Improved Longqing capsule preparation process

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to an improved Longqing capsule preparation process. The preparation process comprises the following steps: pretreatment of medicinal materials; preparing a water extract; preparing an alcohol extract; and forming the preparation. The preparation method of Longqing capsules is improved and optimized in combination with a modern preparation process, the content of berberine hydrochloride and phellodendrine hydrochloride in the Longqing capsules prepared by the preparation process is far higher than that of berberine hydrochloride and phellodendrine hydrochloride in the existing preparation method, the extraction rate of effective components in medicinal materials is greatly increased, meanwhile, the medicine production cycle is shortened, and the production cost is reduced. The medicine effectiveness and the enterprise production efficiency can be improved, and the method has great popularization and application values.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations, and particularly relates to an improved preparation process for Longqing Capsules. Background Art

[0002] Longqing Capsules are one of the main products of Guizhou Yuancheng Pharmaceutical Co., Ltd., and are varieties included in the Class A of the National Medical Insurance and the National Essential Medicines List. They are commonly used clinical medicines for treating heat strangury (frequent urination, urgency of urination, dysuria, short urination, low back pain, and abdominal distension) caused by damp-heat in the lower energizer, and have good therapeutic effects. They have been included in the first part of the Chinese Pharmacopoeia (2020 Edition).

[0003] The prescription of Longqing Capsules is as follows: Alisma orientale 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, Phellodendron amurense 261g. The existing preparation method is as follows: Alisma orientale is pulverized into fine powder; Lonicera japonica, Patrinia scabiosaefolia, Hedyotis diffusa, and Agrimonia pilosa are decocted with water and then concentrated into clear paste; the remaining five flavors such as Plantago asiatica are reflux-extracted with ethanol solution and then concentrated into clear paste; the above-mentioned clear pastes are combined, Alisma orientale fine powder and medicinal excipients are added, and after mixing evenly, granulation is carried out; finally, after drying and sizing, it is filled into capsules. Among them, decoction extraction and reflux extraction are traditional extraction methods for active ingredients in the preparation process of traditional Chinese medicine preparations. Although the various indexes of Longqing Capsules prepared by the above method meet the standard requirements, there are still the following problems: (1) The extraction rate of active ingredients in the medicinal materials is not high, resulting in waste of medicinal materials resources; (2) The production process flow cycle is relatively long and the production efficiency is low.

[0004] To solve the above problems, the present invention uses new technologies and new methods in modern preparation processes to improve and optimize the preparation process of Longqing Capsules, and provides an improved preparation process for Longqing Capsules, aiming to achieve the purposes of improving the extraction rate of active ingredients in medicinal materials, enhancing the effectiveness of drugs, and improving the production efficiency of enterprises. Summary of the Invention

[0005] The purpose of the present invention is to provide an improved preparation process for Longqing Capsules.

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

[0007] The improved preparation process for Longqing Capsules of the present invention includes the following steps:

[0008] S1 Pretreatment of Medicinal Materials:

[0009] Crush Alisma orientale into fine powder, sieve it through a 60-100 mesh sieve, and set aside; cut the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into sections 2-10 cm long, and set aside; crush the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri into coarse powder, sieve it through a 5-15 mesh sieve, and set aside.

[0010] Preparation of aqueous extract in S2:

[0011] Take the long sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa after cutting, add 5-10 times the mass of the medicinal materials of water to each, decoct for 1-3 times respectively, each time for 0.5-1.5 h, and soak for 15-60 min before the first decoction; filter, combine the filtrates, sieve through an 80-120 mesh sieve, and concentrate under reduced pressure at 70-90 °C to a clear paste with a density of 1.25-1.30 at 50 °C.

[0012] Preparation of ethanol extract in S3:

[0013] Take the coarse powder of the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri after crushing, add 4-6 times the mass of the medicinal materials of 50%-70% ethanol solution and 3‰-5‰ of the mass of the medicinal materials of compound enzyme to each; adjust the pH to 4-6 respectively, carry out ultrasonic-assisted enzymatic hydrolysis for 0.5-2 h, and boil to inactivate the enzyme for 1-2 h; filter, combine the filtrates, sieve through an 80-120 mesh sieve, and recover ethanol under reduced pressure at 70-90 °C and concentrate to a clear paste with a density of 1.25-1.30 at 50 °C.

[0014] Among them, the compound enzyme is composed of ligninase, papain and cellulase with a mass ratio of 1:1-2:2.

[0015] Forming of the preparation in S4:

[0016] Mix the clear paste prepared in step S2 and step S3, add the fine powder of Alisma orientale, mix evenly, dry under reduced pressure at 60-70 °C, crush into fine powder, add 0.1%-0.3% of magnesium stearate, granulate by dry granulation method, and fill into capsules.

[0017] Preferably, in the preparation process of the present invention, in the pretreatment of medicinal materials in step S1: the crushed Alisma orientale is sieved through an 80-100 mesh sieve; the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into sections 2-6 cm long; the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri are sieved through a 10-15 mesh sieve after crushing.

[0018] More preferably, in the preparation process of the present invention, in the pretreatment of medicinal materials in step S1: the crushed Alisma orientale is sieved through an 80 mesh sieve; the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into sections 3-5 cm long; the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri are sieved through a 10 mesh sieve after crushing.

[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 sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa after truncation, add 6 - 8 times the mass of the medicinal materials of water to each, decoct 2 - 3 times respectively, each time for 1 - 1.5 h, and soak for 15 - 45 min before the first decoction; filter, combine the filtrates, pass through a 100 - 120 - mesh sieve, and concentrate under reduced pressure at 75 - 85 °C to a clear paste with a density of 1.25 - 1.30 at 50 °C.

[0020] More 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 sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa after truncation, decoct with water 2 times respectively, each time for 1 h, add 8 times the mass of the medicinal materials of water for the first time, add 6 times the mass of the medicinal materials of water for the second time, and soak for 30 min 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 paste with a density of 1.25 - 1.30 at 50 °C.

[0021] Preferably, in the preparation process of the present invention, the preparation of the alcohol extract in step S3 is specifically as follows: Take the coarse powder of the five medicinal materials of Cortex Moutan, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense after pulverization, add 4 - 5 times the mass of the medicinal materials of 55% - 65% ethanol solution and 4‰ - 5‰ of the mass of the medicinal materials of complex enzyme to each; adjust the pH to 5 - 6 respectively, carry out ultrasonic - assisted enzymatic hydrolysis for 1 - 2 h, and boil to inactivate the enzyme for 1 - 1.5 h; filter, combine the filtrates, pass through a 100 - 120 - mesh sieve, recover ethanol under reduced pressure at 75 - 85 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; wherein, the complex enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1.5 - 2:2.

[0022] More preferably, in the preparation process of the present invention, the preparation of the alcohol extract in step S3 is specifically as follows: Take the coarse powder of the five medicinal materials of Cortex Moutan, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense after pulverization, add 4 times the mass of the medicinal materials of 60% ethanol solution and 4‰ of the mass of the medicinal materials of complex enzyme to each; adjust the pH to 5.5 respectively, carry out ultrasonic - assisted enzymatic hydrolysis for 1 h, and boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, pass through a 100 - mesh sieve, recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; wherein, the complex enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1.5:2.

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

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

[0025] Further preferably, in the preparation process of the present invention, in step S4 of preparation and forming of the preparation: the temperature of reduced pressure drying is 65°C; the addition amount of magnesium stearate is 0.2%.

[0026] Advantages of the present invention:

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

[0028] 2. By carrying out single-factor investigation experiments and orthogonal experiments, the present invention investigates the factors affecting the preparation of the ethanol extract of Longqing capsules. The results show that the optimal process conditions for the preparation of the ethanol extract are: the material-liquid ratio is 1:4; the ratio of the composite enzyme (ligninase: papain: cellulase) is 1:1.5:2; the dosage of the composite enzyme is 4‰; the ultrasonic-assisted enzymatic hydrolysis time is 1 h. 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. Description of the drawings

[0029] Figure 1 It is the HPLC chromatogram of the berberine hydrochloride reference solution;

[0030] Figure 2 It is the HPLC chromatogram of the phellodendrine hydrochloride reference solution;

[0031] Figure 3 It is the typical chromatogram for the determination of the content of berberine hydrochloride in the test solution under different material-liquid ratios;

[0032] Figure 4 It is the typical chromatogram for the determination of the content of phellodendrine hydrochloride in the test solution under different material-liquid ratios;

[0033] Figure 5 It is the typical chromatogram for the determination of the content of berberine hydrochloride in the test solution under different ratios of the composite enzyme;

[0034] Figure 6 It is the typical chromatogram for the determination of the content of phellodendrine hydrochloride in the test solution under different ratios of the composite enzyme;

[0035] Figure 7 It is the typical chromatogram for the determination of the content of berberine hydrochloride in the test solution under different dosages of the composite enzyme;

[0036] Figure 8 Typical chromatograms for the determination of the content of berberine hydrochloride in the test solution at different compound enzyme dosages;

[0037] Figure 9 Typical chromatograms for the determination of the content of berberine hydrochloride in the test solution at different ultrasonic-assisted enzymolysis times;

[0038] Figure 10 Typical chromatograms for the determination of the content of berberine hydrochloride in the test solution at different ultrasonic-assisted enzymolysis times. Detailed implementation manners

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

[0040] Example 1

[0041] The improved preparation process of Longqing capsules is as follows:

[0042] S1 Pretreatment of medicinal materials:

[0043] Alisma orientale is pulverized into fine powder and sieved through a 80-mesh sieve for standby; Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into sections 3 - 5 cm long for standby; Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri are pulverized into coarse powder and sieved through a 10-mesh sieve for standby.

[0044] S2 Preparation of water extract:

[0045] Take the cut sections of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, and decoct them with water twice, each time for 1 h. Add 8 times the mass of the medicinal materials of water for the first time and 6 times the mass of the medicinal materials of water for the second time. Soak for 30 min before the first decoction; filter, combine the filtrates, and sieve through a 100-mesh sieve. Concentrate under reduced pressure at 80 °C to a clear paste with a density of 1.25 - 1.30 at 50 °C.

[0046] S3 Preparation of alcohol extract:

[0047] Take the coarse powder of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri, and add 4 times the mass of the medicinal materials of 60% ethanol solution and 4‰ of compound enzyme based on the mass of the medicinal materials; adjust the pH to 5.5 respectively, and carry out ultrasonic-assisted enzymolysis (power is 600 W, frequency is 40 kHz) for 1 h, and boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, and sieve through a 100-mesh sieve. Recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; among them, the compound enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1.5:2.

[0048] S4 Forming of the preparation:

[0049] Mix the clear extract prepared from step S2 and step S3, add the fine powder of Alisma orientale, mix well, dry under reduced pressure at 65°C, pulverize into fine powder, add 0.2% magnesium stearate, granulate by dry granulation method, and fill into capsules, then it is ready.

[0050] Example 2

[0051] The improved preparation process of Longqing Capsules is as follows:

[0052] S1 Pretreatment of medicinal materials:

[0053] Pulverize Alisma orientale into fine powder, sieve through a 60-mesh sieve, and reserve; cut the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into sections 2 - 5 cm long, and reserve; pulverize the five medicinal materials of Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense into coarse powder, sieve through a 5-mesh sieve, and reserve.

[0054] S2 Preparation of aqueous extract:

[0055] Take the cut sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, decoct with water 2 times respectively, each time for 1 h. Add 8 times the mass of water for the first time and 6 times the mass of water for the second time. Soak for 30 min before the first decoction; filter, combine the filtrates, sieve 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.

[0056] S3 Preparation of ethanol extract:

[0057] Take the coarse powder of the five medicinal materials of Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense, add 4 times the mass of 60% ethanol solution of the medicinal materials and 4‰ of the mass of the medicinal materials of compound enzyme; adjust the pH to 5.5 respectively, assist enzymatic hydrolysis by ultrasonic wave (power 600 W, frequency 40 kHz) for 1 h, boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, sieve through a 100-mesh sieve, recover ethanol under reduced pressure at 80°C and concentrate to a clear extract with a density of 1.25 - 1.30 at 50°C; among them, the compound enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1:2.

[0058] S4 Forming of preparation:

[0059] Mix the clear extract prepared from step S2 and step S3, add the fine powder of Alisma orientale, mix well, dry under reduced pressure at 60°C, pulverize into fine powder, add 0.1% magnesium stearate, granulate by dry granulation method, and fill into capsules, then it is ready.

[0060] Example 3

[0061] The improved preparation process of Longqing Capsules is as follows:

[0062] S1 Pretreatment of medicinal materials:

[0063] Crush Alisma orientale into fine powder, sieve it through a 100-mesh sieve, and set aside; cut the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into sections 5 - 10 cm long, and set aside; crush the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri into coarse powder, sieve it through a 15-mesh sieve, and set aside.

[0064] Preparation of water extract in S2:

[0065] Take the cut sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, decoct them with water twice respectively, each time for 1 h. Add 8 times the mass of the medicinal materials of water for the first time and 6 times the mass of the medicinal materials of water for the second time. Soak them for 30 min before the first decoction; filter, combine the filtrates, sieve them through a 100-mesh sieve, and concentrate them under reduced pressure at 80 °C to a clear paste with a density of 1.25 - 1.30 at 50 °C.

[0066] Preparation of ethanol extract in S3:

[0067] Take the coarse powder of the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri after crushing, add 60% ethanol solution 4 times the mass of the medicinal materials and 4‰ of the compound enzyme based on the mass of the medicinal materials; adjust the pH to 5.5 respectively, assist enzymatic hydrolysis by ultrasonic wave (power 600 W, frequency 40 kHz) for 1 h, and boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, sieve them through a 100-mesh sieve, recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; among them, the compound enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:2:2.

[0068] S4 Preparation of the formulation:

[0069] Mix the clear paste prepared in step S2 and step S3, add the fine powder of Alisma orientale, mix evenly, dry under reduced pressure at 70 °C, crush it into fine powder, add 0.3% magnesium stearate, granulate by dry granulation method, and fill into capsules.

[0070] Example 4

[0071] Improved preparation process of Longqing Capsules, the steps are as follows:

[0072] S1 Pretreatment of medicinal materials:

[0073] Crush Alisma orientale into fine powder, sieve it through an 80-mesh sieve, and set aside; cut the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into sections 3 - 5 cm long, and set aside; crush the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri into coarse powder, sieve it through a 10-mesh sieve, and set aside.

[0074] S2 Preparation of water extract:

[0075] Take the long sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa after truncation, add water 10 times the mass of the medicinal materials respectively, soak for 60 min, and decoct for 1.5 h; filter, combine the filtrates, pass through an 80-mesh sieve, and concentrate under reduced pressure at 70 °C to a clear paste with a density of 1.25 - 1.30 at 50 °C.

[0076] Preparation of the ethanol extract in S3:

[0077] Take the coarse powder of the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri after pulverization, add 60% ethanol solution 4 times the mass of the medicinal materials and 4‰ compound enzyme of the mass of the medicinal materials respectively; adjust the pH to 5.5 respectively, assist enzymatic hydrolysis for 1 h by ultrasonic wave (power is 600 W, frequency is 40 kHz), and boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, pass through a 100-mesh sieve, recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; among them, the compound enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1.5:2.

[0078] S4 Forming of the preparation:

[0079] Mix the clear paste prepared in step S2 and step S3, add the fine powder of Alisma orientale, mix evenly, dry under reduced pressure at 65 °C, pulverize into fine powder, add 0.2% magnesium stearate, granulate by dry granulation method, and fill into capsules.

[0080] Example 5

[0081] Improved preparation process of Longqing capsules, the steps are as follows:

[0082] S1 Pretreatment of medicinal materials:

[0083] Pulverize Alisma orientale into fine powder, pass through an 80-mesh sieve, and set aside; truncate the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into sections 3 - 5 cm long, and set aside; pulverize the five medicinal materials of Cortex Moutan, Plantago asiatica, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri into coarse powder, pass through a 10-mesh sieve, and set aside.

[0084] S2 Preparation of the water extract:

[0085] Take the long sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa after truncation, decoct with water 5 times the mass of the medicinal materials for 3 times, each time for 0.5 h, and soak for 15 min before the first decoction; filter, combine the filtrates, pass through a 120-mesh sieve, and concentrate under reduced pressure at 90 °C to a clear paste with a density of 1.25 - 1.30 at 50 °C.

[0086] S3 Preparation of the ethanol extract:

[0087] Take the coarsely powdered Cortex Moutan, Plantaginis Semen, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri, and add 4 times the mass of the medicinal materials of 60% ethanol solution and 4‰ of the mass of the medicinal materials of complex enzyme to each; adjust the pH to 5.5 respectively, and carry out enzymatic hydrolysis for 1 h with ultrasonic assistance (power 600 W, frequency 40 kHz), and boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, pass through a 100-mesh sieve, recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; among them, the complex enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1.5:2.

[0088] S4 Preparation of the preparation:

[0089] Mix the clear paste obtained in Step S2 and Step S3, add the fine powder of Alisma orientale, mix evenly, carry out drying under reduced pressure at 65 °C, crush into fine powder, add 0.2% magnesium stearate, granulate by dry granulation method, and fill into capsules to obtain the product.

[0090] Example 6

[0091] An improved preparation process of Longqing Capsules is as follows:

[0092] S1 Pretreatment of medicinal materials:

[0093] Crush Alisma orientale into fine powder, pass through an 80-mesh sieve, and set aside; cut the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into sections 3 - 5 cm long, and set aside; crush the five medicinal materials of Cortex Moutan, Plantaginis Semen, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri into coarsely powdered, pass through a 10-mesh sieve, and set aside.

[0094] S2 Preparation of water extract:

[0095] Take the long sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa after truncation, decoct with water 2 times respectively, each time for 1 h, add 8 times the mass of the medicinal materials of water for the first time, and add 6 times the mass of the medicinal materials of water for the second time, soak for 30 min 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 paste with a density of 1.25 - 1.30 at 50 °C.

[0096] S3 Preparation of ethanol extract:

[0097] Take the coarsely powdered Cortex Moutan, Plantaginis Semen, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri, and add 4 times the mass of the medicinal materials of 50% ethanol solution and 5‰ of the mass of the medicinal materials of complex enzyme to each; adjust the pH to 4.0 respectively, and carry out enzymatic hydrolysis for 2 h with ultrasonic assistance (power 600 W, frequency 40 kHz), and boil to inactivate the enzyme for 2 h; filter, combine the filtrates, pass through an 80-mesh sieve, recover ethanol under reduced pressure at 70 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; among them, the complex enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1.5:2.

[0098] Forming of S4 preparation:

[0099] Mix the clear extract obtained from Step S2 and Step S3, add the fine powder of Alisma orientale, mix evenly, dry under reduced pressure at 65°C, crush into fine powder, add 0.2% magnesium stearate, granulate by dry granulation method, and fill into capsules.

[0100] Example 7

[0101] Improved preparation process of Longqing capsules, the steps are as follows:

[0102] S1 Pretreatment of medicinal materials:

[0103] Crush Alisma orientale into fine powder, sieve through 80-mesh sieve, and reserve; cut the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into sections 3 - 5 cm long, and reserve; crush the five medicinal materials of Moutan cortex, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense into coarse powder, sieve through 10-mesh sieve, and reserve.

[0104] S2 Preparation of water extract:

[0105] Take the long sections of the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa after cutting, decoct with water 2 times respectively, each time for 1 h, add 8 times the mass of the medicinal materials of water for the first time, add 6 times the mass of the medicinal materials of water for the second time, and soak for 30 min before the first decoction; filter, combine the filtrates, sieve through 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.

[0106] S3 Preparation of alcohol extract:

[0107] Take the coarse powder of the five medicinal materials of Moutan cortex, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense after crushing, add 6 times the mass of the medicinal materials of 70% ethanol solution and 2‰ of the mass of the medicinal materials of complex enzyme to each; adjust the pH to 6.0 respectively, assist enzymatic hydrolysis by ultrasonic wave (power is 600 W, frequency is 40 kHz) for 0.5 h, boil to inactivate the enzyme for 1 h; filter, combine the filtrates, sieve through 120-mesh sieve, recover ethanol under reduced pressure at 90°C and concentrate to a clear extract with a density of 1.25 - 1.30 at 50°C; among them, the complex enzyme is composed of ligninase, papain and cellulase with a mass ratio of 1:1.5:2.

[0108] S4 Forming of preparation:

[0109] Mix the clear extract obtained from Step S2 and Step S3, add the fine powder of Alisma orientale, mix evenly, dry under reduced pressure at 65°C, crush into fine powder, add 0.2% magnesium stearate, granulate by dry granulation method, and fill into capsules.

[0110] In order to further verify the reliability of the present invention and screen out the best scheme, the inventor conducted a series of tests, specifically as follows:

[0111] 1. Instruments and Reagents

[0112] The main instruments are shown in Table 1, and the main reagents are shown 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 Separate Extraction of Single Herbs with the Preparation Method in the Pharmacopoeia

[0121] In the original preparation process of Longqing Capsules, the preparation method of the water extract was as follows: Flos Lonicerae, Herba Patriniae, Herba Hedyotidis Diffusae, and Herba Agrimoniae were decocted with water twice. For the first time, 8 times the mass of the herbs of water was added, soaked for 0.5 h, and decocted for 1 h; for the second time, 6 times the mass of the herbs of water was added and decocted for 1 h; the decoction liquids were combined, filtered, and the filtrate was concentrated to a clear paste with a relative density of 1.25 - 1.30 (50 °C).

[0122] In this study, two methods were used to compare the extraction processes of the herbs in the water extraction part of Longqing Capsules. The water-extracted herbs were extracted at a scale reduced by 10 times according to the prescription amount. The extract was freeze-dried to obtain dry paste powder, and the above methods were evaluated with the dry paste powder yield (dry paste powder yield = weight of the obtained dry paste powder / feeding amount × 100%) as the index, as follows:[[]]

[0123] (1) Separate extraction of single herbs

[0124] Take Herba Hedyotidis Diffusae, Herba Patriniae, Flos Lonicerae, and Herba Agrimoniae, and cut them into sections 3 - 5 cm long with a cutting machine; accurately weigh 52.2 g of each of the above four herbs, in parallel 3 times, and separately put them into a round-bottom flask. For the first time, 420 mL of drinking water was added, soaked for 0.5 h, decocted for 1 h, and filtered; for the second time, 320 mL of drinking water was added, decocted for 1 h, and filtered; the filtrates were combined, heated and concentrated, and freeze-dried to obtain dry paste powder.

[0125] (2) Extraction according to the extraction process in the Chinese Pharmacopoeia

[0126] Take the medicinal materials of *Hedyotis diffusa*, *Patrinia scabiosaefolia*, *Lonicera japonica*, and *Agrimonia pilosa*, and cut them into sections 3 - 5 cm long with a cutting machine; accurately weigh 52.2 g of *Hedyotis diffusa*, 52.2 g of *Patrinia scabiosaefolia*, 26.1 g of *Lonicera japonica*, and 26.1 g of *Agrimonia pilosa*, and put the four herbs into a round-bottom flask (prepare 3 portions). Add 1260 mL of drinking water for the first time, soak for 0.5 h, decoct for 1 h, and filter; add 945 mL of drinking water for the second time, decoct for 1 h, and filter; combine the filtrates, heat and concentrate, and freeze-dry to obtain dry extract powder.

[0127] 2.1.2 Results and Analysis

[0128] Extract the water-extracted part of the medicinal materials in Longqing Capsules according to the method under "2.1 Investigation on the Preparation Method of Water Extract", and the dry extract powder is prepared after freeze-drying the extract. The yields of the dry extract powder under different extraction methods are shown in Table 3.

[0129] Table 3 Yields of Dry Extract Powder under Different Extraction Methods - Water Extract (n = 3)

[0130]

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

[0132] From the above results, it can be seen that when extracting with single herbs separately, the yield of the dry extract powder is 17.02%, while when extracting according to the preparation method in the *Chinese Pharmacopoeia*, the yield of the dry extract powder is 17.32%. Considering the actual situation that the total production volume of Longqing Capsules in our company has exceeded the requirements of the *Pharmacopoeia* specification (2) for a long time, comprehensively considering, the method of extracting with single herbs separately is selected for the preparation of the water extract.

[0133] 2.2 Preparation of Alcohol Extract

[0134] In the original preparation process of Longqing Capsules, the preparation method of the alcohol extract is as follows: For the five herbs of *Plantago asiatica*, *Moutan cortex*, *Paeonia lactiflora*, *Coptis chinensis*, and *Phellodendron amurense*, add 60% ethanol about 3.5 times the mass of the herbs, heat under reflux for extraction 3 times, 3 h for the first time, 2 h for the second time, and 1 h for the third time. Combine the extraction solutions, filter, recover the ethanol from the filtrate, and concentrate to a clear paste with a relative density of 1.25 - 1.30 (50 °C).

[0135] The contents of berberine hydrochloride and phellodendrine hydrochloride in the Longqing Capsules prepared according to the above preparation method meet the requirements of the *Chinese Pharmacopoeia*, but the extraction rate is still relatively low, which leads to waste of medicinal materials resources, and the above preparation process of the alcohol extract has a long cycle, greatly reducing the production efficiency of the enterprise. Therefore, on the basis of 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 with the contents of berberine hydrochloride and phellodendrine hydrochloride as indicators.

[0136] 2.2.1 Determination method for berberine hydrochloride

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

[0138] The chromatographic column is packed with octadecylsilyl silica gel bonded silica gel; the mobile phase is acetonitrile - 0.05 mol / L potassium dihydrogen phosphate solution (50:50) (add 0.4 g of sodium dodecyl sulfate to every 100 mL, and then adjust the pH value to 4.0 with phosphoric acid); the detection wavelength is 345 nm. The number of theoretical plates calculated based on the berberine hydrochloride peak should be not less than 5000.

[0139] (2) Preparation of reference substance solution

[0140] Accurately weigh an appropriate amount of berberine hydrochloride reference substance, weigh it precisely, dissolve it in methanol to prepare a solution containing 20 μg per 1 mL, and you will get it.

[0141] (3) Preparation of test solution

[0142] Take the contents of 3 batches of Longqing capsules under the difference in filling quantity, mix them evenly, grind them finely, weigh each batch of Longqing capsules 2 times repeatedly, respectively take about 0.1 g, weigh it precisely, place it in a stoppered conical flask, accurately add 25 mL of the mixed solution of methanol - hydrochloric acid (100:0.2), tightly stopper it, weigh it, ultrasonically treat it (power 250 W, frequency 40 kHz) for 30 min, let it cool, weigh it again, make up the lost weight with methanol, shake it well, filter it, and take the subsequent filtrate, and you will get it.

[0143] (4) Determination method

[0144] Precisely pipette 10 μL each of the berberine hydrochloride reference substance solution and the test solution of Longqing capsules into the liquid chromatograph, determine it, and you will get it.

[0145] 2.2.2 Determination method for phellodendrine hydrochloride

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

[0147] The chromatographic column is packed with octadecylsilyl bonded silica gel; the mobile phase is acetonitrile - 0.1% phosphoric acid solution (add 0.2 g of sodium dodecyl sulfonate to every 100 mL) (36:64); the detection wavelength is 284 nm. The number of theoretical plates calculated based on phellodendrine hydrochloride should be not less than 5000.

[0148] (2) Preparation of reference substance solution

[0149] Accurately weigh an appropriate amount of phellodendrine hydrochloride, weigh it precisely, dissolve it in the mobile phase to prepare a solution containing 20 μg per 1 mL, and you will get it.

[0150] (3) Preparation of test solution

[0151] Take the contents of 3 batches of Longqing Capsules with difference in filling quantity, mix well, grind finely. Weigh each batch of Longqing Capsules 2 times repeatedly, take about 0.1 g respectively, weigh accurately, place in a stoppered conical flask, accurately add 25 mL of mobile phase, stopper tightly, weigh, ultrasonically treat (power 250 W, frequency 40 kHz) for 30 min, cool, weigh again, make up the lost weight with mobile phase, shake well, centrifuge, and take the supernatant, thus obtaining.

[0152] (4) Determination method

[0153] Accurately pipette 10 μL each of the control solution of berberine hydrochloride and the test solution of Longqing Capsules into a high performance liquid chromatograph for determination, thus obtaining.

[0154] 2.2.3 Investigation on the extraction method of alcohol extract

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

[0156] Crush the five medicinal materials of Cortex Moutan, Plantaginis Semen, Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri Chinensis into coarse powder, sieve through a 10-mesh sieve, and set aside; weigh the above-mentioned five kinds of medicinal material coarse powder after crushing according to the prescription, add 4 times the mass of the medicinal materials of 60% ethanol solution and 3‰ of the mass of the medicinal materials of compound enzyme (composed of ligninase, papain and cellulase with a mass ratio of 1:1.5:2); adjust the pH value to 5.5 respectively, ultrasonically assist enzymatic hydrolysis (power 600 W, frequency 40 kHz) for 2 h, boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, sieve through a 100-mesh sieve, and recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C.

[0157] This study prepares the alcohol extract and Longqing Capsules according to the above technological method, and conducts single-factor investigation experiments on four parameters of solid-liquid ratio, compound enzyme ratio, compound enzyme dosage and enzymatic hydrolysis time that affect the extraction efficiency of the alcohol extract respectively, and designs an orthogonal test to determine the optimal preparation process of the alcohol extract. Among them, the preparation method of Longqing Capsules is specifically as follows: adopt the method of separately extracting single medicinal materials in the item of "2.1 Preparation of water extract" to prepare the water extraction extract, filter and combine the filtrates after decoction, sieve through a 100-mesh sieve, recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; prepare the clear paste of the alcohol extract according to the above ultrasonic-assisted enzymatic hydrolysis method; mix the clear pastes obtained in the above steps, add the fine powder of Alisma orientale, mix well, dry the paste under reduced pressure at 65 °C, crush into fine powder, add 0.2% magnesium stearate, granulate by dry granulation method, and fill into capsules, then it can be obtained.

[0158] 2.2.3.1 Investigation on solid-liquid ratio

[0159] The preparation of the ethanol extract and Longqing capsules was carried out according to the method under "2.2.3 Investigation of the extraction method of the ethanol extract". With other conditions fixed, the extraction of the ethanol extract and the preparation of Longqing capsules were carried out at the solid-liquid ratios of 1:4, 1:5, and 1:6 respectively. The contents of berberine hydrochloride and phellodendrine hydrochloride in Longqing capsules were determined according to the methods under "2.2.1 Determination of the content of berberine hydrochloride" and "2.2.2 Determination of the content of phellodendrine hydrochloride", with 3 parallels. The results are shown in Table 4. The HPLC chromatogram of the berberine hydrochloride reference solution is as shown in Figure 1 shown, and the HPLC chromatogram of the phellodendrine hydrochloride reference solution is as shown in Figure 2 shown. The typical chromatogram for the determination of the content of berberine hydrochloride in the test solution under different solid-liquid ratios is as shown in Figure 3 shown, and the typical chromatogram for the determination of the content of phellodendrine hydrochloride in the test solution under different solid-liquid ratios is as shown in Figure 4 shown.

[0160] Table 4 Results of the determination of the contents of berberine hydrochloride and phellodendrine hydrochloride in Longqing capsules prepared under different solid-liquid ratios (n = 3)

[0161]

[0162]

[0163] It can be seen from the results that with the increase in the amount of extraction solvent used, the contents of berberine hydrochloride and phellodendrine hydrochloride in the prepared Longqing capsules both increased slightly. The contents of berberine hydrochloride and phellodendrine hydrochloride in Longqing capsules measured at the solid-liquid ratios of 1:4 and 1:5 were not much different. Considering comprehensively, the solid-liquid ratio of 1:4 was selected for subsequent research.

[0164] 2.2.3.2 Investigation of the proportion of the composite enzyme

[0165] The preparation of the ethanol extract and Longqing capsules was carried out according to the method under "2.2.3 Investigation of the extraction method of the ethanol extract". The solid-liquid ratio was 1:4. With other conditions fixed, the extraction of the ethanol extract and the preparation of Longqing capsules were carried out using composite enzymes with different proportions respectively. The contents of berberine hydrochloride and phellodendrine hydrochloride in Longqing capsules were determined according to the methods under "2.2.1 Determination of the content of berberine hydrochloride" and "2.2.2 Determination of the content of phellodendrine hydrochloride", with 3 parallels. The results are shown in Table 5. The typical chromatogram for the determination of the content of berberine hydrochloride in the test solution under different proportions of the composite enzyme is as shown in Figure 5 shown, and the results of the determination of the content of phellodendrine hydrochloride in the test solution under different proportions of the composite enzyme are as shown in Figure 6 shown.

[0166] Table 5 Results of the determination of the contents of berberine hydrochloride and phellodendrine hydrochloride in Longqing capsules prepared under different proportions of the composite enzyme (n = 3)

[0167]

[0168]

[0169] It can be seen from the results that when the mass ratio of ligninase: papain: cellulase is 1:1.5:2, the contents of berberine hydrochloride and phellodendrine hydrochloride in the prepared Longqing capsules are the highest. Therefore, the ratio of the composite enzyme (ligninase: papain: cellulase) of 1:1.5:2 is selected for subsequent research.

[0170] 2.2.3.3 Investigation of the dosage of the composite enzyme

[0171] The alcohol extracts and Longqing capsules were prepared according to the method under "2.2.3 Investigation of the extraction method of alcohol extracts". The solid-liquid ratio was 1:4, and the ratio of the composite enzyme (ligninase: papain: cellulase) was 1:1.5:2. With other conditions unchanged, the alcohol extracts and Longqing capsules were prepared with the dosages of the composite enzyme being 3‰, 4‰, and 5‰ respectively. The contents of berberine hydrochloride and phellodendrine hydrochloride in the Longqing capsules were determined according to the methods under "2.2.1 Determination of the content of berberine hydrochloride" and "2.2.2 Determination of the content of phellodendrine hydrochloride", with 3 parallel determinations. The results are shown in Table 6. The typical chromatograms for the determination of the content of berberine hydrochloride in the test solution under different dosages of the composite enzyme are as Figure 7 shown, and the results for the determination of the content of phellodendrine hydrochloride in the test solution under different dosages of the composite enzyme are as Figure 8 shown.

[0172] Table 6 Results of the determination of the contents of berberine hydrochloride and phellodendrine hydrochloride in the Longqing capsules prepared with different dosages of the composite enzyme (n = 3)

[0173]

[0174] It can be seen from the results that when the dosage of the composite enzyme is 4‰, the contents of berberine hydrochloride and phellodendrine hydrochloride in the prepared Longqing capsules are both the highest. Therefore, the dosage of the composite enzyme of 4‰ is selected for subsequent research.

[0175] 2.2.3.4 Investigation of the ultrasonic-assisted enzymatic hydrolysis time

[0176] The ethanol extracts and Longqing capsules were prepared according to the method described in "2.2.3 Investigation on the extraction method of ethanol extracts". The material-liquid ratio was 1:4, the ratio of compound enzymes was 1:1.5:2, the dosage of compound enzymes was 4‰. Keeping other conditions unchanged, the ethanol extracts and Longqing capsules were prepared with ultrasonic-assisted enzymatic hydrolysis times of 0.5 h, 1 h, and 2 h respectively. The contents of berberine hydrochloride and phellodendrine hydrochloride in Longqing capsules were determined according to the methods described in "2.2.1 Determination of the content of berberine hydrochloride" and "2.2.2 Determination of the content of phellodendrine hydrochloride", with 3 parallel determinations. The results are shown in Table 7. The typical chromatograms for the determination of berberine hydrochloride content in the test solution under different ultrasonic-assisted enzymatic hydrolysis times are as Figure 9 shown, and the typical chromatograms for the determination of phellodendrine hydrochloride content in the test solution under different ultrasonic-assisted enzymatic hydrolysis times are as Figure 10 shown.

[0177] Table 7 Results of the determination of the contents of berberine hydrochloride and phellodendrine hydrochloride in Longqing capsules prepared under different ultrasonic-enzymatic hydrolysis times (n = 3)

[0178]

[0179] It can be seen from the results that when the ultrasonic-assisted enzymatic hydrolysis time was 1 h, the contents of berberine hydrochloride and phellodendrine hydrochloride in the prepared Longqing capsules were the highest. Considering comprehensively, the ultrasonic-assisted enzymatic hydrolysis time of 1 h was selected.

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

[0181] Taking the material-liquid ratio (A), the ratio of compound enzymes (B), the dosage of compound enzymes (C), and the ultrasonic enzymatic hydrolysis time (D) as the investigation factors, and each factor was taken at 3 levels to carry out an orthogonal experiment to compare the influence degree of different ethanol extract preparation parameter conditions on the content of active ingredients in Longqing capsules, so as to verify the best process conditions investigated by single factor. The factor level table is shown in Table 8, and the test results and range analysis are shown in Tables 9 - 11.

[0182] Table 8 Factor level table for the orthogonal experimental design of the investigation on the preparation conditions of ethanol extracts

[0183]

[0184] Table 9 Results of the orthogonal experiment for the investigation on the preparation conditions of ethanol extracts

[0185]

[0186]

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

[0188]

[0189] Range analysis of the content of berberine hydrochloride in Longqing Capsules

[0190]

[0191] From the results of the orthogonal experiment, it can be seen that the order of the influence degree of the above four factors on the content of active ingredients in the ethanol extract of Longqing Capsules is: ultrasonic enzymolysis time > dosage of compound enzyme > ratio of compound enzyme > solid-liquid ratio. The optimal extraction process screened by the orthogonal experiment is: solid-liquid ratio is 1:4, ratio of compound enzyme (ligninase: papain: cellulase) is 1:1.5:2; dosage of compound enzyme is 4‰; ultrasonic enzymolysis time is 1 h. The above optimal process conditions are consistent with the results of the single-factor investigation experiment. 2.2.3.5 Comparison between the preparation of ethanol extract by ultrasonic-assisted enzymolysis method and the preparation method in Chinese Pharmacopoeia

[0192] Through the above single-factor investigation experiment and orthogonal experiment, the optimal preparation process of the ethanol extract of Longqing Capsules was determined as: solid-liquid ratio is 1:4; ratio of compound enzyme (ligninase: papain: cellulase) is 1:1.5:2; dosage of compound enzyme is 4‰; ultrasonic-assisted enzymolysis time is 1 h. The research team prepared the ethanol extract by using the above optimal process conditions and the preparation method in Chinese Pharmacopoeia respectively. The ethanol-extracted medicinal materials were extracted at a scale reduced by 10 times according to the prescription amount. The extract was freeze-dried to obtain dry extract powder, and the dry extract powder yield (dry extract powder yield = weight of the obtained dry extract powder / feeding amount × 100%) was used as an index to evaluate the above methods. The results are shown in Table 12.

[0193] Table 12 Dry extract powder yield of ethanol extract under different extraction methods (n = 3)

[0194]

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

[0196] The research team prepared Longqing Capsules by using the optimal process conditions of this study and the preparation method in Chinese Pharmacopoeia respectively, and determined the contents of berberine hydrochloride and berberine hydrochloride in them. The parallel test was carried out 3 times, and the results are shown in Table 13.

[0197] Table 13 Comparison of the contents of active ingredients in Longqing Capsules prepared by different process methods (n = 3)

[0198]

[0199]

[0200] In summary, when the best process conditions of this study were adopted for the preparation of the ethanol extract, the yield of dry extract powder was 23.41%. When the preparation method in the Chinese Pharmacopoeia was used for the preparation of the ethanol extract, the yield of dry extract powder was 20.51%. The yield of dry extract powder prepared by using the best process conditions of this study was slightly higher than that prepared by the method in the Chinese Pharmacopoeia. By comparing the determination results of the contents of berberine hydrochloride and phellodendrine hydrochloride in the Longqing capsules prepared by the above two methods, it can be seen that the contents of the above two active ingredients in the Longqing capsules prepared by using the best process conditions of this study were higher than those of the method in the Chinese Pharmacopoeia, indicating that the preparation method of Longqing capsules provided by this study can improve the content of active ingredients in the drug, help 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 preparation method of Longqing capsules provided by this study significantly shortens the process cycle, helps improve the production efficiency of enterprises, and has great popularization and application value.

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

Claims

1. An improved preparation process of Longqing capsules, characterized in that, It includes the following steps: S1 Pretreatment of medicinal materials: Crush Alisma orientale into fine powder, sieve through a 60 - 100 mesh sieve, and set aside; cut Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa into segments 2 - 10 cm long, and set aside; crush Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense into coarse powder, sieve through a 5 - 15 mesh sieve, and set aside; S2 Preparation of water extract: Take the cut segments of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, add 5 - 10 times the mass of the medicinal materials of water to each, decoct 1 - 3 times respectively, each time for 0.5 - 1.5 h, and soak for 15 - 60 min before the first decoction; filter, combine the filtrates, sieve through an 80 - 120 mesh sieve, and concentrate under reduced pressure at 70 - 90 °C to a clear paste with a density of 1.25 - 1.30 at 50 °C; S3 Preparation of alcohol extract: Take the crushed coarse powder of Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense, add 4 - 6 times the mass of the medicinal materials of 50% - 70% ethanol solution and 3‰ - 5‰ of the mass of the medicinal materials of compound enzyme to each; adjust the pH to 4 - 6 respectively, carry out ultrasonic - assisted enzymatic hydrolysis for 0.5 - 2 h, boil to inactivate the enzyme for 1 - 2 h; filter, combine the filtrates, sieve through an 80 - 120 mesh sieve, and recover ethanol under reduced pressure and concentrate at 70 - 90 °C to a clear paste with a density of 1.25 - 1.30 at 50 °C; Among them, the compound enzyme is composed of ligninase, papain, and cellulase with a mass ratio of 1:1 - 2:2; S4 Preparation of the preparation: Mix the clear pastes prepared in step S2 and step S3, add the fine powder of Alisma orientale, mix evenly, carry out drying under reduced pressure at 60 - 70 °C, crush into fine powder, add 0.1% - 0.3% of magnesium stearate, granulate by dry granulation method, and fill into capsules to obtain the product.

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

3. The preparation process according to claim 2, wherein In step S1, the pretreatment of medicinal materials: after crushing, Alisma orientale is sieved through an 80 mesh sieve; the four medicinal materials of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa are cut into segments 3 - 5 cm long; after crushing, Paeonia suffruticosa, Plantago asiatica, Paeonia lactiflora, Coptis chinensis, and Phellodendron amurense are sieved through a 10 mesh sieve.

4. The preparation process according to claim 1, characterized in that, The specific preparation of the water extract in step S2 is as follows: take the cut segments of Patrinia scabiosaefolia, Lonicera japonica, Hedyotis diffusa, and Agrimonia pilosa, add 6 - 8 times the mass of the medicinal materials of water to each, decoct 2 - 3 times respectively, each time for 1 - 1.5 h, soak for 15 - 45 min before the first decoction; filter, combine the filtrates, sieve through a 100 - 120 mesh sieve, and concentrate under reduced pressure at 75 - 85 °C to a clear paste with a density of 1.25 - 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 specifically as follows: Take the long sections of the four medicinal materials of Patrinia scabiosaefolia Fisch., Lonicera japonica Thunb., Hedyotis diffusa Willd., and Agrimonia pilosa Ledeb. after truncation, and decoct them with water twice, each time for 1 h. For the first time, add 8 times the mass of the medicinal materials of water, and for the second time, add 6 times the mass of the medicinal materials of water. Soak for 30 min 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 paste with a density of 1.25 - 1.30 at 50 °C.

6. The preparation method according to claim 1, wherein The preparation of the ethanol extract in step S3 is specifically as follows: Take the coarse powder of the five medicinal materials of Cortex Moutan, Plantago asiatica L., Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri after pulverization, and add 4 - 5 times the mass of the medicinal materials of 55% - 65% ethanol solution and 4‰ - 5‰ of the mass of the medicinal materials of complex enzyme to each; adjust the pH to 5 - 6 respectively, carry out ultrasonic-assisted enzymatic hydrolysis for 1 - 2 h, and boil to inactivate the enzyme for 1 - 1.5 h; filter, combine the filtrates, pass through a 100 - 120-mesh sieve, recover ethanol under reduced pressure at 75 - 85 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; among them, the complex enzyme is composed of ligninase, papain, and cellulase with 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 specifically as follows: Take the coarse powder of the five medicinal materials of Cortex Moutan, Plantago asiatica L., Radix Paeoniae Rubra, Rhizoma Coptidis, and Cortex Phellodendri after pulverization, and add 4 times the mass of the medicinal materials of 60% ethanol solution and 4‰ of the mass of the medicinal materials of complex enzyme to each; adjust the pH to 5.5 respectively, carry out ultrasonic-assisted enzymatic hydrolysis for 1 h, and boil to inactivate the enzyme for 1.5 h; filter, combine the filtrates, pass through a 100-mesh sieve, recover ethanol under reduced pressure at 80 °C and concentrate to a clear paste with a density of 1.25 - 1.30 at 50 °C; among them, the complex enzyme is composed of ligninase, papain, and cellulase with 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 the preparation of the ethanol extract in step S3, the power of the ultrasonic wave is 600 W and the frequency is 40 kHz.

9. The preparation method according to claim 1, wherein In step S4 for preparation of the preparation into a form: The temperature for vacuum drying is 60 - 65 °C; the addition amount of magnesium stearate is 0.2% - 0.3%.

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

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