Preparation method of Xiaochaihu granules
Technical Field
The invention relates to a preparation method of bupleurum tenue particles. Belongs to the technical field of medicine.
Technical Field
The Xiaochaihu granules are prepared by seven medicinal materials of bupleurum, scutellaria, codonopsis pilosula, liquorice, Chinese date, ginger pinellia and ginger through a modern process. The function and the main treatment of the Xiaochaihu granules are as follows: relieve exterior syndrome, dissipate heat, soothe liver and harmonize stomach. Can be used for treating exogenous diseases with syndromes of pathogenic factors attacking shaoyang, manifested by alternating cold and heat, fullness in chest and hypochondrium, anorexia, vexation, vomiting, bitter taste of mouth, and dry throat.
The bupleurum tenue particles are prepared from 480 parts by weight of bupleurum, 180 parts by weight of scutellaria, 180 parts by weight of codonopsis pilosula, 180 parts by weight of liquorice, 180 parts by weight of Chinese date, 180 parts by weight of ginger processed pinellia, 180 parts by weight of ginger, 750 parts by weight of dextrin, 1.2 parts by weight of steviosin and 42 parts by weight of ethanol.
The preparation method comprises the following steps:
decocting bupleuri radix, Scutellariae radix, radix Codonopsis, Glycyrrhrizae radix and fructus Jujubae in water twice for 1.5 hr each time, mixing decoctions, filtering, and concentrating the filtrate to appropriate amount; according to a percolation method (I O of the first part of Chinese pharmacopoeia 2000 edition) under the items of fluid extract and extract, 70% ethanol is used as a solvent, after the mixture is soaked for 24 hours, the mixture is slowly percolated at the speed of 1-3 ml per minute, about 1800ml of filtrate is collected, the ethanol is recovered, the filtrate is combined with the concentrated solution, the concentrated solution is concentrated to the relative density of 1.32-1.35 (75-80 ℃), and a proper amount of dextrin, steviosin and ethanol are added, mixed uniformly, granulated and dried to prepare 1000g of the ginger pinellia ternate and ginger extract.
The bupleurum tenue particles contain active ingredients such as baicalin, saikoside, gingerol, glycyrrhizic acid, succinic acid and the like, are widely applied to the treatment of upper respiratory tract system diseases clinically, and have definite curative effect, stable quality and good safety. For many years, the Chinese medicinal composition is a first choice medicament for treating upper respiratory system diseases in the field of Chinese medicaments by virtue of safe and reliable curative effects.
The small bupleurum particles as a Chinese medicinal preparation with Chinese characteristics represent new achievements of Chinese medicinal research and application, but with rapid development of science and technology and continuous improvement of the material culture requirements of people, the small bupleurum particles in the traditional process are in the state of beauty and middle deficiency, and new small bupleurum particles can be produced by using high-tech preparation technology.
Disclosure of Invention
The invention aims to provide a preparation method of bupleurum tenue particles.
The purpose of the invention is realized as follows: the extraction method comprises the steps of continuously optimizing the process of the prescription, extracting the medicinal materials in the prescription in proportion, adopting a supercritical fluid extraction technology, and optimizing extraction parameters to ensure that the extraction is more sufficient. The centrifugal technology is applied in the separation process, so that the product has better dissolubility and the quality is easier to ensure. The percolation of ginger and pinellia tuber is changed into ultrasonic extraction technology, so as to shorten the extraction time and improve the dissolution rate of effective components.
1. Extracting radix bupleuri 480 weight parts, radix Scutellariae 180 weight parts, radix Codonopsis 180 weight parts, radix Glycyrrhizae 180 weight parts, and fructus Jujubae 180 weight parts by supercritical fluid extraction with respect to extraction pressure, extraction temperature, extraction time, CO2The flow of the extract is subjected to process research, process screening is carried out according to the parameters, and the optimal extraction process is determined.
2. The separation process comprises the following steps: the method comprises the steps of respectively taking the specific gravity of liquid medicine, the temperature of the liquid medicine, the centrifugal rotating speed and the feeding speed as investigation factors, setting 5 levels for each factor, taking whether the centrifugal liquid is clear or not, the impurity removal rate and the baicalin transfer rate as indexes, and carrying out single factor investigation to preferably select the optimal centrifugal process parameters of the bupleurum tenue particles.
3. And (3) a percolation process: the ginger and the ginger pinellia are subjected to process research aiming at ultrasonic time, ultrasonic frequency, ultrasonic temperature and ethanol concentration by adopting an ultrasonic extraction technology, and process screening is carried out according to the parameters to determine the optimal ultrasonic extraction process.
4. Quality control: the indexes of controlling the succinic acid content and the gingerol content are increased to ensure the quality of the bupleurum tenue particles.
In order to improve the dissolution of effective substances in the bupleurum tenue particle medicinal materials, corresponding extraction parameters are optimized according to experimental parameters.
The preferred process is as follows:
480 parts of Chinese thorowax root, 180 parts of baical skullcap root, 180 parts of pilose asiabell root, 180 parts of liquoric root and 180 parts of Chinese date by adopting a supercritical fluid extraction technology. According to the detection result (refer to the detection method of bupleurum chinense particles in the Chinese pharmacopoeia of 2015 edition), carrying out experimental screening. See Table 1
The extraction in the step 1 is optimized in process, and a supercritical fluid extraction technology is adopted. The transfer rate of baicalin is used as an investigation index, orthogonal experiments are carried out according to the level of 4 factors 3, the content transfer rate is used as a reference index, and the process optimization experiment results and the variance analysis are shown in tables 1, 2 and 3.
Table 1 level table of 4 factors 3 affecting the extraction of bupleurum tenue particles
|
1
|
2
|
3
|
4
|
Factors of the fact
|
Pressure of extraction
|
Temperature of extraction
|
Time of extraction
|
CO2Flow rate of
|
Level 1
|
20MPa
|
35 degree
|
0.5 smallTime of flight
|
25 kg/h
|
Level 2
|
25MPa
|
40 degree
|
1 hour
|
35 kg/h
|
Level 3
|
30MPa
|
45 degree
|
1.5 hours
|
45 kg/h |
TABLE 2 orthogonal Experimental tables for extraction factor screening
TABLE 3 analysis of variance of factors affecting content extraction transfer Rate
Factors of the fact
|
Sum of squares of deviation
|
Degree of freedom
|
F ratio
|
Critical value of F
|
Significance of
|
Pressure of extraction
|
1352.00
|
2
|
676.00
|
19
|
*
|
Temperature of extraction
|
122.00
|
2
|
61.00
|
19
|
*
|
Time of extraction
|
2.00
|
2
|
1.000
|
19
|
|
CO2Flow rate of
|
8.00
|
2
|
4.000
|
19
|
|
Error of the measurement
|
2.00
|
2
|
|
|
|
(F cutoff greater than 19, significant)
As can be seen from the above table: the extraction pressure is the most significant factor, followed by the extraction temperature. Combining the requirements of optimal energy consumption, adopting the extraction pressure of 25Mpa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and CO2The flow rate of the extraction is 25 kg/h, which is the best extraction process.
Because the current standard process of the bupleurum tenue granules describes that decoction liquid is merged and filtered, and the filtrate is concentrated to a proper amount, in the operation stage, when the liquid medicine is filtered, the filtering speed is slow, the filtering time is long, the phenomenon of turbidity of granule dissolubility is easy to occur, and the product quality is not ensured. Experimental research shows that the problems can be solved by adopting a centrifugal process instead of a filtering process, the change of the material basis of the medicine cannot be caused, and the absorption and the utilization of the medicine cannot be obviously influenced. Therefore, the centrifugal technology is adopted, the specific gravity of the liquid medicine, the temperature of the liquid medicine, the centrifugal rotating speed and the feeding speed are respectively taken as investigation factors, each factor is set to 5 levels, whether the centrifugal liquid is clarified or not, the impurity removal rate and the baicalin transfer rate are taken as indexes, single-factor investigation is carried out, and the optimal centrifugal process parameters of the bupleurum tenue particles are preferably selected.
TABLE 4 influence of the specific gravity of the liquid medicine on the clarification, impurity removal rate and transfer rate
TABLE 5 influence of temperature of liquid medicine on clarification, impurity removal rate and transfer rate
TABLE 6 influence of centrifugal speed on clarification, impurity removal rate and transfer rate
TABLE 7 influence of the feed rate on the effect of clarification, impurity removal and transfer rates
According to the investigation result of each single-factor experiment, the optimal centrifugation process of the bupleurum tenue particles is determined as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 2.0m3/h。
In order to improve the preparation efficiency and shorten the percolation time, an ultrasonic extraction technology is adopted, and because the current standard process of the bupleurum particles is described as a percolation method under the items of a flowing extract and a extract of ginger pinellia, ginger (appendix IO of the first part of the 2000 edition of Chinese pharmacopoeia) by using 70% ethanol as a solvent, after soaking for 24 hours, the slow percolation is carried out at the speed of 1-3 ml per minute, and the operation stage has the defects of slow percolation speed, long percolation time and unfavorable preparation efficiency. Experimental research shows that the problems can be solved by adopting an ultrasonic extraction process instead of a percolation process, the substance basis of the medicine cannot be changed, and the absorption and the utilization of the medicine cannot be obviously influenced. Therefore, an ultrasonic extraction technology is adopted, ultrasonic temperature, ultrasonic time, ultrasonic frequency and ethanol concentration are respectively used as investigation factors, each factor is set to 5 levels, the transfer rate of ultrasonic liquid gingerol and succinic acid is used as an index, single-factor investigation is carried out, and the optimal ultrasonic process parameters of the bupleurum tenue particles are preferably selected.
TABLE 8 Effect of ultrasound temperature on gingerol and succinic acid transfer rates
TABLE 9 Effect of ultrasound time on gingerol and succinic acid transfer rates
TABLE 10 Effect of ultrasound frequency on gingerol and succinic acid transfer rates
TABLE 11 Effect of ethanol concentration on gingerol and succinic acid transfer rates
According to the investigation result of each single-factor experiment, the optimal ultrasonic process for determining the bupleurum tenue particles is as follows: the ultrasonic temperature is 45 ℃, the ultrasonic time is 1h, the ultrasonic frequency is 2 times, and the ethanol concentration is 60 percent.
The preferred optimal process is therefore:
480 parts of radix bupleuri, 180 parts of scutellaria baicalensis, 180 parts of codonopsis pilosula, 180 parts of liquorice and 180 parts of Chinese dates, and the preparation method comprises the following steps: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 2.0m3And h, concentrating the centrifugate to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger, using 60% ethanol as a solvent, carrying out ultrasonic extraction for 2 times at the ultrasonic temperature of 45 ℃ for 1 hour each time, collecting about 1800ml of an extracting solution, recovering ethanol, combining with the concentrated solution, and concentrating to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, granulating, drying, and making into 1000 g.
Selecting a sample prepared by an optimal process to prepare a finished product of the bupleurum tenue granules, and carrying out accelerated stability investigation under the following investigation conditions: standing at 40 + -2 deg.C and 75% + -5% relative humidity for 6 months. Samples were taken at month 0, month 1, month 2, month 3 and month 6 of the test period and examined.
Accelerated stability data for the scheme of Table 12
From all the data analyses above, it follows: the sample prepared by the optimal process has better stability than baicalin, succinic acid and gingerol prepared by the standard process, and the obtained product has strong moisture-attracting resistance, strong stability and stable curative effect; the whole process is easy to operate and suitable for popularization and application.
Compared with the prior art, the invention has the beneficial effects that:
1) according to the method provided by the invention, the loss of the active ingredients of the scutellaria baicalensis is effectively reduced through a supercritical fluid extraction technology;
2) the invention solves the problems that when the liquid medicine is filtered, the filtering speed is slow, the filtering time is long, the particle dissolubility is easy to generate turbidity, and the product quality is not ensured easily by a centrifugal technology, so that the product quality is more stable;
3) by adopting the ultrasonic extraction technology, the preparation efficiency is improved, and the time required by percolation is shortened;
4) the invention ensures the quality of the bupleurum tenue particles by increasing the control on the succinic acid content and the gingerol content, and the product quality is more stable and reliable.
In order to better embody the advancement of the invention, the invention adopts a comparative research form and carries out comparative research with other samples.
TABLE 13 comparative experimental conditions
From all the data analyses above, it follows: the sample prepared by the optimal process has better stability than the standard process, and the obtained product has strong moisture-attracting resistance, strong stability and stable curative effect; the whole process is easy to operate and suitable for popularization and application.
Detailed Description
The present invention will be described in further detail with reference to examples.
Example 1: 480 parts of Chinese thorowax root, 180 parts of baical skullcap root, 180 parts of pilose asiabell root and liquoric root180 parts of Chinese date 180 parts by weight, and the steps are as follows: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 2.0m3And h, concentrating the centrifugate to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger, using 60% ethanol as a solvent, carrying out ultrasonic extraction for 2 times at the ultrasonic temperature of 45 ℃ for 1 hour each time, collecting about 1800ml of an extracting solution, recovering ethanol, combining with the concentrated solution, and concentrating to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, granulating, drying, and making into 1000 g.
Example 2: 480 parts of radix bupleuri, 180 parts of scutellaria baicalensis, 180 parts of codonopsis pilosula, 180 parts of liquorice and 180 parts of Chinese dates, and the preparation method comprises the following steps: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 5900r/min, and the feeding speed is 2.0m3And h, concentrating the centrifugate to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger, using 60% ethanol as a solvent, carrying out ultrasonic extraction for 2 times at the ultrasonic temperature of 45 ℃ for 1 hour each time, collecting about 1800ml of an extracting solution, recovering ethanol, combining with the concentrated solution, and concentrating to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, granulating, drying, and making into 1000 g.
Example 3: 480 parts of radix bupleuri, 180 parts of scutellaria baicalensis, 180 parts of codonopsis pilosula, 180 parts of liquorice and 180 parts of Chinese dates, and the preparation method comprises the following steps: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 1.5m3H, concentration of the centrifugateShrink to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger, using 60% ethanol as a solvent, carrying out ultrasonic extraction for 2 times at the ultrasonic temperature of 45 ℃ for 1 hour each time, collecting about 1800ml of an extracting solution, recovering ethanol, combining with the concentrated solution, and concentrating to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, granulating, drying, and making into 1000 g.
Example 4: 480 parts of radix bupleuri, 180 parts of scutellaria baicalensis, 180 parts of codonopsis pilosula, 180 parts of liquorice and 180 parts of Chinese dates, and the preparation method comprises the following steps: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 2.0m3And h, concentrating the centrifugate to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger processed ginger, using 70% ethanol as a solvent, carrying out ultrasonic extraction for 2 times at the ultrasonic temperature of 45 ℃ for 1 hour each time, collecting about 1800ml of an extracting solution, recovering ethanol, combining with the concentrated solution, and concentrating to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, granulating, drying, and making into 1000 g.
Example 5: 480 parts of radix bupleuri, 180 parts of scutellaria baicalensis, 180 parts of codonopsis pilosula, 180 parts of liquorice and 180 parts of Chinese dates, and the preparation method comprises the following steps: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 2.0m3And h, concentrating the centrifugate to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger, 60% ethanol is used as a solvent, ultrasonic extraction is carried out for 2 times at 50 ℃ and 1 hour each time, 1800ml of extracting solution is collected, ethanol is recovered, the ethanol and the concentrated solution are combined and concentrated to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, and granulatingDrying, and making into 1000 g.
Example 6: 480 parts of radix bupleuri, 180 parts of scutellaria baicalensis, 180 parts of codonopsis pilosula, 180 parts of liquorice and 180 parts of Chinese dates, and the preparation method comprises the following steps: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 2.0m3And h, concentrating the centrifugate to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger, using 60% ethanol as a solvent, carrying out ultrasonic extraction for 3 times at the ultrasonic temperature of 45 ℃ for 1 hour each time, collecting about 1800ml of an extracting solution, recovering ethanol, combining with the concentrated solution, and concentrating to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, granulating, drying, and making into 1000 g.
Example 7: 480 parts of radix bupleuri, 180 parts of scutellaria baicalensis, 180 parts of codonopsis pilosula, 180 parts of liquorice and 180 parts of Chinese dates, and the preparation method comprises the following steps: the supercritical fluid extraction technology has the extraction pressure of 25MPa, the extraction temperature of 45 ℃, the extraction time of 0.5 hour and the flow rate of CO2 of 25 kg/hour. Concentrating the extracting solution to a proper amount, centrifuging, wherein the centrifugation parameters are as follows: the specific gravity of the liquid medicine is 1.02, the temperature of the liquid medicine is 75-90 ℃, the centrifugal speed is 6900r/min, and the feeding speed is 2.0m3And h, concentrating the centrifugate to a proper amount. 180 parts of ginger processed pinellia and 180 parts of ginger processed ginger, using 60% ethanol as a solvent, carrying out ultrasonic extraction for 2 times at the ultrasonic temperature of 45 ℃ for 0.5 hour each time, collecting about 1800ml of an extracting solution, recovering ethanol, combining with the concentrated solution, and concentrating to the relative density of 1.32-1.35 (75-80 ℃). Adding 750 weight parts of dextrin, 1.2 weight parts of steviosin and 42 weight parts of ethanol, mixing, granulating, drying, and making into 1000 g.