CN105726476B - A kind of preparation method of shaobei injection - Google Patents
A kind of preparation method of shaobei injection Download PDFInfo
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Abstract
The invention discloses a kind of preparation methods of shaobei injection, first radix paeoniae rubrathe medicinal material is crushed twice, it is extracted twice after being impregnated with acidic aqueous solution, then extracting solution concentrated, add alcohol alcohol precipitation, concentrate again, it adsorbs to obtain total paeony glycoside crude product through large pore resin absorption column, purified again with C18 reverse-phase chromatographic columns, sephadex chromatography, obtain Paeoniflorin monomer;Then Paeoniflorin monomer 100g, gallic acid 37.5g, citric acid 2500g are weighed, by matching liquid, filling, is finally put in storage.The present invention can improve the recovery rate of Paeoniflorin, shorten the preparation time of total paeony glycoside crude product, reduce the loss in separation process, improve the purity of Chinese herbaceous peony glycoside product, purity >=98% of gained Paeoniflorin;Easily operated and industrialized production of the invention, improves economic benefit and product guarantee.
Description
Technical field
The invention belongs to pharmaceutical processing techniques fields, and in particular to a kind of preparation method of shaobei injection.
Background technology
Shaobei injection original name " 2.5%AN parenteral solutions ", " iS-One hemorrhoid liquid ", " ANZHI ZHUSHEYE " have convergence astringent method,
Cooling blood and hemostasis, it is promoting blood circulation and removing blood stasis the effect of, treat each phase internal piles and Anzhi injection treatment in hemostasis, haemorrhoids is made to wither
Contracting.This effective prescription selects dark plum, Chinese gall, the full side of radix paeoniae rubrathe composition, and three medicine compatibilities, dark plum is monarch, and Chinese gall is minister, and two medicines cooperate with
Astriction, radix paeoniae rubrathe stagnation resolvation play using corrigent, and three medicines complement each other to be played convergence stagnation resolvation hemorrhoid is gone to act on altogether.
In line with derived from traditional Chinese medicine, the spirit of Developing TCM, three taste medium-height grass the effective elements of the medicine citric acids of extraction, nutgall
Acid and Paeoniflorin are directly used as medicine, and are configured to injection, pharmacological property effect and the compatibility relationship of former Chinese medicine are not only kept, with traditional Chinese medicine
Preparation compares, and active ingredient is high, controllability is good, impurity is few, irritation is small, stablizes.Produce the lemon in shaobei injection prescription
Acid, gallic acid can be bought needed for production, and Paeoniflorin purchase is less than the purity for meeting production requirement.
Mainly there are water extraction, dilute alcohol percolation, ethanol reflux extraction, Microwave Extraction about the extraction of Paeoniflorin at present
Method, ultrasonic extraction, CO2Supercritical extraction etc., and means of purification is then detached using column chromatography or macroporous absorbent resin.This
A little extracting methods and means of purification overall fault are more for the impurity of Paeoniflorin, and solvent-oil ratio is big, residual is big, long flow path, the later stage
Purification difficult, least a portion of Paeoniflorin are lost in purification with macroreticular resin, decline the yield of product, the purifying side in later stage
Method is difficult to the sterling for reaching more than 98% content.
Invention content
Based on the deficiencies of the prior art, the purpose of the present invention is to provide a kind of preparation method of shaobei injection, simple,
Efficiently, purity and shaobei injection with high accuracy are prepared to low energy consumption.
To achieve these goals, the technical solution adopted by the present invention is:
A kind of preparation method of shaobei injection, includes the following steps:
(1)Weigh radix paeoniae rubrathe medicinal material, through once crushing to obtain the coarse granule that granularity is 50 ~ 300 mesh, then through separating twice,
The Ultramicro-powder that granularity is 1250 ~ 2500 mesh is obtained after sieving;Ultramicro-powder is placed in the acidic aqueous solution of pH=2, Ultramicro-powder with
The solid-to-liquid ratio of acidic aqueous solution is 1:6kg/L is once extracted, press filtration after impregnating 30 ~ 45 minutes using microwave ultrasonic wave method
After obtain an extracting solution and filter residue, into filter residue add in pH=2 acidic aqueous solution carry out second extraction, after press filtration it is secondary
Extracting solution and secondary raffinate are uniformly mixed to obtain mixed extract by extracting solution;
(2)By step(1)The mixed extract of gained is added in concentration tank, temperature be 55 ~ 60 DEG C, vacuum degree≤-
A concentrate is concentrated to give under the conditions of 0.08MPa, the volume of a concentrate is the 15 ~ 17% of mixed extract volume;By one
Secondary concentrate is fitted into Alcohol-settling tank and cools down, and 90 ~ 97% ethyl alcohol are added in into Alcohol-settling tank, until ethyl alcohol is accounted in Alcohol-settling tank in solution
Mass fraction is 80%, and 5 ~ 10 DEG C stand 45 ~ 50 hours, and supernatant is taken to pour into concentration tank again, is 40 DEG C, vacuum degree in temperature
Be concentrated to give secondary concentration liquid under the conditions of≤- 0.08Mpa, the volume of secondary concentration liquid for mixed extract volume 5.5 ~
6.5%;
(3)To step(2)Add in purified water in the secondary concentration liquid of gained, the volume ratio of secondary concentration liquid and purified water is
1:4, pH to 5 ~ 6 is adjusted, is then added in large pore resin absorption column, after adsorbing 6 ~ 8 hours, is rinsed 4 hours with purified water, then
It after rinsing 1 hour respectively with 5% ethanol solution and 10% ethanol solution successively, is eluted with 95% ethanol solution, contact plate collects elution
Liquid;Then eluent is concentrated under reduced pressure, dries dry powder is made, obtain total paeony glycoside crude product;
(4)By step(3)The total paeony glycoside crude product of gained is added in purified water, and the solid-to-liquid ratio of total paeony glycoside crude product and water is
1:10 ~ 15kg/L, using C18 reverse-phase chromatographic columns, second alcohol and water is as mobile phase, gradient elution;Sephadex chromatography is used again
Purifying, is eluted with methanol, is concentrated under reduced pressure to give Paeoniflorin monomer;
Wherein, the condition of gradient elution is:0 ~ 40min, ethyl alcohol 30%;40 ~ 90min, ethyl alcohol 60%, 90 ~ 120min, ethyl alcohol
100%, flow velocity 10mL/min, column temperature are 20 ~ 30 DEG C;
(5)It is 18 ~ 26 DEG C, in the toilet of relative humidity 45 ~ 65% in temperature, weighs Paeoniflorin monomer 100g, nutgall
Sour 37.5g, citric acid 2500g are added in liquid dispensing device;The temperature in liquid dispensing device is adjusted as 40 ~ 50 DEG C, filling jetting is to matching
The total weight of liquid device inner liquid medicine is 100kg, and air pressure in liquid dispensing device, temperature is kept to stablize, is stirred 3 ~ 10 minutes, adjustment is with liquid
Temperature in device is 15 ~ 25 DEG C, filtering;
(6)By step(5)The shaobei injection that products therefrom sterile filling is propped up into 10ml/, 100 degree of leak detections, negative pressure 60
KPa moist heat sterilizations 20 minutes, examine, pack, enter shady and cool library to get.
Preferably, step(5)Described in liquid dispensing device include closed tank body, the tank body is cylindrical in class and tank body
Vertically, the class cylinder is that cylindrical opposite both ends of the surface are that the spherical crown outwardly protruded is surrounded to longitudinal center line
Figure;Rotary wash ball is installed, the side of rotary wash ball is provided with manhole, at manhole at the center of tank body upper surface
Uniform intervals are provided with compressed air inlet, pneumostome, integrated inspection visor, feed inlet, spare mouth, pure steam in the counterclockwise direction
Entrance, vacuum orifice, rupture disk mouth and pressure gauge;The top of tank body circumference side is provided with first circulation mouth, the bottom of tank body
It is provided with hollow between second circulation mouth, tank body circumference side and lower circumference side and the inner wall and outer wall of bottom, and is equipped with
Chuck and runner, the chuck are connected by runner with first circulation mouth and second circulation mouth, and circulation has heat transfer in chuck
Medium;The lower part of tank body circumference side is provided with sampling valve port, pH meter and thermometer, and discharging is provided at the center of tank base
Mouthful, the side of discharge port is equipped with blender;Stabilizer blade is provided with below tank body, the bottom of stabilizer blade is equipped with Weighing module.
Preferably, step(1)The separating twice is by coarse granule and temperature is 0 ~ 8 DEG C, water content is 0.5 ~ 1%
The freeze-drying co-implanted air-stream type ultrafine pulverizer of air crushes.
Preferably, step(1)In once extraction and second extraction are using microwave ultrasonic wave Chinese medicine extraction machine, ultrasonic power
For 1 ~ 2KW, microwave power is 600 ~ 1000W, and primary extraction and second extraction time are 20 ~ 35 minutes, and when second extraction adds
The volume of the acidic aqueous solution entered is 1/2 ~ 2/3 of acidic aqueous solution volume when once extracting.
Preferably, step(1)The acidic aqueous solution is dilute hydrochloric acid solution.
Preferably, step(4)For the C18 reverse-phase chromatographic columns using C18 bonded silica gels as filler, the grain size of filler is 5 μm.
Further, the heat transfer medium is steam and/or cooling water.
The present invention can improve the recovery rate of Paeoniflorin using crushing twice, then impregnated with acidic aqueous solution, shorten the radix paeoniae rubrathe
The preparation time of total glycosides crude product, has the advantages that quick, thorough, efficient;Using C18 reverse-phase chromatographic columns and sephadex color
Spectrum purifying, reduces the loss in separation process, improves the purity of Chinese herbaceous peony glycoside product, purity >=98% of gained Paeoniflorin;Profit
The liquid dispensing device of Weighing module is provided with bottom, by control pressure and temperature, is made with liquid more rapidly, uniformly, accurately;This hair
Bright easily operated and industrialized production improves economic benefit and product guarantee.
Description of the drawings
Fig. 1 is the structure diagram of the liquid dispensing device;
Fig. 2 is the vertical view of Fig. 1.
Specific embodiment
Below by way of preferred embodiment, the present invention is described in more detail, but protection scope of the present invention is not limited to
This.
A kind of preparation method of shaobei injection, includes the following steps:
(1)10kg radix paeoniae rubrathe medicinal materials are weighed, through once crushing to obtain the coarse granule that granularity is 50 ~ 300 mesh, then by coarse granule
With the co-implanted air-stream type ultrafine pulverizer progress separating twice of freeze-drying air that temperature is 4 DEG C, water content is 0.8%, mistake
The Ultramicro-powder that granularity is 1250 ~ 2500 mesh is obtained after sieve;Ultramicro-powder is placed in 60L dilute hydrochloric acid solutions, dilute hydrochloric acid solution
PH=2 are impregnated after forty minutes, will be added in microwave ultrasonic wave Chinese medicine extraction machine together with dilute hydrochloric acid solution and Ultramicro-powder, adjust ultrasound
Wave power is 1KW, and microwave power 600W is once extracted, primary extraction 30 minutes, obtained after press filtration an extracting solution and
Filter residue is added in into filter residue in 40L dilute hydrochloric acid solutions, pH=2 of dilute hydrochloric acid solution, carries out second extraction, and second extraction 30 is divided
Clock obtains secondary raffinate, an extracting solution and secondary raffinate is uniformly mixed to obtain mixed extract after press filtration;
(2)By step(1)The mixed extract of gained is added in concentration tank, temperature be 55 ~ 60 DEG C, vacuum degree≤-
16L is concentrated under the conditions of 0.08MPa, obtains a concentrate;Concentrate is fitted into Alcohol-settling tank and cooled down, to Alcohol-settling tank
95% ethyl alcohol of middle addition, until the mass fraction that ethyl alcohol accounts for solution in Alcohol-settling tank is 80%, 5 ~ 10 DEG C stand 2 days, take supernatant again
It pours into concentration tank, is 40 DEG C, is concentrated into 6L under the conditions of vacuum degree≤- 0.08Mpa in temperature, obtain secondary concentration liquid, it is secondary
Concentrate is without ethanol flavor;
(3)To step(2)In the secondary concentration liquid of gained plus purified water is diluted to 30L, adjusts pH to 5 ~ 6, then adds in
To large pore resin absorption column, after adsorbing 6 hours, rinsed 4 hours with purified water, then successively respectively with 5% ethanol solution and 10% second
Alcoholic solution respectively rinses 1 hour, is then eluted with 95% ethanol solution, contact plate(I.e. using thin layer chromatography and Paeoniflorin standard items
Contact plate result is contrasted), collect eluent;Then eluent is concentrated under reduced pressure, dries dry powder is made, obtain total paeony glycoside crude product;
Total paeony glycoside crude product is polished to be fitted into Brown Glass Brown glass bottles and jars only, with detection to be sampled;
(4)By step(3)The total paeony glycoside crude product of gained is added in purified water, and the solid-to-liquid ratio of total paeony glycoside crude product and water is
1:10kg/L, using C18 reverse-phase chromatographic columns, second alcohol and water is as mobile phase, gradient elution;Whole sephadex again
Sephadex LH-20 chromatogram purifications, are eluted with methanol, are concentrated under reduced pressure to give Paeoniflorin monomer;
Wherein, the condition of gradient elution is:0 ~ 40min, ethyl alcohol 30%;40 ~ 90min, ethyl alcohol 60%, 90 ~ 120min, ethyl alcohol
100%, flow velocity 10mL/min, column temperature are 20 ~ 30 DEG C;Using C18 bonded silica gels as filler, the grain size of filler is C18 reverse-phase chromatographic columns
5μm;
(5)It is 20 DEG C, in the toilet of relative humidity 55% in temperature, Paeoniflorin monomer 100g is weighed under A grades of environment, is not had
Gallate-based 37.5g, citric acid 2500g are added in liquid dispensing device;
The liquid dispensing device includes closed tank body 15, and the tank body 15 is in class cylinder and the longitudinal center line of tank body 15
Vertically, it is the figure that the spherical crown outwardly protruded is surrounded that the class cylinder, which is cylindrical opposite both ends of the surface,;Tank
Rotary wash ball 17 is installed, the right side of rotary wash ball 17 is provided with manhole 1, at manhole 1 at the center of 15 upper surface of body
In the counterclockwise direction uniform intervals be provided with compressed air inlet 2, pneumostome 3, integrated inspection visor 4, feed inlet 5, spare mouth 7,
Pure steam entrance 8, vacuum orifice 9, rupture disk mouth 10 and pressure gauge 11;The top of 15 circumference side of tank body is provided with first circulation
Mouth 6, the bottom of tank body 15 is provided with second circulation mouth 20, hollow between 15 circumference side of tank body and the inner wall and outer wall of bottom,
And equipped with chuck 16 and runner, the chuck 16 is connected, and chuck by runner with first circulation mouth 6 and second circulation mouth 20
Circulation has heat transfer medium in 16, and the heat transfer medium is steam and/or cooling water;The lower part of 15 circumference side of tank body, which is provided with, to be taken
Sample valve port 14, pH meter 13 and thermometer 12 are provided with discharge port 19 at the center of tank base, and the side of discharge port 19 is equipped with
Blender 18;The lower section of tank body 15 is provided with stabilizer blade 21, and the bottom of stabilizer blade 21 is equipped with Weighing module 22;
Before and after liquid dispensing device use, it is both needed to be passed through steam sterilizing from by pure steam entrance 8;First circulation mouth 6 and second
It being all connected at circulation port 20 there are two pipeline, two pipelines are respectively steam circulation duct and cooling water circulation duct, during with liquid,
By being passed through steam from first circulation mouth 6, steam circulates in chuck 16, is flowed out from second circulation mouth 20, adjusts in tank body 15
Temperature be 40 ~ 50 DEG C;Then the gross weight of three kinds of bulk pharmaceutical chemicals and injection water in jetting to tank body 15 is filled by Weighing module 22
For 100kg, air pressure in tank body 15, temperature is kept to stablize, is stirred 3 ~ 10 minutes, by being passed through cooling water from second circulation mouth 20,
Cooling water circulates in chuck 16, is flowed out from first circulation mouth 6, and it is 20 DEG C to adjust the temperature in tank body, filtering;
(6)By step(5)The products therefrom shaobei injection that field monitoring sterile filling is propped up into 10ml/ under B+A environment,
100 degree of leak detections, 60 KPa moist heat sterilizations of negative pressure 20 minutes, examine, pack, enter shady and cool library to get.
By step(5)Gained Paeoniflorin monomer is used according to high effective liquid chromatography for measuring, chromatographic column octadecylsilane
Bonded silica gel is filler, mobile phase methanol:Water=3:7, Detection wavelength 230nm;Sample to be tested weighs 80 DEG C for precision and does
The dry Paeoniflorin monomer to constant weight adds water that the Paeoniflorin solution of 0.08g/L is made;20 μ L samples to be tested and blank are taken respectively
Sample injects high performance liquid chromatograph, measures Paeoniflorin purity >=98%.
Wherein, according to GB/T16292-1996 standards, A grades of cleaniliness classses to be achieved are:It is hundred grades static, dynamic hundred
Grade.The purity requirements of B+A are:A grades(High risk operating space)Reach hundred grades static, hundred grades of dynamic, and residing for the region
Background area is B grades, that is, background area is required to reach hundred grades static, ten thousand grades of dynamic.A grades of environment:Air themperature is 20 ~ 24 DEG C;
Relative air humidity is 45% ~ 60%;Horizontal wind speed >=0.54m/s, vertical velocity >=0.36m/s;The leak detection of high efficiency particulate air filter is big
In 99.97%;300LX < illumination≤600LX;Noise≤75db(Dynamic is tested).B grades of environment:Air themperature is 20 ~ 24 DEG C;It is empty
Gas relative humidity is 45% ~ 60%;Room rate of ventilation >=25 time/hour;Outdoor pressure difference >=10Pa relatively, the difference of same rank
Region keeps certain pressure difference by air flow direction;Horizontal wind speed >=0.54m/s, vertical velocity >=0.36m/s;High efficiency particulate air filter
Leak detection is more than 99.97%;300LX < illumination≤600LX;Noise≤75db(Dynamic is tested).
Claims (7)
1. a kind of preparation method of shaobei injection, which is characterized in that include the following steps:
(1)Radix paeoniae rubrathe medicinal material is weighed, the coarse granule that granularity is 50 ~ 300 mesh is obtained, then through separating twice, sieving through once crushing
The Ultramicro-powder that granularity is 1250 ~ 2500 mesh is obtained afterwards;Ultramicro-powder is placed in the acidic aqueous solution of pH=2, Ultramicro-powder and acidity
The solid-to-liquid ratio of aqueous solution is 1:6kg/L is once extracted after impregnating 30 ~ 45 minutes using microwave ultrasonic wave method, after press filtration
To an extracting solution and filter residue, the acidic aqueous solution that pH=2 are added in into filter residue carries out second extraction, second extraction is obtained after press filtration
Extracting solution and secondary raffinate are uniformly mixed to obtain mixed extract by liquid;
(2)By step(1)The mixed extract of gained is added in concentration tank, is 55 ~ 60 DEG C, vacuum degree≤- 0.08MPa in temperature
Under the conditions of be concentrated to give a concentrate, the volume of a concentrate is the 15 ~ 17% of mixed extract volume;It will once concentrate
Liquid is fitted into Alcohol-settling tank and cools down, and 90 ~ 97% ethyl alcohol are added in into Alcohol-settling tank, until ethyl alcohol is accounted in Alcohol-settling tank, quality is divided in solution
For number for 80%, 5 ~ 10 DEG C stand 45 ~ 50 hours, and supernatant is taken to pour into concentration tank again, temperature be 40 DEG C, vacuum degree≤-
Secondary concentration liquid is concentrated to give under the conditions of 0.08Mpa, the volume of secondary concentration liquid is the 5.5 ~ 6.5% of mixed extract volume;
(3)To step(2)Add in purified water in the secondary concentration liquid of gained, the volume ratio of secondary concentration liquid and purified water is 1:4,
PH to 5 ~ 6 is adjusted, is then added in large pore resin absorption column, after adsorbing 6 ~ 8 hours, is rinsed 4 hours with purified water, then successively
It after rinsing 1 hour respectively with 5% ethanol solution and 10% ethanol solution, is eluted with 95% ethanol solution, contact plate collects eluent;So
Eluent is concentrated under reduced pressure afterwards, dries dry powder is made, obtains total paeony glycoside crude product;
(4)By step(3)The total paeony glycoside crude product of gained is added in purified water, and the solid-to-liquid ratio of total paeony glycoside crude product and water is 1:10
~ 15kg/L, using C18 reverse-phase chromatographic columns, second alcohol and water is as mobile phase, gradient elution;Purified again with sephadex chromatography,
It is eluted with methanol, is concentrated under reduced pressure to give Paeoniflorin monomer;
Wherein, the condition of gradient elution is:0 ~ 40min, ethyl alcohol 30%;40 ~ 90min, ethyl alcohol 60%, 90 ~ 120min, ethyl alcohol
100%, flow velocity 10mL/min, column temperature are 20 ~ 30 DEG C;
(5)It is 18 ~ 26 DEG C, in the toilet of relative humidity 45 ~ 65% in temperature, weighs Paeoniflorin monomer 100g, gallic acid
37.5g, citric acid 2500g are added in liquid dispensing device;It is 40 ~ 50 DEG C to adjust the temperature in liquid dispensing device, and filling jetting is to liquid
The total weight of device inner liquid medicine is 100kg, and air pressure in liquid dispensing device, temperature is kept to stablize, is stirred 3 ~ 10 minutes, adjustment is filled with liquid
Temperature in putting is 15 ~ 25 DEG C, filtering;
(6)By step(5)The shaobei injection that products therefrom sterile filling is propped up into 10ml/, 100 degree of leak detections, 60 KPa of negative pressure are wet
Heat sterilization 20 minutes, examine, pack, enter shady and cool library to get.
2. the preparation method of shaobei injection according to claim 1, it is characterised in that:Step(5)Described in liquid fill
It puts including closed tank body, in the longitudinal center line of class cylinder and tank body vertically, the class is cylindrical for the tank body
Be cylindrical opposite both ends of the surface it is the figure that the spherical crown outwardly protruded is surrounded;Rotation is installed at the center of tank body upper surface
Turn rotating wash bowl, the side of rotary wash ball is provided with manhole, and uniform intervals are provided with compression sky in the counterclockwise direction at manhole
Gas entrance, pneumostome, integrated inspection visor, feed inlet, spare mouth, pure steam entrance, vacuum orifice, rupture disk mouth and pressure gauge;
The top of tank body circumference side is provided with first circulation mouth, and the bottom of tank body is provided with second circulation mouth, tank body circumference side and
Hollow between lower circumference side and the inner wall and outer wall of bottom, and equipped with chuck and runner, the chuck passes through runner and the
One circulation port and second circulation mouth are connected, and circulation has heat transfer medium in chuck;The lower part of tank body circumference side, which is provided with, to be taken
Sample valve port, pH meter and thermometer are provided with discharge port at the center of tank base, and the side of discharge port is equipped with blender;Tank
Stabilizer blade is provided with below body, the bottom of stabilizer blade is equipped with Weighing module.
3. the preparation method of shaobei injection according to claim 1, it is characterised in that:Step(1)Two wheat-middlings
Broken is that coarse granule and temperature is 0 ~ 8 DEG C, water content is 0.5 ~ 1% the co-implanted air blast ultramicro powder of freeze-drying air is broken
Machine crushes.
4. the preparation method of shaobei injection according to claim 1, it is characterised in that:Step(1)In once extraction and
Second extraction uses microwave ultrasonic wave Chinese medicine extraction machine, and ultrasonic power is 1 ~ 2KW, and microwave power is 600 ~ 1000W, is once carried
It takes and the second extraction time is 20 ~ 35 minutes, the volume of acidic aqueous solution that when second extraction adds in is sour when once extracting
The 1/2 ~ 2/3 of property aqueous solution volume.
5. the preparation method of shaobei injection according to claim 1, it is characterised in that:Step(1)The acid water
Solution is dilute hydrochloric acid solution.
6. the preparation method of shaobei injection according to claim 1, it is characterised in that:Step(4)The C18 reverse phases color
Column is composed using C18 bonded silica gels as filler, the grain size of filler is 5 μm.
7. the preparation method of shaobei injection according to claim 2, it is characterised in that:The heat transfer medium is steam
And/or cooling water.
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CN109512807A (en) * | 2018-12-10 | 2019-03-26 | 河南泰丰生物科技有限公司 | A kind of Chinese medicine composition and its preparation method and application |
CN110693895A (en) * | 2019-11-14 | 2020-01-17 | 河南泰丰生物科技有限公司 | Pharmaceutical composition for treating hemorrhoids and preparation thereof |
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102443028A (en) * | 2010-10-09 | 2012-05-09 | 苏州宝泽堂医药科技有限公司 | Method for extracting paeoniflorin from radix paeoniae lactiflorae |
CN103087128A (en) * | 2013-02-05 | 2013-05-08 | 菏泽尧舜牡丹生物科技有限公司 | Method for extracting paeoniflorin from peony seed meal |
CN104072555A (en) * | 2014-06-16 | 2014-10-01 | 南京泽朗医药科技有限公司 | Method for preparing high-purity paeoniflorin |
CN104974203A (en) * | 2015-07-06 | 2015-10-14 | 江苏天晟药业有限公司 | Extracting method of paeoniflorin monomer |
-
2016
- 2016-04-28 CN CN201610272597.4A patent/CN105726476B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102443028A (en) * | 2010-10-09 | 2012-05-09 | 苏州宝泽堂医药科技有限公司 | Method for extracting paeoniflorin from radix paeoniae lactiflorae |
CN103087128A (en) * | 2013-02-05 | 2013-05-08 | 菏泽尧舜牡丹生物科技有限公司 | Method for extracting paeoniflorin from peony seed meal |
CN104072555A (en) * | 2014-06-16 | 2014-10-01 | 南京泽朗医药科技有限公司 | Method for preparing high-purity paeoniflorin |
CN104974203A (en) * | 2015-07-06 | 2015-10-14 | 江苏天晟药业有限公司 | Extracting method of paeoniflorin monomer |
Non-Patent Citations (1)
Title |
---|
收敛化瘀法治疗痔的研究及临床应用;安阿玥等;《中国临床医生杂志》;20081231;第36卷(第3期);第45-47页 * |
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