Preparation method of liver-resolving decoction granules retaining volatile active ingredients

Abstract

The invention provides a preparation method of liver-removing decoction granules capable of retaining volatile effective components. The preparation method comprises the following steps: S1, independently extracting and stabilizing paeonol; s2, a step of carrying out whole-formula extraction; s3, a step of performing concentration; s4, a step of carrying out granulation; s5, carrying out particle finishing; and S6, carrying out subpackaging. The invention aims to overcome the defects in the prior art and provides the preparation method of the liver-removing decoction granules. According to the method, the volatile component paeonol in the moutan bark is independently extracted and stabilized before being decocted through an innovative'shunt treatment 'process, so that the effective component is reserved in the granules to the maximum extent, and the stable product quality and the remarkable curative effect are ensured. Meanwhile, the liver-removing decoction granules prepared by the method provided by the invention have the advantages of high paeonol content, stable quality and convenience in taking and storage.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a preparation method of Huan Gan Decoction granules capable of retaining volatile active ingredients. BACKGROUND

[0002] Huan Gan Decoction, derived from Jing Yue Quan Shu, has the effects of soothing liver and relieving depression and clearing liver and purging fire, and is used for treating liver depression and fire, and is widely used in the treatment of chronic gastritis, gastroesophageal reflux disease and other diseases in modern clinical practice. Traditionally, Huan Gan Decoction is used in the form of decoction, which has the following inherent defects: Inconvenient to carry and store: decoction is time-consuming and laborious, and the volume of decoction is large, which is inconvenient to carry, and needs to be stored in cold storage, which is difficult to adapt to the modern fast-paced life.

[0003] Unstable quality: the composition and efficacy of the decoction are difficult to standardize due to the influence of human factors such as the source of medicinal materials, decoction utensils, fire and time.

[0004] Loss of active ingredients: the core active ingredient of Danpi in the ministerial medicine of Huan Gan Decoction, Danpi, is volatile. In the process of traditional decoction at high temperature, Danpi is easily lost with water vapor, resulting in a significant decrease in the content of the final decoction, affecting the stability and strength of the efficacy.

[0005] In the prior art, changing decoction into granules is a common way to solve the problems of portability and stability. However, if the conventional process of concentrating and granulating after decocting the whole prescription is simply used, the problem of volatilization and loss of Danpi during decoction and storage cannot be solved. Therefore, developing a preparation method of Huan Gan Decoction granules capable of specifically retaining and stabilizing Danpi has become a key technical problem to improve the quality of the modern preparation of the classical prescription.

[0006] In view of the above, the present application provides a preparation method of Huan Gan Decoction granules capable of retaining volatile active ingredients. SUMMARY

[0007] The purpose of the present application is to solve the above-mentioned problems.

[0008] To achieve the above requirements, the technical scheme adopted by the present application is as follows: a preparation method of Huan Gan Decoction granules capable of retaining volatile active ingredients is provided, which comprises the following steps: S1: the step of separate extraction and stabilization of paeonol; S11: water vapor distillation extraction, 560.0g of the root bark of tree peony medicinal decoction pieces are first added with 1-3 times of water, soaked for 1-2 hours, then placed on the upper part of the extractor, 6-10 times of water is placed at the bottom of the extractor, heated for 1h, then the distillation liquid is collected, the collection speed is controlled, and the process is ended when basically no liquid flows out, the water vapor is steamed, the steam pressure is 0.1-0.2MPa, and the temperature is 98-102℃; S12: static precipitation, the collected distillation liquid is left overnight at a temperature of ≤20℃, the middle solution is sucked out with a pipette, and the remaining surface and bottom paeonol crystals are reserved; S13: cyclodextrin inclusion, 84g-252g of β-cyclodextrin is weighed, which is 0.15 times-0.45 times of the amount of the medicinal decoction pieces, the surface and bottom paeonol crystals are added, heated and dissolved, and controlled at 50-60℃, while stirring, the β-cyclodextrin is poured, and stirred for 15min-30min; S14: drying, the liquid of the β-cyclodextrin inclusion is placed in a hot air circulation oven at a temperature of ≤40℃ for low-temperature drying into a solid, that is, β-cyclodextrin inclusion solid of paeonol, which is reserved, and the root bark of tree peony medicinal residue and the remaining decoction liquid are reserved; S2: the step of whole prescription extraction, 6 other medicinal decoction pieces of another 100 times of the standard prescription, that is, 746g of pericarpium citri reticulatae viride, 746g of pericarpium citri reticulatae, 746g of radix paeoniae alba, 560g of fried fructus gardeniae, 560g of rhizoma alismatis, and 933g of fritillariae thunbergii are added with 6-10 times of water into the extraction tank, and the root bark of tree peony medicinal residue and the remaining distillation liquid are added together to supplement to 6-10 times of the root bark of tree peony prescription amount, soaked for 1-4h, then boiled and decocted for 1-2h, refluxed for 1-2 times, the steam pressure is 0.1-0.2MPa, the temperature is 98-102℃, and the process is ended when the liquid is filtered through a 100-200 mesh sieve while hot, the filtrate is mixed, and the decoction liquid is prepared; S3: the step of concentration; S4: the step of granulation; S5: the step of whole granulation; S6: the step of sub-packaging.

[0009] Preferably, the step S3 specifically comprises: vacuum concentration, the vacuum degree is -0.080--0.09MPa, the temperature is 45-55℃, and the process is performed for 1-3h until the density of the extract is 1.05-1.10.

[0010] Preferably, step S4 specifically includes: granulation of the dry extract, further drying the extract under reduced pressure at a temperature of 55℃~60℃ and a vacuum degree of -0.080~-0.09MPa for 12~48h until a dry extract is formed. The dry extract is then pulverized into powder, passed through a No. 2 sieve, and granulated. The total amount of excipients per 100 doses is 750g. The solid amount of paeonol β-cyclodextrin inclusion complex is taken from the output, and the remainder is supplemented with dextrin. After mixing, the mixture is placed in a granulator using a one-step granulation method. The air inlet switch and heating switch are turned on, and the air volume is 15~20. The flow rate is set to m³ / h to ensure good fluidization of the mixed powder. After preheating to a material temperature of 40℃~50℃, the mixture is mixed for 3~5 minutes. Purified water is then sprayed in to begin granulation. During the granulation process, the pump speed is controlled at 0.5~1mL / min, the atomization pressure is 0.22±0.01MPa, and the material temperature is maintained at 40℃~60℃. After spraying, the material temperature is controlled at 50℃~70℃ for drying, which takes 3~5 minutes.

[0011] Preferably, step S4 specifically includes: granulation of the extract: 15g / dose, 7.5g / dose of excipients, the total amount of excipients for 100 doses is 750g, the solid amount of paeonol β-cyclodextrin inclusion complex is taken as the output amount, and the remainder is supplemented with dextrin. After mixing, it is put into the granulator and granulated in one step. The air inlet switch and heating switch are turned on, and the air volume is 15-20 m³ / h to ensure good fluidization of the powder. After preheating to the material temperature of 40℃-50℃, it is mixed for 3-5 minutes. The extract is sprayed in to start granulation. During the granulation process, the liquid pump speed is controlled at 0.5-1mL / min, the atomization pressure is 0.22±0.01MPa, and the material temperature is 40℃-60℃. After the liquid spraying is completed, the material temperature is controlled at 50℃-70℃ for drying for 3-5 minutes.

[0012] Preferably, step S5 specifically includes: granulating the granulated particles using a vibrating screen with an upper layer of screen No. 1 and a lower layer of screen No. 5.

[0013] Preferably, step S6 specifically includes: the horizontal sealing temperature is 135-155℃, the horizontal sealing time is 0.6-2.0 seconds, the vertical sealing temperature is 135-155℃, the vertical sealing time is 0.6-2.0 seconds, and the amount of each bag is 15g per box.

[0014] A liver-strengthening decoction granule is provided, with the following prescription: 746g of green tangerine peel, 746g of dried tangerine peel, 746g of peony root, 560g of peony bark, 560g of gardenia fruit, 560g of alisma rhizome, and 933g of fritillaria bulb.

[0015] The advantages of this method for preparing Huaganjian granules, which retains the volatile active ingredients, are as follows: (1) High efficiency in retaining volatile components: Through the unique process of "distillation extraction followed by cyclodextrin inclusion", the volatile paeonol is transformed into a stable inclusion complex, fundamentally solving the problem of its loss during preparation and storage. Compared with traditional decoctions and granules prepared by conventional co-decoction methods, the granules of this invention have significantly higher paeonol content and better stability, thus ensuring efficacy.

[0016] (2) Stable and controllable product quality: The entire preparation process parameters are clear, standardized production is realized, human and environmental factors are reduced, and the consistency of product quality in different batches is guaranteed.

[0017] (3) It combines portability and efficacy: The final product is granules, which have the advantages of modern dosage forms such as instant preparation and drinking, easy to carry and store, accurate dosage, and better taste. At the same time, due to the retention of key active ingredients, the efficacy is better than or equal to traditional decoctions.

[0018] (4) High utilization rate of medicinal materials: After extracting paeonol, the residue of peony bark is used again for whole-formula water extraction, which makes full use of medicinal resources and conforms to the green and economical production concept. Attached Figure Description

[0019] Figure 1 This is a flowchart illustrating one embodiment of the present application. Detailed Implementation

[0020] In the following description, references to "an embodiment," "an embodiment," "an example," "example," etc., indicate that the described embodiment or example may include a particular feature, structure, characteristic, property, element, or limitation, but not every embodiment or example necessarily includes that particular feature, structure, characteristic, property, element, or limitation. Furthermore, the repeated use of the phrase "an embodiment according to this application," while possibly referring to the same embodiment, does not necessarily refer to the same embodiment.

[0021] For simplicity, certain technical features known to those skilled in the art are omitted in the following description.

[0022] According to one embodiment of this application, a method for preparing Huaganjian granules that retains volatile active ingredients is provided, comprising the following steps: S1: Separate extraction and stabilization of paeonol (this step is the core technology for solving the problem of paeonol's volatility): Steam distillation extraction: Add 1 to 3 times the amount of water to the peony bark slices (560.0g), soak for 1 to 2 hours, and then place them on the upper steam rack of the extractor. Place another 6 to 10 times the amount of water at the bottom of the extractor. Heat for 1 hour and then start collecting the distillate (control the collection rate until there is basically no liquid flowing out) (steam pressure 0.1 to 0.2 MPa, temperature 98 to 102℃).

[0023] Settling: Let the collected distillate stand overnight (temperature ≤20℃), then use a pipette to remove the middle solution, and keep the remaining paeonol crystals on the surface and at the bottom for later use.

[0024] Cyclodextrin inclusion complexation: Weigh 84g-252g of β-cyclodextrin (0.15-0.45 times the amount of the medicinal slices), and crystallize the paeonol on the surface and bottom. Heat to dissolve and control the temperature at 50-60℃, while stirring, pour in the β-cyclodextrin and stir for 15-30 minutes.

[0025] Drying: The encapsulated liquid (paeonol β-cyclodextrin inclusion complex liquid) is dried at low temperature (≤40℃) in a hot air circulating oven to form a solid (paeonol β-cyclodextrin inclusion complex solid) for later use. The peony bark residue and the remaining decoction are reserved for later use.

[0026] S2: The step of full extraction (this step involves re-decocting the peony bark residue from which volatile components have already been extracted, aiming to fully utilize its non-volatile water-soluble components, avoid waste of medicinal materials, and embody the concept of "full component" utilization of medicinal materials): Add 6 other medicinal slices (100 times the standard prescription: 746g of green tangerine peel, 746g of dried tangerine peel, 746g of white peony root, 560g of stir-fried gardenia fruit, 560g of alisma rhizome, and 933g of fritillaria thunbergii) to 6-10 times the amount of water and pour them into an extraction tank. Add the peony bark residue and the remaining distillate (to make up to 6-10 times the amount of peony bark in the prescription) together. Soak for 1-4 hours, then boil and decoct for 1-2 hours. Reflux 1-2 times (steam pressure 0.1-0.2MPa, temperature 98-102℃). While hot, pass through a 100-200 mesh sieve to obtain the filtrate. Mix well to obtain the decoction.

[0027] S3: Concentration step, vacuum concentration (vacuum degree -0.080 to -0.09 MPa, temperature 45 to 55℃) for 1 to 3 hours to obtain an extract with a density of 1.05 to 1.10.

[0028] S4: Granulation step Option 1: Dry Extract Granulation: Continue vacuum drying of the extract at 55℃~60℃ and a vacuum degree of -0.080~-0.09MPa for 12~48h until a dry extract is obtained. The dry extract is then pulverized into powder, passed through a No. 2 sieve, and granulated. The total amount of excipients per 100 doses is 750g (the solid amount of paeonol β-cyclodextrin inclusion complex is taken from the output, and the remainder is supplemented with dextrin). After mixing, the mixture is placed in a granulator using a one-step granulation method. The air inlet and heating switches are turned on (airflow 15–20 m³ / h to ensure good fluidization of the powder). Preheating is performed until the material temperature reaches 40℃~50℃, followed by mixing for 3–5 minutes. Purified water is then sprayed in to begin granulation. During granulation, the infusion pump speed is controlled at 0.5~1mL / min, the atomization pressure at 0.22±0.01MPa, and the material temperature at 40℃~60℃. After spraying, the material temperature is controlled at 50℃~70℃ for drying for 3–5 minutes.

[0029] Option 2: Granulation of extract: 15g / dose, 7.5g / dose of excipients, total excipients for 100 doses are 750g (the solid amount of paeonol β-cyclodextrin inclusion complex is taken from the output, the remainder is supplemented with dextrin). After mixing, put it into the granulator and use the one-step granulation method. Turn on the air inlet switch and heating switch (air volume 15~20 m³ / h, to ensure good fluidization of the powder). Preheat to the material temperature of 40℃~50℃, mix for 3~5 minutes, spray in the extract to start granulation. During the granulation process, control the liquid delivery pump speed at 0.5~1mL / min, the atomization pressure at 0.22±0.01MPa, and the material temperature at 40℃~60℃. After spraying, control the material temperature at 50℃~70℃ for drying, and dry for 3~5 minutes.

[0030] S5: Granulation step: The granulated particles are sized using a vibrating screen with No. 1 screen on the upper layer and No. 5 screen on the lower layer. S6: Packaging steps: Horizontal sealing temperature: 135~155℃, horizontal sealing time: 0.6~2.0 seconds, vertical sealing temperature: 135~155℃, vertical sealing time: 0.6~2.0 seconds, 15g per bag, boxed.

[0031] According to one embodiment of this application, the prescription compatibility of this solution is as follows:

[0032] The pre-processing methods for medicinal materials are as follows:

[0033] According to one embodiment of this application, the following experiment was conducted on the concentration and granulation of paeonol after separate distillation extraction and decoction of the whole formula:

[0034] Comparative Example 1: Experiment on direct concentration and granulation of decoction after whole-formula decoction

[0035] Comparative Example 2: Concentration and Granulation Experiment of Decoction after Full Formula Decoction with Paeonol

[0036] Comparative Example 3: Granulation and Concentration Experiment of Dried Residue after Decoction of the Whole Formula with Paeonol Extraction

[0037] The test results for each example are as follows: The content of paeonol in the final product granules was optimized from the comparative examples (1.01 mg / dose, 10.99 mg / dose, 12.21 mg / dose) to 35.37 mg / dose, which is 35 times that of the conventional method (1.01 mg / dose).

[0038] Test results for each example:

[0039] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the claims.

Claims

1. A method for preparing Huaganjian granules that retains volatile active ingredients, characterized in that, Includes the following steps: S1: The step of separately extracting and stabilizing paeonol; S11: Steam distillation extraction. Take 560.0g of peony bark slices, add 1 to 3 times the amount of water, soak for 1 to 2 hours, and place on the upper steam rack of the extractor. Place another 6 to 10 times the amount of water at the bottom of the extractor. Heat for 1 hour and start collecting the distillate. Control the collection rate until there is basically no liquid flowing out. Steam distillation is carried out at a steam pressure of 0.1 to 0.2 MPa and a temperature of 98 to 102℃. S12: Let the distillate stand overnight at a temperature ≤20℃. Use a pipette to remove the middle solution and keep the remaining paeonol crystals on the surface and bottom for later use. S13: Cyclodextrin inclusion complexation. Weigh 84g to 252g of β-cyclodextrin, which is 0.15 to 0.45 times the amount of medicinal slices. Crystallize the paeonol on the surface and bottom, heat to dissolve and control the temperature at 50 to 60°C. Pour in the β-cyclodextrin while stirring and stir for 15 to 30 minutes. S14: Drying, the liquid after inclusion, the liquid of paeonol β-cyclodextrin inclusion complex is placed in a hot air circulating oven at ≤40℃ for low-temperature drying into a solid, namely paeonol β-cyclodextrin inclusion complex solid for later use, and the peony bark residue and the remaining decoction are reserved for later use. S2: For the step of full extraction, add 6 other medicinal slices, 100 times the standard prescription, namely, 746g of green tangerine peel, 746g of dried tangerine peel, 746g of white peony root, 560g of stir-fried gardenia fruit, 560g of alisma rhizome, and 933g of fritillaria thunbergii, to an extraction tank with 6-10 times the amount of water. Add the dregs of peony bark and the remaining distillate to make up 6-10 times the amount of peony bark in the prescription, and pour them in together. Soak for 1-4 hours, then boil and decoct for 1-2 hours. Reflux 1-2 times at a steam pressure of 0.1-0.2MPa and a temperature of 98-102℃. While hot, pass through a 100-200 mesh sieve to obtain the filtrate. Mix well to obtain the decoction. S3: The concentration step; S4: The granulation step; S5: The granulation step; S6: The step of dispensing.

2. The method for preparing Huaganjian granules that retain volatile active ingredients according to claim 1, characterized in that, Step S3 specifically includes: The solution was concentrated under reduced pressure at a vacuum of -0.080 to -0.09 MPa and a temperature of 45 to 55°C for 1 to 3 hours until a density of 1.05 to 1.10 was obtained.

3. The method for preparing Huaganjian granules that retain volatile active ingredients according to claim 1, characterized in that, Step S4 specifically includes: For dry paste granulation, the extract is further dried under reduced pressure at a temperature of 55℃~60℃ and a vacuum degree of -0.080~-0.09MPa for 12~48h until a dry paste is formed. The dry paste is then pulverized into dry paste powder, passed through a No. 2 sieve, and granulated. The total amount of excipients per 100 doses is 750g. The solid amount of paeonol β-cyclodextrin inclusion complex is taken from the output, and the remainder is supplemented with dextrin. After mixing, it is placed in a granulator and granulated using a one-step granulation method. The air inlet switch and heating switch are turned on, and the air volume is 15–20 m³ / h to ensure good fluidization of the powder mixture. After preheating to a material temperature of 40℃~50℃, it is mixed for 3–5 minutes. Purified water is sprayed in to start granulation. During the granulation process, the infusion pump speed is controlled at 0.5~1mL / min, the atomization pressure is 0.22±0.01MPa, and the material temperature is 40℃~60℃. After the spraying is completed, the material temperature is controlled at 50℃~70℃ for drying for 3–5 minutes.

4. The method for preparing Huaganjian granules that retain volatile active ingredients according to claim 1, characterized in that, Step S4 specifically includes: Granulation of the extract: 15g / dose, 7.5g of excipients, total excipients for 100 doses is 750g. The solid amount of paeonol β-cyclodextrin inclusion complex is taken from the output, and the remainder is supplemented with dextrin. After mixing, it is placed in a granulator using a one-step granulation method. The air inlet switch and heating switch are turned on, with an airflow of 15-20 m³ / h to ensure good fluidization of the mixed powder. After preheating to a material temperature of 40℃-50℃, mix for 3-5 minutes, then spray in the extract to begin granulation. During granulation, control the infusion pump speed at 0.5-1mL / min, the atomization pressure at 0.22±0.01MPa, and the material temperature at 40℃-60℃. After spraying, control the material temperature at 50℃-70℃ for drying for 3-5 minutes.

5. The method for preparing Huaganjian granules that retain volatile active ingredients according to claim 1, characterized in that, Step S5 specifically includes: The granulated particles are then sized using a vibrating screen with sieve No. 1 on the upper layer and sieve No. 5 on the lower layer.

6. The method for preparing Huaganjian granules that retain volatile active ingredients according to claim 1, characterized in that, Step S6 specifically includes: Its horizontal sealing temperature is 135-155℃, and the horizontal sealing time is 0.6-2.0 seconds. Its vertical sealing temperature is 135-155℃, and the vertical sealing time is 0.6-2.0 seconds. Each bag contains 15g and is packaged in a box.

7. A liver-clearing decoction granule, characterized in that, The prescription is as follows: 746g of green tangerine peel, 746g of dried tangerine peel, 746g of peony root, 560g of peony bark, 560g of gardenia fruit, 560g of alisma rhizome, and 933g of fritillaria bulb.

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