CN117122625A - Acanthopanax senticosus extract injection and preparation method thereof - Google Patents
Acanthopanax senticosus extract injection and preparation method thereof Download PDFInfo
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- CN117122625A CN117122625A CN202311290115.4A CN202311290115A CN117122625A CN 117122625 A CN117122625 A CN 117122625A CN 202311290115 A CN202311290115 A CN 202311290115A CN 117122625 A CN117122625 A CN 117122625A
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- Prior art keywords
- preparation
- injection
- acanthopanacis senticosi
- acanthopanax
- radix acanthopanacis
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- CWVRJTMFETXNAD-NXLLHMKUSA-N trans-5-O-caffeoyl-D-quinic acid Chemical compound O[C@H]1[C@H](O)C[C@](O)(C(O)=O)C[C@H]1OC(=O)\C=C\C1=CC=C(O)C(O)=C1 CWVRJTMFETXNAD-NXLLHMKUSA-N 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000009777 vacuum freeze-drying Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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Abstract
The invention belongs to the technical field of medicines, and in particular relates to an acanthopanax root extract injection and a preparation method thereof. The preparation process comprises the following steps: extracting stem of radix Acanthopanacis Senticosi to obtain radix Acanthopanacis Senticosi extract, and purifying to obtain radix Acanthopanacis Senticosi injection; the purification step comprises macroporous resin column chromatographic separation and silica gel column chromatographic separation; the purified solution is sequentially subjected to thick preparation, thin preparation, filling and sealing, sterilization and lamp inspection after being filtered by a silk cloth filter element, filtered by a polyether sulfone filter element and ultrafiltered by an ultrafilter, so as to prepare the acanthopanax injection. The injection prepared by the invention has the specification of 20mL, and the effective components comprise 4.5-5.5mg/mL of total flavone, 0.7-1.0mg/mL of syringin and 0.3-0.5mg/mL of eleutheroside E, and the stability is better.
Description
Technical Field
The invention belongs to the technical field of medicines, and in particular relates to an acanthopanax root extract injection and a preparation method thereof.
Background
The acanthopanax root and the leaf have special fragrance, are slightly bitter and slightly pungent in taste, enter spleen, kidney and heart meridian, have the effects of replenishing qi to invigorate the spleen, tonifying kidney and soothing nerves, have obvious effects on resisting fatigue, resisting inflammation, resisting stress and enhancing immunity, and have certain curative effects on cardiovascular diseases, diabetes, neurasthenia and the like.
The acanthopanax injection is prepared from effective components extracted from acanthopanax of Araliaceae, and contains various effective components such as acanthopanaxoside, isofraxinoside, syringin, hyperoside, and acanthopanax polysaccharide. The acanthopanax root has the functions of regulating metabolism of the organism, improving the nonspecific resistance of the organism to harmful stimulus factors, enhancing the function of a pituitary-adrenal cortex system, improving the adaptability and tolerance of the organism, reducing the damage of various pathogenic factors in vivo and in vitro to the organism, and having the excitation effect and the inhibition effect on the central nervous system. The radix Acanthopanacis Senticosi injection has effects of dilating blood vessel, increasing coronary blood flow, reducing oxygen consumption, lowering blood viscosity, improving blood circulation, tranquilizing, improving sleep, and stimulating appetite. Is mainly used for transient cerebral ischemia attacks, cerebral arteriosclerosis, cerebral thrombosis, cerebral embolism and the like caused by liver and kidney deficiency.
In recent years, adverse reactions have been reported due to their wide clinical application. The adverse reaction types mainly include anaphylactic reaction, anaphylactic shock, systemic anaphylactic reaction and the like, and clinically mainly appear as dizziness, headache, chest distress, dyspnea, blood pressure drop and dysphoria, and partial patients are accompanied with rash, systemic pruritus, fever, chills, nasal obstruction, running nose and the like.
The Chinese patent application 201610646228.7 discloses a preparation method of a composition for improving the stability of an acanthopanax medicinal injection, which comprises the following steps of: (1) Weighing 2-40 g of acanthopanax root extract, and 5-3 g of benzoic acid and/or sodium benzoate; (2) Benzoic acid and sodium benzoate are respectively prepared into solutions of 5mg/100ml to 3g/100ml for standby; (3) Adding the acanthopanax extract into 500ml of water for injection at 30-40 ℃, stirring until the acanthopanax extract is completely dissolved, adding active carbon, stirring for 15min, and filtering for decarbonization, wherein the dosage of the active carbon is 0.02g/100 ml; (4) Regulating the pH value of the filtrate obtained in the step (3) to 5.0-7.0 by using the benzoic acid and/or sodium benzoate solution prepared in the step (2), and adding water for injection at the temperature of 30-40 ℃ to 1000ml; (5) Filtering the liquid medicine obtained in the step (4) until the liquid medicine is clear, filling and sterilizing to obtain the medicine. However, the compatibility of the acanthopanax root and other auxiliary materials is easy to produce side effects.
Chinese patent application CN200310125129.7 discloses reflux extracting radix Acanthopanacis Senticosi with ethanol, adsorbing the extractive solution with macroporous adsorbent resin, eluting with water to remove impurities, eluting with 20-70% ethanol, collecting 20-70% ethanol eluate, and recovering ethanol under reduced pressure to dry to obtain radix Acanthopanacis Senticosi total glycoside component; extracting the residues of radix Acanthopanacis Senticosi with water under heating for three times, mixing the water extracts, concentrating, and recovering ethanol under reduced pressure to dry to obtain total glycosides of radix Acanthopanacis Senticosi; extracting the residues of radix Acanthopanacis Senticosi with water under heating for three times, mixing the water extracts, concentrating, repeatedly precipitating with ethanol for three times, dissolving the precipitate with water to obtain 1% solution, ultrafiltering with hollow fiber column with molecular weight cutoff of 6000-20 ten thousand, and vacuum drying or freeze drying the cutoff concentrate at low temperature to obtain polysaccharide effective component. The method is used for separately extracting the eleutheroside and polysaccharide components, and has the advantages of more steps, complex process and long extraction period.
The Chinese patent application CN201610648413 discloses an extraction method of an acanthopanax composition, which comprises the steps of extracting with water, precipitating with ethanol, extracting concentrated filtrate by adopting an ethanol/salt aqueous two-phase extraction method, collecting ethanol phase, distilling under reduced pressure, and drying under vacuum. The extract composition contains no saccharide, neochlorogenic acid, and cryptochlorogenic acid. Researches show that acanthopanax saccharide has the function of regulating immunity, and chlorogenic acids have the functions of resisting bacteria, relieving fever, resisting thrombus, resisting inflammation, inhibiting platelet aggregation and the like. The Chinese medicine effective substance is a complex chemical component system, and the Chinese medicine extract composition with multiple components and multiple targets is a main form of Chinese medicine treatment, so that it is very necessary to consider the saccharide and chlorogenic acid components during the extraction of acanthopanax.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provide the acanthopanax extract injection which has good stability, high content of active ingredients and simple preparation and the preparation method thereof.
In order to achieve the above purpose of the present invention, the present invention adopts the following specific technical scheme:
a preparation method of an acanthopanax extract injection comprises the following steps: extracting stem of radix Acanthopanacis Senticosi to obtain radix Acanthopanacis Senticosi extract, and purifying to obtain radix Acanthopanacis Senticosi extract injection;
the purification step includes:
(1) Macroporous resin column chromatography separation: the macroporous adsorption resin chromatographic column is as follows: a chromatographic column consisting of an upper layer of D-101, a middle layer of NKA and a lower layer of HPD 750; eluting radix Acanthopanacis Senticosi extract with water for 6-8 retention volumes, eluting with ethanol for 6-8 retention volumes, collecting ethanol eluate, and concentrating to obtain radix Acanthopanacis Senticosi concentrated solution;
(2) Separating by silica gel column chromatography: adding 200-300 mesh silica gel into radix Acanthopanacis Senticosi concentrated solution, mixing, subjecting to silica gel column chromatography, eluting with 4-6 times of mixed solution of ethyl acetate, trifluoroacetic acid and acetone, collecting eluate, concentrating to dry, and dissolving in water to obtain radix Acanthopanacis Senticosi purified solution.
Preferably, the thickness ratio of D-101, NKA and HPD750 in step (1) is 1:1-2:1-2; the ethanol is 60-70wt% ethanol with pH=3-5.
Preferably, the volume ratio of ethyl acetate, trifluoroacetic acid and acetone in the step (2) is 80-89:10-20:1.
Preferably, the preparation process of the acanthopanax injection comprises the following steps:
s1, concentration: filtering the purified acanthopanax liquid sequentially by silk cloth, polyether sulfone filter core and ultrafilter, pouring into a concentrated tank, adding water for injection to a certain volume, adding active carbon, heating, and stirring to obtain a mixed liquid 1;
s2, diluting: cooling the mixed solution 1, sequentially filtering by a plate-and-frame filter and ultrafilter with molecular weight of 8-10KD to a diluting preparation tank, adding water for injection to fix volume, adjusting pH, stirring, sampling, detecting to be qualified, and adding water for injection to a full amount to obtain an intermediate product of the injection;
s3, filling and sealing: filtering and filling and sealing the intermediate products of the injection which are qualified in detection;
s4, sterilizing: sterilizing at 115-116 deg.C for 30-40min;
s5, performing light inspection, labeling and packaging to obtain the product.
Further preferably, the aperture of the silk cloth in the step S1 is 100-500 meshes; the aperture of the polyether sulfone filter element is 0.22-0.8 mu m.
Further preferably, the ultrafilter ultrafiltration in step S1 comprises: sequentially passing through ultrafilter with molecular weight of 90-100KD and ultrafilter with molecular weight of 10-30 KD.
Further preferably, in the step S1, the volume is fixed to 65-75% of the volume of the concentration tank, and activated carbon is added, wherein the addition amount of the activated carbon is 0.2g/mL; the heating temperature is 90-100deg.C, and the heating time is 15-25min.
Further preferably, the temperature after the temperature reduction in the step S2 is 60-70 ℃; the volume is fixed to 80-90% of the volume of the diluting preparation tank, the pH adjusting reagent is NaOH solution with the mass concentration of 30-40%, and the pH is adjusted to 4-6.
Preferably, the preparation method of the acanthopanax root extract comprises the following steps:
1) Pulverizing stem of radix Acanthopanacis Senticosi into 2-10cm sections, sequentially drying at 100-120deg.C and 80-110deg.C under steam pressure less than 0.4MPa to obtain radix Acanthopanacis Senticosi;
2) Decocting radix Acanthopanacis Senticosi with 6-8 times of water at 95-105deg.C for 2-4 hr for 2 times, extracting with ultrasonic and microwave, wherein the ultrasonic power is 280-320w, and the microwave power is 180-220w, filtering to obtain filtrate A;
3) Regulating the pH value of the filtrate A to 10-12 with lime milk, stirring at 45-55r/min for 4-6min, continuously regulating the pH value of the filtrate A to 4-6 with 15-25% sulfuric acid by mass fraction, stirring at 45-55r/min for 8-12min, standing for more than 4h, and collecting supernatant to obtain solution B;
4) Concentrating the solution B to relative density of 1.05-1.20 at 75-85deg.C, adding 85-95% ethanol solution to alcohol content of 80-90%, standing for over 12 hr, and filtering.
The preparation method of the acanthopanax root medicinal material comprises the following steps: selecting and removing impurities and mildewed components in acanthopanax, washing the cleaned and selected medicinal materials with a high-pressure water gun until no dust exists, operating according to the standard operation procedure of 93ZR-8.0B type cutting and kneading machine, crushing into sections of 2-10cm, drying according to the standard operation procedure of a belt dryer after crushing, controlling the temperature of the high-temperature section at 100-120 ℃, the temperature of the low-temperature section at 80-110 ℃, the steam pressure at not more than 0.4MPa, and controlling the drying time at 13-15min (the motor frequency of 50 Hz).
The invention also relates to the acanthopanax extract injection prepared by the preparation method, the specification of the acanthopanax extract injection is 20mL each, and the acanthopanax extract injection comprises 4.5-5.5mg/mL total flavonoids, 0.7-1.0mg/mL syringin and 0.3-0.5mg/mL acanthopanaxoside E.
Compared with the prior art, the invention has the following beneficial effects:
(1) The acanthopanax extract injection has high content of active ingredients, and comprises 4.5-5.5mg/mL of total flavone, 0.7-1.0mg/mL of syringin and 0.3-0.5mg/mL of acanthopanaxoside E;
(2) The stability of the acanthopanax extract injection is further improved.
Drawings
FIG. 1 is a flow chart of the preparation of an injection (20 mL each) of acanthopanax extract in the present invention.
Detailed Description
The technical solutions of the embodiments of the present invention are further clearly described, and the described embodiments are only a part of the present invention, which are used to explain the present invention, but not to limit the present invention, so that other embodiments obtained by other persons skilled in the art without creative efforts fall within the protection scope of the present invention.
Example 1
1. Preparing an acanthopanax root extract:
1) Pulverizing stem of radix Acanthopanacis Senticosi into 5cm pieces, sequentially drying at 110deg.C and 90deg.C for 7min with steam pressure of 0.2MPa to obtain radix Acanthopanacis Senticosi;
2) Decocting radix Acanthopanacis Senticosi with 8 times of water at 100deg.C for 3 hr for 2 times, extracting with ultrasonic and microwave, wherein the ultrasonic power is 300w and the microwave power is 200w, filtering to obtain filtrate A;
3) Regulating the pH value of the filtrate A to 10 by lime milk, stirring at a rotating speed of 50r/min for 5min, continuously regulating the pH value of the filtrate A to 5 by sulfuric acid with a mass fraction of 20%, stirring at a rotating speed of 50r/min for 10min, standing for 5h, and taking supernatant to obtain a solution B;
4) Concentrating the solution B to relative density of 1.20 at 80 ℃, adding ethanol solution with volume fraction of 90% to ethanol content of 85%, standing for 14h, and filtering to obtain the final product.
2. Preparing acanthopanax purified liquid:
(1) Macroporous resin column chromatography separation: the acanthopanax root extract passes through a chromatographic column consisting of an upper layer of D-101, a middle layer of NKA and a lower layer of HPD750, wherein the thickness ratio of D-101, NKA and HPD750 is 1:2:2; eluting with water to 8 retention volumes, eluting with 70wt% ethanol with pH=5 to 8 retention volumes, collecting ethanol eluate, and concentrating to obtain concentrate A;
(2) Separating by silica gel column chromatography: adding a proper amount of 200-300 mesh silica gel into the concentrated solution A, mixing, eluting with a mixed solution of ethyl acetate, trifluoroacetic acid and acetone (the volume ratio of ethyl acetate, trifluoroacetic acid and acetone is 80:19:1) with the volume of 5 times of the column volume by silica gel column chromatography, collecting the eluent, concentrating to dryness, adding water for injection, and dissolving to obtain the acanthopanax purified solution.
3. The preparation flow of the acanthopanax extract injection (each 20mL containing 100mg of total flavonoids) is shown in figure 1, and the preparation process is as follows:
s1, concentration: filtering the acanthopanax purified liquid sequentially by 300-mesh silk cloth, a 0.4-mu m polypropylene filter core, a 100KD molecular weight ultrafilter and a 30KD molecular weight ultrafilter, pouring into a concentrated tank, adding water for injection to a volume of 70% of the total volume, adding 0.2g/mL of activated carbon, heating to 100 ℃, and stirring for 20min to obtain a mixed liquid 1;
s2, diluting: cooling the mixed solution 1 to 70 ℃, sequentially filtering by a plate-frame filter (two layers of filter paper and two layers of 0.45 mu m filter membranes) and ultrafiltering by an ultrafilter with the molecular weight of 10KD to a diluted preparation tank, adding water for injection, fixing the volume to 85% of the whole volume, adding NaOH solution with the mass concentration of 40% to adjust the pH value to 5.0, stirring for 20min, sampling and detecting to be qualified, and adding the water for injection to the whole volume to obtain an intermediate product of the injection;
s3, filling and sealing: finely filtering the intermediate product of the injection which is qualified by detection through a 0.22 mu m filter element, filling 20mL, and sealing;
s4, sterilizing: sterilizing at 115 ℃ for 40min;
s5, performing light inspection, labeling and packaging to obtain the product.
Example 2
1. Preparation of acanthopanax root extract
1) Pulverizing stem of radix Acanthopanacis Senticosi into 8cm sections, sequentially drying at 100deg.C and 80deg.C for 7min respectively, and steam pressure of 0.3MPa to obtain radix Acanthopanacis Senticosi clean medicinal material;
2) Decocting radix Acanthopanacis Senticosi with 6 times of water at 105deg.C for 2 hr for 2 times, extracting with assistance of ultrasonic and microwave, and filtering to obtain filtrate A with ultrasonic power of 320w and microwave power of 220 w;
3) Regulating the pH value of the filtrate A to 10 by lime milk, stirring at a rotating speed of 45r/min for 6min, continuously regulating the pH value of the filtrate A to 6 by sulfuric acid with a mass fraction of 25%, stirring at a rotating speed of 55r/min for 8min, standing for 10h, and taking supernatant to obtain a solution B;
4) Concentrating the solution B to relative density of 1.05 at 85deg.C, adding 85% ethanol solution to ethanol content of 90%, standing for 24 hr, and filtering.
2. Preparing acanthopanax purified liquid:
(1) Macroporous resin column chromatography separation: the acanthopanax root extract passes through a chromatographic column consisting of an upper layer of D-101, a middle layer of NKA and a lower layer of HPD750, wherein the thickness ratio of D-101, NKA and HPD750 is 1:1:1; eluting with water for 6 retention volumes, eluting with 60wt% ethanol with pH=3 for 8 retention volumes, collecting ethanol eluate, and concentrating to obtain concentrate A;
(2) Separating by silica gel column chromatography: adding a proper amount of 200-300 mesh silica gel into the concentrated solution A, mixing, eluting with a mixed solution of ethyl acetate, trifluoroacetic acid and acetone (the volume ratio of ethyl acetate, trifluoroacetic acid and acetone is 89:10:1) with the volume of 6 times of the column by silica gel column chromatography, collecting the eluent, concentrating to dryness, adding the injection, and dissolving with water to obtain the acanthopanax purified solution.
3. Preparation of radix Acanthopanacis Senticosi extract injection (20 mL each containing total flavonoids 100 mg):
s1, concentration: filtering the acanthopanax purified liquid sequentially by a 500-mesh silk cloth filter, a 0.22 mu m polypropylene filter core, a 100KD molecular weight ultrafilter and a 10KD molecular weight ultrafilter, pouring into a concentrated preparation tank, adding water for injection to a volume of 65% of the total volume, adding 0.15g/mL of activated carbon, heating to 90 ℃, and stirring for 25min to obtain a mixed liquid 1;
s2, diluting: cooling the mixed solution 1 to 60 ℃, sequentially filtering by a plate-frame filter (two layers of filter paper and two layers of 0.45 mu m filter membranes) and ultrafiltering by an ultrafilter with the molecular weight of 10KD to a diluted preparation tank, adding water for injection, fixing the volume to 90% of the whole volume, adding a NaOH solution with the mass concentration of 30% to adjust the pH value to 4.0, stirring for 25min, sampling and detecting to be qualified, and adding the water for injection to the whole volume to obtain an intermediate product of the injection;
s3, filling and sealing: finely filtering the intermediate product of the injection which is qualified by detection through a 0.22 mu m filter element, filling 20mL, and sealing;
s4, sterilizing: sterilizing at 116 ℃ for 30min;
s5, performing light inspection, labeling and packaging to obtain the product.
Example 3
1. The preparation process of the acanthopanax extract is the same as in example 1.
2. Preparing acanthopanax purified liquid:
(1) Macroporous resin column chromatography separation: the acanthopanax root extract passes through a chromatographic column consisting of an upper layer of D-101, a middle layer of NKA and a lower layer of HPD750, wherein the thickness ratio of D-101, NKA and HPD750 is 1:1:2; eluting with water for 6 retention volumes, eluting with 70wt% ethanol with pH=5 for 7 retention volumes, collecting ethanol eluate, and concentrating to obtain concentrate A;
(2) Separating by silica gel column chromatography: adding a proper amount of 200-300 mesh silica gel into the concentrated solution A, mixing, eluting with a mixed solution of ethyl acetate, trifluoroacetic acid and acetone (the volume ratio of ethyl acetate, trifluoroacetic acid and acetone is 85:14:1) with the volume of 4 times of the column by silica gel column chromatography, collecting the eluent, concentrating to dryness, adding water for injection, and dissolving to obtain the acanthopanax purified solution.
3. Preparation of acanthopanax extract injection (20 mL each containing 100mg of total flavonoids):
s1, concentration: filtering the acanthopanax purified liquid sequentially by a 100-mesh silk cloth filter, a 0.8 mu m polypropylene filter element filter, a 100KD molecular weight ultrafilter and a 20KD molecular weight ultrafilter, pouring into a concentrated preparation tank, adding water for injection to a volume of 75% of the total volume, adding 0.25g/mL of activated carbon, heating to 100 ℃, and stirring for 15min to obtain a mixed liquid 1;
s2, diluting: cooling the mixed solution 1 to 65 ℃, sequentially filtering by a plate-frame filter (two layers of filter paper and two layers of 0.45 mu m filter membranes) and ultrafiltering by an ultrafilter with the molecular weight of 10KD to a diluted preparation tank, adding water for injection, fixing the volume to 80% of the whole volume, adding NaOH solution with the mass concentration of 40% to adjust the pH value to 6.0, stirring for 15min, sampling and detecting to be qualified, and adding the water for injection to the whole volume to obtain an intermediate product of the injection;
s3, filling and sealing: finely filtering the intermediate product of the injection which is qualified by detection through a 0.22 mu m filter element, filling 20mL, and sealing;
s4, sterilizing: sterilizing at 115 ℃ for 30min;
s5, performing light inspection, labeling and packaging to obtain the product.
Comparative example 1
1. The preparation process of the acanthopanax extract is the same as in example 1.
2. The preparation process of the acanthopanax purified liquid is the same as that of the example 1, and the only difference is that:
(1) Macroporous resin column chromatography separation: the acanthopanax extract passes through a chromatographic column composed of an upper layer of D-101 and a lower layer of HPD750, wherein the total amount of the filler is consistent with that of the embodiment 1, and the thickness ratio of the D-101 to the HPD750 is 1:4; eluting with water for 6 retention volumes, eluting with 70wt% ethanol with pH=5 for 7 retention volumes, collecting ethanol eluate, and concentrating to obtain concentrate A.
Other steps were consistent with example 1.
3. The preparation process of acanthopanax extract injection (each 20mL containing 100mg of total flavonoids) is the same as in example 1.
Comparative example 2
1. The preparation process of the acanthopanax extract is the same as in example 1.
2. The preparation process of the acanthopanax purified liquid is the same as that of the example 1, and the only difference is that:
(1) Macroporous resin column chromatography separation: passing radix Acanthopanacis Senticosi extract through HPD750 chromatographic column, eluting with water for 6 retention volumes, eluting with 70wt% ethanol with pH=5 for 7 retention volumes, collecting ethanol eluate, and concentrating to obtain concentrate A;
other steps were consistent with example 1.
3. The preparation process of acanthopanax extract injection (each 20mL containing 100mg of total flavonoids) is the same as in example 1.
Comparative example 3
1. The preparation process of the acanthopanax extract is the same as in example 1.
2. The preparation process of the acanthopanax purified liquid is the same as that of the example 1, and the only difference is that:
(2) Separating by silica gel column chromatography: adding a proper amount of 200-300 mesh silica gel into the concentrated solution A, performing column chromatography on the mixed solution A by using 3 times of column volume of water for the first time after sample mixing, discarding the eluent, eluting the mixed solution by using 6 times of column volume of ethyl acetate and acetone (the volume ratio of the ethyl acetate to the acetone is 99:1) for the second time, collecting the eluent, and concentrating the eluent to dryness to obtain the acanthopanax concentrate;
other steps were consistent with example 1.
3. The preparation process of acanthopanax extract injection (each 20mL containing 100mg of total flavonoids) is the same as in example 1.
Comparative example 4
1. The preparation process of the acanthopanax extract is the same as in example 1.
2. The preparation process of the acanthopanax purified liquid is the same as that of the example 1, and the only difference is that:
(3) Dissolving radix Acanthopanacis Senticosi concentrate in water, sequentially filtering with 300 mesh silk cloth, 0.4 μm polypropylene filter core, ultrafiltering with 30KD molecular weight ultrafilter, and refrigerating at 5deg.C to obtain purified solution of radix Acanthopanacis Senticosi.
3. The preparation process of acanthopanax extract injection (each 20mL containing 100mg of total flavonoids) is the same as in example 1.
Comparative example 5
Injection disclosed in example 4 of chinese patent application CN 201910570805.2.
Effect testing
Test example 1 quality detection of acanthopanax extract injection
1. The testing method comprises the following steps:
(1) Total flavonoids: rutin is used as a reference substance, the absorbance is measured at the wavelength of 510nm according to a spectrophotometry (appendix VA of 2010 edition of Chinese pharmacopoeia), and the content of total flavonoids in the acanthopanax injection is calculated;
(2) Syringin and eleutheroside E
The determination is carried out according to the appendix VID of the 2010 edition of Chinese pharmacopoeia. A ACQUITY UPLC BEH C (2.1X100 mm,1.7 μm) column was used; acetonitrile is taken as a mobile phase A, a phosphoric acid solution with the volume fraction of 0.1% is taken as a mobile phase B, and the column temperature is 40 ℃; the flow rate is 0.3mL/min; the detection wavelength was 220nm. Gradient elution: at 0min, 5% mobile phase A and 95% mobile phase B; at 3.2min, 9.2% mobile phase A and 90.8% mobile phase B; at 10.0min, 22% mobile phase A and 78% mobile phase B; at 12min, 100% mobile phase A; at 15min, 5% mobile phase A and 95% mobile phase B.
(3) Fingerprint inspection
The measurement is carried out according to high performance liquid chromatography (VID of the first appendix of the Chinese pharmacopoeia of 2010 edition). A Agilent Zorbox Eclipse XDB-C18 (250X 4.6mm,5 μm) liquid chromatography column was used; mobile phase a:0.5% formic acid solution, mobile phase B: acetonitrile-water (30:70), detection wavelength 270nm; column temperature 20 ℃; the flow rate was 0.8mL/min. Gradient elution, 100% mobile phase a at 0min; 88% mobile phase A and 12% mobile phase B at 15 min; 82% mobile phase A and 18% mobile phase B at 21 min; 31% mobile phase A and 69% mobile phase B at 60 min; 100% mobile phase B at 65 min; at 70-75min, 100% mobile phase A.
(4) Total solids of
After evaporation to dryness, the total solids content was calculated by weighing.
(5) Insoluble particles
The detection is carried out by referring to the 2020 edition of Chinese pharmacopoeia-insoluble particle examination method.
Table 1 quality detection results of acanthopanax injection of examples 1-3
Table 2 quality detection results of acanthopanax injection solutions of comparative examples 1 to 5
| Detection index (200 mL) | Comparative example 1 | Comparative example 2 | Comparative example 3 | Comparative example 4 | Comparative example 5 |
| pH | 5.5 | 5.5 | 6.0 | 5.4 | 5.8 |
| Total solids (mg/mL) | 42 | 32 | 33 | 37 | 31 |
| Particles (grains) of 10 μm or more | 790 | 640 | 1524 | 2108 | 3510 |
| Particles (grains) of 25 μm or more | 152 | 193 | 240 | 283 | 307 |
| Finger print similarity | 0.90 | 0.91 | 0.92 | 0.90 | 0.90 |
| Total flavone content (mg/mL) | 4.58 | 5.01 | 4.9 | 4.59 | 4.92 |
| Syringin (mg/mL) | 0.43 | 0.47 | 0.51 | 0.41 | 0.38 |
| Acanthopanax senticosus glycoside E (mg/mL) | 0.28 | 0.31 | 0.37 | 0.18 | 0.19 |
Test example 2 stability test
1. Clarity observation test
According to the relevant requirements of the stability test guidelines of the XIXC pharmaceutical preparation of the second annex of 2005 edition of Chinese pharmacopoeia.
500 injections of the acanthopanax extract prepared in examples 1-3 and comparative examples 1-5 were taken, each 20mL in size, placed in a comprehensive drug stability test box (equipment model LHH-SSG) and subjected to accelerated test at 40+ -2deg.C, and the clarity of each batch of products was observed under a clarity detector after 1 month, 2 months, 3 months and 6 months of the accelerated test, and the test results are shown in Table 3.
TABLE 3 clarity test results of products
2. Quality stability detection
The same batch of acanthopanax extract injection, examples 1-3 and comparative examples 1-5 were left for 3 months at 40.+ -. 2 ℃ for each 20mL, and then the sample quality was examined by the same examination method as in test example 1. The results of the detection are shown in tables 4 to 5.
Table 4 quality test results of the acanthopanax extract injection of examples 1-3 after 3 months
Table 5 quality test results of acanthopanax extract injection of comparative examples 1 to 5 after 3 months
| Detection index (200 mL) | Comparative example 1 | Comparative example 2 | Comparative example 3 | Comparative example 4 | Comparative example 5 |
| pH | 5.3 | 5.2 | 5.4 | 5.3 | 5.3 |
| Particles (grains) of 10 μm or more | 1725 | 2307 | 3098 | 1931 | 5717 |
| Particles (grains) of 25 μm or more | 457 | 421 | 509 | 384 | 529 |
| Total flavone content (mg/mL) | 4.55 | 5.02 | 4.87 | 5.0 | 4.97 |
| Syringin (mg/mL) | 0.38 | 0.41 | 0.43 | 0.40 | 0.29 |
| Acanthopanax senticosus glycoside E (mg/mL) | 0.27 | 0.23 | 0.18 | 0.17 | 0.15 |
The foregoing detailed description is directed to one of the possible embodiments of the present invention, which is not intended to limit the scope of the invention, but is to be accorded the full scope of all such equivalents and modifications so as not to depart from the scope of the invention.
Claims (10)
1. A preparation method of an acanthopanax extract injection is characterized by comprising the following steps: extracting stem of radix Acanthopanacis Senticosi to obtain radix Acanthopanacis Senticosi extract, and purifying to obtain radix Acanthopanacis Senticosi extract injection;
the purification step includes:
(1) Macroporous resin column chromatography separation: the macroporous adsorption resin chromatographic column is as follows: a chromatographic column consisting of an upper layer of D-101, a middle layer of NKA and a lower layer of HPD 750; eluting radix Acanthopanacis Senticosi extract with water for 6-8 retention volumes, eluting with ethanol for 6-8 retention volumes, collecting ethanol eluate, and concentrating to obtain radix Acanthopanacis Senticosi concentrated solution;
(2) Separating by silica gel column chromatography: adding 200-300 mesh silica gel into radix Acanthopanacis Senticosi concentrated solution, mixing, subjecting to silica gel column chromatography, eluting with 4-6 times of mixed solution of ethyl acetate, trifluoroacetic acid and acetone, collecting eluate, concentrating to dry, and dissolving in water to obtain radix Acanthopanacis Senticosi purified solution.
2. The method of claim 1, wherein the thickness ratio of D-101, NKA, and HPD750 in step (1) is 1:1-2:1-2; the ethanol is 60-70wt% ethanol with pH=3-5.
3. The method according to claim 1, wherein the volume ratio of ethyl acetate, trifluoroacetic acid and acetone in step (2) is 80-89:10-20:1.
4. The preparation method according to claim 1, wherein the preparation process of the acanthopanax extract injection comprises the following steps:
s1, concentration: filtering the purified acanthopanax liquid sequentially by silk cloth, polyether sulfone filter core and ultrafilter, pouring into a concentrated tank, adding water to a certain volume, adding active carbon, heating and stirring to obtain a mixed liquid 1;
s2, diluting: cooling the mixed solution 1, sequentially filtering by a plate-frame filter and ultrafiltering by an ultrafilter with a molecular weight of 8-10KD to a diluting preparation tank, adding water to fix volume, adjusting pH, stirring, sampling, detecting to be qualified, and adding water to a full amount to obtain an injection intermediate product;
s3, filling and sealing: filtering and filling and sealing the intermediate products of the injection which are qualified in detection;
s4, sterilizing: sterilizing at 115-116 deg.C for 30-40min;
s5, performing light inspection, labeling and packaging to obtain the product.
5. The method according to claim 4, wherein the aperture of the silk cloth in the step S1 is 100-500 mesh; the aperture of the polyether sulfone filter element is 0.22-0.8 mu m.
6. The method according to claim 4, wherein the ultrafilter ultrafiltration in step S1 comprises: sequentially passing through ultrafilter with molecular weight of 90-100KD and ultrafilter with molecular weight of 10-30 KD.
7. The preparation method according to claim 4, wherein in the step S1, the active carbon is added to the volume of the concentrate tank to be 65-75%, and the addition amount of the active carbon is 0.2g/mL; the heating temperature is 90-100deg.C, and the heating time is 15-25min.
8. The preparation method according to claim 4, wherein the temperature after the temperature reduction in step S2 is 60-70 ℃; the volume is fixed to 80-90% of the volume of the diluting preparation tank, the pH adjusting reagent is NaOH solution with the mass concentration of 30-40%, and the pH is adjusted to 4-6.
9. The preparation method according to claim 1, wherein the preparation method of the acanthopanax extract comprises the steps of:
1) Pulverizing stem of radix Acanthopanacis Senticosi into 2-10cm sections, sequentially drying at 100-120deg.C and 80-110deg.C under steam pressure less than 0.4MPa to obtain radix Acanthopanacis Senticosi;
2) Decocting radix Acanthopanacis Senticosi with 6-8 times of water at 95-105deg.C for 2-4 hr for 2 times, extracting with ultrasonic and microwave, wherein the ultrasonic power is 280-320w, and the microwave power is 180-220w, filtering to obtain filtrate A;
3) Regulating the pH value of the filtrate A to 10-12 with lime milk, stirring at 45-55r/min for 4-6min, continuously regulating the pH value of the filtrate A to 4-6 with 15-25% sulfuric acid by mass fraction, stirring at 45-55r/min for 8-12min, standing for more than 4h, and collecting supernatant to obtain solution B;
4) Concentrating the solution B to relative density of 1.05-1.20 at 75-85deg.C, adding 85-95% ethanol solution to alcohol content of 80-90%, standing for over 12 hr, and filtering.
10. The acanthopanax extract injection prepared by the preparation method of any one of claims 1 to 9, which is characterized by comprising 4.5 to 5.5mg/mL total flavonoids, 0.7 to 1.0mg/mL syringin and 0.3 to 0.5mg/mL acanthopanaxoside E.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101240004A (en) * | 2008-03-18 | 2008-08-13 | 山东大学威海分校 | Technique for preparing eleutheroside B |
| CN104306417A (en) * | 2014-09-28 | 2015-01-28 | 哈尔滨珍宝制药有限公司 | Low-toxicity acanthopanax injection and preparation method thereof |
| CN104739907A (en) * | 2013-12-30 | 2015-07-01 | 哈尔滨珍宝制药有限公司 | Acanthopanax senticosus extract, preparation method thereof and preparation containing the same |
| CN108014153A (en) * | 2017-12-08 | 2018-05-11 | 大兴安岭林格贝寒带生物科技股份有限公司 | A kind of new method that eleutheroside is extracted from wilsonii |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101240004A (en) * | 2008-03-18 | 2008-08-13 | 山东大学威海分校 | Technique for preparing eleutheroside B |
| CN104739907A (en) * | 2013-12-30 | 2015-07-01 | 哈尔滨珍宝制药有限公司 | Acanthopanax senticosus extract, preparation method thereof and preparation containing the same |
| CN104306417A (en) * | 2014-09-28 | 2015-01-28 | 哈尔滨珍宝制药有限公司 | Low-toxicity acanthopanax injection and preparation method thereof |
| CN108014153A (en) * | 2017-12-08 | 2018-05-11 | 大兴安岭林格贝寒带生物科技股份有限公司 | A kind of new method that eleutheroside is extracted from wilsonii |
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