Preparation method of Shugan Shunqi preparation and application thereof

Abstract

The present application relates to the technical field of traditional Chinese medicine preparation, in particular to a preparation method of Shugan Shunqi preparation and application thereof. The preparation method comprises the following steps: obtaining distillation water phase, distillation oil phase and dregs by distilling medicinal material raw materials; separating the distillation water phase, distillation oil phase and dregs and decocting the dregs to obtain decocted liquid; mixing the decocted liquid and distillation water phase to obtain extraction liquid; and mixing the extraction liquid, distillation oil phase and suitable preparation accessories to prepare various Shugan Shunqi preparations. The technical scheme of the present application improves the dissolution degree of effective components in each medicinal material raw material through extraction method, and avoids the addition of honey in traditional Shugan Shunqi preparation through accessory improvement, thereby overcoming the shortcoming that the use of the medicine is limited to a certain group of people.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to a method for preparing a liver-soothing and qi-regulating preparation and its application. Background Technology

[0002] Shugan Shunqi Pills are an optimized version of Chaihu Shugan Powder from the *Jingyue Quanshu* (Complete Works of Jingyue). It is a pure traditional Chinese medicine preparation composed of 13 herbs: Bupleurum, Cyperus (vinegar-processed), White Peony Root, Turmeric, Fried Immature Bitter Orange, Magnolia Bark, Costus Root, Buddha's Hand, Corydalis Rhizome (vinegar-processed), Ligusticum Rhizome, Malan Grass, Tangerine Peel, and Licorice Root. Shugan Shunqi Pills (National Medicine Approval Number Z20026802, Standard Number: WS-11169(ZD-1169)-2002-2011Z) are large, black, honey-coated pills, each weighing approximately 9g. Their functions and indications are: soothing the liver, regulating qi, and relieving pain; used for liver qi stagnation syndrome, characterized by: distension in the hypochondriac region, stabbing pain in the stomach, nausea, vomiting, and acid reflux. Experimental studies have shown that Shugan Shunqi Pills can effectively improve symptoms in functional dyspepsia models and gastrointestinal motility abnormality models, inhibit gastric acid secretion, promote gastrointestinal motility, improve serum gastrointestinal hormone levels, increase pepsin activity, and also have significant pharmacological effects of increasing intestinal absorption and relieving pain.

[0003] In existing technology, Shugan Shunqi Pills are made by grinding raw medicinal herbs into powder, sterilizing them, and then mixing them with a large amount of honey to form pills (the preparation process is described in the Shugan Shunqi Pills standard WS-11169(ZD-1169)-2002-2011Z). The bioavailability of the active ingredients in pills made from raw medicinal herbs is not ideal. After a patient takes the medication, the raw medicinal herbs in the pills need to be processed through the human digestive tract before some of the active ingredients can dissolve and be absorbed to exert their effects. Due to the limited temperature of the intestines and the volume of gastric juice, the utilization rate of the active ingredients in these products made from raw medicinal herbs is very low and the utilization rate is very slow, resulting in insignificant efficacy. Furthermore, Shugan Shunqi Pills contain a large amount of honey and are in large sizes, leading to poor patient compliance and making them unsuitable for long-term use by diabetic patients. Therefore, it is urgent to improve the dosage form of Shugan Shunqi Pills to enhance bioavailability, expand the applicable population, improve patient compliance, and enhance efficacy. Summary of the Invention

[0004] The present invention aims to provide a liver-soothing and qi-regulating preparation to solve the technical problems of existing liver-soothing and qi-regulating pills, such as single dosage form, low transfer rate of effective ingredients, unsatisfactory bioavailability, limited applicable population, and poor drug compliance.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A method for preparing a liver-soothing and qi-regulating preparation includes the following steps performed sequentially:

[0007] S1: The medicinal raw materials are extracted by distillation to obtain a distilled aqueous phase, a distilled oil phase, and a residue; the residue is then extracted by boiling in water to obtain a decoction; the decoction and the distilled aqueous phase are combined to obtain an extract.

[0008] S2: Use an inclusion agent to treat the distilled oil phase to obtain an inclusion solution or inclusion powder;

[0009] After the extract is concentrated, it is prepared into an oral formulation together with an inclusion complex solution or inclusion complex powder and excipients.

[0010] Furthermore, in S1, by weight, the medicinal materials include: 25-35 parts of Magnolia officinalis, 25-35 parts of Ligusticum chuanxiong, 25-35 parts of Cyperus rotundus, 25-35 parts of Paeonia lactiflora, 25-35 parts of Bupleurum chinense, 25-35 parts of Citrus aurantium, 25-35 parts of Curcuma longa, 25-35 parts of Citrus medica, 25-35 parts of Aucklandia lappa, 25-35 parts of Citrus reticulata peel, 20-30 parts of Glycyrrhiza uralensis, 25-35 parts of Corydalis yanhusuo, and 55-65 parts of Eupatorium fortunei.

[0011] Preferably, the medicinal materials include: 31.4 parts Magnolia officinalis, 31.4 parts Ligusticum chuanxiong, 31.4 parts Cyperus rotundus, 31.4 parts Paeonia lactiflora, 31.4 parts Bupleurum chinense, 31.4 parts Citrus aurantium, 31.4 parts Curcuma longa, 31.4 parts Citrus medica, 31.4 parts Aucklandia lappa, 31.4 parts Citrus reticulata, 23.55 parts Glycyrrhiza uralensis, 31.4 parts Corydalis yanhusuo, and 58.85 parts Eupatorium fortunei.

[0012] Furthermore, in S1, the distillation extraction adopts an intermittent distillation extraction method, wherein the intermittent distillation extraction is performed alternately by high-heat distillation and gentle boiling distillation;

[0013] Preferably, the intermittent distillation extraction uses water or alcohol solution as the extraction solvent;

[0014] Preferably, the total extraction time is 1-8 hours;

[0015] Preferably, the intermittent distillation extraction process is carried out in a cycle of first high-heat distillation extraction for 10-20 minutes and then low-boiling distillation extraction for 10-20 minutes.

[0016] This technical solution employs alternating distillation with gentle and intense heat to extract volatile oils from medicinal materials, thereby increasing the yield of volatile oils.

[0017] Furthermore, in step S1, the method for extracting the medicinal residue by decoction is as follows: add 6-8 times the amount of water of the medicinal material and decoct for 2-3 hours for the first extraction; add 6-8 times the amount of water of the medicinal material and adjust the pH value to 7.0-7.5, and decoct for 2-3 hours for the second extraction; mix the extracts obtained from the first and second extractions to obtain the decoction.

[0018] During the extraction preparation stage, the pH value of the extraction system for the second decoction extraction needs to be adjusted to ensure the extraction rate of effective components.

[0019] Furthermore, in S2, the oral formulation is a liver-soothing and qi-regulating composition tablet, prepared by the following steps:

[0020] S2-1-1: Take 3-5 times the mass of distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of hydroxypropyl-β-cyclodextrin of water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution or concentrate and dry the inclusion complex solution to obtain an inclusion complex powder.

[0021] The extract is concentrated and dried to obtain a dry paste. The dry paste is then pulverized and sieved to obtain a medicinal powder.

[0022] S2-1-2: Mix the inclusion complex solution or inclusion complex powder, ointment powder and granulation excipients evenly and then granulate to obtain drug granules;

[0023] Preferably, the granulation excipients include crospovidone and microcrystalline cellulose;

[0024] S2-1-3: Mix the drug granules and tableting excipients at 15-20 rpm for 10-20 minutes to obtain the total mixture;

[0025] Preferably, the tableting excipient is magnesium stearate;

[0026] S2-1-4: The total mixture is compressed and coated to obtain a liver-soothing and qi-regulating composition tablet.

[0027] Furthermore, in S2, the oral formulation is a liver-soothing and qi-regulating composition capsule, prepared by the following steps:

[0028] S2-2-1: Take 3-5 times the mass of distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of hydroxypropyl-β-cyclodextrin of water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution or concentrate and dry the inclusion complex solution to obtain an inclusion complex powder.

[0029] The extract is concentrated and dried to obtain a dry paste. The dry paste is then pulverized and sieved to obtain a medicinal powder.

[0030] S2-2-2: Mix the inclusion complex solution or inclusion complex powder, ointment powder, and pregelatinized starch evenly and then granulate to obtain drug particles;

[0031] S2-2-3: Mix drug particles and micronized silica gel to obtain a total mixture;

[0032] S2-2-4: Fill empty capsules with the total mixture to obtain a liver-soothing and qi-regulating composition capsule.

[0033] Furthermore, in S2, the oral preparation is a liver-soothing and qi-regulating oral liquid, prepared by the following steps:

[0034] S2-3-1: Take 3-5 times the mass of the distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of the hydroxypropyl-β-cyclodextrin in water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution or concentrate and dry the inclusion complex solution to obtain an inclusion complex powder.

[0035] The extract is concentrated into a paste or fluid extract;

[0036] S2-3-2: Take the extract or fluid extract, inclusion complex solution or inclusion complex powder, sweetener, and preservative, mix them, adjust the pH value to 4-5, make up the volume, filter and sterilize to obtain the liver-soothing and qi-regulating oral liquid composition.

[0037] Furthermore, in S2, the liver-soothing and qi-regulating composition granules are prepared by the following steps:

[0038] S2-4-1: Take 3-5 times the mass of distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of hydroxypropyl-β-cyclodextrin of water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution. Then concentrate and dry the inclusion complex solution to obtain an inclusion complex powder.

[0039] The extract is concentrated and dried to obtain a dry paste. The dry paste is then pulverized and sieved to obtain a medicinal powder.

[0040] S2-4-2: Sweetener, flavoring, filler, inclusion complex powder, and ointment powder are wet-granulated and dried to obtain mixed granules; preferably, the filler is either dextrin or soluble starch.

[0041] S2-4-3: Mix the mixed granules and the inclusion compound powder to obtain a total mixture, and then prepare a liver-soothing and qi-regulating composition granule.

[0042] This technical solution also provides a method for preparing a liver-soothing and qi-regulating preparation.

[0043] This technical solution also provides the application of a liver-soothing and qi-regulating preparation in the preparation of a drug for treating functional dyspepsia, or in the preparation of a drug for treating symptoms such as fullness in the hypochondriac region, epigastric pain, nausea and vomiting, belching and acid reflux caused by liver qi stagnation.

[0044] The principle and beneficial effects of this technical solution are as follows:

[0045] This technical solution improves the extraction method of effective components from the raw materials of liver-soothing and qi-regulating preparations, and provides preparation methods for multiple dosage forms, which can effectively improve patient compliance. Specifically, the traditional preparation method of this liver-soothing and qi-regulating pill usually involves directly grinding the medicinal materials into powder for use. The human body has a very low utilization rate of its effective components, and the utilization speed is very slow, resulting in poor efficacy and a certain degree of waste of medicinal resources. Although there are attempts in the existing technology to extract some medicinal materials, such as patent CN101461925B, which uses a method of partially extracting the ethanol from the liver-soothing and qi-regulating composition medicinal materials and pulverizing some raw medicinal materials into powder for use, and then mixing the extract and powder to prepare the finished drug. However, these methods do not fully utilize the distilled oil phase components in medicinal materials. This technical solution is the first to extract the distilled oil phase components from medicinal materials (especially those rich in distilled oil phase components such as Cyperus rotundus, Curcuma longa, Citrus aurantium, Magnolia officinalis, Aucklandia lappa, Citrus medica, Ligusticum chuanxiong, Citrus reticulata peel, and Eriocaulon buergerianum). These distilled oil phase components have excellent liver-soothing and qi-regulating effects, achieving full utilization of the effective components and further enhancing the efficacy of the improved liver-soothing and qi-regulating preparation. Furthermore, the use of intermittent high and low heat during the distillation extraction process can increase the yield of the distilled oil phase. During the decoction extraction of the residue after intermittent distillation, appropriate pH adjustment can increase the amount of marker components obtained. Simultaneously, this technical solution changes the dosage form of the traditional liver-soothing and qi-regulating pills to tablets, capsules, oral liquids, and granules, enriching the drug forms of the liver-soothing and qi-regulating composition and helping to improve patient compliance. In addition, the products of this technical solution do not contain honey or other ingredients, making them suitable for diabetic patients. While maintaining the same daily dosage of raw herbs, the daily dosage is reduced, thus expanding the applicable population. In addition, the use of appropriate inclusion agents, fillers, and disintegrants in the preparation of various dosage forms can further improve the quality of the finished product. Detailed Implementation

[0046] The specific embodiments listed in this invention are merely examples, and the invention is not limited to the specific embodiments described below. For those skilled in the art, any equivalent modifications and substitutions to the embodiments described below are also within the scope of this invention. Therefore, all equivalent transformations and modifications made without departing from the spirit and scope of this invention should be covered within its scope.

[0047] Unless otherwise specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. All reagents or instruments without a specified manufacturer are commercially available, conventional products. Numerous specific details are provided in the following detailed embodiments to better illustrate the invention. Those skilled in the art should understand that the invention can be practiced even without certain specific details. In other embodiments, methods, means, equipment, and steps well-known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0048] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. Unless otherwise specified, all units used in this specification are International Standard Units (SI), and all numerical values ​​and ranges appearing in this invention should be understood to include systematic errors unavoidable in industrial production.

[0049] Example 1

[0050] The formula for the liver-soothing and qi-regulating preparation is detailed in Table 1.

[0051] Table 1: Formulation Composition

[0052]

[0053] This technical solution mainly improves the preparation process and dosage form, without adjusting the formula composition. For the convenience of experimental research, the following formula will be used uniformly in subsequent experiments: Magnolia officinalis 31.4 parts, Ligusticum chuanxiong 31.4 parts, Cyperus rotundus (vinegar-processed) 31.4 parts, Paeonia lactiflora 31.4 parts, Bupleurum chinense 31.4 parts, Citrus aurantium (fried) 31.4 parts, Curcuma longa 31.4 parts, Citrus medica 31.4 parts, Aucklandia lappa 31.4 parts, Citrus reticulata 31.4 parts, Glycyrrhiza uralensis 23.55 parts, Corydalis yanhusuo (vinegar-processed) 31.4 parts, and Eupatorium fortunei 58.85 parts.

[0054] The specific process for preparing the extract using the above-mentioned raw materials is as follows:

[0055] Thirteen medicinal herbs, including Magnolia officinalis, Ligusticum chuanxiong, Cyperus rotundus (processed with vinegar), Paeonia lactiflora, Bupleurum chinense, Citrus aurantium (fried), Curcuma longa, Citrus medica, Aucklandia lappa, Citrus reticulata peel, Glycyrrhiza uralensis, Corydalis yanhusuo (processed with vinegar), and Eriocaulon buergerianum, are added to a volatile oil extractor. 8-10 times the weight of the herbs in water (preferably 8 times the weight of water, or an aqueous alcohol solution can be used as the extraction solvent) are added. Intermittent distillation is performed for 1-8 hours (preferably 3-6 hours, further preferably 6 hours). After extraction, three parts are obtained: a distilled aqueous phase, a distilled oil phase, and the residue. These three phases are then separated. The distilled aqueous phase is passed through a 200-mesh sieve for later use. The specific operation of the intermittent distillation is as follows: high heat distillation for 10-20 minutes (preferably 10 minutes), then adjusting the heat to control the distillation system at a gentle boil for 10-20 minutes (preferably 10 minutes). This process is repeated until the extraction is complete. This means that high-heat distillation and low-heat (micro-boiling heating) distillation are carried out intermittently. Existing technology generally uses steam heating, and the heating intensity is controlled by controlling the steam pressure of the distillation equipment. High-heat refers to controlling the heating steam pressure in the range of 0.04-0.06 MPa in actual operation, while micro-boiling heating (low-heat heating) refers to controlling the steam pressure in the range of 0.01-0.02 MPa.

[0056] After the intermittent distillation extraction is completed, the residue is decocted twice more. The first time, 6-8 times the weight of the medicinal material (preferably 7 times) of water is added, and the decoction is carried out for 2-3 hours (preferably 3 hours). The second time, 6-8 times the weight of the medicinal material (preferably 7 times) of water is added. During the second decoction, sodium hydroxide is used to adjust the pH of the system consisting of the residue and water to 7.0-7.5 (preferably 7.2), and the decoction is carried out for 2-3 hours (preferably 3 hours). Each time, the decoction is passed through a 160-200 mesh sieve (preferably 200 mesh sieve). The distilled aqueous phase and the two decoctions are combined for later use (hereinafter referred to as the extract).

[0057] Various formulations are prepared using extracts and distilled oil phases. The distilled oil phase requires inclusion treatment with an inclusion agent; the extract requires concentration and drying. These are all common steps in the formulation preparation process.

[0058] The method for incorporating the distilled oil phase using an inclusion agent is as follows: Take 3-5 times the mass of volatile oil (hydroxypropyl-β-cyclodextrin, the inclusion agent), and dissolve it in 3-5 times the mass of hydroxypropyl-β-cyclodextrin in water; under stirring conditions of 40-60 rpm, add the volatile oil (distilled oil phase) dropwise at a rate of 1-2 ml / min, and stir for 1.5-2.5 hours after the addition is complete to obtain an inclusion complex solution; concentrate and dry until the moisture content is less than 5.0%, then pulverize and pass through an 80-100 mesh sieve to obtain the inclusion complex powder. Preferably, the inclusion agent is hydroxypropyl-β-cyclodextrin.

[0059] The specific process of extract concentration and drying is as follows: the extract is concentrated into a clear paste with a relative density of 1.20-1.25 and then dried to obtain a dry paste with a dry paste rate of 24%-27%; the dry paste is pulverized and passed through an 80-100 mesh sieve to obtain ointment powder.

[0060] Example 2

[0061] This embodiment provides a method for preparing a liver-soothing and qi-regulating composition tablet:

[0062] The distilled oil phase and extract obtained in Example 1 (obtained using optimal process parameters) were used to prepare a liver-soothing and qi-regulating composition tablet.

[0063] The excipients used in tablet preparation and their dosage ranges are as follows: 4-8 parts crospovidone (6 parts in the specific experiment), 10-20 parts microcrystalline cellulose (15 parts in the specific experiment), and 0.75-1.5 parts magnesium stearate (1.35 parts in the specific experiment). In addition, conventional gastrointestinal coating powder was used to coat the prepared tablets, controlling its content to 2-3% of the tablet weight. In the distillation oil phase inclusion step, hydroxypropyl-β-cyclodextrin was used, and its dosage was determined by the mass of the distilled oil phase. In the dry granulation step, pregelatinized starch was used only as a filler.

[0064] The specific preparation method is as follows:

[0065] (1) Preparation of inclusion complex powder from distilled oil phase: Take 3-5 times (preferably 4 times) of the mass of distilled oil phase of hydroxypropyl-β-cyclodextrin, dissolve it in 3-5 times (preferably 4 times) of the mass of hydroxypropyl-β-cyclodextrin in water, and add the distilled oil phase dropwise at a rate of 1-2 ml / min under stirring conditions of 40-60 rpm (preferably 50 rpm) (control the dropwise speed at about 1 ml / min). After the dropwise addition is completed, stir for 1.5-2.5 hours (preferably 2 hours), dry until the moisture content is less than 5.0%, and then pulverize it through an 80-100 mesh sieve (preferably 80 mesh sieve) to obtain inclusion complex powder;

[0066] (2) The extract is subjected to conventional concentration and drying treatment. First, the extract is concentrated to a relative density of 1.20-1.25 (30-70℃, measured using a Pomeranian hydrometer). Then, the concentrated material is dried to obtain a dry extract, with the dry extract rate controlled at 24-27%. More specifically, the following method can be used:

[0067] Take the extract, start the single-effect concentrator, vacuum degree ≤ -0.09Mpa, temperature ≤ 75℃, steam pressure ≤ 0.30Mpa. Filter the extract through a 250-mesh bag filter and then transfer it into the single-effect concentrator to concentrate it to a relative density of 1.20-1.25 (30-70℃, measured with a Pomeranian hydrometer). Flow the extract into a belt dryer at a rate of 200kg / h. Set the heating temperature of the first stage of the belt dryer to 90-100℃; the second stage to 70-80℃; and the third stage to 50-60℃. Collect the dried extract after the third stage drying, with a dry extract yield of 24-27%.

[0068] (3) Pulverization: Take the dry paste, pulverize it with a water-cooled pulverizer, and pulverize it through an 80-100 mesh sieve for later use (preferably an 80 mesh sieve) to obtain the ointment powder.

[0069] (4) Dry granulation: Take the inclusion complex powder, ointment powder, the prescribed amount of cross-linked povidone, the prescribed amount of microcrystalline cellulose and pregelatinized starch (add an appropriate amount according to the total amount made) and mix them in a three-dimensional motion mixer for 10-20 minutes (preferably 15 minutes). The mixer speed is 40-60 rpm (preferably 50 rpm). The mixed material is added to a dry granulator for granulation. The granulator adopts conventional technical parameter settings: pressure roller pressure 210-230 bar, pressure roller gap 0.4-1.3 mm, feed speed 20-26 rpm, screw feed speed 80-100 rpm, pressure roller speed 20-28 rpm, crushing speed 70-90 rpm, granulation speed 70-90 rpm, and granulation sieve mesh 20 mesh.

[0070] (5) Mixing: Take the whole granules and the prescribed amount of magnesium stearate and mix them in a three-dimensional motion mixer for 10-20 minutes (preferably 15 minutes). Set the mixer speed to 40-60 rpm (preferably 50 rpm). The mixture is then obtained.

[0071] (6) Tableting: Add the total mixture to the hopper of the high-speed tablet press, with each tablet weighing 0.5g. Before tableting, a trial run should be conducted to check the tablet weight (20 tablets are sampled each time and the weight of each tablet is accurately measured), appearance, and adjust the pressure to 80KN-140KN (subsequent experimental studies will use a pressure of about 140KN). After meeting the requirements, tableting should be carried out according to the tableting process parameters. The pressed tablets should be sieved with a tablet sieve machine to remove powder and particles. The qualified tablets should be placed in a clean container, sealed, weighed, and labeled with the product name, specifications, quantity, production time, etc., and then transferred to the coating process.

[0072] (7) Film Coating: Operate according to the "Standard Operating Procedures for BGB-350C High-Efficiency Coating Machine / SOP-SB074". Pour the uncoated tablets into the coating machine, set the technical parameters such as the air inlet temperature and the coating roller speed. Set the air inlet temperature to 40-50℃, turn on the heating, rotate the coating machine at low speed, and adjust the peristaltic pump speed to spray the coating slurry evenly onto the uncoated tablets until the coating slurry is used up. Turn off the heating, continue to introduce air to cool down to below 35℃, stop the coating operation, check the tablet weight difference and disintegration time, put the film-coated tablets into a clean container, seal it, weigh it, and affix the material label as required to obtain the Shugan Shunqi tablets.

[0073] Example 3

[0074] This embodiment provides a method for preparing a liver-soothing and qi-regulating capsule:

[0075] The distilled oil phase and extract obtained in Example 1 (obtained using optimal process parameters) were used to prepare a liver-soothing and qi-regulating composition capsule.

[0076] The excipients used in the preparation of the capsules and their dosage range are as follows: 20-30 parts of pregelatinized starch (30 parts were used in the specific experiment). Micronized silica gel was added when preparing the total mixture, and its dosage was 3-4% of the total mixture (3% was used in this example). The capsule shell used was a conventional gastric-soluble capsule shell.

[0077] The preparation method is as follows:

[0078] The preparation of the distilled oil phase inclusion complex, the concentration and drying of the ointment, and the pulverization were the same as in Example 2. The remaining steps were carried out as follows:

[0079] Dry granulation: Take the inclusion complex powder, ointment powder, and the prescribed amount of pregelatinized starch and mix them in a three-dimensional motion mixer for 10-20 minutes (preferably 15 minutes). The mixer speed is 40-60 rpm (preferably 50 rpm). The mixed material is then added to a dry granulator for granulation. The technical parameters of the granulator are set as follows: pressure roller pressure 210-230 bar, pressure roller gap 0.4-1.3 mm, feed speed 20-26 rpm, screw feed speed 80-100 rpm, pressure roller speed 20-28 rpm, crushing speed 70-90 rpm, granulation speed 70-90 rpm, and granulation is passed through a 40-mesh sieve.

[0080] Total mixture: Take the dry-granulated and sizing particles and micronized silica gel and add them to a three-dimensional motion mixer and mix for 10-20 minutes (preferably 15 minutes). Set the mixer speed to 40-60 rpm (preferably 50 rpm). After mixing, the total mixture is obtained.

[0081] Filling: The total mixture was filled into No. 0 capsules (0.5g / capsule) to prepare a liver-soothing and qi-regulating composition capsule.

[0082] Example 4

[0083] This embodiment provides a preparation method for a liver-soothing and qi-regulating oral liquid composition:

[0084] The distilled oil phase and extract obtained in Example 1 (obtained using optimal process parameters) were used to prepare an oral liquid for soothing the liver and regulating qi.

[0085] The excipients and their dosage ranges used in the preparation of the oral liquid are as follows: sweetener 0.8-1.0% (single sweeteners such as sucralose / stevia / sodium saccharin / sodium cyclophosphamide can be used, or compound sweeteners formed by any two or more of the above can be used; different types can be added in different amounts, see Experimental Example 3 for details), sodium benzoate 0.6-1.0‰ (0.8‰ was used in the specific experiment), flavoring 0.3-0.6% (0.5% was used in the specific experiment, strawberry flavoring). The aforementioned "%" indicates the mass percentage of the excipient in the oral liquid.

[0086] The specific preparation process is as follows:

[0087] (1) Preparation of distilled oil phase inclusion complex: Take 3-5 times (preferably 4 times) of the mass of distilled oil phase hydroxypropyl-β-cyclodextrin, dissolve it in 1.5-2.5 times (preferably 2 times) of water, and slowly add the distilled oil phase (0.5-3 ml / min, preferably controlled within the range of 1-2 ml / min) under stirring conditions (40-60 rpm, preferably 50 rpm). After the addition is complete, stir for 1.5-2.5 hours (preferably 2 hours) to obtain a distilled oil phase hydroxypropyl-β-cyclodextrin inclusion complex solution for later use.

[0088] (2) Concentration and drying: Take the extract, start the single-effect concentrator, vacuum degree ≤ -0.09Mpa, temperature ≤ 75℃, steam pressure ≤ 0.30Mpa, filter the extract through a 250-mesh bag filter and transfer it into the single-effect concentrator, concentrate it to a fluid extract with a relative density of 1.20-1.25 (30-70℃, measured by a Pomeranian hydrometer) for later use.

[0089] (3) Preparation of oral liquid: Take the above-mentioned fluid extract into a sugar dissolving tank, boil and sterilize for 30 minutes, cool, add the inclusion complex solution obtained by distillation of oil phase, add sweetener, preservative and pH adjuster (adjust pH value to 4-5), make up to the mark, stir evenly, filter 3 times with a tubular centrifuge, then fill, sterilize, and package after passing light inspection.

[0090] Example 5

[0091] This embodiment provides a method for preparing a liver-soothing and qi-regulating granule composition:

[0092] The distilled oil phase and extract obtained in Example 1 (obtained using optimal process parameters) were used to prepare a liver-soothing and qi-regulating composition granule.

[0093] The excipients and their dosage ranges used in the preparation of granules are as follows: sweetener 0.04-0.06% (single sweeteners such as sucralose / stevia / sodium cyclolactic acid can be used, or compound sweeteners formed by any two or more of the above can be used; different types can be added in different amounts, see Experimental Example 3 for details), flavoring 0.3-0.6% (0.5% was used in the specific experiment), dextrin 73%-78% (76% was added in the subsequent experiment, strawberry flavoring). The aforementioned "%" indicates the mass percentage of the excipient in the granules.

[0094] The specific preparation process is as follows:

[0095] When preparing granules, the method for obtaining the inclusion complex powder and the ointment powder (concentration, drying, and pulverization) is the same as in Example 2, followed by wet granulation:

[0096] Wet granulation: Place sweetener, flavoring, dextrin and ointment powder into a high-efficiency wet granulator, mix at low speed (800 rpm) for 3-5 minutes, add an appropriate amount of purified water, mix at high speed for 1-2 minutes (1600 rpm), and use a high-speed cutter (3000 rpm) to shear evenly. Discharge the material and pass it through a 16-mesh oscillating granulator.

[0097] Drying: Set the inlet air temperature of the fluidized bed dryer to 100±10℃; keep the particles in a boiling state, draw in wet particles, and then keep the material temperature at 60℃-80℃ until the moisture content is below 5.0%; cool down and discharge to obtain mixed particles.

[0098] Granulation and mixing: The dried granules are granulated through a 16-mesh sieve. The granules and the distilled oil phase inclusion powder are added to a three-dimensional motion mixer and mixed for 10-20 minutes (preferably 15 minutes). The mixer speed is set to 40-60 rpm (preferably 50 rpm). The mixture is then obtained.

[0099] Repackaging: The granules are repackaged into aluminum-plastic composite bags to obtain (3g / bag).

[0100] Experimental Example 1

[0101] Research on oil phase extraction process (preparation of distilled oil phase by batch distillation):

[0102] The oil phase extraction method in this experiment was carried out in accordance with the method of Example 1 (using preferred parameters), except that the intermittent distillation extraction process was slightly modified. Extraction was performed on 20 kg of medicinal materials (each medicinal material was prepared according to the formula ratio), as detailed in Table 2.

[0103] Table 2: Experimental Results of Distillation Oil Phase Extraction Process

[0104]

[0105]

[0106] The above experimental results show that:

[0107] Regarding the distillation heat, the inventors discovered that during the distillation extraction of medicinal materials, using high heat throughout the process resulted in less than ideal efficiency in obtaining the distilled oil phase, and the obtained oil phase was turbid and of poor quality (see No. 1). While using a gentle boiling distillation method throughout the process yielded a clear oil phase, the amount obtained was too small (see No. 3). It is evident that regardless of whether vigorous or gentle extraction conditions were used for continuous distillation of the medicinal materials, the amount of distilled oil obtained was unsatisfactory (not exceeding 20 mL). In experiment No. 2, alternating between high-heat and gentle boiling distillation, it was found that this method effectively increased the extraction yield of the distilled oil phase to 21 mL. This was unexpected by the inventors. Generally, increasing the intensity of distillation extraction can effectively increase the distillation yield of volatile oils. Therefore, following conventional thinking, the expected oil phase yield of No. 2 through intermittent distillation extraction would fall between the results of No. 1 and No. 3. However, the effect of No. 2 actually exceeded that of No. 1 and No. 3, achieving the unexpected technical effect of increasing the extraction yield of the distilled oil phase.

[0108] Regarding the intermittent distillation extraction method, the inventors further tested the interval time of intermittent distillation. Specifically, a distillation fire interval of 10-20 minutes and a distillation time of 3-6 hours are considered suitable (see No. 2, No. 5-7). If the frequency of alternation between high-heat distillation extraction and low-boiling distillation extraction is too low (see No. 8, with an interval of 30 minutes), the extraction yield of the distilled oil phase will also be unsatisfactory, even less than the yield of the distilled oil phase obtained by the full-process high-heat distillation extraction in No. 1.

[0109] In addition, the inventors also attempted to extract the medicinal materials containing a high amount of volatile oil in the formula separately (see No. 9), and the amount of distilled oil phase obtained was slightly higher than that in No. 4. The inventors analyzed that the reason might be that distilling and extracting all the medicinal materials together might lead to certain compatibility reactions between the medicinal materials, resulting in a certain decrease in the yield of the total distilled oil phase. However, batch extraction would increase the complexity of the process for large-scale production, so this method was not ultimately adopted. The results of extracting medicinal materials containing distilled oil phase components separately and combined extraction are similar, so combined extraction is considered to reduce the number of steps and save production costs.

[0110] Finally, the inventors also tried a method of high-heat distillation extraction in the first half and low-boiling distillation extraction in the second half for all medicinal materials (see No. 10), but the extraction effect of the distilled oil phase was not ideal. Therefore, simply alternating between high-heat distillation extraction and low-boiling distillation extraction cannot improve the yield of the distilled oil phase (while ensuring the quality of the distilled oil phase).

[0111] Therefore, in preparing liver-soothing and qi-regulating preparations, the preferred method for oil phase extraction by distillation is to use a method with intermittent distillation fire cycling for 10-20 minutes and a total distillation time of 3-6 hours. The inventors have also preliminarily analyzed the reasons why the above method can increase the amount of oil phase obtained by distillation, which may be as follows: Simmering the herbs extracts the volatile oils, which may float or dissolve in small amounts in the hot water. After accumulating a certain amount, a high flame is used to boil the oil, and the accumulated volatile oils are concentrated and distilled back into the collector for cooling and collection. If a high flame is used continuously, due to the large size of the extractor, the amount of volatile oil is very small, and some volatile oil may remain on the walls of the extractor and not easily return to the collector, resulting in a relatively small amount. Prolonged high-flame distillation may cause incompatibility reactions between substances, leading to turbidity of the volatile oil. Continuous simmering distillation results in insufficient distillation intensity, making it difficult to distill and collect a large amount of volatile oil.

[0112] Experimental Example 2

[0113] The study on the preparation process of the extract (adjustment of pH value during the second decoction extraction) was conducted as follows:

[0114] (1) The extract was prepared according to the optimal process of Example 1 of the present invention, wherein, during the second water decoction extraction, the pH value of the mixture of medicinal residue and water was adjusted to 7.2. After obtaining the final extract, the extract was concentrated into an extract (60°C, density 1.30).

[0115] The content of Magnolia officinalis (calculated as magnolol), the principal herb in the extract, was determined, as well as the identification spots of Aucklandia lappa, Citrus medica, Corydalis yanhusuo, Paeonia lactiflora, and Glycyrrhiza uralensis.

[0116] The determination methods were based on the quality standard of Shugan Shunqi Pill (WS-11169(ZD-1169)-2002-2011Z), which included the thin-layer chromatography identification of Aucklandia lappa, Citrus medica, Corydalis yanhusuo, Paeonia lactiflora, and Glycyrrhiza uralensis, as well as the content of magnolol. Specific experimental results are shown in Table 3.

[0117] (2) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during the second water decoction extraction, the pH value of the mixture of medicinal residue and water was not adjusted, and the decoction extraction was carried out directly.

[0118] (3) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during the first and second water decoction extraction, the pH value of the mixture of medicinal residue and water was adjusted to 7.2, and the pH value of the extraction system was also adjusted to 7.2 during the intermittent distillation extraction.

[0119] (4) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during the second water decoction extraction, the pH value of the mixture of the dregs and water was adjusted to 6.5.

[0120] (5) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during the second water decoction extraction, the pH value of the mixture of the residue and water was adjusted to 8.0.

[0121] (6) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during the second water decoction extraction, the pH value of the mixture of the residue and water was adjusted to 7.0.

[0122] (7) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during the second water decoction extraction, the pH value of the mixture of the residue and water was adjusted to 7.5.

[0123] (8) Prepare the extract according to the optimal process of Example 1 of the present invention, except that: during intermittent distillation extraction, the pH value of the mixture of medicinal materials and water is adjusted to 7.5, and the pH value is not adjusted in the other extraction steps.

[0124] (9) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during the first water decoction extraction, the pH value of the mixture of medicinal residue and water was adjusted to 7.5, and the pH value was not adjusted in the remaining extraction steps.

[0125] (10) The extract was prepared according to the optimal process of Example 1 of the present invention, except that: during intermittent distillation extraction, the pH value of the mixture of medicinal materials and water was adjusted to 7.5; during the first water decoction extraction, the pH value of the mixture of medicinal residue and water was adjusted to 7.5; and the pH value was not adjusted in the remaining extraction steps.

[0126] Table 3: Quality Inspection Results of Liver-Soothing and Qi-Regulating Ointment

[0127]

[0128]

[0129] In the above experiments, experiments (1), (6), and (7) were all conducted according to the operating procedure of this scheme. During the second decoction and extraction process, the pH value of the system composed of the dregs and water was adjusted to 7.0-7.5. This operating method is very effective in ensuring the transfer rate of costus root, citron, corydalis rhizome, peony root, licorice root, and magnolia bark, and in increasing the content of magnolia bark's effective components in the extract (i.e., the extract).

[0130] In Experiment (2), the pH of the system consisting of the residue and water from the second decoction extraction was not adjusted, resulting in a decrease in the content of Magnolia officinalis and relatively weaker spots for the identification of Aucklandia lappa and Corydalis yanhusuo, indicating that the extraction method affects the transfer rate of Magnolia officinalis, Aucklandia lappa, and Corydalis yanhusuo. In Experiment (8), only the pH of the extraction system from the distillation extraction was adjusted to 7.5. In Experiment (9), only the pH of the first decoction extraction was adjusted to 7.5. In Experiment (10), only the pH of the first decoction extraction and the pH of the extraction system from the distillation extraction were adjusted to 7.5. In all the above experiments, the pH of the system consisting of the residue and water from the second decoction extraction was not adjusted to the specified range, which led to a significant decrease in the content of Magnolia officinalis active ingredients in the extract (i.e., the extract). Based on this, adjusting the pH of other extraction process steps will not alleviate the significant decrease in the content of Magnolia officinalis active ingredients, and may even affect the transfer effect of Aucklandia lappa and Corydalis yanhusuo to varying degrees.

[0131] In experiment (4), the pH of the system consisting of the dregs and water from the second decoction was adjusted to a lower level (6.5), and in experiment (5), the pH of the system consisting of the dregs and water from the second decoction was adjusted to a higher level (8.0). The aforementioned experimental results show that adjusting the pH too high or too low will have a negative impact on the content of Magnolia officinalis in the ointment, but will not affect the transfer of the identification components.

[0132] In experiment (3), the pH of the extraction systems for both decoction and distillation was adjusted to 7.2. The aforementioned experimental results show that if the pH of the three extraction systems is adjusted, the spots for distinguishing Costus root and Corydalis rhizome will be relatively weaker, but the content of Magnolia officinalis is not significantly affected.

[0133] The above experimental results indicate that, during the extraction process, the pH value of the extraction system for the second decoction extraction needs to be adjusted to ensure the extraction rate of the effective components.

[0134] Experimental Example 3

[0135] Formulation research

[0136] (1) Investigation on the preparation of inclusion complexes

[0137] The preparation process of the inclusion complex powder is described in the best implementation method of Example 2. The type of inclusion agent was studied, and the effects of hydroxypropyl-β-cyclodextrin and β-cyclodextrin in preparing inclusion complexes were investigated. The specific parameters and experimental results are shown in Table 4.

[0138] Table 4: Selection of Inclusion Complex Formulations

[0139]

[0140] The results showed that hydroxypropyl-β-cyclodextrin had a better encapsulation / solubilizing effect on the distilled oil phase of this product than β-cyclodextrin. Therefore, hydroxypropyl-β-cyclodextrin was selected to prepare the inclusion complex.

[0141] (2) Tablet Formulation Study

[0142] The disintegrants used in tablet preparation were screened, and the formulation composition is shown in Table 5. In Table 5, "extracted ointment" refers to the ointment powder prepared using the optimal method in Example 2.

[0143] Table 5: Screening Formulations for Disintegrants

[0144]

[0145] The preparation process is described in Example 2. During the experiment, the particle shapeability of dry granulation, the disintegration performance of the tablets, the tableting phenomenon, and the brittleness were tested. The test results are shown in Table 6.

[0146] Table 6: Results of Disintegrant Screening Experiments

[0147]

[0148] The results showed that, among the same dosage of crospovidone, crospovidone sodium carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch, crospovidone had the strongest disintegration ability in this product. Therefore, crospovidone was screened for further research, and the disintegration effect was considered when different dosages were added.

[0149] Take 25 parts of the extracted ointment powder, a certain amount of crospovidone (see Table 7), 15 parts of microcrystalline cellulose, a certain amount of pregelatinized starch (see Table 7), about 0.4 parts of the inclusion complex powder prepared by Scheme 1, and 1.35 parts of magnesium stearate, and conduct the study according to Table 7.

[0150] Table 7: Drug prescriptions containing different amounts of crospovidone

[0151]

[0152] The preparation process is the same as the optimal process scheme in Example 2. During the experiment, the particle formation, disintegration performance, tableting phenomenon, brittleness and other conditions of dry granulation were tested. The test results are shown in Table 8.

[0153] Table 8: Results of drug performance tests containing different dosages of crospovidone

[0154]

[0155] The results show that cross-linked polyvinylpyrrolidone with a dosage of 4-8 parts exhibits relatively stable disintegration properties.

[0156] (3) Capsule formulation research

[0157] The fillers used in the preparation of capsules were screened, and the formulation composition is shown in Table 9.

[0158] Table 9: Filler Screening Formulations

[0159]

[0160] The preparation process is described in the optimal process scheme of Example 3. During the experiment, the particle shapeability, capsule disintegration performance, filling condition, disintegration and other conditions of dry granulation were tested. The test results are shown in Table 10.

[0161] Table 10: Results of Filler Screening Experiment

[0162]

[0163] The results showed that, among pregelatinized starch, corn starch, dextrin, microcrystalline cellulose, and lactose, pregelatinized starch and lactose exhibited better disintegration and dispersed evenly after disintegration when used as fillers. Capsules made with corn starch and dextrin adhered to the bottom of the disintegration basket, while capsules made with microcrystalline cellulose floated to the top, resulting in slower disintegration. Therefore, commonly used pregelatinized starch was selected as the filler for this product.

[0164] (4) Granule formulation research

[0165] Take 25 parts of the extracted ointment powder, 74.05 parts of filler, 0.05 parts of sweetener, 0.5 parts of strawberry flavoring, and about 0.4 parts of the inclusion complex powder prepared by Scheme 1 (Table 4). The experimental formula is shown in Table 11.

[0166] Table 11: Sweetener Screening Formulations

[0167]

[0168]

[0169] The preparation process is described in Example 2. During the experiment, the granulation properties, solubility, and taste of the particles were tested. The test results are shown in Table 12.

[0170] Table 12: Results of the screening experiment for sweeteners in granules

[0171]

[0172] The research results show that using dextrin as a filler, sucralose, steviol glycosides and sodium cyclolactic acid alone or in combination, as well as strawberry flavoring, can produce granules with good granule formation, good solubility, and good taste that are acceptable to people.

[0173] (5) Formula study of oral liquid

[0174] Take 25 parts of the extracted ointment powder, 0.05 parts of sweetener, 0.5 parts of strawberry flavoring, and about 0.4 parts of the inclusion complex powder prepared by Scheme 1 (Table 4). The experimental formula is shown in Table 13.

[0175] Table 13: Screening prescriptions for oral liquid sweeteners

[0176]

[0177]

[0178] The preparation process is described in Example 5. During the experiment, the properties, low temperature freeze-thaw cycle test, and long-term stability at room temperature were tested. The test results are shown in Table 14.

[0179] Table 14: Results of the Screening Experiment for Oral Liquid Sweeteners

[0180]

[0181] The results show that oral liquids with stable properties, good taste, and good quality stability can be produced by using sucralose, steviol glycosides, sodium cyclolactic acid alone or in combination, sodium benzoate, and strawberry flavoring.

[0182] Experiment Example 4

[0183] Shugan Shunqi Wan is a pure traditional Chinese medicine preparation produced and marketed by Chongqing Xier'an Pharmaceutical Co., Ltd. (Approval Number: Z20026802). It is a non-prescription Class A drug. Its approved indications in the product instructions are: soothing the liver, regulating qi, and relieving pain; used for symptoms such as fullness in the hypochondriac region, epigastric pain, nausea, vomiting, and acid reflux caused by liver qi stagnation. Clinical use has shown that it can be used to treat functional dyspepsia. Therefore, this embodiment establishes an animal model of functional dyspepsia to conduct a pharmacodynamic study, as detailed below:

[0184] 4.1 Laboratory Animals and Grouping

[0185] Experimental animals: Eighty male SPF-grade SD rats (weighing 200±20g) were randomly divided into a blank control group (n=20) and a model group (n=60) after one week of acclimatization. The model group rats were stimulated using the following method: the distal 1 / 3 of the rat's tail was clamped with a butterfly clamp, causing the rats to become agitated and fight each other, with the clamping time limited to the point of not breaking the skin. Each stimulation lasted half an hour, four times a day for 14 consecutive days. The rats' condition was observed and recorded regularly.

[0186] Modeling method: The rat functional dyspepsia (liver qi stagnation) model was replicated by referring to the rat tail clamping method in existing technical literature (Liu Jing, Li Feng, Tang Xudong, et al. Overview of animal model of functional dyspepsia and its application in TCM research [J]. Global TCM, 2013, 6(12): 955-958.).

[0187] Grouping and Administration: After modeling, the rats in the modeling group were randomly divided into a model control group, a Shugan Shunqi Pills (commercially available product) group, and a Shugan Shunqi Tablets group (tablets prepared using the method described in Example 2), with 20 rats in each group. Administration began on the day modeling ended. The blank control group and the model control group were given the corresponding volume of purified water. The other groups were given a dose of 1.33 g crude drug / kg (based on crude drug content), administered by gavage once daily for 14 consecutive days. During the administration period, the rats in each group had free access to water and food.

[0188] 4.2 Experimental Results and Observations

[0189] 4.2.1 Observe the effects of each group of drugs on the weight gain of a rat model of functional dyspepsia.

[0190] During the administration period, rats were observed daily and weighed weekly. Compared with the blank control group, the model control group rats exhibited irritability, disheveled fur, loss of appetite, loose stools, and slow weight gain, indicating that the functional dyspepsia (liver qi stagnation type) model was successfully established. Two weeks after administration, the symptoms of irritability, disheveled fur, loss of appetite, and loose stools in rats in each dose group of Shugan Shunqi Pill were significantly improved, and the changes in body weight of rats in each group after administration are shown in Table 15.

[0191] Table 15: Effects of the liver-soothing and qi-regulating composition on body weight changes in rats with functional dyspepsia (x-±SD)

[0192]

[0193]

[0194] Note: Compared with the model control group. * p < 0.05 ** p < 0.01;

[0195] Based on the above experimental results, it can be seen that the liver-soothing and qi-regulating composition (including liver-soothing and qi-regulating honey pills and liver-soothing and qi-regulating tablets) provided by the present invention has a good therapeutic effect on improving functional dyspepsia. At the same time, the changes in rat body weight after administration indicate that the improved liver-soothing and qi-regulating tablets have a better effect on improving functional dyspepsia.

[0196] 2.2.2 Observe the effects of each group of drugs on gastric juice parameters in rats with functional dyspepsia.

[0197] ①Gastric fluid volume measurement:

[0198] After the last administration, the rats were fasted for 16-18 hours but allowed to drink water. The rats were then euthanized by dislocation of the neck, and the whole stomach was removed. The gastric juice was extracted and placed in a graduated centrifuge tube and centrifuged at 3000 rpm for 15 min. The supernatant was the total amount of gastric juice secreted by the rats in 5 h, expressed in ml. The amount of gastric juice was recorded.

[0199] ② Measurement of gastric juice acidity (total acidity and total acid output):

[0200] Take 1 ml of the centrifuged gastric fluid into a small Erlenmeyer flask, place the flask on white lined paper, add one drop of phenol red indicator, and titrate with 0.01 mol / L NaOH until the gastric fluid changes from a pale pink to an orange-yellow color, and then from yellow back to a pale pink for 2 seconds without fading (the endpoint of total acidity in the gastric fluid). Record the amount of sodium hydroxide consumed, and calculate the total acidity and the total acidity excreted.

[0201] Total acidity (mol / L) = Sodium hydroxide consumption

[0202] Total acid excretion per hour (mol / L / h) = Total acidity x Gastric juice volume / 5

[0203] ③ Pepsin activity (PP) assay:

[0204] After centrifugation, gastric fluid was collected, and the pepsin activity of rats in each group was measured using a commercially available pepsin kit.

[0205] The experimental results are shown in Table 16:

[0206] Table 16: Effects of each drug group on gastric juice parameters in a rat model of functional dyspepsia (x-±SD)

[0207]

[0208]

[0209] Note: Compared with the model control group. * p < 0.05 ** p < 0.01;

[0210] The experimental results above show that, compared with the model control group, there was no significant difference in gastric juice secretion among the rat groups. Meanwhile, the model control group showed a significant decrease in gastric juice acidity and pepsin activity compared to the blank control group, while the total acid excretion over 1 hour was significantly increased. The liver-soothing and qi-regulating pill and tablet formulations provided by this invention can effectively increase gastric juice acidity and pepsin activity, and effectively reduce the total acid excretion over 1 hour in rats. Furthermore, the liver-soothing and qi-regulating tablets are more effective than the liver-soothing and qi-regulating pill formulation.

[0211] 2.2.3 Observe the effects of each group of drugs on gastrointestinal motility in rats with functional dyspepsia.

[0212] Twenty minutes after the last administration, 5 mL of a black semi-solid paste (containing black activated charcoal powder) was administered orally to each rat. Twenty minutes later, the rats were euthanized by cervical dislocation, and the abdomen was opened, with the cardia and pylorus of the stomach ligated. The stomach was removed, dried with filter paper, and weighed. The stomach body was then cut along the greater curvature, its contents washed away, dried, and its net weight measured. The difference between the total and net stomach weight was used as the weight of the gastric residue, and this was used to calculate the gastric residue rate. Simultaneously, the small intestine was quickly removed, and the total length from the pylorus to the ileocecal region and the distance from the pylorus to the leading edge of the black semi-solid paste were measured. The percentage of this distance to the leading edge of the black semi-solid paste relative to the total length from the pylorus to the ileocecal region was used as the small intestinal propulsion rate, which was then calculated.

[0213] Table 17: Effects of each drug group on gastrointestinal motility in rats with functional dyspepsia (x-±SD)

[0214]

[0215] Note: Compared with the model control group. * p < 0.05 ** p < 0.01;

[0216] The above experiments show that, compared with the model control group, the gastric residue rate of the blank control group was significantly lower, and the small intestinal propulsion rate was also significantly higher. After administration of the liver-soothing and qi-regulating composition, compared with the model control group, both the liver-soothing and qi-regulating honey pill group and the liver-soothing and qi-regulating tablet group can effectively increase the small intestinal propulsion rate and significantly reduce the gastric residue rate, thus suggesting that the liver-soothing and qi-regulating composition can enhance gastrointestinal motility and significantly improve functional dyspepsia in experimental animals.

[0217] Based on the above results, it is speculated that the Shugan Shunqi tablets show better technical effects than the Shugan Shunqi honey pills in improving gastric juice secretion and gastrointestinal motility in rats. This may be because the tablet formulation provided by this invention effectively preserves various volatile oil components in the original medicinal materials through distillation extraction. At the same time, during the tablet preparation process, the pH control during the decoction of the medicinal residue achieves efficient transfer and retention of components such as magnolol, thereby further enhancing the efficacy of the Shugan Shunqi preparation. This has great positive significance for the clinical application of the Shugan Shunqi composition.

[0218] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A method for preparing a liver-soothing and qi-regulating preparation, characterized in that, The following steps are performed sequentially: S1: The medicinal raw materials are extracted by distillation to obtain a distilled aqueous phase, a distilled oil phase, and a residue; the residue is then extracted by boiling in water to obtain a decoction; the decoction and the distilled aqueous phase are combined to obtain an extract. The distillation extraction adopts an intermittent distillation extraction method, wherein the extraction process is carried out in a cycle of first 10-20 minutes of high-heat distillation extraction followed by 10-20 minutes of gentle boiling distillation extraction; the intermittent distillation extraction uses water or alcohol solution as extraction solvent, and the total duration is 1-8 hours; The specific method for extracting the dregs by decoction is as follows: add 6-8 times the weight of the raw medicinal materials to water for the first decoction extraction for 2-3 hours; add 6-8 times the weight of the raw medicinal materials to water and adjust the pH value to 7.0-7.5, and carry out the second decoction extraction for 2-3 hours; mix the extracts obtained from the first and second decoction extractions to obtain the decoction liquid. By weight, the medicinal materials consist of 25-35 parts of Magnolia officinalis, 25-35 parts of Ligusticum chuanxiong, 25-35 parts of Cyperus rotundus, 25-35 parts of Paeonia lactiflora, 25-35 parts of Bupleurum chinense, 25-35 parts of Citrus aurantium, 25-35 parts of Curcuma longa, 25-35 parts of Citrus medica, 25-35 parts of Aucklandia lappa, 25-35 parts of Citrus reticulata peel, 20-30 parts of Glycyrrhiza uralensis, 25-35 parts of Corydalis yanhusuo, and 55-65 parts of Eupatorium fortunei. S2: The distilled oil phase is treated with an inclusion agent to obtain an inclusion solution or inclusion powder; the inclusion agent is hydroxypropyl-β-cyclodextrin; the mass of hydroxypropyl-β-cyclodextrin is 3-5 times that of the distilled oil phase; After the extract is concentrated, it is prepared into an oral formulation together with an inclusion complex solution or inclusion complex powder and excipients.

2. The method for preparing a liver-soothing and qi-regulating preparation according to claim 1, characterized in that: In S1, the medicinal materials consist of 31.4 parts of Magnolia officinalis, 31.4 parts of Ligusticum chuanxiong, 31.4 parts of Cyperus rotundus, 31.4 parts of Paeonia lactiflora, 31.4 parts of Bupleurum chinense, 31.4 parts of Citrus aurantium, 31.4 parts of Curcuma longa, 31.4 parts of Citrus medica, 31.4 parts of Aucklandia lappa, 31.4 parts of Citrus reticulata peel, 23.55 parts of Glycyrrhiza uralensis, 31.4 parts of Corydalis yanhusuo, and 58.85 parts of Eupatorium fortunei.

3. The method for preparing a liver-soothing and qi-regulating preparation according to claim 1, characterized in that: In S2, the oral formulation is a liver-soothing and qi-regulating composition tablet, prepared by the following steps: S2-1-1: Take 3-5 times the mass of distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of hydroxypropyl-β-cyclodextrin of water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution or concentrate and dry the inclusion complex solution to obtain an inclusion complex powder. The extract is concentrated and dried to obtain a dry paste. The dry paste is then pulverized and sieved to obtain a medicinal powder. S2-1-2: Mix the inclusion complex solution or inclusion complex powder, ointment powder and granulation excipients evenly and then granulate to obtain drug granules; S2-1-3: Mix the drug granules and tableting excipients at 15-20 rpm for 10-20 minutes to obtain the total mixture; S2-1-4: The total mixture is compressed and coated to obtain a liver-soothing and qi-regulating composition tablet.

4. The method for preparing a liver-soothing and qi-regulating preparation according to claim 3, characterized in that: In S2-1-2, the granulation excipients include crospovidone and microcrystalline cellulose.

5. The method for preparing a liver-soothing and qi-regulating preparation according to claim 3, characterized in that: In S2-1-3, the tableting excipient is magnesium stearate.

6. The method for preparing a liver-soothing and qi-regulating preparation according to claim 1, characterized in that: In S2, the oral formulation is a liver-soothing and qi-regulating composition capsule, prepared by the following steps: S2-2-1: Take 3-5 times the mass of distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of hydroxypropyl-β-cyclodextrin of water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution or concentrate and dry the inclusion complex solution to obtain an inclusion complex powder. The extract is concentrated and dried to obtain a dry paste. The dry paste is then pulverized and sieved to obtain a medicinal powder. S2-2-2: Mix the inclusion complex solution or inclusion complex powder, ointment powder, and pregelatinized starch evenly and then granulate to obtain drug particles; S2-2-3: Mix drug particles and micronized silica gel to obtain a total mixture; S2-2-4: Fill empty capsules with the total mixture to obtain a liver-soothing and qi-regulating composition capsule.

7. The method for preparing a liver-soothing and qi-regulating preparation according to claim 1, characterized in that: In S2, the oral preparation is a liver-soothing and qi-regulating oral liquid, which is prepared by the following steps: S2-3-1: Take 3-5 times the mass of the distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of the hydroxypropyl-β-cyclodextrin in water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution or concentrate and dry the inclusion complex solution to obtain an inclusion complex powder. The extract is concentrated into a paste or fluid extract; S2-3-2: Take the extract or fluid extract, inclusion complex solution or inclusion complex powder, sweetener, and preservative, mix them, adjust the pH value to 4-5, make up the volume, filter and sterilize to obtain the liver-soothing and qi-regulating oral liquid composition.

8. The method for preparing a liver-soothing and qi-regulating preparation according to claim 1, characterized in that: In S2, the liver-soothing and qi-regulating composition granules are prepared by the following steps: S2-4-1: Take 3-5 times the mass of distilled oil phase of hydroxypropyl-β-cyclodextrin and dissolve it in 3-5 times the mass of hydroxypropyl-β-cyclodextrin of water; under stirring conditions, add the distilled oil phase dropwise, and stir for 1-3 hours after the addition is complete to obtain an inclusion complex solution. Then concentrate and dry the inclusion complex solution to obtain an inclusion complex powder. The extract is concentrated and dried to obtain a dry paste. The dry paste is then pulverized and sieved to obtain a medicinal powder. S2-4-2: Sweeteners, flavorings, fillers, inclusion complex powders and ointment powders are wet-granulated and dried to obtain mixed granules; S2-4-3: Mix the mixed granules and the inclusion compound powder to obtain a total mixture, and then prepare a liver-soothing and qi-regulating composition granule.

9. The method for preparing a liver-soothing and qi-regulating preparation according to claim 8, characterized in that: The filler is either dextrin or soluble starch.

10. A liver-soothing and qi-regulating preparation prepared according to any one of claims 1-9.

11. The use of the liver-soothing and qi-regulating preparation according to claim 10 in the preparation of a drug for treating functional dyspepsia, or in the preparation of a drug for treating fullness in the hypochondriac region, epigastric pain, nausea and vomiting, belching and acid reflux caused by liver qi stagnation.

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