Wind-dispelling orifice-opening preparation composition, preparation method, optimization method, application of wind-dispelling orifice-opening preparation composition and preparation of wind-dispelling orifice-opening preparation composition

Abstract

The invention discloses a wind-dispelling and orifice-freeing preparation composition, a preparation method, an optimization method, application of the wind-dispelling and orifice-freeing preparation composition and a preparation, and belongs to the field of traditional Chinese medicine pharmacy, the wind-dispelling and orifice-freeing preparation composition contains a wind-dispelling and orifice-freeing traditional Chinese medicine composition and a diluent, and the weight ratio of the diluent to the traditional Chinese medicine composition is (0.8-3): 1. According to the invention, the process and auxiliary materials are optimized, so that the content of atractylis glycoside in the preparation is reduced, and the safety of the product is improved. Meanwhile, the quality of the wind-dispelling orifice-freeing preparation composition can be optimized, including reduction of the atractylis glycoside content, reduction of the total ephedrine content and / or reduction of the water content, and compared with the prior art, the wind-dispelling orifice-freeing preparation composition has good quality and long-term stability.

Description

[0001] Priority claim: This invention claims priority to Chinese Patent Application No. 202410547439X, filed on April 30, 2024, the entire contents of which are incorporated herein by reference. Technical Field

[0002] This invention belongs to the field of traditional Chinese medicine pharmaceuticals, specifically relating to a wind-dispelling and orifice-opening preparation composition, preparation method, optimization method, and its application and formulation. Background Technology

[0003] Allergic rhinitis (AR) in children refers to a non-infectious inflammatory disease of the nasal mucosa, primarily mediated by specific IgE, that occurs after exposure to allergens in susceptible children. The prevalence of allergic rhinitis in children in my country is approximately 10%, and this prevalence continues to increase. Genetics and constitution are the main factors, while environment, diet, and disease can also contribute to the occurrence and development of allergic rhinitis. Based on the duration of symptoms, it is classified into intermittent allergic rhinitis and persistent allergic rhinitis. The concept that allergic rhinitis and bronchial asthma are "the same disease of the same airway" has been increasingly confirmed by research. Most asthma patients also have allergic rhinitis (>80%), and many allergic rhinitis patients also have asthma (approximately 50%). Individuals with allergic rhinitis are three times more likely to develop asthma later in life than those without.

[0004] Treatment methods for allergic rhinitis in children mainly include immunotherapy and drug therapy: (1) Immunotherapy: By applying a specific allergen vaccine with gradually increasing doses, the symptoms caused by allergen exposure are reduced, enabling the child to achieve clinical and immune tolerance. It is generally for children over 5 years old who do not respond to conventional drug treatment and whose allergic rhinitis is mainly caused by dust mite allergy; (2) Drug therapy: At present, the main purpose of allergic rhinitis treatment is still to relieve symptoms. Therapeutic drugs include glucocorticoids, antihistamines, leukotriene receptor antagonists, decongestants and mast cell membrane stabilizers. Among them, nasal glucocorticoids are recognized as having a definite curative effect. They have low bioavailability, no obvious systemic side effects, good safety, and are convenient to use, inexpensive, and can be used for a long time. Therefore, they are recommended by WHO and ARIA guidelines as the first-line drugs for the treatment of allergic rhinitis. The mechanism of action of glucocorticoids is to inhibit the activity of phospholipase A2, thereby reducing the synthesis of inflammatory mediators such as prostaglandins and leukotrienes; stabilize mast cell membranes and lysosomal membranes, thereby reducing mast cell degranulation and the release of histamine and pro-inflammatory substances; inhibit the transcription and release of macrophage colony-stimulating factors, and activate neutrophils and macrophages.

[0005] Existing technology (Study on the Effect Mechanism of Xiaofeng Xuanqiao Decoction on a Mouse Model of Allergic Rhinitis, Tao Jialei, Journal of Nanjing University of Traditional Chinese Medicine, 2017-03-10, Journal) records a traditional Chinese medicine composition with the following ingredients: Ephedra 3g, Cinnamon Twig 3g, Magnolia Flower 6g, Xanthium Fruit 6g, Schisandra Fruit 6g, Mume Fruit 6g, Earthworm 6g, and Arisaema Bile 6g. Preliminary evidence suggests its effectiveness against allergic rhinitis in children. However, raw Xanthium Fruit slices are toxic. Therefore, reducing the toxicity of Xanthium Fruit and providing a safer and more effective Xiaofeng Xuanqiao composition is a pressing technical challenge. Summary of the Invention

[0006] The purpose of this invention is to provide a wind-dispelling and orifice-clearing preparation composition, preparation method, optimization method, and its application and formulation. On the one hand, this invention reduces the content of atractylodesin in the preparation by heating and processing Xanthium sibiricum; on the other hand, it reduces the content of atractylodesin in the preparation and improves product safety by optimizing the process and excipients.

[0007] To achieve the above objectives, the present invention adopts the following technical solution:

[0008] In a first aspect, the present invention provides a wind-dispelling and orifice-opening preparation composition, comprising a traditional Chinese medicine composition for wind-dispelling and orifice-opening and a diluent.

[0009] The weight ratio of the diluent to the traditional Chinese medicine composition in this invention is 0.8-3:1; preferably 0.9-2.5:1; more preferably 1-2:1; and even more preferably 1.5-2:1.

[0010] The diluent used in this invention is dextrin.

[0011] In some embodiments, the wind-dispelling and orifice-opening preparation composition is prepared by mixing the traditional Chinese medicine composition with a diluent and then wet granulating it.

[0012] In some embodiments, the binder used in the wet granulation is ethanol, preferably 85%-95% ethanol, more preferably 85% ethanol, wherein the volume ratio of the binder to the weight ratio of the traditional Chinese medicine composition to the diluent is 1-15ml:10-50g, preferably 1-10ml:20-40g, more preferably 2-10ml:20-40g, and even more preferably 2.5-9ml:25-30g.

[0013] In some embodiments, the wet granulation includes extruding through a 16-mesh sieve, drying at 35-70°C, and granulation using sieves No. 1 and No. 5; more preferably, drying at 40-50°C.

[0014] The traditional Chinese medicine composition described in this invention is made from the following raw materials: ephedra, cinnamon twig, magnolia flower, cocklebur, schisandra, dried plum, arisaema cum bile, and earthworm; preferably, it is made from the following raw materials in parts by weight: 2-4 parts ephedra, 2-4 parts cinnamon twig, 3-9 parts magnolia flower, 3-9 parts cocklebur, 3-9 parts schisandra, 3-9 parts dried plum, 3-9 parts arisaema cum bile, and 3-9 parts earthworm; more preferably, 3 parts ephedra, 3 parts cinnamon twig, 6 parts magnolia flower, 6 parts cocklebur, 6 parts schisandra, 6 parts dried plum, 6 parts arisaema cum bile, and 6 parts earthworm.

[0015] In some implementations, the ephedra is preferably honey-processed ephedra, the cocklebur is preferably stir-fried cocklebur, and the schisandra is preferably vinegar-processed schisandra.

[0016] The processing method of stir-fried cocklebur in this invention is as follows: heat and stir-fry the raw cocklebur, remove it, let it cool, remove the thorns, and sift it clean.

[0017] In some embodiments, the heating and frying is performed at 120-140°C for 10-25 minutes, preferably at 120°C for 10-25 minutes, and more preferably at 120°C for 15 minutes.

[0018] Secondly, the present invention provides a method for preparing the aforementioned wind-dispelling and orifice-opening preparation composition, comprising the following steps:

[0019] (1) Extract the volatile oil from cinnamon twig and magnolia flower to obtain filtrate, residue and volatile oil;

[0020] (2) The residue after extracting the volatile oil was combined with other raw materials and water-extracted to obtain an aqueous extract;

[0021] (3) The concentrated water extract was subjected to alcohol precipitation to obtain an alcohol precipitation solution.

[0022] (4) Concentrate the alcoholic solution to obtain an extract;

[0023] Further, it may include: (5) the volatile oil and the extract are combined.

[0024] In some embodiments, the extraction in step (1) is steam distillation; preferably, the amount of water used is 4-16 times the total weight of cinnamon twig and magnolia flower, more preferably 6-12 times, even more preferably 7-9 times, even more preferably 8 times; preferably, the extraction time is 4-9 hours, more preferably 5-7 hours, even more preferably 6 hours; the aqueous extract in step (3) further includes the distilled filtrate obtained after steam distillation extraction of volatile oil.

[0025] In some implementations, the amount of water used in step (2) for water extraction is 4-16 times the total amount of raw materials, preferably 6-12 times.

[0026] The extraction temperature is 80°C or higher, preferably 90-100°C; reflux extraction is preferred; the extraction time is 0.5-3 hours, preferably 1-2 hours; preferably 1.5 hours; and the extraction is performed 1-3 times, preferably 2-3 times, and even more preferably 2 times.

[0027] In some embodiments, the relative density of the water concentrate in step (3) at 40-100°C is 1.05-1.32 g / ml, preferably 1.06-1.26 g / ml, more preferably 1.12-1.20 g / ml, and even more preferably 1.18-1.20 g / ml.

[0028] In some embodiments, the alcohol precipitation in step (3) is as follows: ethanol is added to the concentrate and stirred until the alcohol content reaches 38-65%, and then allowed to stand at 0-25°C for 12-48 hours; during the alcohol precipitation process, the alcohol content after adding alcohol solvent is 40-

[0029] 80%, preferably 50-70%, more preferably 50-60%, and even more preferably 60%; the settling temperature is preferably 4-

[0030] The temperature is 15°C, more preferably 4-10°C; the alcohol precipitation time is preferably 18-36 hours, more preferably 24-48 hours.

[0031] In some embodiments, the concentration in step (4) is vacuum concentration, and the concentration temperature is 40-100°C, preferably.

[0032] 50-90℃, preferably 60-80℃, and even more preferably 70-75℃.

[0033] In some implementations, the volatile oil in step (5) is prepared by inclusion complexation with cyclodextrin. Further, the volatile oil is prepared by inclusion complexation with 8-16 times the weight of cyclodextrin and water, and even further, with 10 times the weight of cyclodextrin.

[0034] In some other embodiments, the original steps (2)-(4) of the preparation method of the wind-dispelling and orifice-opening preparation composition can be replaced by the following steps:

[0035] (II) Extract the dregs obtained in step (1) with other medicinal materials using alcohol to obtain an alcohol extract;

[0036] (III) The alcohol extract obtained in step (II) is concentrated to obtain an extract.

[0037] In some other embodiments, the alcohol extraction in step (II) uses ethanol as the extraction solvent. Preferably, the volume fraction of the ethanol is 45-70%, more preferably 50-65%, and even more preferably 55-60%. The amount of ethanol used is 5-15 times the total weight of the residue and other medicinal materials, preferably 6-12 times, and even more preferably 8-10 times. The number of extractions is 1-5 times, preferably 1-3 times, and even more preferably 2 times. The extraction time for each extraction is 1-3 hours, preferably 1.5-2.5 hours, even more preferably 1.5-2 hours, and even more preferably 1.5 hours.

[0038] In some other embodiments, the original steps (2)-(4) of the preparation method of the wind-dispelling and orifice-opening granules can be replaced by the following steps:

[0039] (ii) Extract the fried Xanthium sibiricum and Schisandra chinensis with alcohol to obtain an alcohol extract and alcohol extract residue;

[0040] (iii) Mix the dregs obtained in step (1), the alcohol-extracted dregs obtained in step (ii), and other medicinal materials and extract with water to obtain an aqueous extract;

[0041] (iv) Concentrate the alcohol extract obtained in step (ii) until there is no alcohol odor, add the filtrate obtained in step (1) and the water extract obtained in step (iii), concentrate, and obtain an extract.

[0042] In some embodiments, the alcohol extraction in step (ii) uses ethanol as the extraction solvent. Preferably, the volume fraction of the ethanol is 45-70%, more preferably 50-65%, and even more preferably 55-60%. The amount of ethanol used is 5-15 times the total weight of the roasted Xanthium sibiricum and Schisandra chinensis, preferably 6-12 times, and even more preferably 8-10 times. The number of extractions is 1-5 times, preferably 1-3 times, and even more preferably 2 times. The extraction time for each extraction is 1-3 hours, preferably 1.5-2.5 hours, even more preferably 1.5-2 hours, and even more preferably 1.5 hours.

[0043] In some embodiments, the amount of water added in step (iii) during water extraction is 8-15 times the total weight of the dregs, alcohol-extracted dregs, and other medicinal materials, preferably 9-14 times; more preferably 10-13 times, even more preferably 10 times; the number of extractions is 1-5 times, preferably 1-3 times, even more preferably 2 times; the extraction time for each extraction is 1-3 hours, preferably 1.5-2.5 hours, even more preferably 1.5-2 hours, even more preferably 1.5 hours.

[0044] Thirdly, the present invention also provides a method for optimizing the quality of a wind-dispelling and orifice-opening preparation composition.

[0045] The quality described in this invention includes reducing the content of atractylodesin, reducing the total ephedrine content, and / or reducing the increase in moisture content.

[0046] In one embodiment, the method is a method for optimizing the reduction of atractylodes glycoside content in a wind-dispelling and nasal-clearing preparation composition.

[0047] In one embodiment, the method is an optimized method for reducing the decrease in total ephedrine content in a wind-dispelling and nasal-clearing preparation composition.

[0048] In one embodiment, the method is an optimized method for reducing the increase in moisture content in a wind-dispelling and nasal-clearing preparation composition.

[0049] In one implementation, the method is to optimize any two of the following: reducing the content of atractylodesin, reducing the decrease in total ephedrine content, and reducing the increase in moisture content.

[0050] In one implementation, the method is to optimize the reduction of atractylodesin content, reduce the reduction of total ephedrine content, and reduce the increase of moisture content.

[0051] In one embodiment, the method is an optimized method for improving the long-term stability of the wind-dispelling and symptom-clearing preparation composition, wherein the long-term stability includes at least one of atractylodes glycoside content, total ephedrine content, and moisture content.

[0052] The optimization method described in this invention includes the following steps:

[0053] S1. Preparation of traditional Chinese medicine composition: Ephedra, cinnamon twig, magnolia flower, schisandra fruit, dried plum, earthworm (processed with wine), arisaema cum bile, and roasted cocklebur are used as raw materials to prepare inclusion complexes and extracts of volatile oils of cinnamon twig and magnolia flower, which are then mixed to obtain the traditional Chinese medicine composition.

[0054] S2. Use dextrin as a diluent and 80-90% ethanol as a binder for wet granulation, then dry and granulate at 40-50℃.

[0055] In some implementations, the stir-frying of cocklebur in step S1 is performed at 120-140℃ for 10-25 minutes, preferably at 120℃ for 10-25 minutes, and more preferably at 120℃ for 15 minutes.

[0056] In some embodiments, the extraction method of volatile oil from cinnamon twig and magnolia flower bud in step S1 is steam distillation; preferably, the amount of water used is 4-16 times the total weight of cinnamon twig and magnolia flower bud, more preferably 6-12 times, even more preferably 7-9 times, and even more preferably 8 times; preferably, the extraction time is 4-9 hours, more preferably 5-7 hours, and even more preferably 6 hours.

[0057] In some implementations, the inclusion complex in step S1 is prepared by inclusion with cyclodextrin.

[0058] In some implementations, the extract described in step S2 is an extract containing roasted Xanthium sibiricum.

[0059] In some embodiments, the preparation method of the extract is as follows: (1) extracting the residue of volatile oil from cinnamon twig and magnolia flower with water and other medicinal materials to obtain an aqueous extract; (2) combining the filtrate of volatile oil from cinnamon twig and magnolia flower with the aqueous extract and concentrating to obtain a concentrated liquid; (3) precipitating the concentrated liquid with pure alcohol, filtering to obtain an alcohol precipitate, and concentrating to obtain the extract.

[0060] Alternatively, (2) extract the volatile oil residue from cinnamon twigs and magnolia flower with other medicinal materials to obtain an alcohol extract; (3) concentrate the alcohol extract to obtain an extract.

[0061] Alternatively, (2) extract the roasted Xanthium sibiricum and Schisandra chinensis with alcohol to obtain an alcohol extract and alcohol-extracted residue; (3) mix the residue of volatile oil extracted from Cinnamomum cassia and Magnolia biondii, the alcohol-extracted residue and other medicinal materials with water to obtain an aqueous extract; (4) concentrate the alcohol extract until there is no alcohol taste, add the filtrate of volatile oil extracted from Cinnamomum cassia and Magnolia biondii and the aqueous extract, concentrate to obtain an extract.

[0062] In some embodiments, the amount of diluent used in step S3 is 1-3 times the mass of the traditional Chinese medicine composition, preferably 1.1-2.5 times; more preferably 1.1-2 times, and even more preferably 1.5 times.

[0063] In some embodiments, the preparation method of the traditional Chinese medicine composition in step S1 is the same as the preparation method of the aforementioned wind-dispelling and orifice-opening preparation composition.

[0064] Fourth aspect: The present invention provides the application of the aforementioned wind-dispelling and nasal-clearing preparation composition or the aforementioned preparation method or the aforementioned optimized method in the preparation of rhinitis drugs, preferably pediatric rhinitis drugs, further for pediatric rhinitis, the symptoms of which include lung qi deficiency and cold syndrome, with symptoms such as: nasal congestion and itching, runny nose with clear discharge, frequent sneezing, and even itching and discomfort in the eyes, ears and throat, aversion to wind and cold, pale tongue, and thin white tongue coating.

[0065] Fifth aspect: The present invention provides a wind-dispelling and nasal-clearing preparation for treating rhinitis, which is made from the aforementioned wind-dispelling and nasal-clearing preparation composition or the aforementioned preparation method or the aforementioned method for optimizing the quality of the wind-dispelling and nasal-clearing preparation composition.

[0066] The dosage form of the wind-dispelling and orifice-opening preparation described in this invention is granules, tablets, or capsules.

[0067] Note: The temperature for "concentration" and "depressurized concentration" in this invention is 70-75℃.

[0068] The beneficial effects of this invention are:

[0069] (1) On the one hand, the present invention reduces the content of atractylodes glycoside by heating and processing Xanthium sibiricum, and on the other hand, it reduces the content of atractylodes glycoside in the preparation by optimizing the process and excipients, thereby improving the safety of the product.

[0070] (2) The present invention can optimize the quality of the wind-dispelling and symptom-clearing preparation composition, including reducing the content of atractylodes glycoside, reducing the total ephedrine content and / or reducing the increase of moisture content. Compared with the prior art, the wind-dispelling and symptom-clearing preparation composition of the present invention has better quality and long-term stability.

[0071] (3) The formulation produced by applying the present invention has a better granule formation rate, uniform color, and good solubility; as a children's medicine, it has a better taste and higher medication compliance compared with traditional decoctions. Detailed Implementation

[0072] The following description of the embodiments is merely to aid in understanding the method and core ideas of the present invention. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from its principles, and these improvements and modifications also fall within the scope of the claims. The following description of the disclosed embodiments enables those skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not limited to the embodiments shown herein, but can be applied to a wider scope consistent with the principles and novel features disclosed herein.

[0073] In this invention, the "multiple" refers to the weight of the material to be treated. For example, in the phrase "take the cinnamon twig and magnolia flower and place them in a distiller, add 8 times the weight of water", the 8 times the weight of water is 8 times the total weight of the cinnamon twig and magnolia flower. In the phrase "prepare an inclusion complex by adding 10 times the amount of β-cyclodextrin and water to the volatile oil", the 10 times refers to 10 times the mass of the volatile oil. In the phrase "mix the dregs with other raw materials and add 10 times the weight of water", the 10 times refers to 10 times the mass of the dregs and other raw materials.

[0074] [Stir-fried cocklebur seeds]

[0075] The processing method for cocklebur is as follows: Place raw cocklebur in a stir-frying pan, heat it over a low flame until it reaches the specified temperature, then remove it, let it cool, remove the thorns, and sift it clean.

[0076] The specific frying temperature and time are shown in Table 1.

[0077] The effects of processing on the content of chlorogenic acid and atractylodes glycoside in Xanthium sibiricum were determined according to the content determination method under the Xanthium sibiricum medicinal material item in Part I of the 2015 edition of the Chinese Pharmacopoeia.

[0078] According to the pharmacopoeia, chlorogenic acid should be determined by high performance liquid chromatography (General Rule 0512).

[0079] Chromatographic conditions and system suitability tests were conducted using octadecylsilane-bonded silica gel as the stationary phase; acetonitrile-0.4% phosphoric acid solution (10:90) as the mobile phase; and a detection wavelength of 327 nm. The theoretical plate number, calculated based on the chlorogenic acid peak, should be no less than 3000.

[0080] Preparation of the reference solution: Weigh an appropriate amount of chlorogenic acid reference standard accurately, place it in a brown volumetric flask, and add 50% methanol to prepare a solution containing 50 μg per ml (store below 10℃).

[0081] Preparation of the test solution: Weigh approximately 0.5 g of the powder (passed through a No. 3 sieve) accurately, place it in a stoppered conical flask, accurately add 25 ml of 5% formic acid in 50% methanol solution, weigh the solution, sonicate (power 300 W, frequency 40 kHz) for 40 minutes, cool, weigh the solution again, replenish the lost weight with 5% formic acid in 50% methanol solution, shake well, filter, and collect the filtrate (placed in a brown bottle) to obtain the test solution.

[0082] The assay involves precisely pipetting 5 μl of both the reference solution and the test solution into a liquid chromatograph and measuring the results.

[0083] Atractylodesin was determined by high performance liquid chromatography (General Rule 0512).

[0084] Chromatographic conditions and system suitability tests were conducted using phenyl-bonded silica gel as the stationary phase; acetonitrile-0.01 mol / L sodium dihydrogen phosphate solution (adjusted to pH 5.4 with 4% sodium hydroxide solution) (20:80) as the mobile phase; and a detection wavelength of 203 nm. The theoretical plate number, calculated based on the atractylodesin peak, should be no less than 5000.

[0085] Preparation of the reference solution: Take an appropriate amount of atractylodesin dipotassium salt reference standard, accurately weigh it, and add 20% methanol to prepare a solution containing 0.1 mg per ml, which is (weight of atractylodesin - weight of atractylodesin dipotassium salt / 1.1048).

[0086] Preparation of the test solution: Take about 1g of the powder (passed through a No. 3 sieve), accurately weigh it, place it in a stoppered conical flask, accurately add 20ml of water, weigh it, sonicate (power 300W, frequency 40kHz) for 40 minutes, cool it, weigh it again, replenish the lost weight with water, shake well, centrifuge (speed 12000 rpm, 5 minutes), take the supernatant and filter it, take the filtrate, and the test solution is obtained.

[0087] The assay involves precisely pipetting 5 μL each of the reference solution and the test solution into a liquid chromatograph and measuring the results.

[0088] The results under different frying conditions are shown in Table 1.

[0089] Table 1. Content of chlorogenic acid and atractylodesin in Xanthium sibiricum at different roasting temperatures and times

[0090]

[0091]

[0092] After stir-frying, compared with raw Xanthium sibiricum slices, the content of atractylodesin was significantly reduced, while the content of chlorogenic acid did not change significantly. Furthermore, the content of atractylodesin actually increased with increasing processing temperature and time. This indicates that other components may be converted into atractylodesin during the stir-frying process.

[0093] Fried cocklebur seeds were prepared by frying at 120℃ for 15 minutes and used as raw materials in subsequent examples and comparative examples.

[0094] Example 1: Preparation of intermediates of traditional Chinese medicine compositions for dispelling wind and clearing the orifices

[0095] Weigh out 180g of honey-processed ephedra, 180g of cinnamon twig, 360g of magnolia flower, 360g of stir-fried cocklebur, 360g of vinegar-processed schisandra, 360g of dried plum, 360g of bile-processed arisaema, and 360g of earthworm as raw materials;

[0096] Take the cinnamon twig and magnolia flower and place them in a distiller, add 8 times the weight of water, and steam distill for 6 hours to extract the volatile oil. Collect the aqueous solution after distillation in a separate container and keep the residue for later use. Use 10 times the amount of β-cyclodextrin and water to form an inclusion complex for later use.

[0097] Mix the dregs with other raw materials, add 10 times the weight of water, reflux and extract for 1.5 hours, extract twice, and collect the aqueous extract;

[0098] The aqueous extract was combined with the distilled aqueous solution and concentrated under reduced pressure at 70-75℃ to obtain a concentrated solution with a relative density of 1.18 g / ml at 50℃.

[0099] Add ethanol to the concentrate and stir continuously until the alcohol content reaches 60%. Let it stand at 4-10℃ for 24-48 hours, filter, and obtain the alcohol precipitate. Concentrate the alcohol precipitate under reduced pressure at 70-75℃ to obtain the extract.

[0100] The extract is dried under reduced pressure and pulverized to obtain the extract powder of the traditional Chinese medicine composition for relieving wind and clearing the orifices. The extract powder can be further mixed with the inclusion compound to obtain the intermediate of the traditional Chinese medicine composition for relieving wind and clearing the orifices.

[0101] Example 2: Preparation of intermediates of traditional Chinese medicine compositions for dispelling wind and clearing the orifices

[0102] Weigh out 180g of honey-processed ephedra, 180g of cinnamon twig, 360g of magnolia flower, 360g of stir-fried cocklebur, 360g of vinegar-processed schisandra, 360g of dried plum, 360g of bile-processed arisaema, and 360g of earthworm as raw materials;

[0103] Take the cinnamon twig and magnolia flower and place them in a distiller, add 8 times the weight of water, and steam distill for 6 hours to extract the volatile oil. Collect the aqueous solution after distillation in a separate container and keep the residue for later use. Prepare an inclusion complex by adding 10 times the amount of β-cyclodextrin and water to the volatile oil for later use.

[0104] Mix the dregs with other raw materials, add 10 times the weight of water, reflux and extract for 1.5 hours, extract twice, and collect the aqueous extract;

[0105] The aqueous extract and the distilled aqueous solution were combined and concentrated under reduced pressure at 70-75℃ to obtain a concentrated solution with a relative density of 1.20 g / ml at 50℃.

[0106] Alcohol precipitation: Add ethanol to the concentrate and stir continuously until the alcohol content reaches 60%. Let it stand at 4-10℃ for 24-48 hours, filter, and obtain the alcohol precipitate. Concentrate the alcohol precipitate under reduced pressure at 70-75℃ to obtain the extract.

[0107] The extract is dried under reduced pressure and pulverized to obtain extract powder. The extract powder can be further mixed with inclusion complex to obtain the intermediate of the traditional Chinese medicine composition for relieving wind and opening the orifices.

[0108] Example 3: Preparation of a Traditional Chinese Medicine Composition for Dispelling Wind and Opening the Orifices

[0109] Weigh out 180g of honey-processed ephedra, 180g of cinnamon twig, 360g of magnolia flower, 360g of stir-fried cocklebur, 360g of vinegar-processed schisandra, 360g of dried plum, 360g of bile-processed arisaema, and 360g of earthworm as raw materials;

[0110] Take the cinnamon twig and magnolia flower and place them in a distiller, add 8 times the weight of water, and steam distill for 6 hours to extract the volatile oil. Collect the aqueous solution after distillation in a separate container and keep the residue for later use. Use 12 times the amount of β-cyclodextrin and water to prepare an inclusion complex for later use.

[0111] Mix the dregs with other raw materials, add 10 times the weight of 60% ethanol, reflux and extract for 1.5 hours, extract twice, and collect the ethanol extract;

[0112] The alcohol extract was concentrated under reduced pressure at 70-75℃ until no alcohol odor remained.

[0113] Add the distilled aqueous solution and continue to concentrate under reduced pressure at 70-75℃ to obtain the extract;

[0114] The extract is dried under reduced pressure and pulverized to obtain extract powder. The extract powder can be further mixed with inclusion complex to obtain the intermediate of the traditional Chinese medicine composition for relieving wind and opening the orifices.

[0115] Example 4: Preparation of intermediates of traditional Chinese medicine compositions for dispelling wind and clearing the orifices

[0116] Weigh out 180g of honey-processed ephedra, 180g of cinnamon twig, 360g of magnolia flower, 360g of stir-fried cocklebur, 360g of vinegar-processed schisandra, 360g of dried plum, 360g of bile-processed arisaema, and 360g of earthworm as raw materials;

[0117] Take the cinnamon twig and magnolia flower and place them in a distiller, add 8 times the weight of water, and steam distill for 6 hours to extract the volatile oil. Collect the aqueous solution after distillation in a separate container and keep the residue for later use. Prepare an inclusion complex by adding 10 times the amount of β-cyclodextrin and water to the volatile oil and keep it for later use.

[0118] Take Xanthium sibiricum and Schisandra chinensis, add 10 times their weight volume of 60% ethanol, reflux for 1.5 hours, extract twice, and collect the ethanol extract and the residue.

[0119] Mix the dregs with other raw materials, add 10 times the weight of water, reflux and extract for 1.5 hours, extract twice, and collect the aqueous extract;

[0120] The alcohol extract was concentrated under reduced pressure at 70-75℃ until no alcohol odor was detected; the distilled aqueous solution and the water extract were added, and the concentration was further reduced under reduced pressure to obtain the extract.

[0121] The extract is dried under reduced pressure and pulverized to obtain extract powder. The extract powder can be further mixed with inclusion complex to obtain the intermediate of the traditional Chinese medicine composition for relieving wind and opening the orifices.

[0122] Example 5: Preparation of intermediates of traditional Chinese medicine compositions for dispelling wind and clearing the orifices

[0123] Weigh out 180g of honey-processed ephedra, 180g of cinnamon twig, 360g of magnolia flower, 360g of stir-fried cocklebur, 360g of vinegar-processed schisandra, 360g of dried plum, 360g of bile-processed arisaema, and 360g of earthworm as raw materials;

[0124] Mix the raw materials, add 10 times their weight of water, soak for 1 hour, reflux for 1.5 hours, extract twice, filter, and collect the aqueous extract;

[0125] The aqueous extract was concentrated under reduced pressure at 70-75℃ to obtain an extract.

[0126] The extract was dried under reduced pressure and pulverized to obtain extract powder.

[0127] Example 6: Preparation of intermediates of traditional Chinese medicine compositions for dispelling wind and clearing the orifices

[0128] Weigh out 1800g of honey-processed ephedra, 1800g of cinnamon twigs, 3600g of magnolia flower buds, 3600g of stir-fried cocklebur, 3600g of vinegar-processed schisandra, 3600g of dried plum, 3600g of bile-processed arisaema, and 3600g of earthworm as raw materials;

[0129] Take the cinnamon twig and magnolia flower and place them in a distiller, add 8 times the weight of water, and steam distill for 6 hours to extract the volatile oil. Collect the aqueous solution after distillation in a separate container and keep the residue for later use. Use 10 times the amount of β-cyclodextrin and water to form an inclusion complex for later use.

[0130] Mix the dregs with other raw materials, add 10 times the weight of water, reflux and extract for 1.5 hours, extract twice, and collect the aqueous extract;

[0131] The aqueous extract was combined with the distilled aqueous solution and concentrated under reduced pressure at 70-75℃ to obtain a concentrated solution with a relative density of 1.18 g / ml at 50℃.

[0132] Add ethanol to the concentrate and stir continuously until the alcohol content reaches 60%. Let it stand at 4-10℃ for 24-48 hours, filter, and obtain the alcohol precipitate. Concentrate the alcohol precipitate under reduced pressure at 70-75℃ to obtain the extract.

[0133] The extract is dried under reduced pressure and pulverized to obtain the extract powder of the traditional Chinese medicine composition for relieving wind and clearing the orifices. The extract powder can be further mixed with the inclusion compound to obtain the intermediate of the traditional Chinese medicine composition for relieving wind and clearing the orifices.

[0134] Example 7: Preparation of a wind-dispelling and orifice-opening preparation composition

[0135] The diluent and the intermediate of the traditional Chinese medicine composition for relieving wind and clearing the orifices prepared in Example 1 (hereinafter referred to as the intermediate) were subjected to wet granulation. An appropriate amount of ethanol was used as a binder in the wet granulation. The obtained wet granules were dried and granulated to obtain the preparation compositions for relieving wind and clearing the orifices S7-1 to S7-12.

[0136] The wind-dispelling and nasal-clearing preparation composition was wet-granulated according to the formulation in Table 2. The granules were passed through a 16-mesh sieve, dried in an oven at 40°C, and then granulated using sieves No. 1 and No. 5. The granulation rate was determined, and the solubility was determined according to the method in the 2015 edition of the Chinese Pharmacopoeia.

[0137] Table 2

[0138]

[0139]

[0140] Note: Δ: indicates easy sieving and uniform color;

[0141] 〇: Indicates that the material is easy to sieve but has uneven color;

[0142] ▲: Indicates that it is not easy to sieve, is prone to clumping, and has a uniform color;

[0143] ◎: Difficult to sieve, prone to clumping, and uneven color;

[0144] ◆: Indicates that the material cannot be sieved, is prone to clumping, and has a uniform color;

[0145] ☉: Indicates that the shape is not yet formed;

[0146] Ideally, it should completely melt within 5 minutes.

[0147] The experimental results showed that when sucrose, mannitol, and lactose were used as diluents, the granules failed to form properly and had uneven color. When dextrin and soluble starch were used as diluents, the granule formation rate was better, the color was more uniform, and the solubility was better. However, soluble starch was prone to clumping and difficult to sieve, resulting in a lower granulation rate. Therefore, dextrin is the better diluent.

[0148] Example 8: Stability Study of the Composition for Dispelling Wind and Opening the Orifices

[0149] Take cinnamon twig and magnolia flower, add 9 times the amount of water and distill for 6 hours to extract volatile oil. Collect the aqueous solution after distillation in a separate container and set aside the residue. Incorporate the volatile oil with 10 times the amount of betacyclodextrin in water, dry at low temperature to obtain the inclusion compound, set aside. Combine the residue with the remaining six herbs such as honey ephedra, add 11 times the amount of water and reflux extract twice, 1 hour each time, filter, and combine the filtrates. Combine the filtrate with the above aqueous solution, concentrate under reduced pressure to a clear extract with a relative density of 1.12-1.18 (60℃), add ethanol to make the alcohol content 60%, refrigerate and stand for 24-48 hours, take the supernatant and filter, concentrate and dry the filtrate under reduced pressure, pulverize, pass through an 80-mesh sieve, and mix with the inclusion compound to obtain intermediate A of the traditional Chinese medicine composition for dispelling wind and opening the orifices.

[0150] Preparation of formulation composition B: Add 2 times the amount of dextrin to intermediate A of the traditional Chinese medicine composition that eliminates wind and clears the orifices, mix evenly, add 12% of 85% ethanol, and granulate (dry in an oven at 40℃) to obtain formulation composition B that eliminates wind and clears the orifices.

[0151] Preparation of formulation composition C: Add 1 part soluble starch, 1 part mannitol and 0.2 parts magnesium stearate to intermediate A of the traditional Chinese medicine composition that eliminates wind and clears the orifices, mix evenly, add 16% of 95% ethanol, and granulate (dry in an oven at 40℃) to obtain formulation composition C for eliminating wind and clearing the orifices.

[0152] The multiples mentioned are all relative to the mass of intermediate A in the traditional Chinese medicine composition.

[0153] The content of atractylodesin in the prepared pharmaceutical composition was determined.

[0154] Content determination method: Refer to the aforementioned determination method and determine the content according to the content determination method under the Xanthium sibiricum decoction piece in Part I of the 2015 edition of the Chinese Pharmacopoeia.

[0155] Preparation method of reference solution: Take an appropriate amount of atractylodesin dipotassium salt reference standard, accurately weigh it, add 20% methanol to prepare a solution containing 0.1 mg per ml, which is the result of (weight of atractylodesin = weight of atractylodesin dipotassium salt / 1.1048).

[0156] Preparation method of test sample: Accurately weigh 3g of sample, place it in a stoppered conical flask, add 25ml of water, weigh again, sonicate for 30min, cool to room temperature, add water to make up the weight loss, shake well, filter, collect the filtrate, accurately measure 15ml of the filtrate, adjust the pH to 5.0 (using 4% sodium hydroxide), load onto D101 macroporous resin (1.5cm diameter, 20cm height), and add 150ml of pH 5.0 water and 50% sodium hydroxide solution respectively. Elute with 200 ml of ethanol, collect the ethanol eluent, evaporate to about 5 ml at 60 °C, pass through a WAX solid-phase extraction column (pre-activated with 6 ml each of methanol and water), wash the equipment with an appropriate amount of water, and pass the eluent through the column. Elute with 6 ml each of water and methanol (both containing 5% formic acid) to remove impurities. Collect 9 ml of methanol (containing 2% ammonia) eluent, evaporate to dryness at 60 °C, dissolve in water and make up to 5 ml, then filter through a 0.45 μm filter to obtain the final product.

[0157] The results are shown in Table 3.

[0158] Table 3. Content of atractylodesin in stir-fried Xanthium sibiricum slices, intermediates, and pharmaceutical compositions.

[0159] Test sample name Atractylodesin (%) Stir-fried Xanthium sibiricum slices 0.19 Wind-dispelling and orifice-opening intermediate A 0.0166 Composition B for dispelling wind and opening the orifices 0.0015 Composition C for dispelling wind and opening the orifices 0.0019

[0160] The prepared formulation composition was packaged in a pharmaceutical composite film, and an influencing factor test was conducted to determine the ephedrine content. The results are shown in Table 4.

[0161] Table 4. Long-term stability test reports of Xiaofeng Xuanqiao preparation compositions B and C

[0162]

[0163] Note: Specifications: 3.5g / bag; Packaging: Pharmaceutical composite film (Changzhou Huajian Pharmaceutical Packaging Materials Co., Ltd., batch number A1910110202R-01); Testing conditions: 25℃±2℃, RH60%±10%.

[0164] Example 9: Preparation of Xiaofeng Xuanqiao Capsules and Granules

[0165] Cinnamon twig and magnolia flower bud are distilled with 9 times the amount of water for 6 hours to extract volatile oil. The aqueous solution after distillation is collected separately, and the residue is kept for later use. The volatile oil is incorporated with 10 times the amount of betacyclodextrin in water and dried at low temperature to obtain the inclusion complex, which is kept for later use. The residue is combined with the remaining six herbs, including honey-processed ephedra, and extracted twice with 11 times the amount of water under reflux for 1 hour each time. The extracts are filtered and the filtrates are combined. The filtrate is combined with the above aqueous solution and concentrated under reduced pressure to a clear extract with a relative density of 1.12-1.18 (60℃). Ethanol is added to make the alcohol content 60%, and the extract is refrigerated and allowed to stand for 24-48 hours. The supernatant is collected, filtered, and the filtrate is concentrated and dried under reduced pressure. The extract is pulverized, passed through an 80-mesh sieve, and mixed with the inclusion complex to obtain the intermediate of the traditional Chinese medicine composition for clearing wind and opening the orifices. 2 times the amount of dextrin is added, mixed evenly, and 12% of 85% ethanol is added. The mixture is granulated (dried in an oven at 40℃) to obtain the preparation composition for clearing wind and opening the orifices.

[0166] The Xiaofeng Xuanqiao preparation composition is filled into capsule shells to prepare Xiaofeng Xuanqiao capsules; the Xiaofeng Xuanqiao preparation composition is filled into pharmaceutical composite film packaging bags, 2-5g per bag, to prepare Xiaofeng Xuanqiao granules.

[0167] The content of this capsule formulation (batch number: 2020060603) showed no significant change under high temperature and high humidity conditions; no significant changes were observed in any of the tested items under light conditions. Long-term stability in aluminum-plastic packaging (25℃±2℃, RH 60%±10%) showed that, according to pharmacopoeia methods, the content of the content-assigning compounds ephedrine and magnolol decreased by less than 3% within 24 months. These results indicate that the formulation composition of this invention has better performance, including lower atractylodesin content and better stability.

[0168] The embodiments described above are merely examples of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A composition for dispelling wind and clearing the orifices, characterized in that, A traditional Chinese medicine composition containing wind-dispelling and orifice-opening properties and a diluent, wherein the weight ratio of the diluent to the traditional Chinese medicine composition is 0.8-3:

1.

2. The wind-dispelling and orifice-opening composition according to claim 1, characterized in that, The weight ratio of the diluent to the traditional Chinese medicine composition is 0.9-2.5:1; more preferably 1-2:1, and even more preferably 1.5-2:1; the diluent is preferably dextrin.

3. The wind-dispelling and orifice-opening preparation composition according to claim 1, characterized in that, It is prepared by the following method: the traditional Chinese medicine composition is mixed with a diluent and then wet granulated.

4. The wind-dispelling and orifice-opening preparation composition according to claim 3, characterized in that, The binder used in the wet granulation is ethanol, preferably 85%-95% ethanol, more preferably 85% ethanol; preferably the volume ratio of the binder to the weight ratio of the traditional Chinese medicine composition to the diluent is 1-15ml:10-50g, more preferably 1-10ml:20-40g, more preferably 2-10ml:20-40g, and even more preferably 2.5-9ml:25-30g.

5. The wind-dispelling and orifice-opening preparation composition according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials: ephedra, cinnamon twig, magnolia flower, cocklebur, schisandra, dried plum, arisaema cum bile, and earthworm; preferably, it is made from the following raw materials in parts by weight: 2-4 parts ephedra, 2-4 parts cinnamon twig, 3-9 parts magnolia flower, 3-9 parts cocklebur, 3-9 parts schisandra, 3-9 parts dried plum, 3-9 parts arisaema cum bile, and 3-9 parts earthworm; more preferably, 3 parts ephedra, 3 parts cinnamon twig, 6 parts magnolia flower, 6 parts cocklebur, 6 parts schisandra, 6 parts dried plum, 6 parts arisaema cum bile, and 6 parts earthworm; the ephedra is preferably honey-processed ephedra, the cocklebur is preferably stir-fried cocklebur, and the schisandra is preferably vinegar-processed schisandra.

6. The method for preparing the wind-dispelling and orifice-opening preparation composition according to any one of claims 1-5, characterized in that, Includes the following steps: (1) Extract the volatile oil from cinnamon twig and magnolia flower to obtain filtrate, residue and volatile oil; (2) The residue after extracting the volatile oil was combined with other raw materials and water-extracted to obtain an aqueous extract; (3) The concentrated water extract was subjected to alcohol precipitation to obtain an alcohol precipitation solution. (4) Concentrate the alcoholic solution to obtain an extract; Further, it may include: (5) the volatile oil and the extract are combined; Further, the extraction in step (1) is steam distillation; preferably, the amount of water used is 4-16 times the total weight of cinnamon twig and magnolia flower, preferably 6-12 times, more preferably 7-9 times, more preferably 8 times; preferably, the extraction time is 4-9 hours, preferably 5-7 hours, more preferably 6 hours; the aqueous extract in step (3) further includes the distilled filtrate obtained after steam distillation of the volatile oil; In step (2), the amount of water used for water extraction is 4-16 times that of all raw materials, preferably 6-12 times, more preferably 7-11 times, more preferably 8-10 times, and more preferably 10 times; the water extraction temperature is above 80℃, preferably 90-100℃; reflux extraction is preferred; the water extraction time is 0.5-3 hours, preferably 1-2 hours, more preferably 1.5 hours; and the number of water extractions is 1-3 times, preferably 2-3 times, and more preferably 2 times. The water concentrate described in step (3) has a relative density of 1.05-1.32 g / ml at 40-100℃, preferably 1.06- 1.26 g / ml, preferably 1.12-1.20 g / ml, more preferably 1.18-1.20 g / ml; The alcohol precipitation in step (3) involves adding ethanol to the concentrate and stirring until the alcohol content reaches 38-65%, then allowing it to stand at 0-25°C for 12-48 hours. During the alcohol precipitation process, the alcohol content after adding the alcohol solvent is 40-80%, preferably 50- 70%, preferably 50-60%, more preferably 60%; the settling temperature is preferably 4-15℃, more preferably 4-10℃; the alcohol precipitation settling time is preferably 18-36 hours, preferably 24-48 hours; The volatile oil mentioned in step (5) is obtained by inclusion complexation with cyclodextrin. Further, the volatile oil is obtained by inclusion complexation with 8-16 times the weight of cyclodextrin and water, and even further, it is obtained by inclusion complexation with 10 times the weight of cyclodextrin.

7. The preparation method according to claim 6, characterized in that, Steps (2)-(4) can be replaced with the following steps: (II) Extract the dregs obtained in step (1) with other medicinal materials using alcohol to obtain an alcohol extract; (III) The alcohol extract obtained in step (II) is concentrated to obtain an extract; In step (II), ethanol is used as the extraction solvent for the alcohol extraction. Preferably, the volume fraction of the ethanol is 45-70%, more preferably 50-65%, and even more preferably 55-60%. The amount of ethanol used is 5-15 times the total weight of the residue and other medicinal materials, preferably 6-12 times, and even more preferably 8-10 times. The number of extractions is 1-5 times, preferably 1-3 times, and even more preferably 2 times. The extraction time for each extraction is 1-3 hours, preferably 1.5-2.5 hours, even more preferably 1.5-2 hours, and even more preferably 1.5 hours. Furthermore, steps (2)-(4) can be replaced with the following steps: (ii) Extract the fried Xanthium sibiricum and Schisandra chinensis with alcohol to obtain an alcohol extract and alcohol extract residue; (iii) Mix the dregs obtained in step (1), the alcohol-extracted dregs obtained in step (ii), and other medicinal materials and extract with water to obtain an aqueous extract; (iv) Concentrate the alcohol extract obtained in step (ii) until there is no alcohol odor, add the filtrate obtained in step (1) and the water extract obtained in step (iii), concentrate, and obtain an extract; In step (ii), ethanol is used as the extraction solvent for the alcohol extraction. Preferably, the volume fraction of the ethanol is 45-70%, more preferably 50-65%, and even more preferably 55-60%. The amount of ethanol used is 5-15 times the total weight of the roasted Xanthium sibiricum and Schisandra chinensis, preferably 6-12 times, and even more preferably 8-10 times. The number of extractions is 1-5 times, preferably 1-3 times, and even more preferably 2 times. The extraction time for each extraction is 1-3 hours, preferably 1.5-2.5 hours, even more preferably 1.5-2 hours, and even more preferably 1.5 hours. In step (iii), the amount of water added during the water extraction is 8-15 times the total weight of the dregs, alcohol-extracted dregs, and other medicinal materials, preferably 9-14 times; more preferably 10-13 times, even more preferably 10 times. The number of extractions is 1-5 times, preferably 1-3 times, even more preferably 2 times. Each extraction takes 1-3 hours, preferably 1.5-2.5 hours, even more preferably 1.5-2 hours, even more preferably 1.5 hours.

8. A method for optimizing the quality of a wind-dispelling and orifice-opening preparation composition, characterized in that, Includes the following steps: S1. Processing Xanthium sibiricum: Stir-fry raw Xanthium sibiricum at 80-140℃ for 5-25 minutes, remove, cool, remove thorns, and sift clean to obtain stir-fried Xanthium sibiricum; the heating and stir-frying is carried out at 120-140℃ for 10-25 minutes, preferably at 120℃ for 10-25 minutes, and more preferably at 120℃ for 15 minutes; S2. Preparation of traditional Chinese medicine composition: Ephedra, cinnamon twig, magnolia flower, schisandra fruit, dried plum, earthworm (processed with wine), arisaema cum bile, and the stir-fried cocklebur obtained in step S1 are used as raw materials to prepare inclusion complexes and extracts of volatile oils of cinnamon twig and magnolia flower, which are then mixed to obtain the traditional Chinese medicine composition. S3. Using dextrin as a diluent and ethanol (85-95% by volume) as a binder, wet granulation is carried out, followed by drying and granulation at 40-50°C; wherein, the amount of the diluent is 1-3 times the mass of the traditional Chinese medicine composition, preferably 1.1-2.5 times; more preferably 1.1-2 times, and even more preferably 1.5 times.

9. The method for optimizing the quality of the wind-dispelling and orifice-opening preparation composition according to claim 8, characterized in that, The preparation method of the extract is as follows: (1) the residue from the extraction of volatile oil from cinnamon twig and magnolia flower is extracted with water along with other medicinal materials to obtain an aqueous extract; (2) the filtrate from the extraction of volatile oil from cinnamon twig and magnolia flower is combined with the aqueous extract and concentrated to obtain a concentrated liquid; (3) the concentrated liquid is precipitated with pure alcohol, filtered to obtain an alcohol precipitate, and concentrated to obtain the extract. Alternatively, (2) extract the volatile oil residue from cinnamon twigs and magnolia flower with other medicinal materials to obtain an alcohol extract; (3) concentrate the alcohol extract to obtain an extract. Alternatively, (2) extract the roasted Xanthium sibiricum and Schisandra chinensis with alcohol to obtain an alcohol extract and alcohol-extracted residue; (3) mix the residue of volatile oil extracted from Cinnamomum cassia and Magnolia biondii, the alcohol-extracted residue and other medicinal materials with water to obtain an aqueous extract; (4) concentrate the alcohol extract until there is no alcohol taste, add the filtrate of volatile oil extracted from Cinnamomum cassia and Magnolia biondii and the aqueous extract, concentrate to obtain an extract.

10. The method according to any one of claims 8 to 9, characterized in that, The quality includes at least one of reducing atractylodesin content, reducing the decrease in total ephedrine content, and reducing the increase in moisture content, as well as the associated long-term stability.

11. The application of the wind-dispelling and nasal-clearing preparation composition according to any one of claims 1 to 5, or the preparation method according to any one of claims 6 to 7, or the method according to any one of claims 8 to 9, in the preparation of a rhinitis drug, preferably a pediatric rhinitis drug, further being pediatric rhinitis, the symptoms of which include lung qi deficiency and cold syndrome, with symptoms such as: nasal congestion and itching, runny nose with clear discharge, frequent sneezing, and even itching and discomfort in the eyes, ears and throat, aversion to wind and cold, pale tongue, and thin white tongue coating.

12. A rhinitis-treating and nasal-clearing preparation, characterized in that, The wind-dispelling and orifice-opening preparation is made from the wind-dispelling and orifice-opening preparation composition according to any one of claims 1 to 5, or the preparation method according to any one of claims 6 to 7, or the method according to any one of claims 8 to 9.

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