12-14h；Decoction after refrigeration adjusts pH value 2.0-2.3, filtrate is with 1.5BV/h's after 0.45 μm of filtering with microporous membrane clarification
Macroporous resin column on flow velocity, is then rinsed with same flow velocity with 0.3~0.5 times of column volume purified water, then with 3~5 volumes
50% ethanol elution of amount, collects eluent again, and it is 5.3~5.5 to adjust pH, and it is 1.15 that 50% eluent is concentrated into relative density
~1.20, obtain condensed cream.
The secondary alcohol precipitation comprises the following steps：Under agitation, the condensed cream obtained to step (4) add 93% with
Upper ethanol causes alcohol content to be 84.5-85.5%, is sufficiently stirred for, and stands 12-16 hours, leaching supernatant, filtrate recycling ethanol
To relative density is 1.14~1.16 without alcohol taste, and when being concentrated into 80 DEG C, the secondary alcohol precipitation cream of siberian Ginseng P.E is obtained.
The hot pressing and ultrafiltration comprise the following steps：The secondary alcohol precipitation cream of siberian Ginseng P.E for taking step (5) to obtain, with note
Penetrate and be diluted with water to general flavone content for 8.0~10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 4.2~4.8, stirs
Mix uniform, 115~121 DEG C sterilize 30~40 minutes, refrigerate 12 hours, after the decoction after refrigeration is clarified through filtering with microporous membrane,
PH value 5.2-5.5 is adjusted, after decoction is clarified through filtering with microporous membrane, successively progress 100,000,30,000 grades of two-stage ultrafiltering, filtrate concentration
It is 1.15~1.18 to relative density, that is, obtains siberian Ginseng P.E.
Preferably, the siberian Ginseng P.E is prepared by following methods：
(1) extract：The water measured again with 8~12 volumes extracts wilsonii medicinal material 2~3 times, extracts 1~2 hour every time, merges
Extract solution, concentration, obtains wilsonii herbal decoction, standby；
(2) first time alcohol precipitation：Under agitation, it is 93 that concentration is added in the wilsonii herbal decoction obtained to step (1)
~95% ethanol causes alcohol content to be 74.5-75.5%, stirs after 15min, stands 6~18 hours, and filtering, filtrate reclaims second
Alcohol obtains an alcohol precipitation cream of siberian Ginseng P.E to relative density is 1.11~1.15 without alcohol taste, and when being concentrated into 80 DEG C, standby
With；
(3) stone sulphur method is handled：Alcohol precipitation cream of the siberian Ginseng P.E that step (2) is obtained is mixed with water, and stirring is equal
After even, filtered, during liquid temperature 45 C to be filtered, adjust pH value to 10.5~11.5 with 20% milk of lime, stir, then use
20% sulphur acid for adjusting pH value continues to stir, stands 4~8 hours to 5.1~5.5, and leaching supernatant simultaneously reclaims and is concentrated into 80 DEG C
When relative density be 1.16~1.19, obtain condensed cream；
(4) macroporous resin adsorption：The wilsonii condensed cream for taking step (3) to obtain, is diluted to general flavone with water for injection and contains
Measure as 8.0~10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 5.0~5.5, stirs, and refrigeration 12~18 is small
When；After decoction after refrigeration is clarified through filtering with microporous membrane, pH value 2.0-2.3 is adjusted, filtrate is with macroreticular resin on 1.5BV/h flow velocitys
Post, is then rinsed with same flow velocity with 0.3~0.5 times of column volume purified water, 50% ethanol then measured again with 3~5 volumes
Elution, collects eluent, and it is 5.3~5.5 to adjust pH, and relative density is 1.13~1.20 when 50% eluent is concentrated into 80 DEG C,
Condensed cream is obtained, it is standby；
(5) secondary alcohol precipitation：Under agitation, it is 93~95% second that concentration is added in the condensed cream obtained to step (4)
Alcohol makes its alcohol content be 84~85.5%, is sufficiently stirred for, and stands 12~16 hours, leaching supernatant, filtrate recycling ethanol to nothing
Alcohol taste, and relative density is 1.14~1.16 when being concentrated into 80 DEG C, obtains the secondary alcohol precipitation cream of siberian Ginseng P.E；
(6) hot pressing and ultrafiltration：The secondary alcohol precipitation cream of siberian Ginseng P.E for taking step (5) to obtain, is diluted to water for injection
General flavone content is 8.0~10.0mg/ml, after stirring, and filtering, filtrate adjusts pH value 4.2~4.8, and high-temp steam sterilizing is cold
Hide 12 hours；After decoction after refrigeration is clarified through filtering with microporous membrane, pH value 5.2~5.5 is adjusted, decoction is clear through filtering with microporous membrane
After clear, successively progress 100,000,30,000 grades of two-stage ultrafiltering, it is 1.15~1.20 that filtrate, which is concentrated into relative density, that is, obtains wilsonii
Extract.
In step (3), the model ADS-F8 of the macroreticular resin, ADS-17, HPD750, D101, HPD100,
HPD450, AB-8 or DM130.
In step (4), the pH value of purified water is 3.0.
A kind of preparation method for Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided, this method comprises the following steps：Wilsonii is extracted
Thing is diluted with water to 6.0~10mg/ml of general flavone, adds activated carbon, and backflow boils absorption 15min, cools down 40-50 DEG C, 0.45 μ
M membrane filtrations with 10,000 ultrafiltration membrance filters, when filter to permeate does not have flow, refilter to clarifying, collect and merging filtrate, stop
Only ultrafiltration, filtrate adjusts pH value to 5.0~6.0, and decoction, through high-temp steam sterilizing, is cooled down, i.e., through 0.22 μm of filter core refined filtration, packing
.
Preferably, it the described method comprises the following steps：Siberian Ginseng P.E is diluted with water to general flavone 6.0mg/ml, adds
Absorption 15 minutes is boiled in 0.2% activated carbon, backflow, is cooled to 40-50 DEG C, through 0.45 μm of membrane filtration to clarification；With 10,000 ultrafiltration
Membrane filtration, when filter to permeate does not have flow, pushes up water in right amount, stops ultrafiltration, censorship, general flavone 2-5mg/ is diluted to according to content
Ml, pH value 5.2~5.5 is adjusted with 20% sodium hydroxide solution；Decoction through 0.22 μm of filter core refined filtration, it is filling in 20ml or 250ml,
In 500ml ampullas, sealing；High-temp steam sterilizing, and it is cooled to less than 60 DEG C in time, produce Radix Et Caulis Acanthopanacis Senticosi injection.
In above-mentioned preparation method, the aperture of miillpore filter used is 0.45 μm.
The high-temp steam sterilizing refers to 115~121 DEG C of steam sterilizings 30~40 minutes.
The Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided has advantages below：
1st, the reason for present invention prepares low concentration potassium ion parenteral solution：After the processing of stone sulphur method, first through macroporous resin treatment,
Remove undesired impurities, the other ions in part can be also increased while reducing ion, then after secondary alcohol precipitation, while forming impurity
Potassium ion can be adsorbed, is together removed.
2nd, the Radix Et Caulis Acanthopanacis Senticosi injection potassium content that the present invention is provided is low, and the potassium content control of said preparation is by country's mark
In standard≤1000 μ g/ml, it is down to 800 μ g/ml (or being calculated as 800 μ g/5mg general flavones), or even below 550 μ g/ml；Undue toxicity
It is small, it is safe.
3rd, shown by zoopery, study subject tolerable concentration reaches 18mg/ by the 5mg/ml in national standard, raising
ml.The Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided, abnormal toxicity test result is better than existing commercially available prod.
Primarily determine that the security for the Ci Wu Jia that the present invention is provided, it is desirable to be the Clinical practice of Ci Wu Jia
Take a firm foundation.
Embodiment
Following examples are used to illustrate the present invention, but are not limited to the scope of the present invention.
Embodiment 1：The preparation of siberian Ginseng P.E
(1) extract：The water (72L) measured again with 12 volumes extracts wilsonii medicinal material 6kg 3 times, extracts 1 hour, merges every time
Extract solution, concentration, obtains wilsonii herbal decoction, standby；
(2) alcohol precipitations：Under agitation, adding 95% ethanol in the wilsonii herbal decoction obtained to step (1) (makes
Alcohol content is sufficiently stirred for up to 75%), stands 6 hours；Filtering, filtrate recycling ethanol continues to be concentrated into relative density to without alcohol taste
For 1.15 (80 DEG C of surveys), an alcohol precipitation cream of siberian Ginseng P.E is obtained, it is standby；
(3) stone sulphur method is handled：Take an alcohol precipitation cream of the siberian Ginseng P.E that step (2) obtains add in right amount fill it is appropriate
Purified water tank in, after the consumption for adding purified water to purified water is 10 times of alcohol precipitation paste volume amount (v/v), stirring 15min, enter
Row filtering, when filtrate is heated to temperature 45 C, pH value is adjusted to 11.0 with 20% milk of lime, stirs 15min, then with 20%
Sulphur acid for adjusting pH value to 5.5, continue to stir 15min, stand 4 hours, start leaching supernatant and reclaim to be concentrated into relative density
For 1.19 (80 DEG C of surveys), condensed cream is obtained；
(4) macroporous resin adsorption：The condensed cream for taking step (3) to obtain is appropriate, adds water for injection and is diluted to 1ml containing total yellow
Ketone about 10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 5.0, stirs, and refrigerates 12 hours；Decoction after refrigeration
After 0.45 μm of filtering with microporous membrane clarification, pH value 2.0 is adjusted with dilute HCl, filtrate is with D101 macroreticular resins on 1.5BV/h flow velocitys
Post, is then rinsed using same flow velocity (1.5BV/h) with 0.3 times of column volume purified water (pH value is 3.0), is then measured with 4 times
50% ethanol elution, collects eluent, and it is 5.4 to adjust pH, and it is 1.13 (80 DEG C of surveys) that 50% eluent is concentrated into relative density, is obtained
It is standby to condensed cream；
(5) secondary alcohol precipitation：Under agitation, adding 95% ethanol in the condensed cream obtained to step (4) (makes alcohol content
Up to 85.5%), 15min is stirred, 16 hours are stood, leaching supernatant (filters to take supernatant) after remaining dregs of a decoction centrifugation, and filtrate is returned
Ethanol is received to without alcohol taste and relative density is concentrated into for 1.14 (80 DEG C of surveys), cream is received and obtains the secondary alcohol precipitation cream of siberian Ginseng P.E, it is standby
With；
(6) hot pressing and ultrafiltration：The secondary alcohol precipitation cream of siberian Ginseng P.E for taking step (5) to obtain, is diluted to water for injection
General flavone content is 10.0mg/ml, after stirring, and filtering, filtrate adjusts pH value 4.2, stirs, and 121 DEG C sterilize 30 minutes,
Refrigeration 12 hours.After decoction after refrigeration is clarified through filtering with microporous membrane, pH value 5.5 is adjusted, decoction is clarified through filtering with microporous membrane
Afterwards, successively progress 100,000,30,000 grades of two-stage ultrafiltering, it is 1.17 (80 DEG C of surveys) that filtrate, which is concentrated into relative density, that is, obtains wilsonii
Extract.
Embodiment 2：The preparation of siberian Ginseng P.E
(1) extract：The water (64L) measured again with 8 volumes extracts wilsonii medicinal material 8kg 2 times, extracts 2 hours, merges every time
Extract solution, concentration, obtains wilsonii herbal decoction, standby；
(2) alcohol precipitations：Under agitation, adding 93% ethanol in the wilsonii herbal decoction obtained to step (1) (makes
Alcohol content is sufficiently stirred for up to 74.5%), stands 12 hours, filtering, and filtrate recycling ethanol continues to be concentrated into relatively extremely without alcohol taste
Density is 1.11 (80 DEG C of surveys), obtains an alcohol precipitation cream of siberian Ginseng P.E, standby；
(3) stone sulphur method is handled：Take an alcohol precipitation cream of the siberian Ginseng P.E that step (2) obtains add in right amount fill it is appropriate
Purified water tank in, after the consumption for adding purified water to purified water is 12 times of alcohol precipitation paste volume amount (v/v), stirring 15min, enter
Row filtering, when filtrate is heated to temperature 45 C, pH value is adjusted to 11.5 with 20% milk of lime, stirs 15min, then with 20%
Sulphur acid for adjusting pH value to 5.3, continue to stir 15min, stand 6 hours, start leaching supernatant and reclaim to be concentrated into relative density
For 1.17 (80 DEG C of surveys), condensed cream is obtained；
(4) macroporous resin adsorption：The condensed cream for taking step (3) to obtain is appropriate, adds water for injection and is diluted to 1ml containing total yellow
Ketone about 8.0mg/ml, after stirring, filtering, filtrate adjusts pH value 5.2, stirs, and refrigerates 14 hours；Decoction warp after refrigeration
After 0.45 μm of filtering with microporous membrane clarification, pH value 2.3 is adjusted with dilute HCl, filtrate is with HPD100 macroreticular resins on 1.5BV/h flow velocitys
Post, is then rinsed using same flow velocity (1.5BV/h) with 0.4 times of column volume purified water (pH value is 3.0), is then measured with 5 times
50% ethanol elution, collects eluent, and it is 5.3 to adjust pH, and it is 1.14 (80 DEG C of surveys) that 50% eluent is concentrated into relative density, is obtained
It is standby to condensed cream；
(5) secondary alcohol precipitation：Under agitation, adding 95% ethanol in the condensed cream obtained to step (4) (makes alcohol content
Up to 84.5%), 15min is stirred, 14 hours are stood, leaching supernatant (filters to take supernatant) after remaining dregs of a decoction centrifugation, and filtrate is returned
Ethanol is received to without alcohol taste and relative density is concentrated into for 1.15 (80 DEG C of surveys), cream is received and obtains the secondary alcohol precipitation cream of siberian Ginseng P.E, it is standby
With；
(6) hot pressing and ultrafiltration：The secondary alcohol precipitation cream of siberian Ginseng P.E for taking step (5) to obtain, is diluted to water for injection
General flavone content is 8.0mg/ml, after stirring, and filtering, filtrate adjusts pH value 4.5, stirs, and 121 DEG C sterilize 35 minutes,
Refrigeration 12 hours.After decoction after refrigeration is clarified through filtering with microporous membrane, pH value 5.4 is adjusted, decoction is clarified through filtering with microporous membrane
Afterwards, successively progress 100,000,30,000 grades of two-stage ultrafiltering, it is 1.18 (80 DEG C of surveys) that filtrate, which is concentrated into relative density, that is, obtains wilsonii
Extract.
Embodiment 3：The preparation of siberian Ginseng P.E
(1) extract：The water (120L) measured again with 12 volumes extracts wilsonii medicinal material 10kg 2 times, extracts 1.5 hours every time,
Merge extract solution, concentration obtains wilsonii herbal decoction, standby；
(2) alcohol precipitations：Under agitation, adding 95% ethanol in the wilsonii herbal decoction obtained to step (1) (makes
Alcohol content is sufficiently stirred for up to 75.5%), stands 18 hours, filtering, and filtrate recycling ethanol continues to be concentrated into relatively extremely without alcohol taste
Density is 1.14 (80 DEG C of surveys), obtains an alcohol precipitation cream of siberian Ginseng P.E, standby；
(3) stone sulphur method is handled：Take an alcohol precipitation cream of the siberian Ginseng P.E that step (2) obtains add in right amount fill it is appropriate
Purified water tank in, after the consumption for adding purified water to purified water is 8 times of alcohol precipitation paste volume amount (v/v), stirring 15min, enter
Row filtering, when filtrate is heated to temperature 45 C, pH value is adjusted to 10.5 with 20% milk of lime, stirs 15min, then with 20%
Sulphur acid for adjusting pH value to 5.1, continue to stir 15min, stand 8 hours, start leaching supernatant and reclaim to be concentrated into relative density
For 1.16 (80 DEG C of surveys), condensed cream is obtained；
(4) macroporous resin adsorption：The condensed cream for taking step (3) to obtain is appropriate, adds water for injection and is diluted to 1ml containing total yellow
Ketone about 10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 5.4, stirs, and refrigerates 12 hours；Decoction after refrigeration
After 0.45 μm of filtering with microporous membrane clarification, pH value 2.2 is adjusted with dilute HCl, filtrate is with DM130 macroreticular resins on 1.5BV/h flow velocitys
Post, is then rinsed using same flow velocity (1.5BV/h) with 0.3 times of column volume purified water (pH value is 3.0), is then measured with 3 times
50% ethanol elution, collects eluent, and it is 5.4 to adjust pH, and it is 1.15 (80 DEG C of surveys) that 50% eluent is concentrated into relative density, is obtained
It is standby to condensed cream；
(5) secondary alcohol precipitation：Under agitation, adding 95% ethanol in the condensed cream obtained to step (4) (makes alcohol content
Up to 85.0%), 15min is stirred, 12 hours are stood, filtering, leaching supernatant (filters to take supernatant) after remaining dregs of a decoction centrifugation, filter
Liquid reclaims ethanol to without alcohol taste and relative density is concentrated into for 1.16 (80 DEG C of surveys), receives cream and obtains the secondary alcohol precipitation of siberian Ginseng P.E
Cream, it is standby；
(6) hot pressing and ultrafiltration：The secondary alcohol precipitation cream of siberian Ginseng P.E for taking step (5) to obtain, is diluted to water for injection
General flavone content is 10.0mg/ml, after stirring, and filtering, filtrate adjusts pH value 4.8, stirs, and 115 DEG C sterilize 40 minutes,
Refrigeration 12 hours, after the decoction after refrigeration is clarified through filtering with microporous membrane, adjusts pH value 5.2, decoction is clarified through filtering with microporous membrane
Afterwards, successively progress 100,000,30,000 grades of two-stage ultrafiltering, it is 1.15 (80 DEG C of surveys) that filtrate, which is concentrated into relative density, that is, obtains wilsonii
Extract.
Embodiment 4：Prepare Radix Et Caulis Acanthopanacis Senticosi injection (every 20ml, containing total flavonoids substance 100mg)
The siberian Ginseng P.E that Example 1 is obtained, general flavone 6.0mg/ml is diluted to water for injection, is added 10g and is lived
Property charcoal, backflow boils absorption 15min (refer to add after charcoal, be heated at reflux to boiling, starting timing 15min, similarly hereinafter), is cooled to
50 DEG C, through 0.45 μm of membrane filtration to clarification；With 10,000 ultrafiltration membrance filters, when filter to permeate does not have flow, water, root are pushed up in right amount
General flavone 5.0mg/ml is diluted to according to content, pH value 5.5 is adjusted with 20% sodium hydroxide solution；Decoction through 0.22 μm of filter core refined filtration,
Filling 20ml, sealing；Through high-temp steam sterilizing, cooling produces Radix Et Caulis Acanthopanacis Senticosi injection.
Embodiment 5：Prepare Radix Et Caulis Acanthopanacis Senticosi injection (every 100ml, containing total flavonoids substance 300mg)
Ingredients, embedding, sterilizing：The siberian Ginseng P.E that Example 2 is obtained, general flavone is diluted to water for injection
7.5mg/ml, adds 12g activated carbons, and backflow boils absorption 15min, is cooled to 40 DEG C, through 0.45 μm of membrane filtration to clarification；With
10000 ultrafiltration membrance filters, when filter to permeate does not have flow, push up water, general flavone 3.0mg/ml are diluted to according to content in right amount, use
20% sodium hydroxide solution adjusts pH value 5.4；Decoction is through 0.22 μm of filter core refined filtration, filling 100ml, sealing；Through high-temp steam sterilizing,
Cooling, produces Radix Et Caulis Acanthopanacis Senticosi injection.
Embodiment 6：Prepare Radix Et Caulis Acanthopanacis Senticosi injection (every 250ml, containing total flavonoids substance 500mg)
Ingredients, embedding, sterilizing：The siberian Ginseng P.E that Example 3 is obtained, general flavone is diluted to water for injection
10.0mg/ml, adds 10g activated carbons, and backflow boils absorption 15min, is cooled to 45 DEG C, through 0.45 μm of membrane filtration to clarification；
With 10,000 ultrafiltration membrance filters, when filter to permeate does not have flow, water is pushed up in right amount, general flavone 2.0mg/ml is diluted to according to content, use
20% sodium hydroxide solution adjusts pH value 5.2；Decoction is through 0.22 μm of filter core refined filtration, filling 250ml, sealing；Through high-temp steam sterilizing,
Cooling, produces Radix Et Caulis Acanthopanacis Senticosi injection.
Embodiment 7：Prepare Radix Et Caulis Acanthopanacis Senticosi injection (every 250ml, containing total flavonoids substance 500mg)
Ingredients, embedding, sterilizing：The siberian Ginseng P.E that Example 3 is obtained, general flavone is diluted to water for injection
8.0mg/ml, adds 15g activated carbons, and backflow boils absorption 15min, is cooled to 50 DEG C, through 0.45 μm of membrane filtration to clarification；With
10000 ultrafiltration membrance filters, when filter to permeate does not have flow, push up water, general flavone 2.0mg/ml are diluted to according to content in right amount, use
20% sodium hydroxide solution adjusts pH value 5.5；Decoction is through 0.22 μm of filter core refined filtration, filling 250ml, sealing；Through high-temp steam sterilizing,
Cooling, produces Radix Et Caulis Acanthopanacis Senticosi injection.
Experimental example 1:Examine potassium content
1st, test medicine
Commercially available product 1, every 20ml, 100mg containing total flavonoids substance；
Commercially available product 2, every 20ml, 100mg containing total flavonoids substance；
Three kinds of Radix Et Caulis Acanthopanacis Senticosi injections of commercially available product 3, wherein every 20ml, 100mg containing total flavonoids substance；Every 100ml,
300mg containing total flavonoids substance；Every 250ml, 500mg containing total flavonoids substance；
The Radix Et Caulis Acanthopanacis Senticosi injection that embodiment 4-7 is made；
Comparative example 1-3：Thorn five is prepared with reference to the embodiment 8,9,10 of the patent of Application No. 201210049755.1
Plus parenteral solution.
2nd, detection method 1：By version in 2010《Chinese Pharmacopoeia》The S injection Related substances separation methods of annex Ⅸ
Potassium ion takes parenteral solution 2ml, is evaporated, first blazing to charing with small fire, then in 500-600 DEG C of blazing to complete ash
Change, plus spirit of vinegar 2ml makes dissolving.Put in 25ml measuring bottles, be diluted with water to scale, mix, be used as need testing solution.10ml is taken to receive
Accurate addition standard potassium ion solution in family name's colorimetric cylinder two, first pipe (take potassium sulfate appropriate, it is finely ground, dried in 110 DEG C to perseverance
Weight, precision weighs 2.23g, put in 1000ml measuring bottles, and add water makes dissolving and be diluted to scale in right amount, shakes up, is used as stock solution.Face
With preceding, precision measures stock solution 10ml, puts in 100ml measuring bottles, is diluted with water to scale, shake up, produces.Per 1ml equivalent to 100
μ g K) 0.8ml, plus alkaline formaldehyde solution (takes formalin, pH value adjusted to 8.0- with 0.1mol/L sodium hydroxide solutions
9.0) 0.6ml, 3% Calcium Disodium Versenate solution 2 drip, 3% sodium tetraphenylborate solution 0.5ml, be diluted with water into 10ml, second pipe
Middle accurate addition need testing solution 1ml, operates, shakes up, first, second two is managed with putting on black paper, from up to down in accordance with the law simultaneously with first pipe
Perspective, the turbidity showed in second pipe is compared with first pipe, must not be denseer (K≤1000 μ g/ml).
3rd, detection method 2：Atomic absorption spectrophotometric determination potassium content
1) instrument and reagent
Instrument：HITACHI 180-50 type atomic absorption spectrophotometers, HIT.
2) preparation of solution
The preparation of reference substance solution takes K storing solutions ultra-pure water to dilute the reference substance solution that high and low 2 kinds of concentration is made.
The preparation of need testing solution takes Ci Wu Jia, dilutes 50~100 times with ultra-pure water, shakes up, produce.
3) determination method
Take reference substance solution and need testing solution to determine the content of K in need testing solution using flame method, calculate ion
Content (mg/ml).Test parameter and reference substance solution concentration see the table below 1.
The test parameter of table 1 and reference substance solution
| Parameter | K |
| Wavelength (nm) | 766.5 |
| Lamp current (mA) | 10.0 |
| Slit (nm) | 2.6 |
| Burn grease head highness | 7.5 |
| Air mass flow (L/min) | 9.4 |
| Acetylene throughput (L/min) | 2.3 |
| Standard series (mg/L) | 0,10,20 |
4th, experimental result：It is shown in Table 2
Each component content in the test medicine of table 2
The result of table 2 is shown：The Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided is in the comparison with different size commercially available product, comparative example
In, while active constituent content in meeting Radix Et Caulis Acanthopanacis Senticosi injection, potassium content should no more than national standard requirement≤
1000 μ g/ml, potassium content is lower, then parenteral solution security is higher.
As a result show：The Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided is with the obvious advantage in the comparison of equivalent specifications, preparation technology
The purpose of preferably control potassium content can be embodied.
Experimental example 2：Undue toxicity is detected
Test medicine (note, " containing total flavonoids substance " is the specification and content standard of each parenteral solution)：
Commercially available product 1, every 20ml, 100mg containing total flavonoids substance；
Commercially available product 2, every 20ml, 100mg containing total flavonoids substance；
Commercially available product 3, three kinds of Radix Et Caulis Acanthopanacis Senticosi injections, wherein every 20ml, 100mg containing total flavonoids substance；Every 100ml,
300mg containing total flavonoids substance；Every 250ml, 500mg containing total flavonoids substance；The wilsonii injection that embodiment 4-7 is made
Liquid；
Comparative example 1-3：Thorn five is prepared with reference to the embodiment 8,9,10 of the patent of Application No. 201210049755.1
Plus parenteral solution.
By the E abnormal toxicity tests methods of one annex of Chinese Pharmacopoeia version in 2010 Ⅹ III.
Experimental procedure：
1st, prepared by test sample：Above sample number branch is taken, 0.45 μm of filter membrane is crossed, it is 20mg/ml (reasons to be concentrated into general flavone content
By concentration), it is sub-packed in 20ml ampoules, 116 DEG C of sterilizing 40min, censorship general flavone concentration after sealing；According to each sample general flavone
Concentration, plus physiological saline is examined to be diluted to general flavone concentration respectively for 5mg/ml, 10mg/ml, 15mg/ml and 18mg/ml, then
0.45 μm of membrane filtration is crossed, it is standby.
2nd, test sample undue toxicity is examined according to the rules：Body weight is taken in 17-20g small white mouses 5, from tail vein injection for examination
Product, every injection 0.5ml test sample of speed 4-5 seconds must not have death in 48 hours to observation post administration；If any death, body is separately taken
10 retrials of 18-19g small white mouses are focused on, whole mouse there must not be death in 48 hours.
Experimental result, it is as shown in table 3 below.
Table 3 examines test sample undue toxicity
| 5mg/ml | 10mg/ml | 15mg/ml | 18mg/ml | |
| Embodiment 4 (20ml) | It is qualified | It is qualified | It is qualified | It is qualified |
| Embodiment 5 (20ml) | It is qualified | It is qualified | It is qualified | It is qualified |
| Embodiment 6 (100ml) | It is qualified | It is qualified | It is qualified | It is qualified |
| Embodiment 7 (250ml) | It is qualified | It is qualified | It is qualified | It is qualified |
| Commercially available product 1 (20ml) | It is qualified | It is qualified | It is unqualified | It is unqualified |
| Commercially available product 2 (20ml) | It is qualified | It is unqualified | It is unqualified | It is unqualified |
| Commercially available product 3 (20ml) | It is qualified | It is qualified | It is unqualified | It is unqualified |
| Commercially available product 3 (100ml) | It is qualified | It is qualified | It is unqualified | It is unqualified |
| Commercially available product 3 (250ml) | It is qualified | It is qualified | It is unqualified | It is unqualified |
| Comparative example 1 (20ml) | It is qualified | It is qualified | It is qualified | It is unqualified |
| Comparative example 2 (100ml) | It is qualified | It is qualified | It is qualified | It is unqualified |
| Comparative example 3 (250ml) | It is qualified | It is qualified | It is qualified | It is unqualified |
The result of table 3 is shown：The Radix Et Caulis Acanthopanacis Senticosi injection that the present invention is provided is in the comparison with different size commercially available product, comparative example
In, sample tolerable concentration complies with the national standard requirements 5mg/ml, but properly increases after sample concentration, and result occurs between each sample
Difference, the Radix Et Caulis Acanthopanacis Senticosi injection tolerable concentration 18mg/ml that the present invention is provided is close to the theoretical concentration 20mg/ of general flavone content
There is not death yet in ml, study subject, compared with other Radix Et Caulis Acanthopanacis Senticosi injections, and abnormal toxicity test result is better than existing commercially available production
Product.
As a result show, the parenteral solution security that the present invention is provided is better than existing commercially available prod.
Although above having made to retouch in detail to the present invention with general explanation, embodiment and experiment
State, but on the basis of the present invention, it can be made some modifications or improvements, this is apparent to those skilled in the art
's.Therefore, these modifications or improvements without departing from theon the basis of the spirit of the present invention, are belonged to claimed
Scope.
Claims (9)
1. a kind of Radix Et Caulis Acanthopanacis Senticosi injection, it is characterised in that contain following active component：1.8-5.5mg/ml containing general flavone, purple fourth
Fragrant glycosides 0.13-0.70mg/ml and eleutheroside E 0.06-0.34mg/ml, the μ g/ml of the quantity of potassium ion≤800；
The preparation method of the parenteral solution comprises the following steps：Siberian Ginseng P.E, is diluted with water for injection, filtering, adjusts pH
Value, refined filtration, embedding, sterilizing produce Radix Et Caulis Acanthopanacis Senticosi injection；
The siberian Ginseng P.E is prepared by following methods：
（1）Extract：The water measured again with 6 ~ 12 volumes extracts wilsonii medicinal material 2 ~ 3 times, extracts 1 ~ 2 hour every time, merges extract solution,
Concentration, obtains wilsonii herbal decoction, standby；
（2）First time alcohol precipitation：Under agitation, to step（1）It is more than 93% that concentration is added in obtained wilsonii herbal decoction
Ethanol cause alcohol content to be 74-86%, be sufficiently stirred for, stand more than 6 hours, filtering, filtrate recycling ethanol to without alcohol taste, and
Relative density is 1.10 ~ 1.18 when being concentrated into 80 DEG C, obtains an alcohol precipitation cream of siberian Ginseng P.E, standby；
（3）The processing of stone sulphur method：By step（2）Alcohol precipitation cream of obtained siberian Ginseng P.E is mixed with water, after stirring,
Filtered, during 40 DEG C ~ 50 DEG C of liquid temperature degree to be filtered, pH value is adjusted to 10.0 ~ 12.0 with 20% milk of lime, stirring, then with 20%
Sulphur acid for adjusting pH value to 5.0 ~ 6.0, continue to stir, stand, leaching supernatant simultaneously reclaims relative density when being concentrated into 80 DEG C and is
1.14 ~ 1.19, obtain condensed cream；
（4）Macroporous resin adsorption：Take step（3）Obtained wilsonii condensed cream, being diluted to general flavone content with water for injection is
7.5 ~ 10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 4.0 ~ 5.5, stirs, and refrigerates more than 12 hours；Refrigeration
After decoction afterwards is clarified through filtering with microporous membrane, adjust pH value 2.0 ± 0.5, filtrate with macroporous resin column on 1.5 ~ 2 BV/h flow velocitys,
Then rinsed, 50% ethanol elution then measured again with 3 ~ 6 volumes, received with 0.3 ~ 0.5 times of column volume purified water with same flow velocity
Collect eluent, it is 5.0 ~ 6.5 to adjust pH, relative density is 1.13 ~ 1.20 when 50% eluent is concentrated into 80 DEG C, obtains condensed cream,
It is standby；
（5）Secondary alcohol precipitation：Under agitation, to step（4）It is that more than 93% ethanol makes it that concentration is added in obtained condensed cream
Alcohol content is 80 ~ 86%, is sufficiently stirred for, and stands more than 12 hours, and leaching supernatant, filtrate recycling ethanol is concentrated extremely without alcohol taste
It is 1.11 ~ 1.20 to relative density at 80 DEG C, obtains the secondary alcohol precipitation cream of siberian Ginseng P.E；
（6）Hot pressing and ultrafiltration：Take step（5）The obtained secondary alcohol precipitation cream of siberian Ginseng P.E, total Huang is diluted to water for injection
Ketone content is 7.5 ~ 10.0mg/ml, after stirring, and filtering, filtrate adjusts pH value 4.0 ~ 5.0, stirs, 115 ~ 121 DEG C go out
Bacterium 30 ~ 40 minutes, refrigerates more than 12 hours；After decoction after refrigeration is clarified through filtering with microporous membrane, pH value 5.5 ± 0.5, medicine are adjusted
After liquid is clarified through filtering with microporous membrane, successively carry out 100,000,30,000 grades of two-stage ultrafiltering, filtrate be concentrated into relative density for 1.11 ~
1.20, that is, obtain siberian Ginseng P.E.
2. parenteral solution according to claim 1, it is characterised in that the Radix Et Caulis Acanthopanacis Senticosi injection contains following active component,
Divided by existing specification：
Every 20ml, general flavone 4.5-5.5 mg/ml, Syringin 0.32-0.70 mg/ml and eleutheroside E 0.15-0.34
Mg/ml, the μ g/ml of the quantity of potassium ion≤800；
Every 100ml, 2.7-3.3 containing general flavone mg/ml, Syringin 0.19-0.42 mg/ml and eleutheroside E 0.09-
0.20 mg/ml, the μ g/ml of the quantity of potassium ion≤500；
Every 250ml, 1.8-2.2 containing general flavone mg/ml, Syringin 0.13-0.28mg/ml and eleutheroside E 0.06-
0.14 mg/ml, the μ g/ml of the quantity of potassium ion≤300.
3. parenteral solution according to claim 1, it is characterised in that the Radix Et Caulis Acanthopanacis Senticosi injection contains following active component,
Divided by existing specification：
Every 20ml, 4.5-5.5 containing general flavone mg/ml, Syringin 0.32-0.70 mg/ml and eleutheroside E 0.15-
0.34 mg/ml, the μ g/ml of the quantity of potassium ion≤550；
Every 100ml, 2.7-3.3 containing general flavone mg/ml, Syringin 0.19-0.42 mg/ml and eleutheroside E 0.09-
0.20 mg/ml, the μ g/ml of the quantity of potassium ion≤360；
Every 250ml, 1.8-2.2 containing general flavone mg/ml, Syringin 0.13-0.28mg/ml and eleutheroside E 0.06-
0.14 mg/ml, the μ g/ml of the quantity of potassium ion≤240.
4. parenteral solution according to claim 1, it is characterised in that the Radix Et Caulis Acanthopanacis Senticosi injection contains following active component,
Divided by existing specification：
Every 20ml, general flavone 5.14-5.23 mg/ml, Syringin 0.36-0.5 mg/ml and eleutheroside E 0.17-
0.25mg/ml, the μ g/ml of the quantity of potassium ion≤550；
The preparation method of the parenteral solution comprises the following steps：
Siberian Ginseng P.E is diluted with water to 6.0 ~ 10mg/ml of general flavone, adds activated carbon, and absorption 15min, cooling are boiled in backflow
40-50 DEG C, 0.45 μm of membrane filtration with 10,000 ultrafiltration membrance filters, when filter to permeate does not have flow, is refiltered, collected to clarifying
And merging filtrate, stop ultrafiltration, filtrate adjusts pH value to 5.0 ~ 6.0, and decoction is through 0.22 μm of filter core refined filtration, packing, through high-temperature steam
Sterilizing, cooling, is produced.
5. a kind of method for preparing the parenteral solution described in claim any one of 1-4, it is characterised in that this method includes following step
Suddenly：Siberian Ginseng P.E, is diluted with water for injection, filtering, regulation pH value, refined filtration, and embedding, sterilizing produce Radix Et Caulis Acanthopanacis Senticosi injection；
The siberian Ginseng P.E is prepared by following methods：
（1）Extract：The water measured again with 6 ~ 12 volumes extracts wilsonii medicinal material 2 ~ 3 times, extracts 1 ~ 2 hour every time, merges extract solution,
Concentration, obtains wilsonii herbal decoction, standby；
（2）First time alcohol precipitation：Under agitation, to step（1）It is more than 93% that concentration is added in obtained wilsonii herbal decoction
Ethanol cause alcohol content to be 74-86%, be sufficiently stirred for, stand more than 6 hours, filtering, filtrate recycling ethanol to without alcohol taste, and
Relative density is 1.10 ~ 1.18 when being concentrated into 80 DEG C, obtains an alcohol precipitation cream of siberian Ginseng P.E, standby；
（3）The processing of stone sulphur method：By step（2）Alcohol precipitation cream of obtained siberian Ginseng P.E is mixed with water, after stirring,
Filtered, during 40 DEG C ~ 50 DEG C of liquid temperature degree to be filtered, pH value is adjusted to 10.0 ~ 12.0 with 20% milk of lime, stirring, then with 20%
Sulphur acid for adjusting pH value to 5.0 ~ 6.0, continue to stir, stand, leaching supernatant simultaneously reclaims relative density when being concentrated into 80 DEG C and is
1.14 ~ 1.19, obtain condensed cream；
（4）Macroporous resin adsorption：Take step（3）Obtained wilsonii condensed cream, being diluted to general flavone content with water for injection is
7.5 ~ 10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 4.0 ~ 5.5, stirs, and refrigerates more than 12 hours；Refrigeration
After decoction afterwards is clarified through filtering with microporous membrane, adjust pH value 2.0 ± 0.5, filtrate with macroporous resin column on 1.5 ~ 2 BV/h flow velocitys,
Then rinsed, 50% ethanol elution then measured again with 3 ~ 6 volumes, received with 0.3 ~ 0.5 times of column volume purified water with same flow velocity
Collect eluent, it is 5.0 ~ 6.5 to adjust pH, relative density is 1.13 ~ 1.20 when 50% eluent is concentrated into 80 DEG C, obtains condensed cream,
It is standby；
（5）Secondary alcohol precipitation：Under agitation, to step（4）It is that more than 93% ethanol makes it that concentration is added in obtained condensed cream
Alcohol content is 80 ~ 86%, is sufficiently stirred for, and stands more than 12 hours, and leaching supernatant, filtrate recycling ethanol is concentrated extremely without alcohol taste
It is 1.11 ~ 1.20 to relative density at 80 DEG C, obtains the secondary alcohol precipitation cream of siberian Ginseng P.E；
（6）Hot pressing and ultrafiltration：Take step（5）The obtained secondary alcohol precipitation cream of siberian Ginseng P.E, total Huang is diluted to water for injection
Ketone content is 7.5 ~ 10.0mg/ml, after stirring, and filtering, filtrate adjusts pH value 4.0 ~ 5.0, stirs, 115 ~ 121 DEG C go out
Bacterium 30 ~ 40 minutes, refrigerates more than 12 hours；After decoction after refrigeration is clarified through filtering with microporous membrane, pH value 5.5 ± 0.5, medicine are adjusted
After liquid is clarified through filtering with microporous membrane, successively carry out 100,000,30,000 grades of two-stage ultrafiltering, filtrate be concentrated into relative density for 1.11 ~
1.20, that is, obtain siberian Ginseng P.E.
6. method according to claim 5, it is characterised in that the first time alcohol precipitation, comprises the following steps：In stirring bar
Under part, to step（1）The ethanol that obtained wilsonii herbal decoction addition concentration is more than 93% is so that alcohol content is 74.5-
75.5%, it is sufficiently stirred for, stands 6-18 hours, filtering, filtrate recycling ethanol is extremely without alcohol taste, and relative density when being concentrated into 80 DEG C
For 1.11 ~ 1.15, an alcohol precipitation cream of siberian Ginseng P.E is obtained.
7. method according to claim 5, it is characterised in that the macroporous resin adsorption comprises the following steps：By step
（3）Obtained wilsonii condensed cream, general flavone content is diluted to water for injection for 8.0 ~ 10.0mg/ml, after stirring, mistake
Filter, filtrate adjusts pH value 5.0 ~ 5.4, stirs, and refrigerates 12-14h；Decoction after refrigeration is clarified through 0.45 μm of filtering with microporous membrane
Afterwards, pH value 2.0-2.3 is adjusted, filtrate is with macroporous resin column on 1.5BV/h flow velocity, then with same flow velocity with 0.3 ~ 0.5 times
Column volume purified water is rinsed, 50% ethanol elution then measured again with 3 ~ 5 volumes, collects eluent, and it is 5.3 ~ 5.5 to adjust pH, will
It is 1.15 ~ 1.20 that 50% eluent, which is concentrated into relative density, obtains condensed cream.
8. method according to claim 5, it is characterised in that this method comprises the following steps：Siberian Ginseng P.E water
6.0 ~ 10mg/ml of general flavone is diluted to, activated carbon is added, backflow boils absorption 15min, cools down 40-50 DEG C, 0.45 μm of filter membrane mistake
Filter with 10,000 ultrafiltration membrance filters, when filter to permeate does not have flow, refilters, collected and merging filtrate, stop ultrafiltration to clarifying,
Filtrate adjusts pH value to 5.0 ~ 6.0, and decoction, through high-temp steam sterilizing, is cooled down, produced through 0.22 μm of filter core refined filtration, packing.
9. a kind of method for preparing the parenteral solution described in claim any one of 1-4, it is characterised in that this method includes following step
Suddenly：Siberian Ginseng P.E, is diluted with water for injection, filtering, regulation pH value, refined filtration, and embedding, sterilizing produce Radix Et Caulis Acanthopanacis Senticosi injection；
The siberian Ginseng P.E is prepared by following methods：
（1）Extract：The water measured again with 8 ~ 12 volumes extracts wilsonii medicinal material 2 ~ 3 times, extracts 1 ~ 2 hour every time, merges extract solution,
Concentration, obtains wilsonii herbal decoction, standby；
（2）First time alcohol precipitation：Under agitation, to step（1）It is 93 ~ 95% that concentration is added in obtained wilsonii herbal decoction
Ethanol make it that alcohol content is 74.5-75.5%, stirring 15min after, stand 6 ~ 18 hours, filtering, filtrate recycling ethanol is to without alcohol
Taste, and relative density is 1.11 ~ 1.15 when being concentrated into 80 DEG C, obtains an alcohol precipitation cream of siberian Ginseng P.E, it is standby；
（3）The processing of stone sulphur method：By step（2）Alcohol precipitation cream of obtained siberian Ginseng P.E is mixed with water, after stirring,
Filtered, during liquid temperature 45 C to be filtered, pH value adjusted to 10.5 ~ 11.5 with 20% milk of lime, stirring, then with 20% sulfuric acid
PH value is adjusted to 5.1 ~ 5.5, continues to stir, stands 4 ~ 8 hours, leaching supernatant simultaneously reclaims relative density when being concentrated into 80 DEG C and is
1.16 ~ 1.19, obtain condensed cream；
（4）Macroporous resin adsorption：Take step（3）Obtained wilsonii condensed cream, being diluted to general flavone content with water for injection is
8.0 ~ 10.0mg/ml, after stirring, filtering, filtrate adjusts pH value 5.0 ~ 5.5, stirs, and refrigerates 12 ~ 18 hours；After refrigeration
Decoction clarified through filtering with microporous membrane after, adjust pH value 2.0-2.3, filtrate is with macroporous resin column on 1.5 BV/h flow velocitys, then
Rinsed with same flow velocity with 0.3 ~ 0.5 times of column volume purified water, 50% ethanol elution then measured again with 3 ~ 5 volumes, collection is washed
De- liquid, it is 5.3 ~ 5.5 to adjust pH, and relative density is 1.13 ~ 1.20 when 50% eluent is concentrated into 80 DEG C, obtains condensed cream, standby
With；
（5）Secondary alcohol precipitation：Under agitation, to step（4）It is that 93 ~ 95% ethanol make it that concentration is added in obtained condensed cream
Alcohol content is 84 ~ 85.5%, is sufficiently stirred for, and stands 12 ~ 16 hours, leaching supernatant, and filtrate recycling ethanol is and dense to without alcohol taste
Relative density is 1.14 ~ 1.16 when being reduced to 80 DEG C, obtains the secondary alcohol precipitation cream of siberian Ginseng P.E；
（6）Hot pressing and ultrafiltration：General flavone content is diluted to water for injection for 8.0 ~ 10.0mg/ml, after stirring, filtering,
Filtrate adjusts pH value 4.2 ~ 4.8, and high-temp steam sterilizing is refrigerated 12 hours；After decoction after refrigeration is clarified through filtering with microporous membrane, adjust
PH value 5.2 ~ 5.5, after decoction is clarified through filtering with microporous membrane, successively progress 100,000,30,000 grades of two-stage ultrafiltering, filtrate are concentrated into
Relative density is 1.15 ~ 1.20, that is, obtains siberian Ginseng P.E.
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| CN108261431A (en) * | 2018-03-12 | 2018-07-10 | 大连军门保健食品有限公司 | A kind of wilsonii total flavone injection and the method that manyprickle acanthopanax general flavones is extracted from slender acanthopanax ginseng |
| CN109010398B (en) * | 2018-09-28 | 2022-03-04 | 黑龙江省格润药业有限责任公司 | Acanthopanax senticosus injection and preparation process thereof |
| CN110237110B (en) * | 2019-06-28 | 2022-05-17 | 黑龙江金九药业股份有限公司 | Acanthopanax senticosus extract and extraction method and application thereof |
| CN117122625A (en) * | 2023-10-07 | 2023-11-28 | 黑龙江金九药业股份有限公司 | Acanthopanax senticosus extract injection and preparation method thereof |
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