An Improved Process for Preparing Longqing Capsules

Abstract

This invention relates to the field of traditional Chinese medicine preparation technology, specifically to an improved preparation process for Longqing capsules. The preparation process includes the following steps: pretreatment of medicinal materials; preparation of aqueous extracts; preparation of alcoholic extracts; and formulation. This invention improves and optimizes the preparation method of Longqing capsules by combining modern pharmaceutical processes. The Longqing capsules prepared using this invention have significantly higher contents of berberine hydrochloride and phellodendron chinense hydrochloride than those prepared using current methods, greatly improving the extraction rate of effective components from the medicinal materials while shortening the drug production cycle. This helps improve drug efficacy and enterprise production efficiency, and has significant value for widespread application.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to an improved preparation process for Longqing capsules. Background Technology

[0002] Longqing Capsules are one of the main products of Guizhou Yuancheng Pharmaceutical Co., Ltd. It is a Class A drug under the National Medical Insurance and a drug listed in the National Essential Medicines List. It is a commonly used clinical drug for treating heat strangury (frequent urination, urgency, painful urination, short urination, back pain, and lower abdominal distension) caused by damp-heat in the lower jiao. It has good therapeutic effects and has been included in Part I of the 2020 edition of the Chinese Pharmacopoeia.

[0003] The prescription for Longqing Capsules is as follows: Alisma plantago-aquatica 261g, Plantago asiatica 52.5g, Patrinia scabiosaefolia 522g, Lonicera japonica 261g, Paeonia suffruticosa 261g, Hedyotis diffusa 522g, Paeonia lactiflora 261g, Agrimonia pilosa 261g, Coptis chinensis 261g, and Phellodendron chinense 261g. The current preparation method is as follows: Alisma plantago-aquatica is pulverized into a fine powder; Lonicera japonica, Patrinia scabiosaefolia, Hedyotis diffusa, and Agrimonia pilosa are decocted in water and concentrated into a clear extract; the remaining five herbs, including Plantago asiatica, are extracted by reflux with an ethanol solution and concentrated into a clear extract; the above clear extracts are combined, and the Alisma plantago-aquatica powder and pharmaceutical excipients are added, mixed well, and granulated; finally, after drying and granulation, the granules are filled into capsules. Among them, decoction extraction and reflux extraction are traditional extraction methods for effective components in the preparation of traditional Chinese medicine preparations. Although the various indicators of the Longqing capsules prepared by the above methods meet the standard requirements, the following problems still exist: (1) The extraction rate of effective components in medicinal materials is not high, resulting in the waste of medicinal material resources; (2) The production process has a long cycle and low production efficiency.

[0004] To address the aforementioned issues, this invention utilizes new technologies and methods in modern pharmaceutical processes to improve and optimize the preparation process of Longqing Capsules, providing an improved Longqing Capsule preparation process aimed at increasing the extraction rate of effective components from medicinal materials, enhancing drug efficacy, and improving enterprise production efficiency. Summary of the Invention

[0005] The purpose of this invention is to provide an improved preparation process for Longqing capsules.

[0006] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0007] The improved preparation process of Longqing capsules described in this invention includes the following steps:

[0008] S1 Pre-processing of medicinal materials:

[0009] Grind Alisma plantago-aquatica into fine powder and pass it through a 60-100 mesh sieve for later use; cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 2-10 cm long pieces for later use; grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into coarse powder and pass it through a 5-15 mesh sieve for later use.

[0010] Preparation of S2 water extract:

[0011] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and add 5 to 10 times the amount of water to each herb. Decoction them separately 1 to 3 times, each time for 0.5 to 1.5 hours. Soak the herbs for 15 to 60 minutes before the first decoction. Filter the mixture, combine the filtrates, pass them through an 80 to 120 mesh sieve, and concentrate them under reduced pressure at 70 to 90°C to obtain a clear extract with a density of 1.25 to 1.30 at 50°C.

[0012] Preparation of S3 alcohol extract:

[0013] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4-6 times the weight of the medicinal materials to a 50%-70% ethanol solution and 3‰-5‰ of the medicinal materials to a compound enzyme. Adjust the pH to 4-6, perform ultrasonic-assisted enzymatic hydrolysis for 0.5-2 hours, and boil to inactivate the enzyme for 1-2 hours. Filter, combine the filtrates, pass through an 80-120 mesh sieve, recover the ethanol under reduced pressure at 70-90℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃.

[0014] The complex enzyme is composed of ligninase, papain and cellulase in a mass ratio of 1:1 to 2:2.

[0015] S4 Formulation:

[0016] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, mixed well, dried under reduced pressure at 60-70°C, pulverized into fine powder, and 0.1%-0.3% magnesium stearate is added. The mixture is then granulated by dry method and filled into capsules.

[0017] Preferably, in the preparation process of the present invention, in step S1, the pretreatment of medicinal materials is as follows: Alisma plantago-aquatica is pulverized and passed through an 80-100 mesh sieve; Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into 2-6 cm long segments; and Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense are pulverized and passed through a 10-15 mesh sieve.

[0018] In a further preferred embodiment, in the preparation process of the present invention, in step S1, the pretreatment of medicinal materials is as follows: Alisma plantago-aquatica is pulverized and passed through an 80-mesh sieve; Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into 3-5 cm long segments; and Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense are pulverized and passed through a 10-mesh sieve.

[0019] Preferably, in the preparation process of the present invention, the preparation of the water extract in step S2 is specifically as follows: take the long segments of the four medicinal materials, Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, add 6 to 8 times the amount of water of each medicinal material, decoct them 2 to 3 times, each time for 1 to 1.5 hours, and soak them for 15 to 45 minutes before the first decoction; filter, combine the filtrates, pass them through a 100 to 120 mesh sieve, and concentrate them under reduced pressure at 75 to 85°C to a clear extract with a density of 1.25 to 1.30 at 50°C.

[0020] In a further preferred embodiment, the preparation of the water extract in step S2 of the preparation process of the present invention is as follows: take long sections of the four medicinal materials, namely Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, and decoct them with water twice, each time for 1 hour. The first time, add 8 times the amount of water of the medicinal materials and the second time, add 6 times the amount of water of the medicinal materials. Soak for 30 minutes before the first decoction; filter, combine the filtrates, pass through a 100-mesh sieve, and concentrate under reduced pressure at 80°C to a clear extract with a density of 1.25 to 1.30 at 50°C.

[0021] Preferably, in the preparation process of the present invention, the preparation of the ethanol extract in step S3 specifically involves: taking coarse powder of five medicinal materials—peony bark, plantain seed, red peony root, coptis root, and phellodendron bark—and adding 4-5 times the weight of the medicinal materials in a 55%-65% ethanol solution and 4‰-5‰ of the medicinal materials' weight in a compound enzyme; adjusting the pH to 5-6, performing ultrasonic-assisted enzymatic hydrolysis for 1-2 hours, and boiling to inactivate the enzyme for 1-1.5 hours; filtering, combining the filtrates, passing them through a 100-120 mesh sieve, recovering the ethanol under reduced pressure at 75-85°C, and concentrating to a clear extract with a density of 1.25-1.30 at 50°C; wherein the compound enzyme is composed of ligninase, papain, and cellulase in a mass ratio of 1:1.5-2:2.

[0022] In a further preferred embodiment, the preparation of the ethanol extract in step S3 of the present invention specifically involves: taking coarse powders of five medicinal materials—peony bark, plantain seed, red peony root, coptis root, and phellodendron bark—and adding 4 times the weight of the medicinal materials in a 60% ethanol solution and 4‰ of the medicinal materials' weight in a compound enzyme; adjusting the pH to 5.5, performing ultrasonic-assisted enzymatic hydrolysis for 1 hour, and boiling to inactivate the enzyme for 1.5 hours; filtering, combining the filtrates, passing them through a 100-mesh sieve, recovering the ethanol under reduced pressure at 80°C, and concentrating the extract to a density of 1.25–1.30 at 50°C; wherein the compound enzyme is composed of ligninase, papain, and cellulase in a mass ratio of 1:1.5:2.

[0023] Preferably, in the preparation process of the present invention, the ultrasonic power in step S3, the preparation of the alcohol extract, is 600W and the frequency is 40kHz.

[0024] Preferably, in the preparation process of the present invention, in step S4 formulation forming: the temperature of vacuum drying is 60-65°C; and the amount of magnesium stearate added is 0.2%-0.3%.

[0025] In a further preferred embodiment, in the preparation process of the present invention, in step S4 formulation forming: the temperature of vacuum drying is 65°C; and the amount of magnesium stearate added is 0.2%.

[0026] The beneficial effects of this invention are:

[0027] 1. This invention provides an improved preparation process for Longqing capsules. The Longqing capsules prepared using this invention contain 12.38 mg / 0.5g of berberine hydrochloride and 0.75 mg / 0.5g of berberine hydrochloride. The contents of these two active ingredients are much higher than those of Longqing capsules prepared according to the current method in the Chinese Pharmacopoeia (containing 9.16 mg / 0.5g and 0.58 mg / 0.5g, respectively), which greatly increases the content of active ingredients in the drug and is of great significance for improving the utilization rate of medicinal materials and enhancing the therapeutic effect of the drug.

[0028] 2. This invention investigated the factors affecting the preparation of the ethanol extract of Longqing Capsules through single-factor experiments and orthogonal experiments. The results showed that the optimal process conditions for the preparation of the ethanol extract were: a material-to-liquid ratio of 1:4; a compound enzyme ratio (ligninase:papain:cellulase) of 1:1.5:2; a compound enzyme dosage of 4‰; and an ultrasonic-assisted enzymatic hydrolysis time of 1 hour. The above preparation process can greatly shorten the process cycle of Longqing Capsules, which is of great significance for improving the production efficiency of enterprises. Attached Figure Description

[0029] Figure 1 The HPLC chromatogram of berberine hydrochloride reference solution;

[0030] Figure 2 The HPLC chromatogram of the berberine hydrochloride reference solution is shown below.

[0031] Figure 3 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different solid-liquid ratios;

[0032] Figure 4 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different solid-liquid ratios;

[0033] Figure 5 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different ratios of compound enzymes;

[0034] Figure 6 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different ratios of compound enzymes;

[0035] Figure 7 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different amounts of compound enzymes;

[0036] Figure 8 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different amounts of compound enzymes;

[0037] Figure 9 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different ultrasound-assisted enzymatic hydrolysis times;

[0038] Figure 10 Typical chromatograms for the determination of berberine hydrochloride content in test sample solutions under different ultrasound-assisted enzymatic hydrolysis times. Detailed Implementation

[0039] The technical solution of the present invention will be described in detail below with reference to specific embodiments. The following embodiments are for explanation and illustration only, and do not constitute a limitation on the technical solution of the present invention.

[0040] Example 1

[0041] The improved preparation process of Longqing Capsules includes the following steps:

[0042] S1 Pre-processing of medicinal materials:

[0043] Grind Alisma plantago-aquatica into a fine powder, pass it through an 80-mesh sieve, and set aside. Cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 3-5cm long pieces and set aside. Grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into a coarse powder, pass it through a 10-mesh sieve, and set aside.

[0044] Preparation of S2 water extract:

[0045] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and decoct them separately twice with water, one hour each time. For the first decoction, add 8 times the amount of water as the herbs and for the second decoction, add 6 times the amount of water as the herbs. Soak the herbs for 30 minutes before the first decoction. Filter the mixture, combine the filtrates, pass them through a 100-mesh sieve, and concentrate them under reduced pressure at 80°C to obtain a clear extract with a density of 1.25–1.30 at 50°C.

[0046] Preparation of S3 alcohol extract:

[0047] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4 times the weight of the medicinal materials to a 60% ethanol solution and 4‰ of the weight of the medicinal materials to a compound enzyme. Adjust the pH to 5.5, and use ultrasound (600W power, 40kHz frequency) to assist enzymatic hydrolysis for 1 hour. Boil to inactivate the enzyme for 1.5 hours. Filter, combine the filtrates, pass through a 100-mesh sieve, recover the ethanol under reduced pressure at 80℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The compound enzyme consists of ligninase, papain, and cellulase in a mass ratio of 1:1.5:2.

[0048] S4 Formulation:

[0049] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, dried under reduced pressure at 65°C, pulverized into fine powder, and 0.2% magnesium stearate is added. The mixture is then granulated by dry granulation and encapsulated.

[0050] Example 2

[0051] The improved preparation process of Longqing Capsules includes the following steps:

[0052] S1 Pre-processing of medicinal materials:

[0053] Grind Alisma plantago-aquatica into a fine powder, pass it through a 60-mesh sieve, and set aside. Cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 2-5cm long pieces and set aside. Grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into a coarse powder, pass it through a 5-mesh sieve, and set aside.

[0054] Preparation of S2 water extract:

[0055] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and decoct them separately twice with water, one hour each time. For the first decoction, add 8 times the amount of water as the herbs and for the second decoction, add 6 times the amount of water as the herbs. Soak the herbs for 30 minutes before the first decoction. Filter the mixture, combine the filtrates, pass them through a 100-mesh sieve, and concentrate them under reduced pressure at 80°C to obtain a clear extract with a density of 1.25–1.30 at 50°C.

[0056] Preparation of S3 alcohol extract:

[0057] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4 times the weight of the medicinal materials to a 60% ethanol solution and 4‰ of the weight of the medicinal materials to a compound enzyme. Adjust the pH to 5.5, and use ultrasound (600W power, 40kHz frequency) to assist enzymatic hydrolysis for 1 hour. Boil to inactivate the enzyme for 1.5 hours. Filter, combine the filtrates, pass through a 100-mesh sieve, recover the ethanol under reduced pressure at 80℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The compound enzyme consists of ligninase, papain, and cellulase in a mass ratio of 1:1:2.

[0058] S4 Formulation:

[0059] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, dried under reduced pressure at 60°C, pulverized into fine powder, and 0.1% magnesium stearate is added. The mixture is then granulated by dry granulation and encapsulated.

[0060] Example 3

[0061] The improved preparation process of Longqing Capsules includes the following steps:

[0062] S1 Pre-processing of medicinal materials:

[0063] Grind Alisma plantago-aquatica into a fine powder, pass it through a 100-mesh sieve, and set aside. Cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 5-10cm long pieces and set aside. Grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into a coarse powder, pass it through a 15-mesh sieve, and set aside.

[0064] Preparation of S2 water extract:

[0065] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and decoct them separately twice with water, one hour each time. For the first decoction, add 8 times the amount of water as the herbs and for the second decoction, add 6 times the amount of water as the herbs. Soak the herbs for 30 minutes before the first decoction. Filter the mixture, combine the filtrates, pass them through a 100-mesh sieve, and concentrate them under reduced pressure at 80°C to obtain a clear extract with a density of 1.25–1.30 at 50°C.

[0066] Preparation of S3 alcohol extract:

[0067] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4 times the weight of the medicinal materials to a 60% ethanol solution and 4‰ of the weight of the medicinal materials to a compound enzyme. Adjust the pH to 5.5, and use ultrasound (600W power, 40kHz frequency) to assist enzymatic hydrolysis for 1 hour. Boil to inactivate the enzyme for 1.5 hours. Filter, combine the filtrates, pass through a 100-mesh sieve, recover the ethanol under reduced pressure at 80℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The compound enzyme consists of ligninase, papain, and cellulase in a mass ratio of 1:2:2.

[0068] S4 Formulation:

[0069] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, dried under reduced pressure at 70°C, pulverized into fine powder, and 0.3% magnesium stearate is added. The mixture is then granulated by dry granulation and encapsulated.

[0070] Example 4

[0071] The improved preparation process of Longqing Capsules includes the following steps:

[0072] S1 Pre-processing of medicinal materials:

[0073] Grind Alisma plantago-aquatica into a fine powder, pass it through an 80-mesh sieve, and set aside. Cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 3-5cm long pieces and set aside. Grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into a coarse powder, pass it through a 10-mesh sieve, and set aside.

[0074] Preparation of S2 water extract:

[0075] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and add 10 times their weight of water to each herb. Soak for 60 minutes and decoct for 1.5 hours. Filter, combine the filtrates, pass through an 80-mesh sieve, and concentrate under reduced pressure at 70°C to obtain a clear extract with a density of 1.25–1.30 at 50°C.

[0076] Preparation of S3 alcohol extract:

[0077] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4 times the weight of the medicinal materials to a 60% ethanol solution and 4‰ of the weight of the medicinal materials to a compound enzyme. Adjust the pH to 5.5, and use ultrasound (600W power, 40kHz frequency) to assist enzymatic hydrolysis for 1 hour. Boil to inactivate the enzyme for 1.5 hours. Filter, combine the filtrates, pass through a 100-mesh sieve, recover the ethanol under reduced pressure at 80℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The compound enzyme consists of ligninase, papain, and cellulase in a mass ratio of 1:1.5:2.

[0078] S4 Formulation:

[0079] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, dried under reduced pressure at 65°C, pulverized into fine powder, and 0.2% magnesium stearate is added. The mixture is then granulated by dry granulation and encapsulated.

[0080] Example 5

[0081] The improved preparation process of Longqing Capsules includes the following steps:

[0082] S1 Pre-processing of medicinal materials:

[0083] Grind Alisma plantago-aquatica into a fine powder, pass it through an 80-mesh sieve, and set aside. Cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 3-5cm long pieces and set aside. Grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into a coarse powder, pass it through a 10-mesh sieve, and set aside.

[0084] Preparation of S2 water extract:

[0085] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and decoct them three times with five times their weight of water, each time for 0.5 hours. Soak the herbs for 15 minutes before the first decoction. Filter the decoction, combine the filtrates, pass them through a 120-mesh sieve, and concentrate them under reduced pressure at 90°C to obtain a clear extract with a density of 1.25–1.30 at 50°C.

[0086] Preparation of S3 alcohol extract:

[0087] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4 times the weight of the medicinal materials to a 60% ethanol solution and 4‰ of the weight of the medicinal materials to a compound enzyme. Adjust the pH to 5.5, and use ultrasound (600W power, 40kHz frequency) to assist enzymatic hydrolysis for 1 hour. Boil to inactivate the enzyme for 1.5 hours. Filter, combine the filtrates, pass through a 100-mesh sieve, recover the ethanol under reduced pressure at 80℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The compound enzyme consists of ligninase, papain, and cellulase in a mass ratio of 1:1.5:2.

[0088] S4 Formulation:

[0089] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, dried under reduced pressure at 65°C, pulverized into fine powder, and 0.2% magnesium stearate is added. The mixture is then granulated by dry granulation and encapsulated.

[0090] Example 6

[0091] The improved preparation process of Longqing Capsules includes the following steps:

[0092] S1 Pre-processing of medicinal materials:

[0093] Grind Alisma plantago-aquatica into a fine powder, pass it through an 80-mesh sieve, and set aside. Cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 3-5cm long pieces and set aside. Grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into a coarse powder, pass it through a 10-mesh sieve, and set aside.

[0094] Preparation of S2 water extract:

[0095] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and decoct them separately twice with water, one hour each time. For the first decoction, add 8 times the amount of water as the herbs and for the second decoction, add 6 times the amount of water as the herbs. Soak the herbs for 30 minutes before the first decoction. Filter the mixture, combine the filtrates, pass them through a 100-mesh sieve, and concentrate them under reduced pressure at 80°C to obtain a clear extract with a density of 1.25–1.30 at 50°C.

[0096] Preparation of S3 alcohol extract:

[0097] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4 times the weight of the medicinal materials to a 50% ethanol solution and 5‰ of the weight of the medicinal materials to a compound enzyme. Adjust the pH to 4.0, and use ultrasound (600W power, 40kHz frequency) to assist enzymatic hydrolysis for 2 hours. Boil to inactivate the enzyme for 2 hours. Filter, combine the filtrates, pass through an 80-mesh sieve, recover the ethanol under reduced pressure at 70℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The compound enzyme consists of ligninase, papain, and cellulase in a mass ratio of 1:1.5:2.

[0098] S4 Formulation:

[0099] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, dried under reduced pressure at 65°C, pulverized into fine powder, and 0.2% magnesium stearate is added. The mixture is then granulated by dry granulation and encapsulated.

[0100] Example 7

[0101] The improved preparation process of Longqing Capsules includes the following steps:

[0102] S1 Pre-processing of medicinal materials:

[0103] Grind Alisma plantago-aquatica into a fine powder, pass it through an 80-mesh sieve, and set aside. Cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 3-5cm long pieces and set aside. Grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into a coarse powder, pass it through a 10-mesh sieve, and set aside.

[0104] Preparation of S2 water extract:

[0105] Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and decoct them separately twice with water, one hour each time. For the first decoction, add 8 times the amount of water as the herbs and for the second decoction, add 6 times the amount of water as the herbs. Soak the herbs for 30 minutes before the first decoction. Filter the mixture, combine the filtrates, pass them through a 100-mesh sieve, and concentrate them under reduced pressure at 80°C to obtain a clear extract with a density of 1.25–1.30 at 50°C.

[0106] Preparation of S3 alcohol extract:

[0107] Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 6 times the weight of the medicinal materials to a 70% ethanol solution and 2‰ of the weight of the medicinal materials to a compound enzyme. Adjust the pH to 6.0, and use ultrasound (600W power, 40kHz frequency) to assist enzymatic hydrolysis for 0.5h. Boil to inactivate the enzyme for 1h. Filter, combine the filtrates, pass through a 120-mesh sieve, recover the ethanol under reduced pressure at 90℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The compound enzyme consists of ligninase, papain, and cellulase in a mass ratio of 1:1.5:2.

[0108] S4 Formulation:

[0109] The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, dried under reduced pressure at 65°C, pulverized into fine powder, and 0.2% magnesium stearate is added. The mixture is then granulated by dry granulation and encapsulated.

[0110] To further verify the reliability of the present invention and select the optimal solution, the inventors conducted a series of experiments, as follows:

[0111] 1. Instruments and reagents

[0112] The main instruments are listed in Table 1, and the main reagents are listed in Table 2.

[0113] Table 1 Main Instruments

[0114]

[0115] Table 2 Main Reagents

[0116]

[0117]

[0118] 2. Experimental Methods

[0119] 2.1 Preparation of water extract

[0120] 2.1.1 Comparison of single-herb extraction with the preparation method in the Pharmacopoeia

[0121] In the original preparation process of Longqing Capsules, the water extract was prepared as follows: honeysuckle, patrinia, oldenlandia diffusa, and agrimony were decocted twice with water. For the first decoction, 8 times the weight of the medicinal materials were added to water, and the herbs were soaked for 0.5 hours and decocted for 1 hour. For the second decoction, 6 times the weight of the medicinal materials were added to water and decocted for 1 hour. The decoctions were combined, filtered, and the filtrate was concentrated to a clear extract with a relative density of 1.25 to 1.30 (50°C).

[0122] This study compared the extraction processes of the medicinal materials in the water-extracted portion of Longqing Capsules using two methods. The water-extracted medicinal materials were extracted at a 10-fold reduction of the prescribed amount. The extract was then freeze-dried to obtain a dry extract powder. The dry extract powder yield (dry extract powder yield = weight of dry extract powder / amount of raw materials × 100%) was used as the indicator to evaluate the above methods, as detailed below:

[0123] (1) Extraction of single medicinal materials

[0124] Take the herbs Oldenlandia diffusa, Patrinia scabiosifolia, Lonicera japonica, and Agrimonia pilosa, and cut them into 3-5 cm long segments using a cutting machine. Accurately weigh 52.2 g of each of the above four herbs, and add them to round-bottom flasks three times in parallel. For the first time, add 420 mL of drinking water, soak for 0.5 h, decoct for 1 h, and filter. For the second time, add 320 mL of drinking water, decoct for 1 h, and filter. Combine the filtrates, heat to concentrate, and freeze dry to obtain a dry extract powder.

[0125] (2) Extraction shall be carried out in accordance with the extraction process in the Chinese Pharmacopoeia.

[0126] Take the herbs Hedyotis diffusa, Patrinia scabiosifolia, Lonicera japonica, and Agrimonia pilosa, and cut them into 3-5 cm long segments using a cutting machine. Accurately weigh 52.2 g of Hedyotis diffusa, 52.2 g of Patrinia scabiosifolia, 26.1 g of Lonicera japonica, and 26.1 g of Agrimonia pilosa, and put them into a round-bottom flask (prepare 3 portions). First, add 1260 mL of drinking water, soak for 0.5 h, decoct for 1 h, and filter. Second, add 945 mL of drinking water, decoct for 1 h, and filter. Combine the filtrates, heat to concentrate, and freeze dry to obtain a dry extract powder.

[0127] 2.1.2 Results and Analysis

[0128] The water-extracted medicinal materials in Longqing Capsules were extracted according to the methods in "2.1 Investigation on the preparation method of water extract". The extract was freeze-dried to obtain dry extract powder. The yield of dry extract powder under different extraction methods is shown in Table 3.

[0129] Table 3. Yield of dry extract powder and water extract under different extraction methods (n=3)

[0130]

[0131] Note: A is Patrinia scabiosifolia; B is Agrimonia pilosa; C is Lonicera japonica; D is Hedyotis diffusa.

[0132] The results above show that when extracting the dry extract separately using single herbs, the yield of dry extract powder is 17.02%, while when extracting according to the method of the Chinese Pharmacopoeia, the yield of dry extract powder is 17.32%. Considering the long-standing situation that the total amount of Longqing Capsules produced by our company exceeds the requirements of the Pharmacopoeia specification (2), we have chosen the method of extracting the water extract separately using single herbs.

[0133] 2.2 Preparation of alcohol extract

[0134] In the original preparation process of Longqing Capsules, the method for preparing the ethanol extract is as follows: Plantago seed, peony bark, red peony root, coptis root, and phellodendron bark are added to 60% ethanol at a weight of about 3.5 times that of the medicinal materials, and the mixture is heated and refluxed for extraction three times: 3 hours for the first extraction, 2 hours for the second extraction, and 1 hour for the third extraction. The extracts are combined, filtered, and the ethanol is recovered from the filtrate and concentrated to a clear paste with a relative density of 1.25-1.30 (50℃).

[0135] The berberine hydrochloride and berberine hydrochloride contents in the Longqing capsules prepared according to the above method meet the requirements of the Chinese Pharmacopoeia. However, the extraction rate is still low, which leads to a waste of medicinal resources. Furthermore, the preparation process of the above-mentioned alcohol extract is lengthy, greatly reducing the production efficiency of enterprises. Therefore, based on in-depth analysis of the raw medicinal materials, the research team improved the preparation process of the alcohol extract of Longqing capsules and optimized the established extraction process using the contents of berberine hydrochloride and berberine hydrochloride as indicators.

[0136] 2.2.1 Method for determining the content of berberine hydrochloride

[0137] (1) Chromatographic conditions and system suitability test

[0138] The chromatographic column was packed with octadecyl silica gel and silane-bonded silica gel; the mobile phase was acetonitrile-0.05 mol / L potassium dihydrogen phosphate solution (50:50) (with 0.4 g sodium dodecyl sulfate added per 100 mL, and the pH adjusted to 4.0 with phosphoric acid); the detection wavelength was 345 nm. The theoretical plate number, calculated based on the berberine hydrochloride peak, should be no less than 5000.

[0139] (2) Preparation of reference solution

[0140] Accurately weigh an appropriate amount of berberine hydrochloride reference standard, and add methanol to prepare a solution containing 20 μg per 1 mL.

[0141] (3) Preparation of the test solution

[0142] Take the contents of three batches of Longqing capsules with different filling amounts, mix them well, grind them into a fine powder, weigh each batch of Longqing capsules twice, take about 0.1g of each batch, weigh accurately, place them in a stoppered conical flask, accurately add 25mL of a methanol-hydrochloric acid (100:0.2) mixed solution, seal tightly, weigh, sonicate (power 250W, frequency 40kHz) for 30min, cool, weigh again, make up the weight loss with methanol, shake well, filter, and take the filtrate to obtain the product.

[0143] (4) Determination method

[0144] Accurately pipette 10 μL each of the berberine hydrochloride reference solution and the Longqing capsule test solution into the liquid chromatograph and determine the result.

[0145] 2.2.2 Determination method for berberine hydrochloride content

[0146] (1) Chromatographic conditions and system suitability test

[0147] The chromatographic column was packed with octadecylsilane-bonded silica gel; the mobile phase was acetonitrile-0.1% phosphoric acid solution (with 0.2 g sodium dodecyl sulfonate per 100 mL) (36:64); the detection wavelength was 284 nm. The theoretical plate number, calculated based on berberine hydrochloride, should be no less than 5000.

[0148] (2) Preparation of reference solution

[0149] Accurately weigh an appropriate amount of berberine hydrochloride, and add it to the mobile phase to prepare a solution containing 20 μg per 1 mL.

[0150] (3) Preparation of the test solution

[0151] Take the contents of three batches of Longqing capsules with different filling amounts, mix them well, grind them into a fine powder, weigh each batch of Longqing capsules twice, take about 0.1g of each batch, weigh accurately, place them in a stoppered conical flask, accurately add 25mL of mobile phase, seal tightly, weigh, sonicate (power 250W, frequency 40kHz) for 30min, cool, weigh again, make up the weight loss with mobile phase, shake well, centrifuge, and take the supernatant to obtain the product.

[0152] (4) Determination method

[0153] Accurately pipette 10 μL each of the berberine hydrochloride reference solution and the Longqing capsule test solution, inject them into the high-performance liquid chromatograph, and determine the result.

[0154] 2.2.3 Investigation of extraction methods for alcohol extracts

[0155] After in-depth analysis of the prescription medicinal materials, the research team plans to use an ultrasound-assisted enzymatic hydrolysis method to prepare the alcohol extract. The specific plan is as follows:

[0156] The five medicinal herbs, namely, peony bark, plantain seed, red peony root, coptis root, and phellodendron bark, were pulverized into coarse powder and passed through a 10-mesh sieve. The pulverized coarse powder of the five herbs was weighed according to the prescription, and 4 times the weight of the herbs in a 60% ethanol solution and 3‰ of the herbs' weight in a compound enzyme (composed of ligninase, papain, and cellulase in a mass ratio of 1:1.5:2) were added to each. The pH was adjusted to 5.5, and the mixture was subjected to enzymatic hydrolysis assisted by ultrasound (600W power, 40kHz frequency) for 2 hours, followed by boiling to inactivate the enzyme for 1.5 hours. The mixture was filtered, the filtrates were combined, passed through a 100-mesh sieve, and the ethanol was recovered under reduced pressure at 80℃ and concentrated to a clear extract with a density of 1.25–1.30 at 50℃.

[0157] This study prepared the ethanol extract and Longqing capsules according to the above-mentioned process. Single-factor experiments were conducted to investigate four parameters affecting the extraction efficiency of the ethanol extract: material-to-liquid ratio, compound enzyme ratio, compound enzyme dosage, and enzymatic hydrolysis time. Orthogonal experiments were also designed to determine the optimal preparation process for the ethanol extract. Specifically, the preparation method for Longqing capsules was as follows: Aqueous extracts were prepared using the single-herb extraction method described in section "2.1 Preparation of Aqueous Extracts". The filtrates after decoction were filtered and combined, passed through a 100-mesh sieve, and the ethanol was recovered under reduced pressure at 80℃ and concentrated to a clear extract with a density of 1.25–1.30 at 50℃. The ethanol extract was then prepared using the ultrasound-assisted enzymatic hydrolysis method described above. The clear extract obtained in the above steps was mixed with fine powder of Alisma plantago-aquatica, mixed thoroughly, dried under reduced pressure at 65℃, pulverized into a fine powder, and 0.2% magnesium stearate was added. The mixture was then granulated using a dry granulation method and filled into capsules.

[0158] 2.2.3.1 Study on the feed-liquid ratio

[0159] The alcohol extract and Longqing capsules were prepared according to the method described in section "2.2.3 Investigation of Extraction Methods for Alcohol Extracts". With other conditions kept constant, the alcohol extract and Longqing capsules were prepared at material-to-liquid ratios of 1:4, 1:5, and 1:6, respectively. The contents of berberine hydrochloride and berberine hydrochloride in Longqing capsules were determined according to the methods described in sections "2.2.1 Determination of Berberine Hydrochloride Content" and "2.2.2 Determination of Phellodendron Acid Hydrochloride Content". Triple replicates were performed, and the results are shown in Table 4. The HPLC chromatogram of the berberine hydrochloride reference solution is shown below. Figure 1 As shown, the HPLC chromatogram of the berberine hydrochloride reference solution is as follows. Figure 2 As shown, typical chromatograms for the determination of berberine hydrochloride content in the test sample solution under different material-to-liquid ratios are as follows. Figure 3 As shown, typical chromatograms for the determination of berberine hydrochloride content in the test solution under different material-to-liquid ratios are as follows: Figure 4 As shown.

[0160] Table 4. Results of berberine hydrochloride and phellodendron chinense hydrochloride content determination in Longqing capsules prepared under different material-to-liquid ratios (n=3)

[0161]

[0162]

[0163] The results show that the contents of berberine hydrochloride and phellodendron chinense hydrochloride in the prepared Longqing capsules increased slightly with the increase of the extraction solvent. The contents of berberine hydrochloride and phellodendron chinense hydrochloride in the Longqing capsules at solid-liquid ratios of 1:4 and 1:5 were not significantly different. Considering all factors, a solid-liquid ratio of 1:4 was selected for further research.

[0164] 2.2.3.2 Investigation of the ratio of complex enzymes

[0165] The alcohol extract and Longqing capsules were prepared according to the method described in section 2.2.3, with a solid-liquid ratio of 1:4. Other conditions were kept constant. Different proportions of compound enzymes were used for the extraction of the alcohol extract and the preparation of Longqing capsules. The contents of berberine hydrochloride and berberine hydrochloride in Longqing capsules were determined according to the methods described in sections 2.2.1 and 2.2.2. The results were obtained in triplicate and are shown in Table 5. Typical chromatograms of berberine hydrochloride content determination in the test solution under different compound enzyme ratios are shown below. Figure 5 As shown, the results of the determination of berberine hydrochloride content in the test sample solution under different compound enzyme ratios are as follows: Figure 6 As shown.

[0166] Table 5. Results of berberine hydrochloride and phellodendron chinense hydrochloride content determination in Longqing capsules prepared with different compound enzyme ratios (n=3)

[0167]

[0168]

[0169] The results showed that the highest content of berberine hydrochloride and phellodendron chinense hydrochloride was found in the prepared Longqing capsules when the mass ratio of ligninase:papain:cellulase was 1:1.5:2. Therefore, a ratio of 1:1.5:2 for the compound enzyme (ligninase:papain:cellulase) was selected for subsequent research.

[0170] 2.2.3.3 Investigation into the dosage of compound enzyme

[0171] The alcohol extract and Longqing capsules were prepared according to the method described in section 2.2.3, "Explanation of Extraction Methods for Alcohol Extracts". The material-to-liquid ratio was 1:4, and the ratio of the compound enzyme (ligninase:papain:cellulase) was 1:1.5:2. With other conditions fixed, the alcohol extract and Longqing capsules were prepared at compound enzyme dosages of 3‰, 4‰, and 5‰, respectively. The contents of berberine hydrochloride and berberine hydrochloride in Longqing capsules were determined according to the methods described in sections 2.2.1 and 2.2.2, "Determination of Berberine Hydrochloride Content". Triple replicates were performed, and the results are shown in Table 6. Typical chromatograms of berberine hydrochloride content determination in the test solution under different compound enzyme dosages are shown below. Figure 7 As shown, the results of the determination of berberine hydrochloride content in the test sample solution under different amounts of compound enzyme are as follows: Figure 8 As shown.

[0172] Table 6. Results of berberine hydrochloride and phellodendron chinense hydrochloride content determination in Longqing capsules prepared with different amounts of compound enzymes (n=3)

[0173]

[0174] The results showed that the highest contents of berberine hydrochloride and phellodendron chinense hydrochloride were obtained in the prepared Longqing capsules when the dosage of the compound enzyme was 4‰. Therefore, a dosage of 4‰ of the compound enzyme was selected for subsequent research.

[0175] 2.2.3.4 Investigation of Ultrasound-Assisted Enzymatic Hydrolysis Time

[0176] The alcohol extract and Longqing capsules were prepared according to the method described in section 2.2.3, "Explanation of Extraction Methods for Alcohol Extracts". The material-to-liquid ratio was 1:4, the ratio of compound enzymes was 1:1.5:2, and the dosage of compound enzymes was 4‰. Other conditions were kept constant. The alcohol extract and Longqing capsules were prepared at ultrasound-assisted enzymatic hydrolysis times of 0.5 h, 1 h, and 2 h, respectively. The contents of berberine hydrochloride and berberine hydrochloride in Longqing capsules were determined according to the methods described in sections 2.2.1 and 2.2.2, "Determination of Berberine Hydrochloride Content". Triple replicates were performed, and the results are shown in Table 7. Typical chromatograms of berberine hydrochloride content in the test solution under different ultrasound-assisted enzymatic hydrolysis times are shown below. Figure 9 As shown, typical chromatograms for the determination of berberine hydrochloride content in the test sample solution under different ultrasound-assisted enzymatic hydrolysis times are as follows. Figure 10 As shown.

[0177] Table 7. Determination of berberine hydrochloride and phellodendron chinense hydrochloride content in Longqing capsules prepared under different ultrasound-enzymatic hydrolysis times (n=3)

[0178]

[0179] The results showed that the highest contents of berberine hydrochloride and phellodendron chinense hydrochloride were obtained in the prepared Longqing capsules when the ultrasound-assisted enzymatic hydrolysis time was 1 hour. Taking all factors into consideration, an ultrasound-assisted enzymatic hydrolysis time of 1 hour was selected.

[0180] 2.2.3.5 Orthogonal experimental design for the effect of different process parameters on the content of effective ingredients in Longqing capsules

[0181] Using the material-to-liquid ratio (A), the proportion of compound enzyme (B), the dosage of compound enzyme (C), and the ultrasonic enzymatic hydrolysis time (D) as the factors under investigation, an orthogonal experiment was conducted with three levels for each factor to compare the influence of different alcohol extract preparation parameters on the content of effective components in Longqing capsules, in order to verify the optimal process conditions for single-factor investigation. The factor level table is shown in Table 8, and the experimental results and range analysis are shown in Tables 9-11.

[0182] Table 8. Factor Levels of Orthogonal Experimental Design for the Preparation Conditions of Alcohol Extracts

[0183]

[0184] Table 9 Results of the orthogonal experiment for the preparation conditions of the alcohol extract.

[0185]

[0186]

[0187] Table 10. Range analysis of berberine hydrochloride content in Longqing capsules.

[0188]

[0189] Table 11 Range analysis of berberine hydrochloride content in Longqing capsules

[0190]

[0191] The orthogonal experiment results showed that the order of influence of the four factors on the content of effective components in the ethanol extract of Longqing capsules was: ultrasonic enzymatic hydrolysis time > compound enzyme dosage > compound enzyme ratio > solid-liquid ratio. The optimal extraction process screened by the orthogonal experiment was: solid-liquid ratio of 1:4, compound enzyme ratio of 1:1.5:2, compound enzyme dosage of 4‰, and ultrasonic enzymatic hydrolysis time of 1 hour. The above optimal process conditions are consistent with the results of the single-factor investigation experiment. 2.2.3.5 Comparison between the ultrasonic-assisted enzymatic hydrolysis method for preparing ethanol extract and the method in the Chinese Pharmacopoeia

[0192] Through the above single-factor experiments and orthogonal experiments, the optimal preparation process of the ethanol extract of Longqing capsules was determined to be: a material-to-liquid ratio of 1:4; a compound enzyme ratio (ligninase:papain:cellulase) of 1:1.5:2; a compound enzyme dosage of 4‰; and an ultrasound-assisted enzymatic hydrolysis time of 1 hour. The research team used the above optimal process conditions and the preparation method in the Chinese Pharmacopoeia to prepare the ethanol extract. The medicinal materials were extracted by reducing the prescription amount by 10 times. The extract was freeze-dried to obtain a dry extract powder. The yield of the dry extract powder (yield of dry extract powder = weight of dry extract powder / amount of raw materials × 100%) was used as the indicator to evaluate the above methods. The results are shown in Table 12.

[0193] Table 12 Yield of dry extract powder and alcohol extract under different extraction methods (n=3)

[0194]

[0195] Note: A is Coptis chinensis; B is Phellodendron chinense; C is Paeonia lactiflora; D is Paeonia suffruticosa; E is Plantago asiatica.

[0196] The research team prepared Longqing capsules using the optimal process conditions of this study and the preparation method in the Chinese Pharmacopoeia, and determined the contents of berberine hydrochloride and berberine hydrochloride in the capsules. The results were obtained in triplicate and are shown in Table 13.

[0197] Table 13 Comparison of active ingredient content in Longqing capsules prepared by different processing methods (n=3)

[0198]

[0199]

[0200] In summary, the yield of dry extract was 23.41% when prepared using the optimal process conditions of this study, compared to 20.51% when prepared using the method in the Chinese Pharmacopoeia. The yield of dry extract prepared using the optimal process conditions of this study is slightly higher than that prepared using the method in the Chinese Pharmacopoeia. A comparison of the content determination results of berberine hydrochloride and phellodendron chinense hydrochloride in Longqing capsules prepared using the two methods shows that the content of these two active ingredients in Longqing capsules prepared using the optimal process conditions of this study is higher than that prepared using the method in the Chinese Pharmacopoeia. This indicates that the Longqing capsule preparation method provided in this study can increase the content of active ingredients in the drug, which helps to improve the utilization rate of medicinal materials and is of great significance for improving the therapeutic effect of the drug. At the same time, the Longqing capsule preparation method provided in this study significantly shortens the process cycle, which helps to improve the production efficiency of enterprises and has great potential for widespread application.

[0201] Although the present invention has been described in detail above with general descriptions, specific embodiments, and experiments, modifications or improvements can be made to it, which will be obvious to those skilled in the art. Therefore, all such modifications or improvements made without departing from the spirit of the present invention fall within the scope of protection claimed by the present invention.

Claims

1. An improved preparation process for Longqing capsules, characterized in that, Includes the following steps: S1 Pre-processing of medicinal materials: Grind Alisma plantago-aquatica into fine powder and pass it through a 60-100 mesh sieve for later use; cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into 2-10 cm long pieces for later use; grind Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense into coarse powder and pass it through a 5-15 mesh sieve for later use. Preparation of S2 water extract: Take long sections of the four herbs—Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa—and add 5 to 10 times the amount of water to each herb. Decoction them separately 1 to 3 times, each time for 0.5 to 1.5 hours. Soak the herbs for 15 to 60 minutes before the first decoction. Filter the mixture, combine the filtrates, pass them through an 80 to 120 mesh sieve, and concentrate them under reduced pressure at 70 to 90°C to obtain a clear extract with a density of 1.25 to 1.30 at 50°C. Preparation of S3 alcohol extract: Take the coarse powder of five medicinal materials: peony bark, plantain seed, red peony root, coptis root, and phellodendron bark. Add 4-6 times the weight of the medicinal materials to a 50%-70% ethanol solution and 3‰-5‰ of the medicinal materials to a compound enzyme. Adjust the pH to 4-6, perform ultrasonic-assisted enzymatic hydrolysis for 0.5-2 hours, and boil to inactivate the enzyme for 1-2 hours. Filter, combine the filtrates, pass through an 80-120 mesh sieve, recover the ethanol under reduced pressure at 70-90℃, and concentrate to a clear extract with a density of 1.25-1.30 at 50℃. The complex enzyme is composed of ligninase, papain and cellulase in a mass ratio of 1:1 to 2:

2. S4 Formulation: The clear paste obtained in steps S2 and S3 is mixed with fine powder of Alisma plantago-aquatica, mixed well, dried under reduced pressure at 60-70°C, pulverized into fine powder, and 0.1%-0.3% magnesium stearate is added. The mixture is then granulated by dry method and filled into capsules.

2. The preparation process according to claim 1, characterized in that, In step S1, the pre-processing of medicinal materials: Alisma plantago-aquatica is pulverized and passed through an 80-100 mesh sieve; Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into 2-6 cm long segments; Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense are pulverized and passed through a 10-15 mesh sieve.

3. The preparation process according to claim 2, characterized in that, In step S1, the pre-processing of medicinal materials: Alisma plantago-aquatica is pulverized and passed through an 80-mesh sieve; Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into 3-5cm long segments; Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron chinense are pulverized and passed through a 10-mesh sieve.

4. The preparation process according to claim 1, characterized in that, The preparation of the water extract in step S2 is as follows: Take long sections of the four medicinal materials, namely Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, and add 6 to 8 times the amount of water to each of the medicinal materials. Decoction is carried out 2 to 3 times, each time for 1 to 1.5 hours. Before the first decoction, the herbs are soaked for 15 to 45 minutes. The filtrates are filtered, combined, and passed through a 100 to 120 mesh sieve. The filtrates are concentrated under reduced pressure at 75 to 85°C to a clear extract with a density of 1.25 to 1.30 at 50°C.

5. The preparation process according to claim 4, characterized in that, The preparation of the water extract in step S2 is as follows: Take long sections of the four medicinal materials, namely Patrinia scabiosifolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, and decoct them separately twice with water, each time for 1 hour. For the first decoction, add 8 times the amount of water as the medicinal materials and for the second decoction, add 6 times the amount of water as the medicinal materials. Soak for 30 minutes before the first decoction. Filter, combine the filtrates, pass through a 100-mesh sieve, and concentrate under reduced pressure at 80°C to a clear extract with a density of 1.25-1.30 at 50°C.

6. The preparation method according to claim 1, characterized in that, The preparation of the ethanol extract in step S3 is as follows: Take the coarse powder of five medicinal materials, namely, peony bark, plantain seed, red peony root, coptis root, and phellodendron bark, and add 4-5 times the weight of the medicinal materials in 55%-65% ethanol solution and 4‰-5‰ of the weight of the medicinal materials in compound enzyme solution; adjust the pH to 5-6, perform ultrasonic-assisted enzymatic hydrolysis for 1-2 hours, and boil to inactivate the enzyme for 1-1.5 hours; filter, combine the filtrates, pass through a 100-120 mesh sieve, recover the ethanol under reduced pressure at 75-85℃ and concentrate to a clear extract with a density of 1.25-1.30 at 50℃; wherein, the compound enzyme is composed of ligninase, papain and cellulase in a mass ratio of 1:1.5-2:

2.

7. The preparation method according to claim 6, characterized in that, The preparation of the ethanol extract in step S3 is as follows: Take the coarse powder of five medicinal materials, namely, peony bark, plantain seed, red peony root, coptis root, and phellodendron bark, and add 4 times the weight of the medicinal materials in 60% ethanol solution and 4‰ of the weight of the medicinal materials in compound enzyme. Adjust the pH to 5.5, perform ultrasonic-assisted enzymatic hydrolysis for 1 hour, and boil to inactivate the enzyme for 1.5 hours. Filter, combine the filtrates, pass through a 100-mesh sieve, recover the ethanol under reduced pressure at 80°C, and concentrate to a clear extract with a density of 1.25-1.30 at 50°C. The compound enzyme is composed of ligninase, papain, and cellulase in a mass ratio of 1:1.5:

2.

8. The preparation method according to any one of claims 1, 6, or 7, characterized in that, In step S3, the ultrasonic power in the preparation of the alcohol extract is 600W and the frequency is 40kHz.

9. The preparation method according to claim 1, characterized in that, In step S4, formulation forming: the temperature for vacuum drying is 60-65°C; the amount of magnesium stearate added is 0.2%-0.3%.

10. The preparation method according to claim 9, characterized in that, In step S4, formulation forming: the vacuum drying temperature is 65°C; the amount of magnesium stearate added is 0.2%.

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