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CN-122005672-A - Preparation method of Chaishao oral liquid

CN122005672ACN 122005672 ACN122005672 ACN 122005672ACN-122005672-A

Abstract

The invention discloses a preparation method of a Chaishao oral liquid, which belongs to the technical fields of traditional Chinese medicine preparations and pharmaceutical engineering, and aims at the different physicochemical properties of four medicinal materials of radix bupleuri, white paeony root, immature bitter orange and liquorice, a differential airflow superfine grinding technology is adopted to grind hard medicinal materials to D90 which is less than or equal to 15 mu m, crispy medicinal materials to D90 which is less than or equal to 25 mu m, gradient warm soaking and variable temperature countercurrent dynamic extraction are carried out, variable frequency ultrasonic wave assistance (25-35 kHz) is introduced in a high-temperature extraction stage, the dissolution of active ingredients is improved by utilizing the synergistic effect, the extract is subjected to fractional filtration through a ceramic membrane of 0.2 mu m and 5000Da, impurities are effectively removed, small molecular active parts are reserved, and finally three-effect falling film low-temperature vacuum concentration and xylitol-stevioside taste correction of a specific proportion are adopted. The invention solves the problems of low extraction rate, more impurities and poor stability of the traditional process, and the prepared oral liquid has high content of active ingredients, good clarity, good taste and good process reproducibility, and is suitable for industrial production.

Inventors

  • ZHAO QINGSEN
  • WANG RUI
  • LIU XUE
  • WANG YUE
  • ZHU HAIRUI

Assignees

  • 徐州天意药业股份有限公司

Dates

Publication Date
20260512
Application Date
20260309

Claims (8)

  1. 1. The preparation method of the chaishao oral liquid is characterized by comprising the following steps: Firstly, preprocessing and cleaning medicinal materials, weighing bupleurum, white peony root, immature bitter orange and liquorice according to the prescription, wherein the bupleurum needs to be processed by vinegar and the white peony root needs to be processed by wine; Step two, differential superfine grinding, namely respectively grinding the cleaned and selected medicinal materials in an airflow superfine grinder, controlling the feeding speed to be 10-15kg/h and the grinding pressure to be 0.6-0.8MPa, wherein the bupleurum root and the immature bitter orange are ground to have the cell wall breaking rate of more than or equal to 95 percent and the particle size distribution D90 of less than or equal to 15 mu m, and the white paeony root and the liquorice are ground to have the cell wall breaking rate of more than or equal to 90 percent and the particle size distribution D90 of less than or equal to 25 mu m; Step three, gradient warm soaking softening, namely uniformly mixing the crushed medicinal materials according to a prescription proportion, adding purified water with the amount which is 6-8 times of the total weight of the medicinal materials, placing the medicinal materials into an extraction tank with a jacket, and performing warm soaking in a gradient heating mode, namely stirring and warm soaking for 20-30 minutes at 30-35 ℃, then heating to 50-55 ℃ at a rate of 1-2 ℃ per minute, and continuing warm soaking for 10-15 minutes until the medicinal materials fully absorb water and swell; The method comprises the steps of carrying out variable-temperature countercurrent dynamic extraction, adding purified water which is 8-10 times of the total amount of the medicine materials into the medicine materials subjected to the warm soaking, starting a variable-frequency stirring paddle, controlling the rotating speed to be 60-80r/min, adopting a variable-temperature extraction process, wherein the first stage is carried out for 40-50 minutes at 75-80 ℃, the second stage is carried out for heating to 90-95 ℃ and preserving heat for 30-40 minutes, and extracting solution is extracted from the bottom of a tank through a circulating pump, is heated through a plate heat exchanger and is sprayed from the tangential direction of the top of the tank to form dynamic turbulence, and the circulating flow rate is 1.5-2.0m/s; Step five, ultrasonic field intensity assists in dissolving out, in the second stage of changing the temperature and extracting, turn on the embedded supersonic generator synchronously, the supersonic frequency is set to 25-35kHz, the sound intensity density is controlled to 0.5-1.0W/cm 2 , the acting time is synchronous with the second stage extracting time; Step six, filtering impurities by a ceramic membrane, pumping the extract into a ceramic membrane filtration system after extraction is finished, removing fine particles and bacteria by a microfiltration membrane with the aperture of 0.2 mu m, removing macromolecular impurities such as polysaccharide, protein and the like by an ultrafiltration membrane with the molecular weight cutoff of 5000Da, and collecting permeate; step seven, concentrating in vacuum at low temperature, pumping the permeate liquid into a falling film evaporator, concentrating under the conditions of vacuum degree of-0.085 to-0.095 MPa and feed liquid temperature of 45-55 ℃ until the relative density reaches 1.10-1.15 (60 ℃ heat measurement); precipitating with ethanol, blending, adding 95% ethanol into the concentrated solution to reach ethanol content of 60% -65%, stirring uniformly, standing, refrigerating for 12-24 hr, collecting supernatant, recovering ethanol, adjusting pH to 4.5-5.5, and adding correctant; And step nine, filling and sterilizing, namely, finely filtering the prepared liquid medicine by 0.22 mu m, filling, and adopting a wet heat sterilization process for 30 minutes at 115 ℃ to obtain the Chaishao oral liquid.
  2. 2. The method for preparing the chaihao oral liquid according to claim 1, wherein the crushed granularity difference of the bupleurum, the immature bitter orange, the white paeony root and the liquorice in the second step is based on the difference of medicine materials, wherein the bupleurum and the immature bitter orange are substantially hard, have strong fibers and require higher wall breaking rate to release the saikosaponin and the synephrine, and the white paeony root and the liquorice are relatively loose in texture and moderately crushed to avoid excessive absorption of active ingredients.
  3. 3. The preparation method of the chaishao oral liquid according to claim 1, which is characterized in that the specific control logic of the variable-temperature countercurrent dynamic extraction in the fourth step is that the saponin components with poor heat sensitivity are extracted at low temperature for a long time in the first stage, the flavonoid and aglycone components with good heat resistance are extracted at high temperature for a short time in the second stage, and the channeling phenomenon caused by compaction of medicinal material layers is avoided by dynamic circulation.
  4. 4. The method for preparing a chaishao oral liquid according to claim 1, wherein the ultrasonic generator in the fifth step is a variable frequency type, the frequency of the ultrasonic generator is modulated by sine waves in the extraction process, the modulation period is 10-20 seconds, and the frequency is scanned between 20 kHz and 40kHz, so as to avoid dead angles of extraction caused by standing wave effect.
  5. 5. The method for preparing a chashao oral liquid according to claim 1, wherein in the sixth step, the ceramic membrane is an alumina/zirconia composite membrane, the pore diameter tolerance of the membrane is controlled to be + -0.01 μm, the filtration transmembrane pressure difference (TMP) is controlled to be 0.1-0.3MPa, and pulse type backflushing cleaning is adopted, the backflushing frequency is once every 15 minutes, and the backflushing time is 30 seconds.
  6. 6. The preparation method of the chaishao oral liquid according to claim 1, which is characterized in that in the step (7), three-effect falling film evaporation is adopted for low-temperature vacuum concentration, the one-effect temperature is 65-70 ℃, the two-effect temperature is 55-60 ℃, the three-effect temperature is 45-50 ℃, and the retention rate of active ingredients is improved by more than 15% compared with single-effect concentration.
  7. 7. The preparation method of the chaihao oral liquid according to claim 1, wherein the flavoring agent is a compound of xylitol and stevioside, the weight ratio of the xylitol to the stevioside is 10:1, and the adding amount is 2% -4% of the total amount of the liquid medicine, so that the bitter taste of the chaihao and the sweet taste of the liquorice are covered, and the mouthfeel is improved.
  8. 8. The preparation method of the chaihao oral liquid is characterized by comprising the steps of taking radix bupleuri slices, uniformly stirring the radix bupleuri slices with rice vinegar, moistening until the vinegar is absorbed, placing the radix bupleuri slices in a stir-frying container, heating the radix bupleuri slices with slow fire, stir-frying the radix bupleuri slices to dryness, taking out the radix bupleuri slices and cooling the radix bupleuri slices, taking 15kg of the radix paeoniae alba slices with rice vinegar per 100kg of the radix bupleuri slices, uniformly stirring the radix paeoniae alba slices with yellow wine, moistening the radix bupleuri slices until the wine is absorbed, placing the radix bupleuri slices in the stir-frying container, heating the radix bupleuri slices with slow fire, stir-frying the radix paeoniae alba slices to slight yellow, taking out the radix paeoniae alba slices and cooling the radix paeoniae alba slices with 10kg of yellow wine per 100kg of the radix paeoniae alba slices.

Description

Preparation method of Chaishao oral liquid Technical Field The invention relates to the technical fields of traditional Chinese medicine preparations and pharmaceutical engineering, in particular to a preparation method of a Chaishao oral liquid. Background The Chaishao oral liquid is derived from the modified and converted aspects of the classical prescription of 'Sixisan', mainly comprises medicinal materials such as bupleurum, white paeony root, immature bitter orange, liquorice and the like, has the effects of soothing liver and regulating qi, and softening liver and relieving pain, and is widely used for treating symptoms such as liver and gall qi depression, hypochondriac distending pain and the like. However, the preparation of traditional Chinese medicine oral liquid mostly adopts a simple water decoction method, and has the following technical bottlenecks: 1. the extraction efficiency is low, the traditional decoction method relies on natural permeation and diffusion, so that the effective components (such as saikosaponin and synephrine) are difficult to dissolve out completely for bupleurum with hard texture and immature bitter orange, and the decomposition is easy to cause for the heat-sensitive components after long-time high-temperature decoction. 2. The impurity is difficult to remove, and the conventional water extract contains a large amount of tannins, resins, polysaccharides and proteins, so that not only is the taste affected, but also precipitation or turbidity is easily generated in the storage process, and the clarity and stability of the preparation are affected. 3. The prior art is mostly in a one-pot mode, and the difference treatment on medicinal materials with different properties is lacking, so that the loss of active ingredients is large, and the difference between batches is obvious. Therefore, development of a high-efficiency preparation method capable of carrying out differentiation treatment on physicochemical properties of different medicinal materials in the chaishao oral liquid and combining with a modern separation technology is a technical problem to be solved at present. Disclosure of Invention The invention aims to provide a preparation method of a chaishao oral liquid, which solves the problems of incomplete extraction of active ingredients, incomplete impurity removal and poor preparation stability by the whole process of differential superfine grinding, gradient warm leaching, variable temperature countercurrent dynamic extraction, ultrasonic assistance, ceramic membrane fine filtration and low temperature concentration and realizes the efficient and stable production of the chaishao oral liquid. In order to achieve the aim of the invention, the invention adopts the following technical scheme: The preparation method of the chaishao oral liquid is characterized by comprising the following steps: (1) Pretreatment of medicinal materials and control of processed products The invention selects the genuine medicinal materials and emphasizes the influence of processing on the medicinal effect. The vinegar prepared from radix bupleuri can enhance the liver soothing and pain relieving effects, the vinegar can promote the dissolution of saikosaponin, and the wine prepared from radix paeoniae alba can alleviate the cold property and enhance the liver softening effect. The specific process comprises the steps of taking radix bupleuri slices, stirring rice vinegar uniformly, moistening, stir-frying with slow fire (15 kg/100kg of vinegar), taking radix paeoniae alba slices, stirring yellow wine uniformly, moistening, stir-frying with slow fire to slight yellow (10 kg/100kg of wine). The stir-frying of liquorice with honey and the stir-frying of immature bitter orange with bran can be performed according to the need, but the embodiment uses the raw materials as medicines to keep the alkaloid activity. (2) Differential superfine grinding (jet milling) The traditional ball mill has high crushing heat production and is easy to cause the loss of thermosensitive components. The invention adopts fluidized bed jet milling. Bupleurum root and immature bitter orange are hard in texture and have many fiber bundles. The crushing pressure was set at 0.7MPa, the feed rate was 12kg/h, and the target particle size D90=12.+ -. 3. Mu.m. At the granularity, the cell wall breaking rate is more than 95%, and the instant dissolution rate of the saikosaponin is improved by 3 times. Radix Paeoniae alba and Glycyrrhrizae radix, which contain starch and saccharide and are easy to adhere. The pulverizing pressure was set at 0.6MPa, and the target particle size d90=20±5 μm. The moisture absorption enhancement and the active ingredient adsorption caused by excessive crushing are avoided. The key point is that the two powders are mixed after being crushed respectively, so that the segregation phenomenon caused by the hardness difference is avoided, and the mixing uniformity is ensured. (3) Gradient temperatu