Preparation process of flavored Huoxiang Zhengqi mixture

Abstract

This invention belongs to the field of pharmaceutical technology and relates to a preparation process of a modified Huoxiang Zhengqi compound. The preparation process is as follows: Pinellia ternata and Angelica dahurica are percolated; Pogostemon cablin, Perilla frutescens, Citrus reticulata peel, Magnolia officinalis, and Atractylodes macrocephala are extracted in groups for 2-5 hours, and the total volatile oil is collected. The residues of each group are decocted with water, and the decoctions of each group are collected; Poria cocos, Platycodon grandiflorus, Glycyrrhiza uralensis, Areca catechu peel, Ziziphus jujuba, and Zingiber officinale are decocted with water to obtain a decoction; the total volatile oil is added to an inclusion material, and inclusion is obtained using an ultrasonic-assisted method; the percolation and decoctions are combined, concentrated, and centrifuged to obtain a supernatant; a preservative is added to the supernatant and the inclusion material to obtain the final product. This invention extracts medicinal materials containing volatile oils in groups and uses a cyclodextrin inclusion complexation process, which not only improves the total extraction rate of volatile oils, but also increases the content of hesperidin, hydrated oxypenicillin, magnolol, honokiol, patchouli flavonol, and baicalein, while improving the taste and flavor of the flavored patchouli flavonoid compound.

Description

Technical Field

[0001] The present invention belongs to the technical field of medicine and relates to a preparation process of Jiawei Huoxiang Zhengqi Mixture. Background Art

[0002] The earliest record of Huoxiang Zhengqi appeared in the national pharmacopoeia "Taiping Huimin Heji Jufang" promulgated in the Song Dynasty of China. Its clinical application has a history of more than a thousand years. It has the effects of relieving exterior syndrome and resolving dampness, regulating qi and harmonizing the middle, and is mainly used for treating colds, gastrointestinal discomfort, etc. caused by exogenous wind-cold, internal injury of dampness stagnation or summer injury of dampness and heat. Its formula feature is to relieve exterior and interior syndromes simultaneously and take into account regulating the spleen and stomach. Huoxiang Zhengqi Mixture is made from 13 traditional Chinese medicines, including Pogostemonis Herba, Perillae Folium, Angelicae Dahuricae Radix, Atractylodis Macrocephalae Rhizoma Praeparatum, Citri Reticulatae Pericarpium, Pinelliae Rhizoma Praeparatum, Magnoliae Officinalis Cortex Praeparatus, Poria, Platycodonis Radix, Glycyrrhizae Radix Et Rhizoma, Arecae Pericarpium, Jujuba Fructus, Zingiberis Rhizoma Recens.

[0003] The preparation method of Jiawei Huoxiang Zhengqi Mixture (Huoxiang Zhengqi Mixture) recorded in the Chinese Pharmacopoeia 2025 edition is as follows: For Pinelliae Rhizoma Praeparatum and Angelicae Dahuricae Radix, according to the percolation method under the items of tincture and extract, using 70% ethanol as the solvent for percolation, and recovering ethanol; for Pogostemonis Herba, Atractylodis Macrocephalae Rhizoma Praeparatum, Magnoliae Officinalis Cortex Praeparatus, Citri Reticulatae Pericarpium and Perillae Folium, distill and extract volatile oil, the medicinal residues are decocted with water three times together with the remaining six herbs including Poria, etc., the decoction liquids are combined, filtered, the filtrate is concentrated to an appropriate amount, combined with the percolate, allowed to stand, filtered, then concentrated to about 1000 ml, an appropriate amount of preservative is added, cooled, the above-mentioned volatile oil is added, and water is added to 1000 ml, and stirred evenly to obtain the product.

[0004] Volatile oil is the effective component in Pogostemonis Herba, Atractylodes macrocephala, Magnoliae officinalis, Citrus reticulata and Perilla frutescens in Jiawei Huoxiang Zhengqi Mixture. Volatile oil is insoluble in water and is volatile under normal temperature and pressure. Its extraction quality directly affects the efficacy of aromatic dampness resolution of the product. After the volatile oil in the existing Jiawei Huoxiang Zhengqi Mixture is extracted from five herbs simultaneously, the medicinal residues are mixed and decocted with other medicinal flavors. Not only is the extraction efficiency of volatile oil low, but due to the interaction of various components in the herbs, after the medicinal residues after extracting volatile oil are decocted with water together with the other six herbs, their chemical components change differently, ultimately resulting in differences in the medicinal effects.

[0005] In addition, the existing Jiawei Huoxiang Zhengqi Mixture mixes the volatile oil with other components by conventional methods, and the presence of volatile oil also affects the taste and flavor of Jiawei Huoxiang Zhengqi Mixture.

[0006] Therefore, developing a Jiawei Huoxiang Zhengqi Mixture that not only conforms to the properties of traditional Chinese medicine, but also can improve the content of effective components in the formula and has a good taste is the direction that researchers have been working hard on. Summary of the Invention

[0007] In order to overcome the shortcomings of the prior art, the technical problem solved by the present invention is to provide a preparation process for a flavored Huoxiang Zhengqi compound. The preparation process can not only increase the content of volatile oil in the flavored Huoxiang Zhengqi compound, but also increase the content of other effective ingredients, and improve the taste and flavor of the flavored Huoxiang Zhengqi compound.

[0008] This invention is achieved through the following technical solution: This invention provides a preparation process for a flavored Huoxiang Zhengqi compound: The aforementioned flavored Huoxiang Zhengqi compound is prepared from the following raw materials: Patchouli 120-150 parts, Perilla leaf 40-50 parts, Angelica dahurica 40-50 parts, stir-fried Atractylodes macrocephala 80-100 parts, dried tangerine peel 80-100 parts, ginger-processed Pinellia ternata 80-100 parts, ginger-processed Magnolia officinalis 80-100 parts, Poria cocos 40-50 parts, Platycodon grandiflorus 80-100 parts, Glycyrrhiza uralensis 80-100 parts, Areca peel 40-50 parts, jujube 20-25 parts, fresh ginger 10-15 parts.

[0009] Preferably, the flavored Huoxiang Zhengqi compound is prepared from the following raw materials: 150 parts of patchouli, 50 parts of perilla leaf, 50 parts of angelica dahurica, 100 parts of stir-fried atractylodes macrocephala, 100 parts of dried tangerine peel, 100 parts of ginger-processed pinellia, 100 parts of ginger-processed magnolia bark, 50 parts of poria cocos, 100 parts of platycodon grandiflorus, 100 parts of licorice root, 50 parts of areca peel, 25 parts of jujube, and 15 parts of fresh ginger.

[0010] The modified Huoxiang Zhengqi compound is prepared by the following process: Pinellia ternata and Angelica dahurica are percolated; volatile oils from Pogostemon cablin, Perilla frutescens, Citrus reticulata peel, Magnolia officinalis, and Atractylodes macrocephala are extracted in groups for 2-5 hours, and the total volatile oil is collected. The residues from each group are decocted with water, and the decoctions are collected. Poria cocos, Platycodon grandiflorus, Glycyrrhiza uralensis, Areca catechu peel, Ziziphus jujuba, and Zingiber officinale are decocted with water to obtain a decoction. The total volatile oil is added to an inclusion compound, and an inclusion compound is obtained using an ultrasonic-assisted method. The percolate, decoction, and inclusion compound are combined, and a preservative is added to prepare the modified Huoxiang Zhengqi compound.

[0011] Specifically, the preparation process includes the following steps: (1) Add ginger, Pinellia ternata and Angelica dahurica to ethanol, soak, and percolate to obtain percolate; (2) Patchouli, perilla leaves, tangerine peel, ginger magnolia bark, and stir-fried atractylodes macrocephala were extracted into groups for 2-5 hours. The total volatile oil was collected. The residue of each group was decocted with 4-8 times the amount of medicinal slices of water 2-3 times, each time for 1-2 hours. The decoction of each group was collected. Extract the volatile oil from any two or three of the following ingredients in combination for 2-4 hours; extract the volatile oil from the other ingredients individually or in groups for 4-5 hours. (3) Take the prescribed amount of Poria cocos, Platycodon grandiflorus, Glycyrrhiza uralensis, Areca catechu peel, Jujube and fresh ginger, add water and decoct 2 to 3 times, 1 to 2 hours each time, and collect the decoction; (4) Combine the percolate from step (1), the decoction from steps (2) and (3), concentrate, let stand, centrifuge, and collect the supernatant; (5) Take the total volatile oil extracted in step (2), add the inclusion material, and use the ultrasonic-assisted method to include it to obtain the volatile oil inclusion complex; (6) Take the supernatant from step (4), the inclusion complex from step (5), and an appropriate amount of preservative, mix them well and set aside. (7) The mixture obtained in step (6) is filtered through a microporous membrane and water is added to the prescription amount to obtain the flavored Huoxiang Zhengqi compound.

[0012] In step (1), the ethanol is 65-75% ethanol, preferably 70%.

[0013] In step (2), the volatile oil of patchouli and perilla leaves is extracted together for 2-3 hours, and the volatile oil of other components is extracted alone or in combination for 4-5 hours. Alternatively, extract volatile oil from perilla leaves and dried tangerine peel together for 3-4 hours, and extract volatile oil from other components alone or in combination for 4-5 hours; Alternatively, the volatile oils of patchouli, perilla leaves, and tangerine peel can be extracted together for 3-4 hours, while the volatile oils of other components can be extracted individually or in combination for 4-5 hours. Furthermore, the volatile oil was extracted from patchouli and perilla leaves together for 2-3 hours, the volatile oil was extracted from tangerine peel and ginger magnolia bark together for 4-5 hours, and the volatile oil was extracted from stir-fried atractylodes macrocephala alone for 4-5 hours. Alternatively, volatile oils can be extracted from patchouli and perilla leaves together for 2-3 hours, while volatile oils can be extracted from tangerine peel, ginger-processed magnolia bark, and stir-fried atractylodes macrocephala separately for 4-5 hours. Alternatively, volatile oils can be extracted from a combination of patchouli, perilla leaves, and dried tangerine peel for 3-4 hours, or from a combination of ginger-processed magnolia bark and stir-fried atractylodes macrocephala for 4-5 hours. Alternatively, extract volatile oil from perilla leaves and dried tangerine peel together for 3-4 hours, extract volatile oil from patchouli and stir-fried atractylodes macrocephala together for 4-5 hours, or extract volatile oil from magnolia bark alone for 4-5 hours.

[0014] In step (3), the amount of water used is 4 to 8 times the total amount of medicinal materials.

[0015] In step (4), the decoction is concentrated to 0.8 to 1.2 times the prescription amount.

[0016] In step (4), centrifugation is performed at 8000-10000 rpm for 45-80 min.

[0017] In step (5), the inclusion material is dissolved in water, the total volatile oil is slowly added dropwise to the aqueous solution of the inclusion material, and the inclusion volatile oil is placed in an ultrasonic cell disruptor.

[0018] The volume ratio of the total volatile oil to the mass ratio of the inclusion material is 1:6~14, preferably 1:6~12 (ml / g); The packaged power is 150-300W, preferably 250-300W.

[0019] The encapsulation time is 15-30 minutes, preferably 20-25 minutes.

[0020] The inclusion material is at least one of β-cyclodextrin (β-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD), polyethylene glycol (PEG), and chitosan (CS), preferably hydroxypropyl-β-cyclodextrin.

[0021] In step (6), the preservative is at least one of potassium sorbate, sodium benzoate, sodium dehydroacetate, and methylparaben; In step (7), the pore size of the microporous filter membrane is 0.22μm~0.8μm; In step (7), the volume ratio of the supernatant to the Huoxiang Zhengqi mixture is 3~4:5, and the mass-volume ratio of the inclusion compound to the Huoxiang Zhengqi mixture is 4~5:50.

[0022] In step (7), the mass-to-volume ratio of the inclusion compound to the supernatant is 1:6-10.

[0023] Compared with the prior art, the present invention has the following beneficial effects: 1. This invention improves the extraction efficiency and purity of volatile oils by extracting them in groups from medicinal materials containing volatile oils. The main volatile oil-containing medicinal materials in the modified Huoxiang Zhengqi compound are patchouli, perilla leaves, stir-fried atractylodes macrocephala, tangerine peel, and ginger-processed magnolia bark. These medicinal materials have significant differences in the polarity and boiling point of their volatile oil components. Group extraction, based on the characteristics of each medicinal material, avoids the problems of high-boiling-point components being difficult to distill and low-boiling-point components being prematurely lost during mixed extraction, significantly improving the yield and purity of the target volatile oil.

[0024] This invention, by extracting medicinal materials containing volatile oils in groups, avoids interference and damage from non-volatile oil components. During mixed extraction, water-soluble impurities such as tannins, polysaccharides, and proteins in the medicinal materials condense with water vapor and mix into the volatile oil. These impurities can cause emulsification and separation difficulties in the volatile oil, and also increase the difficulty of subsequent refining. Group extraction reduces the mixing of impurities and avoids the damage to heat-sensitive components in the volatile oil caused by high-temperature, long-term extraction.

[0025] This invention reduces the difficulty of subsequent formulation processes by extracting volatile oil-containing medicinal materials in groups. The volatile oils extracted and refined in groups are more stable. When preparing compound preparations, stable dispersion can be achieved more efficiently through techniques such as solubilization and inclusion. This avoids problems such as turbidity, layering, and precipitation in the preparation caused by low purity and high impurities of the volatile oil.

[0026] The present invention provides a flavored Huoxiang Zhengqi compound with better taste and flavor by encapsulating volatile oils and mixing them with other ingredients.

[0027] The preparation process of this invention is applicable to other preparations made with the formula of Jiawei Huoxiang Zhengqi, such as Jiawei Huoxiang Zhengqi oral liquid and Jiawei Huoxiang Zhengqi water. Attached Figure Description

[0028] Figure 1 The effect of the ratio of hydroxypropyl-β-cyclodextrin to volatile oil on inclusion rate and oil content in Example 6.

[0029] Figure 2 The effect of ultrasonic power on inclusion rate and oil content in Example 7.

[0030] Figure 3 The effect of inclusion time on inclusion rate and oil content in Example 8. Detailed Implementation

[0031] Example 1: Preparation of Enhanced Huoxiang Zhengqi Mixture 1 prescription: Patchouli 150g, Perilla leaf 50g, Angelica dahurica 50g, stir-fried Atractylodes macrocephala 100g, dried tangerine peel 100g, ginger-processed Pinellia ternata 100g, ginger-processed Magnolia officinalis 100g, Poria cocos 50g, Platycodon grandiflorus 100g, Glycyrrhiza uralensis 100g, Areca peel 50g, jujube 25g, fresh ginger 15g.

[0032] Prepare 1000mL of flavored Huoxiang Zhengqi mixture, and dispense it into 100 bottles, each containing 10mL.

[0033] Preparation process: (1) Take 100g of ginger-processed Pinellia ternata and 50g of Angelica dahurica, coarsely crush them, add about 50ml of 70% ethanol to soak for 1 hour, continue to add about 150ml of 70% ethanol to soak for 24 hours, continue to add 70% ethanol to percolate, take 3 times the amount of the prescription amount of the filtrate, concentrate it, recover the ethanol, and obtain the percolate.

[0034] (2) Take 150g of patchouli and 50g of perilla leaves according to the prescription, add 8 times the amount of water and decoct for 3 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. Take 100g of dried tangerine peel and 100g of ginger and magnolia bark, add 8 times the amount of water and decoct for 4 hours. Collect the volatile oil. Add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour. Combine and collect the decoction. Take 100g of stir-fried Atractylodes macrocephala according to the prescription, add 8 times the amount of water and decoct for 5 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. (3) Take the prescription amount of 50g of Poria cocos, 100g of Platycodon grandiflorus, 100g of Glycyrrhiza uralensis, 50g of Areca peel, 25g of Jujube, and 15g of fresh ginger. Add 6 times the amount of water and decoct for 1.5h, add 4 times the amount of water and decoct for 1h, and add 4 times the amount of water and decoct for 1h respectively. Combine and collect the decoction.

[0035] (4) Combine the percolate from step (1) and the decoction from steps (2) to (3), concentrate to 1.2 times the prescription amount, let stand at 4℃ for 48 hours, centrifuge at 8000 rpm for 60 minutes, and collect the supernatant for later use.

[0036] (5) Take hydroxypropyl-β-cyclodextrin (HP-β-CD), dissolve it in water, slowly add the total volatile oil from step (2) to the aqueous solution of HP-β-CD, place it in an ultrasonic cell disruptor, and use ultrasonic-assisted method to encapsulate the total volatile oil from step (2). The encapsulation power is 250W and the time is 20min. After encapsulation, add an appropriate amount of sodium benzoate and mix it with the supernatant from step (4) for later use. The volume-to-mass ratio of total volatile oil to hydroxypropyl-β-cyclodextrin is 1:12 (ml:g).

[0037] (6) Pass the mixture prepared in step (5) through 0.45μm and 0.22μm microporous filter membranes three times each, and add water to the prescription amount to obtain 1000 mL of Jiawei Huoxiang Zhengqi Mixture.

[0038] Example 2: Preparation of Flavored Huoxiang Zhengqi Mixture 2 The prescription is as in Example 1.

[0039] Preparation process: (1) Take 100g of ginger-processed Pinellia ternata and 50g of Angelica dahurica, coarsely crush them, add about 50ml of 70% ethanol to soak for 1 hour, continue to add about 150ml of 70% ethanol to soak for 24 hours, continue to add 70% ethanol to percolate, take 5 times the amount of the prescription amount of the filtrate, concentrate it, recover the ethanol, and obtain the percolate.

[0040] (2) Take 150g of patchouli, 50g of perilla leaves and 100g of tangerine peel according to the prescription, add 8 times the amount of water and decoct for 4 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. Take 100g of Magnolia officinalis and 100g of Atractylodes macrocephala (fried) according to the prescription, add 8 times the amount of water and decoct for 4 hours. Collect the volatile oil. Add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively. Combine and collect the decoction.

[0041] (3) Take the prescription amount of 50g of Poria cocos, 100g of Platycodon grandiflorus, 100g of Glycyrrhiza uralensis, 50g of Areca peel, 25g of Jujube, and 15g of fresh ginger. Add 6 times the amount of water and decoct for 1.5h, add 4 times the amount of water and decoct for 1h, and add 4 times the amount of water and decoct for 1h respectively. Combine and collect the decoction.

[0042] (4) Combine the percolate from step (1) and the decoction from steps (2) to (3), concentrate to 1.2 times the prescription amount, let stand at 4℃ for 48 hours, centrifuge at 10000 rpm for 45 minutes, and collect the supernatant for later use.

[0043] (5) Take hydroxypropyl-β-cyclodextrin (HP-β-CD), dissolve it in water, slowly add the total volatile oil from step (2) to the aqueous solution of HP-β-CD, place it in an ultrasonic cell disruptor, and use ultrasonic-assisted method to encapsulate the total volatile oil from step (2). The encapsulation power is 250W and the time is 20min. After encapsulation, add an appropriate amount of sodium benzoate and mix it with the supernatant from step (4) for later use. The volume-to-mass ratio of volatile oil to hydroxypropyl-β-cyclodextrin is 1:12 (ml:g).

[0044] (6) Pass the mixture prepared in step (5) through 0.45μm and 0.22μm microporous membranes three times each, and add water to the prescription amount to obtain 1000mL of Jiawei Huoxiang Zhengqi Mixture.

[0045] Example 3: Preparation of Flavored Huoxiang Zhengqi Mixture 3 The prescription is as in Example 1.

[0046] Preparation process: (1) Take 100g of ginger-processed Pinellia ternata and 50g of Angelica dahurica, coarsely crush them, add about 50ml of 70% ethanol to soak for 1 hour, continue to add about 150ml of 70% ethanol to soak for 24 hours, continue to add 70% ethanol to percolate, take 3 times the amount of the prescription amount of the filtrate, concentrate it, recover the ethanol, and obtain the percolate.

[0047] (2) Take 150g of patchouli and 50g of perilla leaves according to the prescription, add 8 times the amount of water and decoct for 3 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. Take 100g of the prescribed amount of dried tangerine peel, add 8 times the amount of water and decoct for 4 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours, add 4 times the amount of water and decoct for 1 hour, and combine and collect the decoction. Take 100g of stir-fried Atractylodes macrocephala according to the prescription, add 8 times the amount of water and decoct for 5 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. Take 100g of the prescribed amount of Magnolia officinalis, add 8 times the amount of water and decoct for 4 hours. Collect the volatile oil. Add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour. Combine and collect the decoctions.

[0048] (3) Take the prescription amount of 50g of Poria cocos, 100g of Platycodon grandiflorus, 100g of Glycyrrhiza uralensis, 50g of Areca peel, 25g of Jujube, and 15g of fresh ginger. Add 6 times the amount of water and decoct for 1.5h, add 4 times the amount of water and decoct for 1h, and add 4 times the amount of water and decoct for 1h respectively. Combine and collect the decoction.

[0049] (4) Combine the percolate from step (1) and the decoction from steps (2) to (3), concentrate to 1.2 times the prescription amount, let stand at 4℃ for 48 hours, centrifuge at 8000 rpm for 60 minutes, and collect the supernatant for later use.

[0050] (5) Take hydroxypropyl-β-cyclodextrin (HP-β-CD), dissolve it in water, slowly add the total volatile oil from step (2) to the aqueous solution of HP-β-CD, place it in an ultrasonic cell disruptor, and use ultrasonic-assisted method to encapsulate the volatile oil in step (2) at a power of 250W for 20 minutes. After encapsulation, add an appropriate amount of sodium benzoate and mix it with the supernatant from step (4) for later use. The volume-to-mass ratio of volatile oil to hydroxypropyl-β-cyclodextrin is 1:12 (ml:g).

[0051] (6) Pass the mixture prepared in step (5) through 0.45μm and 0.22μm microporous filter membranes three times each, and add water to the prescription amount to obtain 1000 mL of Jiawei Huoxiang Zhengqi Mixture.

[0052] Example 4: Preparation of Flavored Huoxiang Zhengqi Mixture 4 The prescription is as in Example 1.

[0053] Preparation process: (1) Take 100g of ginger-processed Pinellia ternata and 50g of Angelica dahurica according to the prescription, coarsely crush them, add about 50ml of 70% ethanol to soak for 1 hour, continue to add about 150ml of 70% ethanol to soak for 24 hours, percolate and take 3 times the amount of the prescription filtrate, concentrate, recover the ethanol, and obtain the percolate.

[0054] (2) Take 100g of dried tangerine peel and 50g of perilla leaves according to the prescription, add 8 times the amount of water and decoct for 4 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. Take 100g of the prescribed amount of Magnolia officinalis, add 8 times the amount of water and decoct for 4 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. Take 150g of the prescribed amount of patchouli and 100g of stir-fried atractylodes macrocephala, add 8 times the amount of water and decoct for 5 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. (3) Take the prescription amount of 50g of Poria cocos, 100g of Platycodon grandiflorus, 100g of Glycyrrhiza uralensis, 50g of Areca peel, 25g of Jujube, and 15g of fresh ginger. Add 6 times the amount of water and decoct for 1.5h, add 4 times the amount of water and decoct for 1h, and add 4 times the amount of water and decoct for 1h respectively. Combine and collect the decoction.

[0055] (4) Combine the percolate from step (1) and the decoction from steps (2) to (3), concentrate to 1.2 times the prescription amount, let stand at 4℃ for 48 hours, centrifuge at 10000 rpm for 80 minutes, and collect the supernatant for later use.

[0056] (5) Take hydroxypropyl-β-cyclodextrin (HP-β-CD), dissolve it in water, slowly add the total volatile oil from step (2) to the aqueous solution of HP-β-CD, place it in an ultrasonic cell disruptor, and use ultrasonic-assisted method to encapsulate the total volatile oil from step (2) at a power of 250W for 20 minutes. After encapsulation, add an appropriate amount of sodium benzoate and mix it with the supernatant from step (4) for later use. The volume-to-mass ratio of volatile oil to hydroxypropyl-β-cyclodextrin is 1:12 (ml:g).

[0057] (6) Pass the solution prepared in step (5) through 0.45μm and 0.22μm microporous filter membranes three times each, and add water to the prescription amount to obtain 1000 mL of Jiawei Huoxiang Zhengqi Mixture.

[0058] Comparative Example 1: Preparation of Enhanced Huoxiang Zhengqi Mixture 5 The prescription and preparation process are the same as in Example 1, except for step (2), which is as follows: Take 150g of the prescribed amount of patchouli, add 8 times the amount of water and decoct for 3 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours, add 4 times the amount of water and decoct for 1 hour, and combine and collect the decoction. Take 50g of the prescribed amount of perilla leaves, add 8 times the amount of water and decoct for 3 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours, add 4 times the amount of water and decoct for 1 hour, and combine and collect the decoction. Take 100g of the prescribed amount of dried tangerine peel, add 8 times the amount of water and decoct for 4 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours, add 4 times the amount of water and decoct for 1 hour, and combine and collect the decoction. Take 100g of the prescribed amount of Magnolia officinalis, add 8 times the amount of water and decoct for 4 hours, collect the volatile oil, add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively, and combine and collect the decoction. Take 100g of stir-fried Atractylodes macrocephala according to the prescription, add 8 times the amount of water and decoct for 5 hours. Collect the volatile oil. Add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour respectively. Combine and collect the decoction.

[0059] Comparative Example 2: Preparation of Enhanced Huoxiang Zhengqi Mixture 6 The prescription and preparation process are the same as in Example 1, except for step (2), which is as follows: Take the prescribed amount of 150g of patchouli, 50g of perilla leaf, 100g of dried tangerine peel, 100g of ginger-processed magnolia bark, and 100g of stir-fried atractylodes macrocephala. Add 8 times the amount of water and decoct for 4 hours. Collect the volatile oil. Add 6 times the amount of water to the residue and decoct for 1.5 hours and 4 times the amount of water to the residue and decoct for 1 hour. Combine and collect the decoction.

[0060] Comparative Example 3: Preparation of Enhanced Huoxiang Zhengqi Mixture 7 Prepared according to the preparation method under the "Modified Huoxiang Zhengqi Mixture" section in Part I of the 25th edition of the Chinese Pharmacopoeia: 100g of ginger-processed Pinellia ternata and 50g of Angelica dahurica were percolated according to the percolation method under the section on fluid extracts and extracts (General Rule 0189), using 70% ethanol as solvent, and the ethanol was recovered. 150g of Pogostemon cablin, 100g of stir-fried Atractylodes macrocephala, 100g of ginger-processed Magnolia officinalis, 100g of Citrus reticulata peel, and 50g of Perilla frutescens leaves were distilled to extract volatile oil. The residue and the remaining six herbs, including Poria cocos, were decocted three times with water, with the water volume being 8 times, 6 times, and 4 times respectively, and the decoction times being 2 hours, 1.5 hours, and 1 hour respectively. The decoctions were combined, filtered, and the filtrate was concentrated to an appropriate volume. It was then combined with the percolate, allowed to stand, filtered, and concentrated again to about 1000ml. An appropriate amount of preservative was added, and the mixture was cooled. The above-mentioned volatile oil was added, and water was added to 1000ml. The mixture was stirred well to obtain the final product.

[0061] Example 5: Total extraction rate of volatile oils obtained from Examples 1-4 and Comparative Examples 1-3 Determination method: According to Method A of volatile oil determination in Volume IV, 2204 of the 25th edition of the Chinese Pharmacopoeia, after the volatile oil extraction is completed, stop heating, let it stand for a while, open the lower piston of the measuring device, and slowly release water until the upper end of the oil layer reaches 5mm above the 0 line of the scale. Read the amount of volatile oil, calculate the content (%) of volatile oil in the sample, and calculate the total extraction rate of volatile oil.

[0062] The total extraction rate of volatile oils in Examples 1-4 and Comparative Examples 1-3 was determined according to the above method, and the results are shown in Table 1.

[0063]

[0064] Table 1 shows that group extraction of volatile oils significantly improves the total extraction rate. This may be due to the different temperature sensitivities of volatile oil components in different medicinal materials, thus resulting in a significantly higher efficiency compared to mixed extraction. Furthermore, combining different medicinal materials may promote the extraction of volatile oil components compared to extracting them individually. Therefore, group extraction of volatile oils is more efficient than extracting all medicinal materials containing volatile oils individually or in combination.

[0065] Example 6: Effect of hydroxypropyl-β-cyclodextrin dosage on volatile oil inclusion rate and oil content Weigh 2.4 g of hydroxypropyl-β-cyclodextrin (HP-β-CD) and add 7.2 mL of distilled water. Dissolve the cyclodextrin in water at 60 °C with stirring to form an aqueous solution. Take 0.4 mL, 0.3 mL, 0.24 mL, 0.2 mL, and 0.17 mL of the total volatile oil from Comparative Example 3, respectively, and slowly add them dropwise to the above aqueous cyclodextrin solution. Place the solution in an ultrasonic cell disruptor, set the ultrasonic power to 200 W, and the ultrasonic time to 30 min to encapsulate the volatile oil. Investigate the encapsulation rate and oil content of the volatile oil when the volume ratio (g / mL) of hydroxypropyl-β-cyclodextrin to volatile oil is 6:1, 8:1, 10:1, 12:1, and 14:1. The results are shown below. Figure 1 .

[0066] The results showed that as the ratio of cyclodextrin to volatile oil gradually increased from 6:1 to 14:1, both the inclusion efficiency and the content of volatile oil released after cyclodextrin degradation showed a synchronous decreasing trend: the inclusion efficiency was highest and the absolute amount of volatile oil encapsulated was largest at 6:1; both decreased continuously with the increase of the cyclodextrin ratio, and tended to stabilize after 12:1, with the inclusion efficiency and encapsulated oil content being only about 52% and 3.9% at 14:1. This indicates that a low cyclodextrin ratio is more conducive to improving the inclusion efficiency and loading of volatile oil, while excessive cyclodextrin will significantly weaken the inclusion effect, and further increasing the cyclodextrin ratio beyond 12:1 has no significant gain. It can be seen that within the range of 6:1-14:1, the inclusion efficiency can reach more than 50%, and the inclusion efficiency and oil content of volatile oil at the low ratio are higher than those at the high ratio.

[0067] Example 7: Effect of ultrasonic power on inclusion rate and oil content in inclusion of hydroxypropyl-β-cyclodextrin Weigh 2.4 g of hydroxypropyl-β-cyclodextrin (HP-β-CD) and add 7.2 mL of distilled water. Dissolve the cyclodextrin in water at 60 °C with stirring to form an aqueous cyclodextrin solution. Take 0.2 mL of the total volatile oil from Comparative Example 3 and slowly add it dropwise to the above cyclodextrin aqueous solution. Place the solution in an ultrasonic cell disruptor and set the ultrasonic power to 100 W, 150 W, 200 W, 250 W, and 300 W for 20 min to encapsulate the volatile oil. Inclusion efficiency and oil content were investigated at different inclusion powers. Results are shown below. Figure 2 .

[0068] The results show that when the power is 150-300W, the encapsulation rate can reach more than 50%, and the encapsulation rate and oil content are both optimal at 250W.

[0069] Example 8: Effect of inclusion time on inclusion rate and oil content in hydroxypropyl-β-cyclodextrin inclusion complexation. 2.4 g of hydroxypropyl-β-cyclodextrin (HP-β-CD) was weighed and added to 7.2 mL of distilled water. The solution was dissolved in the solution by stirring at 60 °C. 0.2 mL of the total volatile oil from Comparative Example 3 was slowly added dropwise to the above cyclodextrin solution. The mixture was placed in an ultrasonic cell disruptor, with the ultrasonic power set to 250 W, and ultrasonic times set to 10 min, 15 min, 20 min, 25 min, and 30 min, to encapsulate the volatile oil. The encapsulation rate and oil content under different encapsulation time conditions were investigated. The results are shown below. Figure 3 .

[0070] The results showed that the inclusion rate could reach over 50% when the time was 15-30 min, and the inclusion rate and oil content were both optimal when the time was 20 min.

[0071] Example 9: Determination of the content of main active ingredients in Jiawei Huoxiang Zhengqi Mixture The main active ingredients in the modified Huoxiang Zhengqi compound were determined, including hesperidin (the main ingredient in tangerine peel), hydrated oxypenicillin (the main ingredient in angelica dahurica), magnolol and honokiol (the main ingredients in magnolia bark), patchouli flavonol (the main ingredient in patchouli), and baicalin in the volatile oil of patchouli. The results are shown in Table 2.

[0072] Determination methods: Refer to the determination methods for hesperidin under the item "Jiawei Huoxiang Zhengqi Heji" in Part I of the 25th edition of the Chinese Pharmacopoeia, the determination methods for hydrated oxypenicillin under the item "Baizhi", the determination methods for magnolol and honokiol under the item "Houpo", and the determination methods for patchouli flavonol and baicaleol under the item "Guanghuoxiang".

[0073]

[0074] Table 2 shows that the preparation process described in this invention has no significant effect on the content of the active ingredients hydrated oxidized imperatorin and patchouli flavonol, but it can significantly increase the content of hesperidin, magnolol, and honokiol or baicalein, especially the content of the volatile oil component baicalein. Under the group extraction conditions of Examples 1 and 4, not only was the volatile oil content significantly increased, but the content of other active ingredients was also promoted.

[0075] Example 10: Taste evaluation of the flavored Huoxiang Zhengqi compound. The taste of Examples 1, 2, 3, and 4, and Comparative Examples 1 and 2, was evaluated against commercially available Huoxiang Zhengqi Water, Huoxiang Zhengqi Oral Liquid, and Huoxiang Zhengqi Mixture.

[0076] Evaluation Method: The evaluation team consisted of 5 evaluators who had received basic sensory training. Training was provided before the experiment to familiarize them with the evaluation criteria. To avoid the order effect, a randomized, blinded method was used for tasting. All samples were compared using equivalent amounts of raw medicinal materials. All samples were prepared to the same equivalent concentration of raw medicinal materials. Each tasting volume was fixed at 10 ml. The tasting procedure involved the evaluator gargling the sample for 10 seconds, spitting it out, immediately rinsing their mouth with water, and tasting the next sample after at least 5 minutes. The experimenter scored each sample based on the evaluator's description and facial expressions. Each sample was evaluated by 5 evaluators, who assigned scores according to different levels.

[0077] Evaluation indicators and scoring table (Table 3): A 9-point sensory scoring method was used, with higher scores indicating better taste and less off-flavor. The results are shown in Table 4.

[0078]

[0079]

[0080] The experimental results show that the Huoxiang Zhengqi mixture prepared by encapsulating volatile oil with water-soluble cyclodextrin has a significantly improved taste compared with traditional liquid preparations (Huoxiang Zhengqi Water, Oral Liquid, and commercially available Huoxiang Zhengqi mixture), especially in reducing the spicy and irritating taste and unpleasant odor, thus improving patients' medication compliance.

[0081] In summary, the preparation process of this invention employs group extraction of five medicinal materials containing volatile oils, thereby improving the extraction efficiency of volatile oils. By encapsulating the obtained volatile oils, the pungent and irritating taste of volatile oils such as patchouli oil and perilla leaf oil is effectively masked, resulting in a significant improvement in the taste and flavor of the prepared Huoxiang Zhengqi compound. Simultaneously, it increases the content of other major components in the medicinal materials, such as hesperidin, hydrated oxypenicillin, magnolol, honokiol, and patchouli flavonol, thus effectively enhancing its efficacy.

Claims

1. A preparation process for a flavored Huoxiang Zhengqi compound, characterized in that, Pinellia ternata and Angelica dahurica were percolated. Patchouli, Perilla frutescens, Citrus reticulata peel, Magnolia officinalis, and Atractylodes macrocephala were extracted for volatile oil in groups for 2-5 hours. The total volatile oil was collected, and the residues of each group were decocted with water to collect the decoction. Poria cocos, Platycodon grandiflorus, Glycyrrhiza uralensis, Areca catechu peel, Ziziphus jujuba, and Zingiber officinale were decocted with water to obtain a decoction. The total volatile oil was added to inclusion material and included using an ultrasonic-assisted method to obtain inclusion complex. The percolated liquid and decoction were combined, concentrated, and centrifuged to obtain the supernatant. The supernatant and inclusion complex were added to a preservative to prepare a modified Huoxiang Zhengqi compound.

2. The preparation process of the flavored Huoxiang Zhengqi compound according to claim 1, characterized in that, Volatile oils were extracted from any two or three of the following: patchouli, perilla leaf, and dried tangerine peel. Volatile oils were extracted from the other components individually or in groups.

3. The preparation process of the flavored Huoxiang Zhengqi compound according to claim 2, characterized in that, The volatile oils of patchouli and perilla leaves are extracted together, while the volatile oils of other components are extracted individually or in combination; or the volatile oils of perilla leaves and tangerine peel are extracted together, while the volatile oils of other components are extracted individually or in combination; or the volatile oils of patchouli, perilla leaves, and tangerine peel are extracted together, while the volatile oils of other components are extracted individually or in combination.

4. The preparation process of the flavored Huoxiang Zhengqi compound according to claim 3, characterized in that, The volatile oils were extracted from a combination of patchouli and perilla leaves, and from a combination of tangerine peel and magnolia bark, and from a single stir-fried atractylodes macrocephala. Alternatively, the volatile oils were extracted from a combination of patchouli and perilla leaves, and from a single combination of tangerine peel, magnolia bark, and stir-fried atractylodes macrocephala. Alternatively, the volatile oils were extracted from a combination of patchouli, perilla leaves, and tangerine peel, and from a combination of magnolia bark and stir-fried atractylodes macrocephala. Alternatively, the volatile oils were extracted from a combination of perilla leaves and tangerine peel, and from a combination of patchouli and stir-fried atractylodes macrocephala, and from a single combination of magnolia bark.

5. The preparation process of the flavored Huoxiang Zhengqi compound according to any one of claims 1-4, characterized in that, Pinellia ternata and Angelica dahurica are percolated with 65-75% ethanol.

6. The preparation process of the flavored Huoxiang Zhengqi compound according to claim 1, characterized in that, The inclusion material is at least one of β-cyclodextrin, hydroxypropyl-β-cyclodextrin, polyethylene glycol, and chitosan, preferably hydroxypropyl-β-cyclodextrin.

7. The preparation process of the flavored Huoxiang Zhengqi compound according to claim 6, characterized in that, The volume ratio of total volatile oil to the mass ratio of the inclusion material is 1:6~14, preferably 1:6~12.

8. The preparation process of the flavored Huoxiang Zhengqi compound according to claim 1, characterized in that, In the aforementioned Huoxiang Zhengqi Mixture, the volume ratio of the supernatant to the Huoxiang Zhengqi Mixture is 3~4:5, and the mass-volume ratio of the inclusion compound to the Huoxiang Zhengqi Mixture is 4~5:

50.

9. The preparation process of the flavored Huoxiang Zhengqi compound according to any one of claims 1-8, characterized in that, The aforementioned flavored Huoxiang Zhengqi compound is prepared from the following raw materials: 120-150 parts of patchouli, 40-50 parts of perilla leaf, 40-50 parts of angelica dahurica, 80-100 parts of stir-fried atractylodes macrocephala, 80-100 parts of tangerine peel, 80-100 parts of ginger-processed pinellia, 80-100 parts of ginger-processed magnolia bark, 40-50 parts of poria cocos, 80-100 parts of platycodon grandiflorus, 80-100 parts of licorice root, 40-50 parts of areca peel, 20-25 parts of jujube, and 10-15 parts of fresh ginger; preferably, 150 parts of patchouli, 50 parts of perilla leaf, 50 parts of angelica dahurica, 100 parts of stir-fried atractylodes macrocephala, 100 parts of tangerine peel, 100 parts of ginger-processed pinellia, 100 parts of ginger-processed magnolia bark, 50 parts of poria cocos, 100 parts of platycodon grandiflorus, 100 parts of licorice root, 50 parts of areca peel, 25 parts of jujube, and 15 parts of fresh ginger.

10. The application of the preparation process described in claims 1-9 in the preparation of Jiawei Huoxiang Zhengqi Mixture, Jiawei Huoxiang Zhengqi Oral Liquid, and Jiawei Huoxiang Zhengqi Water.

Images