Plant compound preparation for relieving cough and asthma and airway inflammation of children and preparation method of plant compound preparation

Abstract

The invention discloses a plant compound preparation for relieving children cough and asthma and airway inflammation and a preparation method thereof, and relates to the technical field of traditional Chinese medicine preparations. The preparation is prepared from a modified sophora flower bud extract, a fermented pericarpium citri reticulatae extract and a low-sensitivity tussilago farfara extract according to the weight ratio of 1: (3-4): (0.8-1.2), quercetin in the modified sophora flower bud extract is quantified to be 1.2%-2.0% through a high performance liquid chromatography method, and small molecule hesperidin in the fermented pericarpium citri reticulatae extract is quantified to be 2.5%-3.5% through a liquid chromatography-mass spectrometry method. The tussilagone in the low-sensitivity tussilago farfara extract is quantified to be 0.8%-1.5% through a gas chromatography-mass spectrometry method. A mild process is adopted for preparation, the preparation is an oral granule special for children, the dosage is fixed according to ages, the safety is high and the compliance is good through experimental verification, the cough and asthma recurrence rate is reduced through multi-target cooperation, and the pharmaceutical composition is suitable for children of 3-12 years old.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation technology, specifically to a plant-based compound preparation for relieving cough, asthma and airway inflammation in children and its preparation method. Background Technology

[0002] Coughing, wheezing, and airway inflammation are common pediatric conditions. Their pathogenesis is closely related to airway mucosal inflammation, abnormal mucus secretion, and bronchospasm. Treatment must balance the efficacy of cough suppression, anti-inflammation, and expectoration with the safety of medications for children. Currently, most clinically used preparations are chemically synthesized drugs, which, although fast-acting, are prone to drug resistance and gastrointestinal discomfort with long-term use. Traditional Chinese medicine preparations, while mild, suffer from poor absorption of active ingredients, ineffective removal of sensitizing impurities, and poor palatability, leading to low medication compliance in children and affecting treatment efficacy.

[0003] Existing plant-based children's formulations often lack targeted optimization: some fail to precisely remove allergenic macromolecular impurities, posing a high risk of allergies; some active ingredients exist in large molecular form, which is poorly absorbed by children's intestines, resulting in insufficient bioavailability; and most neglect children's taste preferences, failing to modify the flavor, making them unsuitable for the physiological and usage needs of children aged 3-12. Therefore, developing a children's-specific plant-based compound formulation with clearly defined ingredients, low allergenicity and safety, good palatability, high bioavailability, and the ability to exert synergistic antitussive and anti-inflammatory effects through multiple targets has become an urgent need in the field of pediatric formulations. Summary of the Invention

[0004] To address the problems existing in the above-mentioned background technology, this invention proposes a plant-based compound preparation for relieving cough, wheezing and airway inflammation in children and its preparation method. This preparation, through the synergistic ratio of three plant extracts and a proprietary modification process, has clear antitussive, anti-inflammatory and expectorant effects. At the same time, it performs well in terms of low allergenicity and safety, oral palatability and component absorption efficiency, and can meet the physiological characteristics and medication needs of children aged 3-12 years.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: A plant-based compound preparation for relieving cough, wheezing, and airway inflammation in children, said compound preparation being prepared from the following raw materials in parts by weight: 1 part modified Sophora japonica flower extract, 3-4 parts fermented tangerine peel extract, and 0.8-1.2 parts hypoallergenic coltsfoot flower extract; The modified Sophora japonica extract contained 1.2%-2.0% quercetin, which was detected by high performance liquid chromatography. The content of small molecule hesperidin in the fermented tangerine peel extract is 2.5%-3.5%, and the quantification is performed by liquid chromatography-mass spectrometry. The content of coltsfoot ketone in the low-sensitivity coltsfoot flower extract was 0.8%-1.5%, and the quantification was performed by gas chromatography-mass spectrometry.

[0006] Preferably, the preparation process of the modified Sophora japonica extract is as follows: Sophora japonica buds are pulverized and passed through a 40-mesh sieve, dissolved in 10-15 times their weight of purified water, and 0.3%-0.5% of cellulase by weight of the raw materials is added. The mixture is enzymatically hydrolyzed at 50-55°C for 2-3 hours. The hydrolysate is then infused with β-cyclodextrin at a weight ratio of 1:2-3 at 45-50°C for 1-1.5 hours. Finally, the mixture is spray-dried at a low temperature below 40°C to obtain a micro powder with a particle size of 5-10 μm.

[0007] Preferably, the preparation process of the fermented tangerine peel extract is as follows: tangerine peel is pulverized and passed through a 60-mesh sieve, 8-10 times its weight of purified water is added, sterilized at 121℃ for 20 min, and then cooled to 35-37℃; Lactobacillus rhamnosus (CGMCC 1.3724) bacterial culture is inoculated at an inoculum size of 3%-5% of the total weight of the system, and 0.5%-1% of galactooligosaccharides as substrate is added to the system. Fermentation is carried out under anaerobic conditions for 24-36 h; after filtration of the fermentation broth, it is concentrated at 60℃ to an extract with a relative density of 1.10-1.15, 3 times its volume of 95% ethanol is added and stirred, and refrigerated at 4℃ for 12 h to precipitate. After filtration, the ethanol is recovered and dried to obtain the fermented tangerine peel extract.

[0008] Preferably, the preparation process of the hypoallergenic coltsfoot flower extract is as follows: take coltsfoot flower raw material, add 12-15 times the weight of 70% ethanol, reflux extract twice, 1.5 h each time; combine the extracts, concentrate under reduced pressure at 50℃ until there is no alcohol odor, purify using a 30kDa ultrafiltration membrane at 0.2-0.3 MPa pressure, and collect the permeate; add β-glucosidase to the permeate at a weight of 0.2%-0.4% of the permeate, and debitter at 35℃ for 1 h; after the enzymatic hydrolysate is concentrated and dried, the residual amount of allergens is detected to be 0.003%-0.01%, thus obtaining the hypoallergenic coltsfoot flower extract.

[0009] Preferably, the preparation is an oral granule, and the excipients include fructooligosaccharides, steviol glycosides and child-safe strawberry flavoring. The strawberry flavoring conforms to GB 2760 standard and has a particle size of 50-100 μm. The amount of strawberry flavoring added is 0.1%-0.3% of the total weight of the preparation.

[0010] Preferably, the dosage of the compound preparation is designed according to age stratification: 0.5 g each time, twice a day for children aged 3-6 years; 1.0 g each time, twice a day for children aged 7-12 years.

[0011] Preferably, the preparation method of the plant-based compound preparation for relieving cough, wheezing, and airway inflammation in children includes the following specific preparation steps: S1. Prepare modified Sophora japonica flower extract, fermented tangerine peel extract and low-sensitivity coltsfoot flower extract respectively; S2. Mix the three extracts at a weight ratio of 1:(3-4):(0.8-1.2), add 15%-20% of the total weight of the preparation of fructooligosaccharides, 0.3%-0.5% of steviol glycosides, and 0.1%-0.3% of child-safe strawberry flavoring, and place in a three-dimensional mixer to mix at 20-30 rpm for 15-20 min until homogeneous; add 25%-35% of the total weight of the extracts and excipients of purified water, and stir to obtain a soft material that can be formed into a ball by hand but crumbles easily when touched; granulate through an 18-mesh sieve, and dry the wet granules at below 45℃ for 2-3 h, controlling the granule moisture content to 3%-5%; finally, granulate through a 20-mesh sieve to screen for particles with a diameter of 50-100 μm, thus obtaining oral granules. The beneficial effects of this invention are as follows: The plant-based compound preparation prepared by this invention has significant antitussive, anti-inflammatory, and expectorant effects, with an inhibition rate of over 90% against airway inflammatory factors in children, and a 24-hour cough relief efficiency of over 85%; processed with a proprietary low-allergen process, the residual amount of allergens is 0.003%-0.01%, and the incidence of allergies is ≤0.3%, indicating extremely high safety; after modification, the active ingredients of the extract are in small molecule form, increasing bioavailability by over 40% compared to traditional preparations; combined with a palatable strawberry flavor, medication compliance reaches over 90%; the three active ingredients work synergistically, avoiding the side effects of chemical preparations, and the age-stratified dosage is precisely tailored to children aged 3-12 years, possessing comprehensive advantages of safety, high efficiency, and strong adaptability. Attached Figure Description

[0012] The accompanying drawings are provided to further illustrate the invention and form part of the specification. They are used together with the embodiments of the invention to explain the invention and do not constitute a limitation thereof.

[0013] Figure 1 This is a bar chart comparing the reduction rate of cough frequency and the amount of phenol red excreted in different samples of this invention; Figure 2 This is a bar chart comparing the inhibition rates of inflammatory factors in different samples of this invention. Detailed Implementation

[0014] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0015] Example 1: This embodiment 1 presents a plant-based compound preparation for relieving cough, asthma, and airway inflammation in children. The compound preparation is prepared from the following raw materials in parts by weight: 1 part modified Sophora japonica flower extract, 3.5 parts fermented tangerine peel extract, and 1.0 part hypoallergenic coltsfoot flower extract; This embodiment describes a method for preparing a plant-based compound preparation for relieving cough, wheezing, and airway inflammation in children. The specific preparation steps are as follows: S1. Take Sophora japonica flowers, crush them and pass them through a 40-mesh sieve. Add 12 times the weight of purified water and 0.4% of cellulase by weight of Sophora japonica flower raw material. Enzymatically hydrolyze at 52℃ for 2.5 h. After filtering the hydrolysate, add 2.5 times the weight of β-cyclodextrin. Stir and encapsulate at 48℃ for 1.2 h. Spray dry at below 40℃ and collect 5-10 μm micro powder. S2. Take dried tangerine peel, crush it through a 60-mesh sieve, add 9 times its weight of purified water, sterilize it with high-pressure steam at 121℃ for 20 min, and cool it to 36℃; inoculate it with 4% of the total weight of Lactobacillus rhamnosus culture, add 0.8% of the total weight of galactooligosaccharides, and anaerobic ferment for 30 h; after filtering the fermentation broth, concentrate it to a relative density of 1.12 at 60℃ (measured at 60℃), add 3 times its volume of 95% ethanol, refrigerate at 4℃ for 12 h to precipitate, and then recover the ethanol and dry it. S3. Take Coptis chinensis flowers, add 13 times their weight of 70% ethanol and reflux twice (1.5 h each time); concentrate the extract under reduced pressure at 50℃ until there is no alcohol odor, purify by ultrafiltration membrane of 30 kDa (0.25 MPa), add 0.3% β-glucosidase by weight of permeate to the permeate, and enzymatically hydrolyze at 35℃ for 1 h; concentrate, dry and then detect. S4. Mix the above three extracts at a weight ratio of 1:3.5:1.0, add 18% oligofructose, 0.4% steviol glycosides, and 0.2% strawberry flavoring by weight of the total preparation, and mix at 25 rpm for 18 min in a three-dimensional mixer; add 30% purified water by weight of the total weight of the extracts and excipients to make a soft mass, granulate through an 18-mesh sieve, vacuum dry at 42℃ for 2.5 h (moisture content 4%), granulate through a 20-mesh sieve, and screen for 50-100 μm particles to obtain oral granules.

[0016] Example 2: This embodiment 2 presents a plant-based compound preparation for relieving cough, asthma, and airway inflammation in children. The compound preparation is prepared from the following raw materials in parts by weight: 1 part modified Sophora japonica flower extract, 4 parts fermented tangerine peel extract, and 1.2 parts hypoallergenic coltsfoot flower extract; In this embodiment, the preparation method of a plant-based compound preparation for relieving cough, asthma and airway inflammation in children is the same as in Example 1, except that the ratio of the three extracts is adjusted to 1:4:1.2.

[0017] Comparative Example 1: The compound formulation of Comparative Example 1 was prepared from the following raw materials in parts by weight: 1 part unmodified Sophora japonica flower extract, 3.5 parts fermented tangerine peel extract, and 1.0 part hypoallergenic coltsfoot flower extract; The preparation method of the compound preparation in this comparative example is the same as that in Example 1, except that the Sophora japonica extract is not modified. Sophora japonica flowers are crushed and passed through a 40-mesh sieve, and directly extracted by reflux with 12 times the weight of purified water for 5 hours. After filtration and drying, the powder is collected.

[0018] Comparative Example 2: The compound formulation of Comparative Example 2 was prepared from the following raw materials in parts by weight: 1 part modified Sophora japonica flower extract, 3.5 parts dried tangerine peel extract, and 1.0 part hypoallergenic coltsfoot flower extract; The preparation method of the compound preparation in this comparative example is the same as that in Example 1, except that there is no fermentation process of tangerine peel. Tangerine peel is crushed and passed through a 60-mesh sieve, and directly extracted twice by reflux with 13 times its weight of 70% ethanol (1.5 h each time), and then concentrated and dried.

[0019] Comparative Example 3: The compound formulation of Comparative Example 3 was prepared from the following raw materials in parts by weight: 1 part modified Sophora japonica flower extract, 3.5 parts fermented tangerine peel extract, and 1.0 part coltsfoot flower extract; The preparation method of the compound formulation in this comparative example is the same as that in Example 1, except that the coltsfoot flower hypoallergenic process is omitted. Coltsfoot flowers are taken and directly extracted twice by reflux with 13 times their weight of 70% ethanol (1.5 h each time), then concentrated and dried.

[0020] Performance testing 1. Determination of active ingredient content Three extracts and the final formulation sample were taken in appropriate amounts, pulverized, passed through an 80-mesh sieve, and accurately weighed. The quercetin sample was extracted with methanol by ultrasonic extraction for 30 min, cooled, and diluted to 25 mL. The sample was filtered through a 0.45 μm organic phase filter membrane and determined by high performance liquid chromatography (HPLC). A C18 column was used, the mobile phase was methanol-0.1% phosphoric acid aqueous solution (50:50, v / v), the detection wavelength was 254 nm, the flow rate was 1.0 mL / min, and the column temperature was 30℃. The quercetin content was calculated by external standard method. The sample for small molecule hesperidin determination was extracted with 50% methanol by ultrasonic extraction for 40 min, and after being diluted to a fixed volume and filtered, it was analyzed by liquid chromatography-mass spectrometry (LC-MS). The chromatographic column was a C18 column, and the mobile phase was acetonitrile-0.2% formic acid aqueous solution with gradient elution. The mass spectrometry was performed using an electrospray ionization source (ESI) in positive ion mode. The retention time and characteristic ion peaks were used to distinguish between small molecule hesperidin and macromolecules. The content was calculated by external standard method. The coltsone content was determined by reflux extraction with diethyl ether for 1 h, followed by concentration and dilution with n-hexane. The extract was then filtered through a 0.45 μm organic phase filter membrane and analyzed by gas chromatography-mass spectrometry (GC-MS) using an HP-5MS capillary column. The temperature program was as follows: initial temperature 60℃, hold for 2 min, increase to 250℃ at 10℃ / min, hold for 5 min, injection port temperature 230℃, mass spectrometry ion source temperature 200℃, and ion monitoring mode (SIM) was selected. The coltsone content was calculated using the external standard method. The accuracy of the data was verified through three parallel experiments to ensure that the content of each active ingredient complies with the scope defined in the claims.

[0021] Table 1. Data on the determination of active ingredient content and allergen residue in different samples.

[0022] The contents of quercetin, small molecule hesperidin, coltsfoot ketone, and allergen residues in Examples 1 and 2 all meet the standards of the claims. In Comparative Example 2, small molecule hesperidin was not detected due to the absence of tangerine peel fermentation, and in Comparative Example 3, the absence of coltsfoot flower hypoallergenic process resulted in excessive allergen residues. This proves that the core process and formulation of the present invention are the key to ensuring that the ingredients meet the standards and that there are safe residues.

[0023] 2. Pharmacodynamic testing The cough suppression test used an ammonia-induced cough mouse model. Healthy ICR mice were randomly divided into groups (Examples 1-2, Comparative Examples 1-3, and a blank control group), with 15 mice in each group. Except for the blank control group, which was given an equal volume of purified water, the other groups were given the same dose as children by gavage once a day for 3 consecutive days. One hour after the last administration, the mice were placed in a sealed container containing 5% ammonia for 30 seconds. The cough latency and number of coughs were recorded within 24 hours, and the reduction rate of coughs was calculated. The anti-inflammatory test used an LPS-induced airway inflammation mouse model. After adaptive feeding, mice were divided into groups. The model group and the drug treatment group were established by intranasal instillation of LPS to establish the inflammation model. The blank control group was instilled with an equal volume of physiological saline, and the model group was instilled with an equal volume of LPS solution (without the preparation). The drug treatment group was simultaneously administered the above-mentioned dose by gavage for 5 consecutive days. 24 hours after the last administration, the mice were sacrificed, and the airway tissue was isolated. The levels of inflammatory factors TNF-α, IL-6, and IL-1β were detected by ELISA and the inhibition rate was calculated. The degree of airway mucosal edema was observed by HE staining of pathological sections (score 1-4 points). The expectorant test was performed using a mouse phenol red excretion assay. Mice were divided into groups and administered the drug by gavage according to the dosage. The blank control group was given an equal volume of purified water. 30 minutes after the last administration, 5% phenol red saline solution was injected intraperitoneally. 30 minutes later, the mice were sacrificed, the trachea was separated and flushed with saline solution, the flushing fluid was collected, and the absorbance value was measured using a spectrophotometer to calculate the amount of phenol red excreted from the trachea. All tests were performed in triplicate. The synergistic efficacy of the formulation and the difference from the control group were quantified by comparing the data of each group.

[0024] Table 2. Pharmacodynamic test data of different samples

[0025] The antitussive, anti-inflammatory, and expectorant indicators of Examples 1 and 2 were significantly better than those of the comparative examples. The efficacy of Comparative Examples 1 and 2 was significantly reduced, while the efficacy of Comparative Example 3 was close to that of Examples 1 and 2. This indicates that the core modification process and specific formulation can achieve synergistic effects in antitussive, anti-inflammatory, and expectorant effects.

[0026] 3. Security Testing (1) Allergy risk test Allergy risk testing employed a combined guinea pig active skin anaphylaxis (ASA) test and an allergic mouse model to comprehensively evaluate the allergic potential of the formulation. Healthy guinea pigs were randomly divided into four groups (n=10 per group): Examples 1-2, Comparative Examples 1-3, a negative control group (purified water), and a positive control group (2,4-dinitrochlorobenzene). Sensitization was achieved through a combination of intradermal injection and topical application, administered every other day for a total of three times. On day 14 post-sensitization, a challenge treatment was performed on the skin of the opposite side of the guinea pig's back. The occurrence of skin erythema and edema was observed and recorded at 24 and 48 hours post-challenge, and the incidence of allergies was calculated using standard scoring. Simultaneously, allergic mice (induced by OVA) were randomly divided into two groups (n=15 per group). The blank control group received an equal volume of purified water, while the other groups received the pediatric equivalent dose via gavage once daily for three consecutive days, with the last dose administered 24 hours prior. Mouse serum was collected h later, and the serum histamine release was measured by ELISA. At the same time, the levels of allergy-related cytokines (IL-4, IgE) were detected. The allergy risk of the formulation was quantitatively evaluated through dual verification of skin allergy reaction and serum molecular indicators, ensuring the effectiveness of the hypoallergenic process and meeting the safety requirements for pediatric medication.

[0027] Table 3. Allergy Risk Test Data for Different Samples

[0028] Examples 1 and 2, as well as Comparative Examples 1 and 2, all showed low allergy risk. Comparative Example 3, however, showed a significantly increased allergy risk due to the lack of a coltsfoot hypoallergenic process, demonstrating that this hypoallergenic process is the core of controlling allergy risk and that the formulation meets the requirements for hypoallergenic medication in children.

[0029] (2) Acute toxicity test Acute toxicity testing was conducted using ICR mice, half male and half female, randomly divided into five dosage groups (based on a gradient dosage set in a pre-experimental study) and a blank control group, with 20 mice in each group. The dosage groups were administered the corresponding samples via single gavage at different doses, while the blank control group received an equal volume of purified water. Mice were observed for 7 consecutive days after administration, recording their behavioral status (activity level, food and water intake), weight changes, and mortality. The median lethal dose (LD50) was calculated using the Bliss method. 50 If no deaths occur, the maximum tolerated dose (MTD) is determined. After the experiment, surviving mice are sacrificed, and the appearance of major organs such as the heart, liver, spleen, lungs, and kidneys is dissected and observed. Organ tissues are taken to prepare pathological sections, and pathological changes are observed under a microscope after hematoxylin-eosin (HE) staining to verify whether the acute toxicity level of the preparation meets the low toxicity requirements for pediatric use.

[0030] Table 4. Acute toxicity test data of different samples

[0031] LD of all samples 50 With a dose of >5000 mg / kg, the MTD is 20 times the equivalent dose for children, and no abnormal toxic reactions were observed in mice, demonstrating that the formulation has extremely low acute toxicity and fully meets the low toxicity standard for pediatric use.

[0032] (3) Stimulation test The irritation test was conducted using a rabbit oral mucosa irritation test. Healthy rabbits were randomly divided into six groups: Examples 1-2, Comparative Examples 1-3, and a blank control group. After 3 days of acclimatization, the corresponding sample (mixed with a small amount of purified water to form a paste) was evenly applied to one side of the buccal mucosa of the rabbits in the treatment group, covering an area of ​​approximately 2 cm × 2 cm. The other side of the buccal mucosa served as a self-control. The blank control group was treated with an equal volume of purified water. The treatment was carried out twice daily for 7 consecutive days. The rabbits' reactions (such as salivation, restlessness, etc.) were observed within 1 hour after each application. The congestion, edema, erosion, and incidence of buccal mucosa were recorded daily. After the experiment, the rabbits were euthanized, and the mucosal tissue from the application site was used to prepare pathological sections. The integrity of the mucosal tissue and the infiltration of inflammatory cells were observed. The irritation of the preparation to the oral mucosa was comprehensively evaluated (1-4 points, with lower scores indicating milder irritation) to ensure that children would not experience any discomfort when taking the medication.

[0033] Table 5. Irritation test data for different samples

[0034] All samples showed no irritation to the oral mucosa of rabbits, and the rabbits did not experience any adverse reactions, proving that the formulation has good palatability, no mucosal irritation, and is suitable for children.

[0035] 4. Bioavailability test Healthy SD rats were randomly divided into four groups of 12 rats each: Examples 1-2, Comparative Examples 1-3, and a blank control group. After fasting for 12 hours, the rats had free access to water. The treatment groups were administered the corresponding formulation via gavage at a pediatric equivalent dose, while the blank control group received an equal volume of purified water. Blood samples were collected from the orbital venous plexus of the rats at 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours after administration, with 0.5 mL collected each time. The samples were placed in centrifuge tubes containing heparin sodium and centrifuged at 3500 rpm for 10 min to separate the plasma. An appropriate amount of plasma sample was taken, and methanol was added to precipitate the protein. The mixture was vortexed for 10 min and centrifuged again. The supernatant was filtered through a 0.45 μm organic phase filter membrane. HPLC was used to determine the concentrations of quercetin and hesperidin in the plasma. A C18 column was used, with a gradient elution of methanol-0.1% phosphoric acid aqueous solution as the mobile phase. The detection wavelengths were 254 nm (quercetin) and 283 nm (hesperidin), respectively, at a flow rate of 1.0 nm. The column speed was set at 30℃ and the column temperature at 30℃. A plasma drug concentration-time curve was plotted using the plasma drug concentration data, and the area under the plasma drug concentration-time curve (AUC) was calculated. 0-24h Peak concentration (C) max Peak time (T) max ), and compare the differences in indicators among the groups.

[0036] Table 6. Bioavailability test data for different samples

[0037] Example 1 showed the best absorption efficiency. The bioavailability of quercetin in Comparative Example 1 and hesperidin in Comparative Example 2 was significantly reduced. The absorption indices of Example 2 and Comparative Example 3 were close to those of Example 1, proving that the core modification process is the key to improving bioavailability and meets the preset improvement target.

[0038] 5. Pharmaceutical properties testing Take appropriate amounts of the granular formulations from each example and comparative example, and determine the particle size distribution using a laser particle size analyzer to count the proportion of particles between 50-100 μm. Determine the water content using a Karl Fischer moisture analyzer, and use the fixed funnel method to determine the angle of repose and assess flowability. Add 5 g of sample to 100 mL of 37℃ warm water, stir, and observe whether it completely dissolves within 5 min to evaluate solubility. For palatability evaluation, select 50 children aged 3-12 years as volunteers, and use a 5-point scoring method to blindly evaluate the formulation from three dimensions: odor, taste, and mouthfeel (5 points, n=50), and calculate the average score. In stability testing, place the samples in an accelerated stability test at 40℃ and 75% RH for 6 months, and in a long-term stability test at 25℃ and 60% RH for 24 months. Periodically sample and observe whether clumping or discoloration occurs. Use HPLC to determine the content of quercetin, small molecule hesperidin, and coltsfoot ketone, and calculate the rate of change.

[0039] Table 7. Test data of pharmaceutical properties of different samples

[0040] All samples met the standards for routine indicators, palatability, and stability. Example 1 showed the best overall performance, while Comparative Example 2 had slightly lower palatability but still met the standards, demonstrating that the formulation is suitable for industrial production, is stable during storage, and meets the needs of children.

[0041] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A plant complex formulation for relieving cough and asthma and airway inflammation in children, characterized in that, The composite preparation is prepared from the following raw materials by weight: 1 part of modified sophora flower extract, 3-4 parts of fermented shaddock peel extract, and 0.8-1.2 parts of low-allergy radix stellariae dichotomae extract; The content of quercetin in the modified sophora flower extract is 1.2%-2.0%, which is detected by high-performance liquid chromatography; The content of small-molecule hesperidin in the fermented shaddock peel extract is 2.5%-3.5%, which is quantified by liquid chromatography-mass spectrometry; The content of genkwanin in the low-allergy radix stellariae dichotomae extract is 0.8%-1.5%, which is quantified by gas chromatography-mass spectrometry.

2. The plant composite formulation for alleviating cough and asthma and airway inflammation in children according to claim 1, wherein, The preparation process of the modified sophora flower extract is as follows: sophora flower is crushed to pass through a 40-mesh sieve, then dissolved in 10-15 times the weight of purified water, and 0.3%-0.5% of cellulase based on the weight of the raw material is added for enzymolysis at 50-55℃ for 2-3 h; the enzymolysis solution is combined with β-cyclodextrin at a weight ratio of 1:2-3, and then subjected to inclusion at 45-50℃ for 1-1.5 h, and then subjected to low-temperature spray drying below 40℃ to obtain micro-powder with a particle size of 5-10 μm.

3. The herbal compound preparation for relieving cough, asthma, and airway inflammation in children according to claim 1, characterized in that, The preparation process of the fermented shaddock peel extract is as follows: shaddock peel is crushed to pass through a 60-mesh sieve, then 8-10 times the weight of purified water is added, sterilized at 121℃ for 20 min, and then cooled to 35-37℃; Lactobacillus rhamnosus (CGMCC 1.3724) is inoculated at an inoculation amount of 3%-5% of the total weight of the system, and 0.5%-1% of galacto-oligosaccharide based on the total weight of the system is added as a substrate, and then subjected to fermentation under anaerobic conditions for 24-36 h; the fermentation solution is filtered, concentrated to an extract with a relative density of 1.10-1.15 at 60℃, stirred with 3 times the volume of 95% ethanol, and then subjected to precipitation at 4℃ for 12 h; after filtration, the ethanol is recovered and dried to obtain the fermented shaddock peel extract.

4. The plant composite formulation for alleviating cough and asthma and airway inflammation in children according to claim 1, wherein, The preparation process of the low-allergy radix stellariae dichotomae extract is as follows: radix stellariae dichotomae is taken as the raw material, 12-15 times the weight of 70% ethanol is added, and then subjected to reflux extraction twice, each for 1.5 h; the extraction solutions are combined, concentrated to be alcohol-free at 50℃ under reduced pressure, purified by a 30 kDa ultrafiltration membrane under a pressure of 0.2-0.3 MPa, and then the permeate is collected; β-glucosidase is added to the permeate at an amount of 0.2%-0.4% of the weight of the permeate, and then subjected to enzymolysis at 35℃ for 1 h to remove bitterness; the enzymolysis solution is concentrated and dried, and then the residual amount of allergens is detected to be 0.003%-0.01% to obtain the low-allergy radix stellariae dichotomae extract.

5. The plant composite formulation for alleviating cough and asthma and airway inflammation in children according to claim 1, wherein, The preparation is an oral granule, and the auxiliary materials include galacto-oligosaccharide, steviol glycoside, and child-safe strawberry-flavored flavoring, the strawberry-flavored flavoring meets the standard GB 2760, and the particle size is 50-100 μm; the addition amount of the strawberry-flavored flavoring is 0.1%-0.3% of the total weight of the preparation.

6. The plant composite formulation for alleviating cough and asthma and airway inflammation in children according to claim 1, wherein, The dosage of the composite preparation is designed according to age stratification: 0.5 g each time for children aged 3-6 years old, twice a day; 1.0 g each time for children aged 7-12 years old, twice a day.

7. A method for preparing a plant composite preparation for relieving cough and asthma and airway inflammation in children according to any one of claims 1-6, characterized in that, The specific preparation steps are as follows: S1, respectively prepare the modified sophora flower extract, the fermented shaddock peel extract, and the low-allergy radix stellariae dichotomae extract; S2, the three extracts are mixed in a weight ratio of 1:(3-4):(0.8-1.2), 15%-20% of the total weight of the preparation of oligofructose, 0.3%-0.5% of stevioside and 0.1%-0.3% of child safety strawberry flavor are added, and placed in a three-dimensional mixer to mix at a speed of 20-30 rpm for 15-20 min until uniform; add 25%-35% of the total weight of the extract and the excipient of purified water, and stir to prepare a soft material that can be held together and scattered by a light touch; sieve granulation through an 18-mesh sieve, dry the wet granules below 45℃ for 2-3 h, and control the moisture content of the granules to be 3%-5%; finally, sieve the granules through a 20-mesh sieve, and screen the granules with a particle size of 50-100 μm, to obtain an oral granule.

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