Chamomile extract compound preparation for treating asthma and application thereof

Abstract

The invention belongs to the field of biological medicines and plant preparations, and discloses a chamomile extract compound preparation for treating asthma and an application of the chamomile extract compound preparation. The preparation consists of a German chamomile extract (containing alpha-bisabolol), a hedera helix extract (containing alpha-hederin), EDTA-2Na (Ethylene Diamine Tetraacetic Acid), rosmarinic acid and pharmaceutic adjuvants, and can be prepared into aerosol. The preparation method comprises the following steps: extracting active ingredients of chamomile and hedera helix through supercritical CO2, and performing high-pressure homogenization (20,000 psi) to form a nano suspension with D90 less than or equal to 5 microns (NGI + verifies that FPF is less than 3 microns and the proportion is greater than or equal to 70%). The compound inhibits an NF-kB / STAT3 inflammatory pathway and PDE4 activity through a multi-target synergistic effect, and significantly improves airway hyperreactivity. In addition, the invention further provides an aerosol spray prepared from the compound, and the aerosol spray is suitable for long-term control and acute attack treatment of children asthma.

Description

Technical Field

[0001] The invention belongs to the field of biomedicine and botanical preparations, and specifically discloses a chamomile extract compound preparation for treating asthma and application thereof. Background Art

[0002] Asthma is a common chronic inflammatory airway disease affecting a large number of patients worldwide. Clinically, it presents with recurrent episodes of wheezing, shortness of breath, and coughing, which severely impact quality of life. While current mainstream treatments (such as glucocorticoids and β2-receptor agonists) can effectively control symptoms, long-term use can lead to drug resistance, local side effects, or systemic adverse reactions. In recent years, natural plant extracts have become a research hotspot due to their multi-target effects, low toxicity, and anti-inflammatory potential. Chamomile (Matricaria chamomilla) is traditionally used to alleviate airway inflammation, and its active ingredients (such as flavonoids and terpenes) have been shown to have antioxidant, anti-inflammatory, and bronchodilatory effects. However, single-ingredient extracts often have limited efficacy, and existing compound preparations lack optimization in terms of ingredient ratio, bioavailability, and synergistic mechanisms. Therefore, developing a compound preparation based on chamomile extract that enhances efficacy, minimizes side effects, and defines its application scenarios through scientific compatibility has significant clinical value and market prospects. Summary of the Invention

[0003] To address the above issues, the present invention discloses a chamomile extract compound preparation for treating asthma and its use. Through a scientific formula and rational preparation process, this compound preparation combines multiple ingredients with anti-inflammatory, immune, and airway-improving properties, aiming to provide a safe, effective, and convenient medication for preventing or improving respiratory diseases in children, particularly asthma. The present invention also provides the use of this compound preparation in the preparation of a medication to further enhance its therapeutic efficacy for pediatric asthma.

[0004] The purpose of the present invention is achieved through the following technical solutions.

[0005] A chamomile extract compound preparation for treating asthma, comprising the following raw materials in parts by weight:

[0006] 10-25 parts of German chamomile extract, 5-15 parts of ivy extract, 1-5 parts of EDTA-2Na, 3-8 parts of rosmarinic acid, 5-10 parts of sucralose, and 5-10 parts of natural pear flavor;

[0007] The compound preparation is an atomized aerosol;

[0008] The preparation method of the above-mentioned compound preparation comprises the following steps:

[0009] a) preparing German chamomile extract and ivy extract respectively;

[0010] b) Preparation of aqueous phase: Take 80% of the total water, heat to 40-50°C, add EDTA-2Na and sucralose, and stir until completely dissolved;

[0011] c) Alcohol phase preparation: dissolving rosmarinic acid and ivy extract in ethanol, and accelerating dissolution with ultrasound assistance;

[0012] d) Slowly mixing the aqueous phase and the alcohol phase: pour the mixture obtained in step c) into the mixture obtained in step b) in a thin stream, stirring continuously to avoid local precipitation.

[0013] e) adding chamomile extract: pre-moisten the German chamomile extract with a small amount of ethanol and then add it to the mixture;

[0014] f) Flavor emulsification: premix natural pear flavor with lecithin, homogenize and then add to the system;

[0015] g) High-pressure homogenization: using a high-pressure homogenizer at a pressure of 15,000-20,000 psi, for 3 cycles, to control the particle size D90 to ≤ 5 μm;

[0016] h) Formulation into a nebulized aerosol.

[0017] Furthermore, in the above-mentioned compound preparation, the preparation of the German chamomile extract in step a) comprises the following steps:

[0018] The stamens of fresh chamomile plants are selected, dried, and crushed to less than 60 mesh. 60%-80% ethanol is added at a solid-liquid ratio of 1:12-15, and reflux extraction is performed at 50°C-85°C for 3-5 times, each time for 1-1.5 hours. After further concentration by vacuum distillation, impurities are removed by centrifugation. Subsequently, ultrasonic wave-assisted cell wall destruction is used, and subcritical extraction is combined to achieve efficient separation. Finally, a high-purity product is obtained by molecular distillation or spray drying, with the α-bisabolol content controlled to be ≥90% and the flavonoid content to be ≥80%.

[0019] Furthermore, in the above-mentioned compound preparation, the preparation of the German chamomile extract in step a) comprises the following steps: the parameters of the reduced pressure distillation are set to T = 40-50°C, P = -0.09 MPa, the parameters of the centrifugal separation are set to r = 10000 rpm, t = 15 min; the parameters of the ultrasonic assistance are set to f = 40 kHz, p = 50 W / L, t = 30 min.

[0020] Furthermore, in the above-mentioned compound preparation, propane is used as solvent during the combined subcritical extraction, P=5MPa, T=50°C for the primary extraction of flavonoids, and P=8MPa, T=60°C for the secondary extraction of volatile oils.

[0021] Furthermore, in the above-mentioned compound preparation, the preparation of the ivy extract in step a) comprises the following steps:

[0022] Fresh ivy leaves and tender stems were used as raw materials, dried at 40°C and then crushed to 60 mesh. Gradient ethanol extraction combined with ultrasound-assisted extraction was used to maximize the yield of α-ivy saponins. The extract was concentrated under reduced pressure, dynamically purified by HPD-300 resin, and then subjected to subcritical propane extraction for targeted enrichment of active ingredients. Finally, molecular distillation was used to obtain the standard extract.

[0023] Furthermore, in the above-mentioned compound preparation, the gradient ethanol extraction is performed by using 70% ethanol with a solid-liquid ratio of 1:15 and refluxing at 75° C. for 3 times, each time for 1.5 hours.

[0024] Furthermore, for the above-mentioned compound preparation, the ultrasonic-assisted parameters are set to f=40kHz, p=100W / L, the reduced pressure concentration adopts T=45°C, P=-0.085MPa, the dynamic purification uses 70% ethanol elution, the purity is ≥60%, the subcritical propane extraction adopts P=6MPa, T=55°C, and the molecular distillation adopts T=85°C, P=0.05Pa.

[0025] Furthermore, in the above-mentioned compound preparation, the step h) of preparing the preparation into an atomized aerosol comprises the following steps:

[0026] Quantitative filling into a breath-triggered device in a Class A clean environment, and NGI+ testing ensures that FPF < 3μm accounts for ≥ 70%.

[0027] The present invention also discloses the use of the compound preparation in preparing health products or medicines for preventing / treating respiratory diseases in children.

[0028] Compared with the existing technology, the present invention has the following advantages and beneficial effects:

[0029] 1. Through the innovative combination of German chamomile extract (containing α-bisabolol) and ivy extract (α-hederin), a multi-target synergistic system is constructed to reduce inflammatory factors and effectively relieve bronchospasm;

[0030] 2. High-efficiency lung deposition rate: High-pressure homogenization treatment makes the aerosolized particles D90 ≤ 5μm and achieves high-efficiency lung deposition rate of FPF < 3μm, which is greatly improved compared with traditional preparations;

[0031] 3. Excellent taste and easy to take: EDTA-2Na / rosmarinic acid biphasic antioxidant network and sucralose optimize taste;

[0032] 4. Safety and reliability: All raw materials used in this invention are derived from natural plant essences and high-purity bioactive ingredients. Combined with advanced extraction and purification technologies, the non-toxic and side-effect-free characteristics of the product are guaranteed from the source. In addition, through precise ingredient ratios and optimized preparation processes, mutual interference between components is effectively eliminated, thereby significantly improving synergistic efficiency and final use effect.

[0033] In summary, the chamomile extract compound preparation for treating asthma and its application provided by the present invention are of great significance, particularly for the prevention and treatment of childhood asthma. The development and application of this product will provide new options and hope for the treatment of childhood asthma. DETAILED DESCRIPTION

[0034] A chamomile extract compound preparation for treating asthma, comprising the following raw materials in parts by weight:

[0035] 10-25 parts of German chamomile extract, 5-15 parts of ivy extract, 1-5 parts of EDTA-2Na, 3-8 parts of rosmarinic acid, 5-10 parts of sucralose, and 5-10 parts of natural pear flavor;

[0036] The compound preparation is an atomized aerosol;

[0037] The preparation method of the above-mentioned compound preparation comprises the following steps:

[0038] a) preparing German chamomile extract and ivy extract respectively;

[0039] b) Preparation of aqueous phase: Take 80% of the total water, heat to 40-50°C, add EDTA-2Na and sucralose, and stir until completely dissolved;

[0040] c) Alcohol phase preparation: dissolving rosmarinic acid and ivy extract in ethanol, and accelerating dissolution with ultrasound assistance;

[0041] d) Slowly mixing the aqueous phase and the alcohol phase: pour the mixture obtained in step c) into the mixture obtained in step b) in a thin stream, stirring continuously to avoid local precipitation.

[0042] e) adding chamomile extract: pre-moisten the German chamomile extract with a small amount of ethanol and then add it to the mixture;

[0043] f) Flavor emulsification: premix natural pear flavor with lecithin, homogenize and then add to the system;

[0044] g) High-pressure homogenization: Use a high-pressure homogenizer at a pressure of 15,000-20,000 psi, cycle 3 times, and control the particle size D90 ≤ 5 μm.

[0045] h) Preparation into a nebulized aerosol

[0046] The preparation of the German chamomile extract in step a) comprises the following steps:

[0047] The stamens of fresh chamomile plants are selected, dried, and crushed to less than 60 mesh. 60%-80% ethanol is added at a solid-liquid ratio of 1:12-15, and reflux extraction is performed at 50°C-85°C for 3-5 times, each time for 1-1.5 hours. After further concentration by vacuum distillation, impurities are removed by centrifugation. Subsequently, ultrasonic wave-assisted cell wall destruction is used, and subcritical extraction is combined to achieve efficient separation. Finally, a high-purity product is obtained by molecular distillation or spray drying, with the α-bisabolol content controlled to be ≥90% and the flavonoid content to be ≥80%.

[0048] The preparation of the German chamomile extract in step a) comprises the following steps: the parameters of the reduced pressure distillation are set to T = 40-50°C, P = -0.09 MPa, the parameters of the centrifugal separation are set to r = 10000 rpm, t = 15 min; the parameters of the ultrasonic assistance are set to f = 40 kHz, p = 50 W / L, t = 30 min.

[0049] The combined subcritical extraction uses propane as solvent, P=5MPa, T=50°C for primary extraction of flavonoids, and P=8MPa, T=60°C for secondary extraction of volatile oil.

[0050] The preparation of the ivy extract in step a) comprises the following steps:

[0051] Fresh ivy leaves and tender stems were used as raw materials, dried at 40°C and then crushed to 60 mesh. Gradient ethanol extraction combined with ultrasound-assisted extraction was used to maximize the yield of α-ivy saponins. The extract was concentrated under reduced pressure, dynamically purified by HPD-300 resin, and then subjected to subcritical propane extraction for targeted enrichment of active ingredients. Finally, molecular distillation was used to obtain the standard extract.

[0052] The gradient ethanol extraction was performed using 70% ethanol with a solid-liquid ratio of 1:15 and reflux at 75° C. for 3 times, each time for 1.5 hours.

[0053] The ultrasonic-assisted parameters were set to f=40 kHz, p=100 W / L, the reduced pressure concentration adopted T=45°C, P=-0.085 MPa, the dynamic purification used 70% ethanol elution with a purity ≥60%, the subcritical propane extraction adopted P=6 MPa, T=55°C, and the molecular distillation adopted T=85°C, P=0.05 Pa.

[0054] Furthermore, in the above-mentioned compound preparation, the step h) of preparing the preparation into an atomized aerosol comprises the following steps:

[0055] Quantitative filling into a breath-triggered device in a Class A clean environment, and NGI+ testing ensures that FPF < 3μm accounts for ≥ 70%.

[0056] In order to make the purpose, technical solutions and advantages of the present invention clearer, the present invention is further described in detail below. However, it should be understood that the specific embodiments described herein are merely for the purpose of explaining the present invention and are not intended to limit the scope of the invention. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concept of the present invention. All raw materials in the embodiments of the present invention can be obtained through commercial channels.

[0057] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below with reference to the embodiments.

[0058] Example 1

[0059] Nebulized aerosol

[0060] 1. Raw material composition:

[0061] raw material 1 group 2 groups 3 groups 4 groups 5 groups German chamomile extract 25 20 15 10 0 Ivy extract 15 15 15 15 15 EDTA-2Na 5 5 5 5 5 Rosmarinic acid 8 8 8 8 8 Sucralose 10 10 10 10 10 Natural pear flavor 10 10 10 10 10

[0062] 2. Preparation process of compound preparation:

[0063] 1) Extraction of German chamomile extract:

[0064] The method comprises the following steps: selecting the stamens of fresh chamomile plants, drying them, and crushing them to a size below 60 mesh; adding 60%-80% ethanol at a material-liquid ratio of 1:12-15; and reflux extraction at 50-85°C for 3-5 times, each time for 1-1.5 hours; further concentrating the product by vacuum distillation at T=40-50°C and P=-0.09 MPa; and removing impurities by centrifugation at r=10000 rpm and t=15 minutes; then destroying the residual cell walls by ultrasonic wave assisted at f=40 kHz, P=50 W / L and t=30 minutes; using propane as a solvent and combining subcritical extraction at P=5 MPa and T=50°C to achieve primary extraction of flavonoids; and achieving secondary extraction of volatile oils at P=8 MPa and T=60°C to achieve efficient separation; and finally obtaining a high-purity product by molecular distillation at 80°C and 0.1 Pa or spray drying at 180°C with air inlet, wherein the α-bisabolol content is controlled to be ≥90% and the flavonoid content is controlled to be ≥80%.

[0065] 2) Preparation of Ivy Extract:

[0066] Fresh ivy leaves and tender stems were used as raw materials, dried at 40°C and then crushed to 60 mesh. Gradient extraction was performed using 70% ethanol at a solid-liquid ratio of 1:15, refluxed at 75°C for three times, each time for 1.5 h. Ultrasonic extraction was performed with f=40 kHz, p=100 W / L to maximize the yield of α-ivy saponins. The extract was concentrated under reduced pressure at T=45°C and P=-0.085 MPa, then dynamically purified by HPD-300 resin, and then subjected to subcritical propane extraction at P=6 MPa and T=55°C to directionally enrich the active ingredients. Finally, molecular distillation was performed at T=85°C and P=0.05 Pa to obtain the standard extract.

[0067] 3) Preparation of aqueous phase: Take 80% of the total water, heat to 40-50°C, add EDTA-2Na and sucralose, and stir until completely dissolved;

[0068] 4) Alcohol phase preparation: dissolve rosmarinic acid and ivy extract in ethanol, and accelerate dissolution with ultrasound assistance;

[0069] 5) Slowly mixing the aqueous phase and the alcohol phase: Pour the mixture obtained in step c) into the mixture obtained in step b) in a thin stream, stirring continuously to avoid local precipitation.

[0070] 6) Adding chamomile extract: Pre-moisten the German chamomile extract with a small amount of ethanol and then add it to the mixture;

[0071] 7) Flavor emulsification treatment: premix natural pear flavor with lecithin, homogenize and then add to the system;

[0072] 8) High-pressure homogenization: Use a high-pressure homogenizer at a pressure of 15,000-20,000 psi, cycle 3 times, and control the particle size D90 ≤ 5 μm;

[0073] 3. Preparation process of atomized aerosol:

[0074] Quantitative filling into a breath-triggered device in a Class A clean environment, and NGI+ testing ensures that FPF < 3μm accounts for ≥ 70%.

[0075] Example 2

[0076] 1. Raw material composition:

[0077] raw material 1 group 2 groups 3 groups 4 groups 5 groups Ivy extract 15 10 5 1 0 German chamomile extract 25 25 25 25 25 EDTA-2Na 5 5 5 5 5 Rosmarinic acid 8 8 8 8 8 Sucralose 10 10 10 10 10 Natural pear flavor 10 10 10 10 10

[0078] 2. Preparation process of compound preparation:

[0079] Same as Example 1.

[0080] 3. Preparation process of atomized aerosol:

[0081] Same as Example 1.

[0082] Example 3

[0083] 1. Raw material composition:

[0084] raw material 1 group 2 groups 3 groups 4 groups 5 groups Rosmarinic acid 8 6 4 2 0 Ivy extract 25 25 25 25 25 EDTA-2Na 5 5 5 5 5 Ivy extract 15 15 15 15 15 Sucralose 10 10 10 10 10 Natural pear flavor 10 10 10 10 10

[0085] 2. Preparation process of compound preparation:

[0086] Same as Example 1.

[0087] 3. Preparation process of atomized aerosol:

[0088] Same as Example 1.

[0089] Example 4

[0090] Drug combination

[0091] One part of fluticasone propionate (FP) was added to the active ingredient in Example 1. The remaining components and preparation process were the same as those in Example 1.

[0092] Raw material composition:

[0093] raw material 1 group 2 groups 3 groups 4 groups 5 groups 6 groups 7 groups German chamomile extract 25 25 0 0 0 0 25 Fluticasone propionate 5 0 3 0 1.6 0 25 Ivy extract 0 0 15 15 0 0 15 Rosmarinic acid 0 0 0 0 8 8 8 EDTA-2Na 5 5 5 5 5 5 5 Sucralose 10 10 10 10 10 10 10 Natural pear flavor 10 10 10 10 10 10 10

[0094] Test Case

[0095] The above active ingredients are added to ultrapure water to prepare an active solution.

[0096] 1. In vitro cell protection experiment

[0097] 1. Cell Culture and Model Establishment

[0098] Cell line: mouse tracheal smooth muscle cells (GPSMC).

[0099] Culture medium: DMEM / F12 (3:1) containing 10% FBS, hFGF2+ITS-X+0.1 μM retinoic acid.

[0100] Induced injury: LPS 10-100 ng / mL stimulation for 24 hours induced the release of inflammatory factors.

[0101] Group Processing conditions Negative control group Pure water treatment Model Group LPS 50 ng / mL Example 1 LPS 50ng / mL+50μg / mL Example 1 active solution Example 2 LPS 50ng / mL+50μg / mL Example 2 active solution Example 3 LPS 50ng / mL+50μg / mL Example 3 active solution Example 4 LPS 50ng / mL+50μg / mL Example 4 active solution Positive control group LPS 50 ng / mL + 50 μg / mL fluticasone propionate

[0102] 2. Experimental Grouping

[0103] 3. Detection indicators

[0104] IL-6 inhibition rate detection: enzyme-linked immunosorbent assay (ELISA).

[0105] NF-KB nuclear translocation inhibition rate detection: immunofluorescence (IF) and anti-p65 antibody labeling were used.

[0106] Oxidative stress: ROS levels (DCFH-DA fluorescent probe).

[0107] Cell viability: CCK-8 reagent (absorbance at 450 nm).

[0108] Blood eosinophil count (EOS): Use fluorescent dyes CD16-FITC + CD193-PE and incubate at 37°C for 5 minutes.

[0109] The experimental results are as follows:

[0110] Table 1 Experimental data results of Example 1

[0111]

[0112] * p<0.01 vs model group; ##p<0.01+lowest dose group; p<0.05 vs model group

[0113] Experimental Conclusion 1: The experimental data from Example 1 show that as the content of German chamomile ingredients increases, the positive rate of NF-κB nuclear translocation gradually decreases. The main reason is that α-bisabolol in German chamomile specifically activates the PPARγ nuclear receptor, binds to the PPAR response element (PPRE) on DNA, and significantly upregulates the transcriptional activity of the IκBα gene, thereby accelerating the regeneration and accumulation of IκBα protein. This process forms a negative feedback loop, continuously neutralizing free NF-κB p65-p50 dimers, ultimately blocking NF-κB nuclear translocation and achieving cascade inhibition of inflammatory signaling. This mechanism complements the IκKβ inhibitory effect of flavonoids, and together they constitute the core molecular basis for chamomile's multi-target anti-inflammatory effects.

[0114] Table 2 Experimental data results of Example 2

[0115]

[0116] * p<0.01 vs model group; ##p<0.01 vs lowest dose group; p<0.05 vs model group

[0117] Experimental conclusion 2: The experimental results of Example 2 show that the content of ivy contributes weakly to the inhibition of IL-6 / NF-KB (<5%); under the condition of a fixed 25 parts of chamomile, when the ivy was reduced from 15 parts to 0 parts, the IL-6 inhibition rate only decreased by 4.9% (80.1%→75.2%), and the NF-KB inhibition rate decreased by 6.6% (80.5%→73.9%), both of which were not statistically significant (p>0.05). The reason is that the main active ingredient of ivy, α-ivy saponin, targets the PDE4-cAMP pathway and has no direct cross-effect with the NF-KB signal; this indicates the limitations of ivy in regulating inflammatory factors.

[0118] When the amount of ivy was increased from 0 to 15, the cAMP level increased from 2.2 to 9.5 pmol / mL (R 2 =0.92), the dilation rate of isolated tracheal rings increased by 45% simultaneously, and the EOS inhibition rate exceeded 60% when ivy ≥10 parts was taken. This is because ivy extract exerts its core functions of bronchial dilation and immune regulation through the PDE4-cAMP-EOS axis. Although it contributes little to the inhibition of IL-6 / NF-KB, it forms a dual synergy with chamomile in terms of time, space and mechanism, providing a precise basis for the combination treatment of asthma.

[0119] Table 3 Comparison of experimental results of Example 1 and Example 2

[0120] comparison group Difference in IL-6 inhibition rate Difference in NF-kB inhibition rate Example 1 ↓68.4％ ↓73.6％ Example 2 ↓4.9％ ↓6.6％

[0121] Experimental conclusion 3: The results of Example 1 and Example 2 show that after removing chamomile (Example 1-5 group), the IL-6 inhibition rate plummeted from 78.9% to 10.5% (a decrease of 68.4%), and the NF- K The inhibition rate of B decreased from 73.6% to 0% (a decrease of 73.6%), indicating that chamomile is the absolute leading component of the anti-inflammatory effect; transcriptome sequencing showed that NF- K The expression of B downstream genes (IL6, TNF, CXCL8) was downregulated by 70-80%, while that of the ivy group was only downregulated by 5-8%. The apigenin in chamomile directly binds to IKKβ kinase, inhibiting I K Bα phosphorylation, blocking NF- K B nuclear translocation, the absence of chamomile led to uncontrolled inflammation, while the absence of ivy only slightly affected inflammatory indicators.

[0122] When Ivy drops from 15 to 0, IL-6 / NF- KB inhibition rates decreased by only 4.9% / 6.6% (p>0.05), confirming its minimal contribution to inflammation suppression. However, cAMP levels plummeted from 9.5 pmol / mL to 2.2 pmol / mL (a 77% decrease), and EOS inhibition rates decreased from 70.2% to 48.6% (a 21.6% decrease), indicating its core function is airway regulation.

[0123] Table 4 Experimental data results of Example 3

[0124]

[0125] *p<0.01 vs model group; ##p<0.01 vs lowest dose group; p<0.05 vs model group

[0126] Experimental Conclusion 4: The ROS scavenging rate of the 8-dose rosmarinic acid group (72%) was significantly higher than that of the 0-dose group (20%), but the IL-6 inhibition rate was only increased by 7%. Its specific antioxidant effect is mainly due to its catechol structure that can efficiently quench ·OH.

[0127] Table 5 Experimental data results of Example 4

[0128]

[0129] *p<0.01 vs model group; ##p<0.01 vs lowest dose group; p<0.05 vs model group

[0130] Experimental Conclusion 5:

[0131] 1. Based on the experimental data, the IL-6 inhibition rate in the model group was 0, indicating that inflammation was activated after model establishment, leading to high IL-6 production. Groups 1 and 7, however, had higher IL-6 inhibition rates, demonstrating that chamomile has a strong inhibitory effect on IL-6. The combination of chamomile, FP, ivy, and rosmarinic acid further enhanced the inhibitory effect. This is primarily due to the fact that the active ingredients in chamomile, such as flavonoids and terpenoids, reduce IL-6 production by inhibiting the activation of nuclear factor-κB (NF-κB). NF-κB is a key transcription factor regulating the expression of inflammation-related genes. Chamomile components block the NF-κB signaling pathway, preventing it from entering the cell nucleus and binding to the IL-6 gene promoter, thereby inhibiting IL-6 transcription and synthesis. FP has a role in regulating immune cell function. It inhibits IL-6 secretion by immune cells such as macrophages, reducing IL-6 release by affecting intracellular signal transduction pathways.

[0132] 2. Verification of anti-inflammatory synergy: By comparing the data of Group 1, Group 2 and Group 5, the results showed that the IL-6 inhibition rate of chamomile alone was 78.9%, the IL-6 inhibition rate of FP alone was 82.4%, and the IL-6 inhibition rate of chamomile and FP combined was 92.5%, indicating that the synergistic effect exceeds the simple superposition of single ingredients. This is mainly because chamomile inhibits IKKβ and FP promotes the synthesis of IκBα. The two greatly enhance the synergistic anti-inflammatory effect by doubly blocking the NF-κB pathway.

[0133] 3. Independent contribution of ivy: In the absence of chamomile (group 3), the EOS inhibition rate of FP+ivy (75.3%) was still close to that of the positive control, indicating that ivy independently regulates immune infiltration through the PDE4-cAMP-EOS axis.

[0134] 4. Cytoprotective effect: Rosmarinic acid significantly increased the cell survival rate of the combined group (1.20) compared with FP alone (1.15) (p < 0.05), which was attributed to its ROS clearance (88%) and TEER value improvement (85Ω·cm 2 ) double protection.

[0135] Based on the above embodiments and test examples, the following conclusions can be drawn:

[0136] The chamomile extract compound preparation for treating asthma provided by the present invention has a significant therapeutic effect on asthma and is expected to become a safe, effective and convenient medicine for improving or treating respiratory diseases in young children, especially asthma.

[0137] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Therefore, based on the innovative concept of the present invention, changes and modifications to the embodiments described herein, or equivalent structural or equivalent process transformations made using the contents of the present invention specification, directly or indirectly applying the above technical solutions to other related technical fields are all included in the scope of protection of the patent of the present invention.

Claims

1. A chamomile extract compound preparation for treating asthma, characterized in that: It is composed of the following raw materials in parts by weight: 10-25 parts of German chamomile extract, 5-15 parts of ivy extract, 1-5 parts of EDTA-2Na, 3-8 parts of rosmarinic acid, 5-10 parts of sucralose, and 5-10 parts of natural pear flavor; The compound preparation is an atomized aerosol; The preparation method of the above-mentioned compound preparation comprises the following steps: a) preparing German chamomile extract and ivy extract respectively; b) Preparation of aqueous phase: Take 80% of the total water, heat to 40-50°C, add EDTA-2Na and sucralose, and stir until completely dissolved; c) Alcohol phase preparation: dissolving rosmarinic acid and ivy extract in ethanol, and accelerating dissolution with ultrasound assistance; d) Slowly mixing the aqueous phase and the alcohol phase: pour the mixture obtained in step c) into the mixture obtained in step b) in a thin stream, stirring continuously to avoid local precipitation. e) adding chamomile extract: pre-moisten the German chamomile extract with a small amount of ethanol and then add it to the mixture; f) Flavor emulsification: premix natural pear flavor with lecithin, homogenize and then add to the system; g) High-pressure homogenization: using a high-pressure homogenizer at a pressure of 15,000-20,000 psi, for 3 cycles, to control the particle size D90 to ≤ 5 μm; h) Formulation into a nebulized aerosol.

2. The compound preparation according to claim 1, characterized in that The preparation of the German chamomile extract in step a) comprises the following steps: The stamens of fresh chamomile plants are selected, dried, and crushed to less than 60 mesh. 60%-80% ethanol is added at a solid-liquid ratio of 1:12-15, and reflux extraction is performed at 50°C-85°C for 3-5 times, each time for 1-1.5 hours. After further concentration by vacuum distillation, impurities are removed by centrifugation. Subsequently, ultrasonic wave-assisted cell wall destruction is used, and subcritical extraction is combined to achieve efficient separation. Finally, a high-purity product is obtained by molecular distillation or spray drying, with the α-bisabolol content controlled to be ≥90% and the flavonoid content to be ≥80%.

3. The compound preparation according to claim 2, characterized in that The parameters of the reduced pressure distillation were set to T = 40-50°C, P = -0.09 MPa, the parameters of the centrifugal separation were set to r = 10000 rpm, t = 15 min, and the parameters of the ultrasonic assistance were set to f = 40 kHz, p = 50 W / L, t = 30 min.

4. The compound preparation according to claim 2, characterized in that The combined subcritical extraction uses propane as solvent, P=5MPa, T=50°C for primary extraction of flavonoids, and P=8MPa, T=60°C for secondary extraction of volatile oils.

5. The compound preparation according to claim 1, characterized in that The preparation of the ivy extract in step a) comprises the following steps: Fresh ivy leaves and tender stems were used as raw materials, dried at 40°C and then crushed to 60 mesh. Gradient ethanol extraction combined with ultrasound-assisted extraction was used to maximize the yield of α-ivy saponins. The extract was concentrated under reduced pressure, dynamically purified by HPD-300 resin, and then subjected to subcritical propane extraction to directionally enrich the active ingredients. Finally, molecular distillation was used to obtain the standard extract.

6. The compound preparation according to claim 5, characterized in that The gradient ethanol extraction was performed using 70% ethanol with a solid-liquid ratio of 1:15 and reflux at 75° C. for 3 times, each time for 1.5 hours.

7. The compound preparation according to claim 5, characterized in that The ultrasonic-assisted parameters were set as f=40 kHz, p=100 W / L, the reduced pressure concentration adopted T=45°C, P=-0.085 MPa, the dynamic purification used 70% ethanol elution with a purity of ≥60%, the subcritical propane extraction adopted P=6 MPa, T=55°C, and the molecular distillation adopted T=85°C, P=0.05 Pa.

8. The compound preparation according to claim 1, characterized in that The step h) of preparing the atomized aerosol comprises the following steps: Quantitative filling into a breath-triggered device in a Class A clean environment, and NGI+ testing ensures that FPF < 3μm accounts for ≥ 70%.

9. Use of the compound preparation according to any one of claims 1 to 8 in the preparation of a pharmaceutical spray preparation for relieving / treating childhood asthma.

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