A product rich in paeonol and a method for preparing the product

Abstract

The application provides a kind of rich in paeonol liver decoction product and its preparation method, the innovation point of the application is "in situ one-step inclusion process of paeonol aromatic water and cyclodextrin": by omitting the separation and purification step of paeonol, paeonol is directly included with cyclodextrin in the extraction of aromatic water; not only maximizes the retention of paeonol in liver decoction product, solves the disadvantages of large loss of paeonol in the prior art, complicated process, organic solvent residue, higher cost, etc., and finally realizes the efficient retention of core active ingredients and the quality stability of liver decoction product, with high creativity, practicality and industrialization value.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a liver-strengthening decoction product rich in paeonol and its preparation method. Background Technology

[0002] Huagan Decoction is one of the classic prescriptions listed in the "Catalogue of Ancient Classic Prescriptions (First Batch)" published by the State Administration of Traditional Chinese Medicine. It was first recorded in Zhang Jingyue's "Complete Works of Jingyue: Eight New Prescriptions" during the Ming Dynasty. It consists of green tangerine peel, dried tangerine peel, white peony root, peony bark, gardenia (fried), alisma, and fritillaria thunbergii. It has the effects of soothing the liver and relieving stagnation, clearing liver heat, and is mainly used to treat liver stagnation with heat. Paeonol is the core effective component of peony bark, possessing important pharmacological effects such as anti-inflammatory, analgesic, hepatoprotective, and antioxidant properties. Its content directly determines the clinical efficacy of Huagan Decoction preparations.

[0003] However, paeonol is a typical heat-sensitive and volatile component, which is highly volatile and degraded during the preparation of traditional Chinese medicine preparations. Currently, existing preparation processes for Huagan Decoction, such as patent CN108888686A, employ a combined extraction method, resulting in low paeonol content in the preparation, significantly different from the baseline sample of classic prescriptions, and failing to guarantee consistency in clinical efficacy. Patent CN121570543A addresses the inclusion of paeonol with cyclodextrin after crystallization. The inventors of this application, through reproducing this patented process, found that although this process can effectively retain paeonol to a certain extent, its process stability is insufficient. The crystallization and heating dissolution processes are difficult to control, leading to poor batch-to-batch reproducibility, uncontrollable sample stability, high energy consumption, and unsuitability for large-scale industrial production.

[0004] To address the aforementioned issues, the inventors focused on key processes such as the extraction and inclusion methods of paeonol, providing a simple, cost-effective, and industrially scalable method for preparing a paeonol-rich decoction product. While preserving the efficacy of traditional decoctions, this method achieves efficient retention of core active ingredients and full control over the quality of the preparation, providing a safe, effective, stable, and convenient paeonol granule formulation for clinical use. Summary of the Invention

[0005] The main objective of this invention is to provide a method for preparing a liver-strengthening decoction product rich in paeonol. By optimizing key processes such as the extraction and inclusion methods of paeonol, the inventors can not only effectively retain the heat-sensitive component paeonol, but also achieve a quality consistency with the reference sample.

[0006] To achieve the above objectives, the present invention provides a method for preparing a liver-strengthening decoction product rich in paeonol, comprising the following steps:

[0007] (1) The peony bark medicinal material or decoction pieces are heated and refluxed separately to extract aromatic water rich in paeonol; then the peony bark residue after extracting aromatic water is combined with the other medicinal materials or decoction pieces in the Huagan Decoction prescription for extraction, decocted with water, and filtered to obtain the extract;

[0008] (2) Add cyclodextrin or its derivative directly to the aromatic water in step (1) to encapsulate paeonol in the aromatic water with cyclodextrin or its derivative to obtain paeonol encapsulation solution.

[0009] (3) The extract from step (1) is concentrated under reduced pressure to obtain a concentrated solution. The concentrated solution is then mixed with the paeonol inclusion solution from step (2) and spray-dried to obtain a dry powder. Alternatively, excipients may be added or not, granulation may be performed or not, and packaging may be performed or not, to obtain the Huagan Decoction product.

[0010] The liver-strengthening decoction product described in this invention refers to a product based on the classic formula of liver-strengthening decoction, containing green tangerine peel, dried tangerine peel, white peony root, peony bark, gardenia (fried), alisma, and fritillaria thunbergii as core medicinal ingredients. The core medicinal ingredients can be replaced by medicinal materials, processed slices, or extracts with equivalent efficacy. At the same time, other pharmaceutically acceptable excipients or other medicinal ingredients that have synergistic effects with this formula can be added.

[0011] In some embodiments, the prescription for Huagan Decoction in step (1) of the present invention includes green tangerine peel, dried tangerine peel, white peony root, peony bark, gardenia (fried), alisma, and fritillaria thunbergii.

[0012] In a further preferred embodiment, the prescription ratio of Huagan Decoction in step (1) of the present invention is as follows by weight (g): 298.4g of green tangerine peel, 298.4g of dried tangerine peel, 298.4g of white peony root, 224g of peony bark, 224g of gardenia (fried), 224g of alisma, and 373.2g of fritillaria thunbergii.

[0013] In some embodiments, the cyclodextrin or its derivative in step (2) is at least one of β-cyclodextrin or hydroxypropyl-β-cyclodextrin.

[0014] Preferably, in step (2), the mass-volume ratio of the amount of cyclodextrin added to the aromatic water is 1g: 8-12mL.

[0015] Preferably, the encapsulation method in step (2) is magnetic stirring or colloid milling.

[0016] Preferably, the encapsulation method in step (2) is magnetic stirring.

[0017] Furthermore, when magnetic stirring is used for inclusion in step (2), the reaction conditions are: stirring at 40-60°C for 2-4 hours at a stirring speed of 600-1000 r / min.

[0018] In some embodiments, the extraction step of aromatic water in step (1) is as follows: add water (mL / g) equivalent to 3 to 8 times the weight of peony bark slices to the peony bark slices, heat and reflux to extract 1 to 3 times, and collect aromatic water (mL / g) equivalent to 1 to 4 times the weight of peony bark slices.

[0019] Preferably, the extraction step of aromatic water in step (1) is as follows: add water (mL / g) with a volume equivalent to 4 times the weight of the peony bark slices to the peony bark slices, heat and reflux to extract once, extract for 60 min, and collect aromatic water (mL / g) equivalent to 1.5 to 2 times the weight of the peony bark slices.

[0020] Further, the extraction steps of the extract in step (1) are as follows: the peony bark residue after extracting aromatic water is combined with the remaining medicinal pieces in the Huagan Decoction prescription and extracted. Water (mL / g) equivalent to 5 to 10 times the total weight of the medicinal pieces is added and extracted for 30 to 60 minutes at a slight boiling state. The extract is then filtered through a 200-mesh filter cloth while hot and extracted 1 to 3 times to obtain the extract.

[0021] Preferably, in the extraction process of step (1), the combined water volume for extraction is 7 times the total weight of the medicinal slices (mL / g), the extraction is performed once, and the extraction time is 60 min.

[0022] In some embodiments, the vacuum concentration in step (3) is carried out at 60-80°C to concentrate to a relative density of 1.04-1.10 (measured at 60°C).

[0023] In some embodiments, the spray drying conditions in step (3) are an inlet air temperature of 160-180°C, an outlet air temperature of 90-110°C, and the moisture content of the resulting material is not higher than 6.0%.

[0024] In some embodiments, the granulation in step (3) is dry granulation.

[0025] In some embodiments, the excipients in step (3) include, but are not limited to, maltodextrin, dextrin, and lactose, and the amount added is 40-70% of the total weight of the preparation.

[0026] On the other hand, the present invention also provides a liver-strengthening decoction product rich in paeonol prepared by the above method.

[0027] Furthermore, the present invention also provides the application of the above preparation method in related drugs or medicinal materials, wherein the drugs or medicinal materials are related drugs or drug formulations containing peony bark.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] This invention provides a method for preparing a liver-strengthening decoction product rich in paeonol. The core process involves a one-step encapsulation of paeonol-containing aromatic water with cyclodextrin. First, aromatic water is extracted separately from peony bark slices. Then, a specific proportion of cyclodextrin is directly added to the aromatic water for encapsulation, effectively preserving the paeonol content in the liver-strengthening decoction product. This invention features a simplified preparation process, strong equipment adaptability, easy operation, good stability, and suitability for large-scale production. Furthermore, the liver-strengthening decoction product prepared using this method exhibits excellent stability. Attached Figure Description

[0030] Figure 1 This is a flowchart of the preparation process in Example 2 of the present invention. Detailed Implementation

[0031] The following description provides examples of the technical solutions of the present invention. This description is intended to further illustrate the present invention and facilitate understanding of the implementation conditions and means of the present invention. It should not be considered as a limitation of the present invention.

[0032] The main sources of the medicinal materials (all from the same batch) and the production equipment involved in the specific embodiments and comparative examples are as follows:

[0033] 1. Instruments and reagents

[0034] 1.1 Main Instruments

[0035] Table 1. Main Instruments

[0036]

[0037] 1.2 Main Reagents

[0038] Hesperidin reference standard (National Institutes for Food and Drug Control, batch number: 110721-202220, purity 97.2%); Paeonol reference standard (National Institutes for Food and Drug Control, batch number: 110708-202309, purity 99.9%); Paeoniflorin reference standard (National Institutes for Food and Drug Control, batch number: 110736-202548, purity 98.9%); Geniposide reference standard (National Institutes for Food and Drug Control, batch number: 110749-202320, purity 98.1%); Maltodextrin (Xi'an Tianzheng Pharmaceutical Excipients Co., Ltd., pharmaceutical grade, batch number: 2023020955); Dextrin (Dongguan Dongyue Glucose Factory, pharmaceutical grade, batch number: 230801); Betacyclodextrin (Qufu Tianli Pharmaceutical Excipients Co., Ltd., pharmaceutical grade, batch number: 20250213).

[0039] 2. Medicinal materials, processed medicinal slices, and reference samples

[0040] 2.1 Medicinal materials and their sources

[0041] Table 2. Information on Medicinal Herbs

[0042]

[0043] 2.2 Medicinal slices and their processing methods

[0044] Table 3. Information on Medicinal Herbs

[0045]

[0046] 2.3 Preparation of reference samples

[0047] [Standard Prescription] Green tangerine peel 7.46g, dried tangerine peel 7.46g, white peony root 7.46g, peony bark 5.60g, stir-fried gardenia fruit 5.60g, alisma rhizome 5.60g, fritillaria bulb 9.33g.

[0048]

Preparation

[0049] Table 4. Determination of Active Ingredient Content in Reference Samples

[0050]

[0051] The term "single prescription" in this invention refers to the complete dosage of the original medicinal materials corresponding to a standard prescription prepared according to the predetermined ratio of medicinal materials and the fixed dosage of the prescription in the traditional Chinese medicine composition of this invention. All indicators in this invention expressed in "mg / single prescription" are based on the dosage of this standard prescription as the measurement reference standard.

[0052] Example 1: Investigation of Process Conditions

[0053] (1) Investigation on the extraction methods of paeonol

[0054] Since the indicative component paeonol is a heat-sensitive component, it is significantly lost during the concentration and drying process. Therefore, the extraction process is being optimized, and two extraction methods are being considered.

[0055] Extraction Method 1: Extraction of aromatic water from the whole formula: Weigh all the medicinal pieces (5 times the standard prescription, 37.3g of green tangerine peel, 37.3g of dried tangerine peel, 37.3g of white peony root, 28g of peony bark, 28g of stir-fried gardenia fruit, 28g of alisma rhizome, and 46.65g of fritillaria thunbergii) into a distillation flask, add 6 times the volume of water (1.455L), heat and reflux for 60 minutes, collect the distillate, which is 85mL of aromatic water; sieve the decoction in the distillation flask through a 200-mesh sieve to obtain 800mL of extract, concentrate the extract under reduced pressure at 60℃ to obtain concentrated liquid, and vacuum dry at 55℃ to obtain 35.91g of dry powder.

[0056] Extraction Method 2: Extraction of aromatic water from peony bark slices alone: ​​Weigh peony bark slices (5 times the standard prescription, 28g), add 6 times the volume of water (168mL), heat under reflux to extract aromatic water for 40min, and collect 50mL of aromatic water; then add the peony bark residue after aromatic water extraction to the remaining slices (5 times the standard prescription, green tangerine peel 37.3g, dried tangerine peel 37.3g, white peony root 37.3g, stir-fried gardenia fruit 28g, alisma rhizome 28g, and fritillaria bulb 46.65g), add 6 times the volume of water (1455mL), gently boil and extract for 60min, pass through a 200-mesh sieve while hot to obtain 850mL of extract, concentrate the extract under reduced pressure at 60℃ to obtain 350mL of concentrate, and vacuum dry at 55℃ to obtain 40.91g of dry powder.

[0057] Extracts (40 mL), concentrates (30 mL), aromatic water (5 mL), and dry extract powder (0.2 g) from the two extraction methods were taken respectively, and the contents of the active ingredients - geniposide, paeoniflorin, hesperidin, and paeonol were determined. The results are shown in Table 5.

[0058] The results showed that in extraction method one, paeonol was significantly lost during the concentration and drying of the extract, with only 2.2451 mg / single prescription remaining in the dried extract powder, a large difference from the paeonol content in the reference sample. The aromatic water also only contained 10.2136 mg / single prescription. In contrast, extraction method two, when extracting aromatic water from peony bark alone, yielded a content as high as 40.6262 mg / single prescription, which was more conducive to the enrichment of paeonol. Therefore, subsequent studies used extraction method two for paeonol extraction. However, since the sample was observed to be viscous after vacuum drying and could not be powdered, spray drying was subsequently used in the final study.

[0059] Table 5. Investigation of Paeonol Extraction Methods

[0060]

[0061] (2) Investigation on the method of adding paeonol

[0062] Based on the extraction process research results in (1), paeonol is mainly concentrated in aromatic water. Considering the stability of the components, it is necessary to adopt a suitable method to transfer paeonol from the aromatic water to the dry extract powder, and to maintain the stability of the preparation during storage. Now, aromatic water, concentrated solution and dry extract powder are prepared according to extraction method two in (1), and the method of adding paeonol is investigated.

[0063] Method 1: The aromatic water (50 mL) prepared in Method 2 is refrigerated and allowed to stand to precipitate paeonol crystals. The filtered and dried crystals (0.25 g) are then directly ground and mixed with the prepared dry extract powder (40.91 g) to obtain Huagan Decoction powder.

[0064] Method 2: The aromatic water (50 mL) prepared in Method 2 is included with 5 g of β-cyclodextrin. The resulting inclusion complex is then mixed with the prepared concentrate (350 mL) and spray-dried to obtain a dry powder, which is the liver-cleansing decoction powder.

[0065] An experiment was conducted to investigate the influencing factors of two different methods of adding the liver-strengthening decoction powder:

[0066] High temperature experiment: The liver-nourishing powder prepared by the two methods was placed in a suitable constant temperature device and the temperature was set to 60℃.

[0067] High humidity experiment: The Huagan Decoction powder prepared by the two methods was placed in a constant humidity desiccator with the opening open, and subjected to a relative humidity of 90%±5%.

[0068] Samples were taken after 10 days of storage. The contents of geniposide, paeoniflorin, hesperidin, and paeonol, as well as the transfer rate of each component, were determined. The results are shown in Table 6.

[0069] The results showed that in high-temperature environments, when paeonol was added using method one, the loss rate was relatively high compared to the original sample, with only 14.80% retained. However, when added using method two, the loss was less, with 96.72% of paeonol retained. In high-humidity environments, when added using method one, only 49.97% of paeonol was retained, while when added using method two, there was almost no loss, with 99.92% retained. Therefore, subsequent treatments using inclusion methods to improve the stability of paeonol were recommended.

[0070] Table 6. Results of the investigation on the method of adding paeonol

[0071]

[0072] *Transfer rate (%) = (Content of influencing factors (high temperature, high humidity) in experimental sample / Content of original sample) * 100%.

[0073] (3) Examination of inclusion mode

[0074] Based on the research results on the addition method of paeonol in (2), the inclusion method was optimized as follows to improve the stability of paeonol:

[0075] ① Inclusion method one: Weigh 224g of peony bark slices (40 times the prescription amount) and add 1800mL of water. Reflux and extract for 60min, and collect 440mL of aromatic water. Weigh 44g of β-cyclodextrin and prepare a suspension with 132mL of water. Grind the suspension in a colloid mill and slowly add the above 440mL of aromatic water. Grind for 3 hours. Mix the inclusion solution with the maltodextrin aqueous solution and spray dry to obtain the inclusion powder (inlet air temperature of spray drying: 160℃).

[0076] ② Inclusion method two: Weigh 224g of peony bark slices (40 times the prescription amount) and add 1800mL of water. Reflux and extract for 60min. Collect 440ml of aromatic water. Add 44g of β-cyclodextrin directly to the aromatic water. Dissolve completely in a 65℃ water bath and keep warm at 45℃. Stir magnetically for 3h at 800r / min. Mix the inclusion solution with the maltodextrin aqueous solution and spray dry to obtain the inclusion powder (inlet air temperature of spray drying is 160℃).

[0077] ③ Inclusion Method 3: Weigh 224g of peony bark slices (40 times the prescription amount), add 1800mL of water, reflux for 60min, and collect 440mL of aromatic water. Place the collected aromatic water in a 4℃ refrigerator overnight for crystallization, filter out the crystals, and dry at 40℃ to obtain paeonol crystals (2g). Weigh 44g of β-cyclodextrin, add 240mL of water, dissolve completely at 65℃, dissolve the paeonol crystals in 8mL of ethanol, add the solution, and incubate in a 45℃ water bath. Stir magnetically for 3h at 800r / min to obtain an inclusion solution. Mix the inclusion solution with a maltodextrin aqueous solution and spray dry to obtain the inclusion powder (inlet air temperature for spray drying: 160℃).

[0078] ④ Inclusion Method Four: Weigh 224g of peony bark slices (40 times the prescription amount), add 1800mL of water, reflux for 60min, and collect 440mL of aromatic water. Place the collected aromatic water in a 4℃ refrigerator overnight for crystallization, filter out the crystals, and dry at 40℃ to obtain paeonol crystals (2g). Weigh 44g of β-cyclodextrin, add 240mL of water, dissolve completely at 65℃, add the crystals directly, and incubate in a 45℃ water bath. Stir magnetically for 3h at 800r / min to obtain an inclusion solution. Mix the inclusion solution with a maltodextrin aqueous solution and spray dry to obtain the inclusion powder (inlet air temperature for spray drying: 160℃).

[0079] The content of paeonol in the inclusion powder was determined, and the results are shown in Table 7.

[0080] The results showed that the inclusion powders prepared by inclusion methods three and four had lower paeonol content and required low-temperature crystallization and drying, resulting in longer processing times and instability. In particular, inclusion method three had residual organic solvent issues. The inclusion powders prepared by inclusion methods one and two had higher paeonol content (35.51 mg / single formulation and 40.98 mg / single formulation, respectively), within ±30% of the baseline paeonol content (33.11 mg / single formulation). Therefore, considering process stability, operability, production losses, and cost control, inclusion method two was prioritized for further research.

[0081] Table 7. Results of the investigation on the inclusion mechanism of paeonol

[0082]

[0083] Example 2

[0084] This embodiment provides a method for preparing Huaganjian granules rich in paeonol, the steps of which are as follows:

[0085] (1) Weigh out 224g of peony bark slices (40 times the standard prescription) and add 896mL of water. Heat and reflux to extract once. Collect about 380mL of aromatic water equivalent to 1.7 times the weight of the peony bark slices. Then combine the peony bark slice residue after extracting the aromatic water with the other 6 slices (298.4g of green tangerine peel, 298.4g of dried tangerine peel, 298.4g of white peony root, 224g of stir-fried gardenia fruit, 224g of alisma rhizome, and 373.2g of fritillaria thunbergii) and extract again. Add about 13.58L of water equivalent to 7 times the total weight of the medicinal materials. Heat and reflux to extract once for 40min. Filter the hot extract through a 200-mesh filter cloth to obtain about 9L of extract.

[0086] (2) Add 38g of β-cyclodextrin to the aromatic water (380mL) obtained in step (1), place it in a constant temperature heating magnetic stirrer to heat and dissolve, then keep it at 50℃ for 3h and 800r / min to obtain the inclusion solution;

[0087] (3) The extract obtained in step (1) is concentrated under reduced pressure (temperature 60-80℃) until the relative density is 1.04~1.10 (measured at 60℃) to obtain a concentrated solution. The concentrated solution is then mixed with the inclusion solution obtained in step (2) and spray-dried to obtain a dried liver decoction powder (spray drying parameters: inlet air temperature 160~180℃, outlet air temperature 90~110℃, atomization frequency 300Hz, feed speed 14~25rpm, and the moisture content of the obtained material should not be higher than 6.0%). The dried liver decoction powder and maltodextrin are passed through a No. 5 sieve respectively, and the liver decoction powder is weighed. The dried extract powder and maltodextrin (mass ratio 10:4.5) were weighed and placed in a three-dimensional mixer and mixed for 20 minutes. After checking the uniformity of the mixture, a mixed powder was obtained and then dry granulated (dry granulation parameters: pressure roller hydraulic pressure 90~120 bar, feeding speed 20 rpm, pressure roller speed 6 rpm, granulation speed 100 rpm, and sieve aperture 1.0 mm). Finally, the mixture was packaged using a packaging machine with a packaging specification of 14g / bag. The packaging material was a polyester / aluminum / polyethylene pharmaceutical composite film, and the sealing temperature was 150±5℃ to obtain Huagan Decoction Granules (with packaging).

[0088] Three batches of samples were prepared in parallel to investigate the stability of the process, and the results are shown in Table 8.

[0089] The results show that the fluctuation range of the yield and content of each index in the three batches of parallel samples was less than ±5%, indicating that the process is stable and reproducible.

[0090] Table 8. Results of the process stability study

[0091]

[0092] Example 3

[0093] This embodiment provides another method for preparing Huaganjian granules rich in paeonol, the steps of which are as follows:

[0094] (1) Weigh out 224g of peony bark slices (40 times the standard prescription) and add 896mL of water. Heat and reflux to extract once. Collect 403mL of aromatic water, which is about 1.8 times the weight of the peony bark slices. Then, combine the peony bark slice residue after extracting the aromatic water with 6 other slices (298.4g of green tangerine peel, 298.4g of dried tangerine peel, 298.4g of white peony root, 224g of stir-fried gardenia fruit, 224g of alisma rhizome, and 373.2g of fritillaria thunbergii) and extract again. Add 15.52L of water, which is 8 times the total weight of the medicinal materials. Heat and reflux to extract once for 40min. Filter the hot extract through a 200-mesh filter cloth to obtain the extract.

[0095] (2) Add 33g of hydroxypropyl-β-cyclodextrin to the aromatic water (403mL) in step (1), dissolve it in an appropriate amount of water, place it in a colloid mill and grind it for 2~4h to obtain the inclusion solution;

[0096] (3) The extract obtained by vacuum concentration in step (1) is mixed with the inclusion solution in step (2) and spray-dried to obtain Huaganjian dry powder. Maltodextrin (mass ratio of 10:4.5) is added to the Huaganjian dry powder and then granulated and packaged to obtain Huaganjian granules (the conditions and parameters of vacuum concentration, spray drying, dry granulation and packaging process are the same as in Example 2).

[0097] Comparative Example 1: Whole-formula extraction, concentration, drying, and granulation

[0098] Weigh out each of the following medicinal slices (40 times the standard prescription: 298.4g of green tangerine peel, 298.4g of dried tangerine peel, 298.4g of white peony root, 224g of peony bark, 224g of stir-fried gardenia fruit, 224g of alisma rhizome, and 373.2g of fritillaria thunbergii), add 13.58L of water, connect a reflux condenser, boil, maintain a gentle boil, and reflux for 40 minutes to obtain 9.4L of extract. After concentration under reduced pressure, spray dry to obtain a dry powder. Add maltodextrin (mass ratio 10:4.5) to the dry powder and granulate by dry granulation to obtain Huaganjian granules (the conditions and parameters of the reduced pressure concentration, spray drying, dry granulation, and packaging process are the same as in Example 2).

[0099] Comparative Example 2: The aromatic water extracted from the whole formula was combined, then concentrated, dried, and granulated.

[0100] Weigh out each of the following medicinal slices (40 times the standard prescription: 298.4g of green tangerine peel, 298.4g of dried tangerine peel, 298.4g of white peony root, 224g of peony bark, 224g of stir-fried gardenia fruit, 224g of alisma rhizome, and 373.2g of fritillaria bulb), add 13.58L of water, heat under reflux for 40 minutes, and collect 9L of extract and about 380mL of aromatic water. Add 38g of β-cyclodextrin to the aromatic water, heat to dissolve, place in a constant temperature magnetic stirrer, keep warm at 45~50℃, and stir magnetically for 2~4 hours at 800r / min to obtain the inclusion solution. The inclusion solution is used for later use. The extract was concentrated under reduced pressure to obtain a concentrated solution, which was then mixed with an inclusion solution and spray-dried to obtain a dry extract powder. The dry extract powder was then added to maltodextrin (mass ratio 10:4.5) and dry granulated to obtain Huaganjian granules (the conditions and parameters of the reduced pressure concentration, spray drying, dry granulation and packaging process are the same as in Example 2).

[0101] The effective ingredient content of Examples 1-2, the reference sample, and Comparative Examples 1-2 were determined respectively, and the results are shown in Table 9.

[0102] The results showed that the effective component contents of Examples 1 and 2 were within ±30% of the baseline sample, consistent with the quality of the classic formula Huagan Decoction. Compared with Comparative Examples 2 and 3, the content of paeonol was significantly increased (35.18 mg / prescription ~ 39.17 mg / prescription), effectively preserving the volatile component paeonol.

[0103] Table 9. Results of active ingredient content determination in the examples and comparative examples

[0104]

[0105] Example 4: Stability test of Huaganjian granules

[0106] (1) Examination of influencing factors

[0107] High temperature test: The Huagan Decoction Granules (with packaging) in Example 2 were placed at 60℃ for 10 days, and samples were taken for testing on days 0, 5 and 10. High humidity test: The Huagan Decoction Granules (with packaging) in Example 2 were placed at 25℃ and RH 92.5%±5% for 10 days, and samples were taken for testing on days 0, 5 and 10. The results are shown in Table 10.

[0108] The results showed that the content of active ingredients in the Huaganjian granules remained stable under high temperature and high humidity conditions (the degradation rate of active ingredients was <5%), and the content of paeonol was 38.4~40mg / single prescription.

[0109] Table 10. Examination of Influencing Factors

[0110]

[0111] (2) Accelerated stability test

[0112] The Huaganjian granules from Example 2 were packaged and tested at 40℃±2℃ and RH75%±5%. Samples were taken at the end of the 0th, 1st, 2nd and 3rd months of the test period, and the results are shown in Table 11.

[0113] The results showed that the content of active ingredients in the Huaganjian granules remained basically stable within 3 months of accelerated stability testing. Among them, the content of paeonol was about 39~40mg / prescription, which was consistent with the baseline sample mass (23.18~43.04mg / prescription).

[0114] Table 11. Accelerated stability test results

[0115]

[0116] The above description is merely a preferred embodiment of the present invention and should not be construed as a limitation thereof. Without departing from the scope or spirit of the present invention, those skilled in the art can make various improvements and variations to the specific embodiments described in this specification. Any simple changes, equivalent variations, or modifications made to the above content that do not substantially depart from the technical solution of the present invention are still within the protection scope of the present invention.

Claims

1. A method for preparing a liver-strengthening decoction product rich in paeonol, characterized in that, Includes the following steps: (1) The peony bark medicinal material or decoction pieces are heated separately and refluxed with water to obtain aromatic water rich in paeonol; then the peony bark residue after extracting aromatic water is combined with the other medicinal materials or decoction pieces in the Huagan Decoction prescription for extraction, decocted with water, and filtered to obtain the extract; (2) Add cyclodextrin or its derivative directly to the aromatic water in step (1) to encapsulate paeonol in the aromatic water with cyclodextrin or its derivative to obtain paeonol encapsulation solution. (3) The extract from step (1) is concentrated under reduced pressure to obtain a concentrated solution. The concentrated solution is then mixed with the inclusion solution from step (2) and spray-dried to obtain a dry powder. Optionally, excipients may be added, granulation may be optional, and packaging may be optional to obtain a liver-strengthening decoction product rich in paeonol.

2. The preparation method according to claim 1, characterized in that, The prescription for Huagan Decoction mentioned in step (1) includes green tangerine peel, dried tangerine peel, white peony root, peony bark, gardenia (fried), alisma, and fritillaria thunbergii.

3. The preparation method according to claim 1 or 2, characterized in that, The prescription ratio of Huagan Decoction in step (1) is as follows by weight (g): 298.4g of green tangerine peel, 298.4g of dried tangerine peel, 298.4g of white peony root, 224g of peony bark, 224g of gardenia (fried), 224g of alisma, and 373.2g of fritillaria thunbergii.

4. The preparation method according to claim 1, characterized in that, The cyclodextrin or its derivative mentioned in step (2) is at least one of β-cyclodextrin or hydroxypropyl-β-cyclodextrin.

5. The preparation method according to any one of claims 1-4, characterized in that, In step (1), the mass-volume ratio of cyclodextrin added to aromatic water is 1g: 8-12mL.

6. The preparation method according to claim 1, characterized in that, The encapsulation method in step 2) is magnetic stirring or colloid milling; preferably, the encapsulation method in step 2) is magnetic stirring.

7. The preparation method according to claim 6, characterized in that, When magnetic stirring is used for the inclusion method in step 2), the reaction conditions are: stirring at 40-60℃ for 2-4 hours at a stirring speed of 600-1000 r / min.

8. The preparation method according to any one of claims 1-7, characterized in that, In step (3), the vacuum concentration is carried out at 60-80°C until the relative density is 1.04-1.10, and the concentration is measured at 60°C.

9. The preparation method according to any one of claims 1-8, characterized in that, In step (3), the spray drying conditions are an inlet air temperature of 160-180°C, an outlet air temperature of 90-110°C, and the moisture content of the resulting material is not higher than 6.0%.

10. The preparation method according to any one of claims 1-9, characterized in that, In step (3), the granulation is dry granulation.

11. The preparation method according to any one of claims 1-10, characterized in that, The excipients mentioned in step (3) include, but are not limited to, maltodextrin, dextrin, and lactose, and their addition amount is 40-70% of the total weight of the preparation.

12. A liver-clearing decoction product rich in paeonol, characterized in that, It is prepared by the preparation method according to any one of claims 1-11.

13. The application of the preparation method according to any one of claims 1 to 11 in the extraction, inclusion, and quality control of paeonol in related drugs or medicinal materials, wherein, The drug or herbal formula contains peony bark or related drugs or formulas.

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