CN105726476B - A kind of preparation method of shaobei injection - Google Patents

A kind of preparation method of shaobei injection Download PDF

Info

Publication number
CN105726476B
CN105726476B CN201610272597.4A CN201610272597A CN105726476B CN 105726476 B CN105726476 B CN 105726476B CN 201610272597 A CN201610272597 A CN 201610272597A CN 105726476 B CN105726476 B CN 105726476B
Authority
CN
China
Prior art keywords
liquid
shaobei
tank body
extraction
preparation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201610272597.4A
Other languages
Chinese (zh)
Other versions
CN105726476A (en
Inventor
杨利娟
李婷
张新宇
黄炯
沙薇
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Henan Taifeng Biotechnology Co Ltd
Original Assignee
Henan Taifeng Biotechnology Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Henan Taifeng Biotechnology Co Ltd filed Critical Henan Taifeng Biotechnology Co Ltd
Priority to CN201610272597.4A priority Critical patent/CN105726476B/en
Publication of CN105726476A publication Critical patent/CN105726476A/en
Application granted granted Critical
Publication of CN105726476B publication Critical patent/CN105726476B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/71Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/192Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/185Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19Carboxylic acids, e.g. valproic acid
    • A61K31/194Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/65Paeoniaceae (Peony family), e.g. Chinese peony
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0019Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/10Preparation or pretreatment of starting material
    • A61K2236/15Preparation or pretreatment of starting material involving mechanical treatment, e.g. chopping up, cutting or grinding
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/33Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30Extraction of the material
    • A61K2236/39Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/51Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/53Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50Methods involving additional extraction steps
    • A61K2236/55Liquid-liquid separation; Phase separation

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Dermatology (AREA)
  • Medicines Containing Plant Substances (AREA)

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

A kind of preparation method of shaobei injection
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.
CN201610272597.4A 2016-04-28 2016-04-28 A kind of preparation method of shaobei injection Active CN105726476B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201610272597.4A CN105726476B (en) 2016-04-28 2016-04-28 A kind of preparation method of shaobei injection

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201610272597.4A CN105726476B (en) 2016-04-28 2016-04-28 A kind of preparation method of shaobei injection

Publications (2)

Publication Number Publication Date
CN105726476A CN105726476A (en) 2016-07-06
CN105726476B true CN105726476B (en) 2018-06-19

Family

ID=56287447

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201610272597.4A Active CN105726476B (en) 2016-04-28 2016-04-28 A kind of preparation method of shaobei injection

Country Status (1)

Country Link
CN (1) CN105726476B (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108114652A (en) * 2016-11-29 2018-06-05 宜兴龙驰药化设备有限公司 A kind of magnetic agitation Agitation Tank
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
US20230065462A1 (en) * 2020-01-19 2023-03-02 Henan Taifeng Biological Technology Co., Ltd. Pharmaceutical composition and use thereof
CN111603802A (en) * 2020-05-10 2020-09-01 上海灿实工程设备有限公司 Adsorption tank for blood products
CN117074520B (en) * 2023-10-12 2024-01-05 四川聚元药业集团有限公司 Detection system for component analysis of white peony root extracting solution

Citations (4)

* Cited by examiner, † Cited by third party
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

Patent Citations (4)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
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 *

Also Published As

Publication number Publication date
CN105726476A (en) 2016-07-06

Similar Documents

Publication Publication Date Title
CN105726476B (en) A kind of preparation method of shaobei injection
US9687516B2 (en) Preparation method for extractive of jinxuan hemorrhoid washing powder botanicals
CN101485705A (en) Cooked Panax notoginseng and cooked Panax notoginseng standard extract and application thereof
CN111358839A (en) Formula granules of polygonum capitatum and preparation method thereof
CN110025650A (en) The content assaying method of gypenosides in the preparation method and Herb Gynostemmae Pentaphylli extract of a kind of Herb Gynostemmae Pentaphylli extract
CN102416028A (en) Preparation method of cooked panax notoginseng extract and total ripe panax notoginseng saponins
CN102824431A (en) Method for extracting hawthorn flavone by using pressurized liquid extraction (APLE) technique
CN102343020B (en) Process for preparing Guifudihuang dripping pill
WO2024066596A1 (en) Rehmannia and lycium root bark decoction water extract solution, rehmannia and lycium root bark decoction water extract paste, rehmannia and lycium root bark decoction preparation and preparation method therefor, and quality control standard for rehmannia and lycium root bark decoction preparation
CN103156920A (en) Drying method for schisandra chinensis extract
CN104277086A (en) Extraction method of scutellarin in scutellariae barbatae
CN102343021B (en) New process method for preparing Guifudihuang capsule
CN108704007A (en) A kind of preparation method of Radix Polygalae active ingredient
CN110078595A (en) A method of extracting cannabidiol
CN115317588A (en) Preparation method of Baoyuan decoction, baoyuan extract and Baoyuan solid preparation
CN104857245A (en) Preparation method and application of total saponins from flos hosta ventricosa
CN101856472B (en) Production method of spur pain-relieving capsule
CN101069704A (en) Clerodendranthus spicatus urinary-stone-resisting extract and preparing method thereof
CN102940724A (en) Preparation method of traditional Chinese medicine compound capsule for diminishing inflammation
CN101322734A (en) Codonopsis lanceolata total saponins with antiinflammatory immunity function and preparation thereof
CN109567207A (en) It is a kind of can reducing blood lipid blood glucose fish oil krill oil capsule and preparation method thereof
CN105919112B (en) Ginseng and fritillaria ussuriensis health food and preparation method and application thereof
CN108126054A (en) A kind of extracting method of Guangxi Camellia nitidissima general flavone
CN108904675A (en) A method of quickly preparing Rhizoma Paridis extract
CN109745368B (en) Preparation method of rhizoma cimicifugae formula granules

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant