Improved compound fructus xanthii traditional Chinese medicine composition for treating allergic rhinitis

Abstract

The invention relates to an improved compound cocklebur fruit traditional Chinese medicine composition for treating allergic rhinitis, which is prepared from cocklebur fruit, folium mori, rhizoma phragmitis, platycodon grandiflorum, liquorice, rhizoma atractylodis, rhizoma zingiberis, radix sophorae flavescentis, rabdosia rubescens and cortex mori radicis according to a specific weight part ratio. The improved compound traditional Chinese medicine composition with a new prescription can effectively inhibit the key biological sites of the occurrence and development of rhinitis and improve the symptoms of rhinitis, and compared with the original compound fructus xanthii prescription, the improved compound traditional Chinese medicine composition has higher treatment efficiency and wider applicability to most people.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine and the technology of traditional Chinese medicine compositions, and in particular to a modified compound Xanthium sibiricum traditional Chinese medicine composition for treating allergic rhinitis. Background Technology

[0002] Allergic rhinitis (AR), also known as allergic rhinitis, is a non-infectious chronic inflammatory disease of the nasal mucosa that occurs in atopic individuals after exposure to allergens. AR is a common chronic nasal disease affecting 10% to 20% of the world's population, and has become a global health problem. A national survey in 2011 showed that the self-reported prevalence of AR among adults in China reached 17.6%.

[0003] Under current technology, commonly used Western medicine treatments for allergic rhinitis (AR) are divided into first-line and second-line drugs. First-line drugs include nasal corticosteroids, second-generation oral and nasal antihistamines, and oral leukotriene receptor antagonists; second-line drugs include oral corticosteroids, oral and nasal mast cell membrane stabilizers, nasal decongestants, and nasal anticholinergics. These combinations form the common Western medicine treatments for allergic rhinitis, including oral / intranasal antihistamines, intranasal corticosteroids, decongestants, leukotriene receptor antagonists, sodium cromoglycate, and anticholinergics. In addition, Western medicine treatments also include subcutaneous / sublingual desensitization therapy, surgical treatments such as anterior ethmoidal, posterior ethmoidal, and pterygopalatine nerve blocks, septoplasty, and partial inferior turbinate resection, or methods such as cryotherapy, laser irradiation, and cauterization of the nasal mucosa to reduce nasal mucosal sensitivity.

[0004] While Western medicine can effectively control the main symptoms of allergic rhinitis, the risks of drug toxicity, side effects, and surgical complications cannot be ignored. For example, long-term use of corticosteroids and antihistamines may pose health risks, especially to children and the elderly. Furthermore, while desensitization therapy represents a future trend, its risks of anaphylactic shock, high cost, and uncertain efficacy make it difficult for patients to accept. Surgical treatment is a destructive procedure with risks of complications. Therefore, current Western medicine treatments for allergic rhinitis primarily rely on oral antihistamines and topical corticosteroid nasal sprays. While these may provide temporary relief, relapse or even worsening symptoms are common upon discontinuation, and long-term use can lead to significant side effects such as drowsiness and dry mouth. Existing immunotherapy also carries risks and uncertain efficacy. In contrast, the holistic approach of traditional Chinese medicine (TCM) makes it a preferred solution for treating allergic rhinitis.

[0005] Allergic rhinitis falls under the category of "nose" in Traditional Chinese Medicine (TCM). Its etiology and pathogenesis have been widely considered by physicians throughout history to be caused by both internal and external factors, primarily wind and cold. Internal causes are often attributed to dysfunction of the internal organs, mainly deficiency of the lungs, spleen, and kidneys; external causes are often attributed to wind and cold, or invasion of pathogenic factors into the lungs. Treatment primarily focuses on strengthening the body's resistance and consolidating its foundation with oral medications, while external treatments often utilize pungent, aromatic, and nasal-opening herbs. TCM offers effective treatment for allergic rhinitis due to its relatively low cost, ease of use, and minimal side effects. It also has unique advantages in enhancing immunity and treating allergic diseases. In 2012, the European Guidelines for the Diagnosis and Treatment of Rhinosinusitis (EPOS) stated that there is sufficient evidence (Evidence Ia) to demonstrate the significant therapeutic value of TCM for rhinosinusitis, recommending its clinical use (Grade A). my country's Guidelines for the Diagnosis and Treatment of Allergic Rhinitis also recommend TCM treatment.

[0006] Compound Xanthium sibiricum tablets (also known as Rhinitis No. 3) are an in-house preparation of Peking University Third Hospital. They have shown good efficacy in treating allergic rhinitis and have been widely recognized and used clinically. However, recent studies have shown that Compound Xanthium sibiricum tablets only have a good effect on certain subtypes of allergic rhinitis. Therefore, there is an urgent need for an improved traditional Chinese medicine composition to enhance its efficacy for allergic rhinitis patients and expand its applicable population. Summary of the Invention

[0007] To address the shortcomings of existing technologies, this invention proposes a modified compound Xanthium sibiricum herbal composition for treating allergic rhinitis. Based on traditional Chinese medicine theory and epigenetics of Chinese medicine, the modified compound Xanthium sibiricum formula is modified to produce a new prescription. This modified compound herbal composition can effectively inhibit key biological sites in the progression of rhinitis and improve rhinitis symptoms. Compared with the original compound Xanthium sibiricum formula, it has higher therapeutic efficiency and wider applicability to most population groups.

[0008] To achieve the above objectives, the technical solution adopted by the present invention includes:

[0009] A modified compound Xanthium sibiricum herbal composition for treating allergic rhinitis, characterized in that it is composed of raw materials in the following weight ratios:

[0010] 5-15 parts of Xanthium sibiricum, 7-22 parts of Morus alba leaf, 7-22 parts of Phragmites communis rhizome, 4-14 parts of Platycodon grandiflorus, 1-5 parts of Glycyrrhiza uralensis, 3-11 parts of Atractylodes lancea, 3-11 parts of Zingiber officinale, 4-14 parts of Sophora flavescens, 4-14 parts of Rabdosia rubescens and 4-14 parts of Morus alba root bark.

[0011] Furthermore, the traditional Chinese medicine composition is composed of raw materials in the following weight ratios:

[0012] 9 parts of Xanthium sibiricum, 15 parts of mulberry leaf, 15 parts of reed rhizome, 9 parts of Platycodon grandiflorus, 3 parts of licorice root, 7 parts of Atractylodes lancea, 7 parts of dried ginger, 9 parts of Sophora flavescens, 9 parts of Rabdosia rubescens, and 9 parts of mulberry bark.

[0013] This invention also relates to an oral Chinese medicine preparation for treating allergic rhinitis, characterized in that it is prepared using the Chinese medicine composition described above and a raw material containing the active ingredient of the Chinese medicine composition.

[0014] Furthermore, the oral preparation of traditional Chinese medicine is a decoction of traditional Chinese medicine.

[0015] The present invention also relates to a method for preparing a traditional Chinese medicine oral preparation for treating allergic rhinitis, characterized in that it is prepared using the traditional Chinese medicine composition as described above and a raw material containing the active ingredient of the traditional Chinese medicine composition.

[0016] Further, the preparation method includes:

[0017] S1. Mix the Chinese herbal medicine composition as described above, add water to form a mixed raw material, soak and perform a heating extraction operation, filter to generate an extract;

[0018] S2. Perform atmospheric pressure concentration on the extract to generate a traditional Chinese medicine decoction.

[0019] Furthermore, the weight ratio of the traditional Chinese medicine composition to water in the mixed raw materials is 1:5 to 1:10.

[0020] Further, step S1 includes soaking the mixed raw materials for 1 to 2 hours, heating and maintaining the temperature at 80 to 100°C for 0.5 to 2 hours for heat extraction.

[0021] Furthermore, step S1 also includes:

[0022] Repeat the heating extraction operation 2 to 3 times.

[0023] Further, step S2 includes:

[0024] The extract is concentrated under normal pressure to reduce its volume to one-third of its original volume, thus producing a traditional Chinese medicine decoction.

[0025] The medicinal effects of each herb in the herbal composition of this invention are as follows:

[0026] Xanthium sibiricum fruit, also known as cocklebur, is the fruit of the plant Xanthium sibiricum Patr. (family Asteraceae), including its involucre. Its properties are pungent, bitter, and warm. Its functions include dispelling wind and dampness, and it enters the Lung meridian. It is used to treat headaches due to wind-cold, sinusitis, and numbness and pain with contractures.

[0027] Mulberry leaves are the dried leaves of the mulberry tree (Morus alba L.), a plant in the Moraceae family. Their properties are sweet, bitter, and cold. They have the functions of dispersing wind-heat, clearing the lungs and moistening dryness, and clearing the liver and improving eyesight. They enter the lung and liver meridians. They are used to treat: dry cough due to lung heat, dizziness, headache, and red, blurred vision.

[0028] Reed rhizome is the fresh or dried rhizome of the grass Phragmites communis Trin. Properties: Sweet, cold. Functions: Clears heat and generates fluids, relieves irritability, stops vomiting, and promotes urination. It enters the Lung meridian. Indications: Fever with thirst, vomiting due to stomach heat, cough due to lung heat, lung abscess with purulent sputum, and painful urination due to heat.

[0029] Platycodon grandiflorum (Jacq.) A.DC., a plant in the Campanulaceae family, is a dried root. Its properties are bitter, pungent, and neutral. Its functions include clearing the lungs, relieving sore throat, resolving phlegm, and draining pus. It enters the Lung meridian. It is indicated for cough with excessive phlegm, chest tightness, sore throat, hoarseness, lung abscess with purulent sputum, and sores that have formed pus but have not yet ulcerated.

[0030] Licorice is the dried root of the legume *Glycyrrhiza uralensis* Fisch. Its properties are sweet and neutral. Its functions include tonifying the spleen and replenishing qi, clearing heat and detoxifying, resolving phlegm and relieving cough, alleviating spasms and pain, and harmonizing other herbs. It enters the heart, lung, spleen, and stomach meridians. It is used for spleen and stomach weakness, fatigue, palpitations, shortness of breath, cough with excessive phlegm, abdominal and limb spasms and pain, carbuncles and boils, and to alleviate the toxicity and harshness of other medications.

[0031] Atractylodes lancea is the dried rhizome of the plant Atractylodes lancea (Thunb.) in the Asteraceae family. Its properties are pungent, bitter, and warm. Its functions are to dry dampness, strengthen the spleen, dispel wind and cold. It enters the spleen, stomach, and liver meridians. It is used to treat abdominal distension, diarrhea, edema, beriberi, rheumatic pain, common cold due to wind-cold, and night blindness.

[0032] Dried ginger is the dried rhizome of the ginger plant (Zingiber officinale Rosc.), belonging to the ginger family. It is pungent and hot in nature. Its functions include warming the middle jiao (spleen and stomach), dispelling cold, restoring yang and unblocking the meridians, drying dampness and resolving phlegm. It enters the spleen, stomach, kidney, heart, and lung meridians. It is used for abdominal pain due to cold, vomiting and diarrhea, cold limbs and weak pulse, and cough with phlegm and wheezing.

[0033] Sophora flavescens is the dried root of the legume Sophora flavescens Ait. It is bitter and cold in nature. Its functions include clearing heat and drying dampness, killing parasites, and promoting diuresis. It is used to treat dysentery, hematochezia, jaundice, urinary retention, leukorrhea, vulvar swelling and itching, eczema, damp sores, pruritus, scabies, and leprosy.

[0034] Rabdosia rubescens (Hamst.) CYWu et Hsuan, a plant belonging to the genus Rabdosia in the Lamiaceae family, is used medicinally in its entirety. Its properties are: bitter and sweet; slightly cold in nature. Its functions include: clearing heat and detoxifying; promoting blood circulation and relieving pain. It is used to treat: sore throat; headache from colds; bronchitis; chronic hepatitis; rheumatic joint pain; and snake and insect bites.

[0035] Mulberry bark is the dried root bark of the mulberry (Morus alba L.), a plant in the Moraceae family. Its properties are sweet and cold. Its functions include clearing lung heat and relieving asthma, promoting diuresis and reducing swelling. It is used for cough and asthma due to lung heat, edema with abdominal distension and scanty urine, and facial and skin edema.

[0036] The beneficial effects of this invention are as follows:

[0037] The modified compound Xanthium sibiricum herbal composition for treating allergic rhinitis described in this invention, based on traditional Chinese medicine theory and epigenetics of Chinese medicine, modifies the original compound Xanthium sibiricum formula to create a new modified compound herbal composition. This composition inherits the advantages of traditional Chinese medicine's syndrome differentiation and prescription, while also leveraging the precision of modern molecular diagnostics and treatment. It is convenient for clinical application, has definite efficacy, and can effectively inhibit key biological sites in the progression of rhinitis and improve rhinitis symptoms. In particular, the modified compound Xanthium sibiricum herbal composition of this invention can inhibit the expression of key gene sites PDE4D, GSK3B, and S100A12, which are found in clinical studies to be crucial for the progression of allergic rhinitis. It has the advantages of rapid onset of action, convenient use, and no side effects. Compared with the original compound Xanthium sibiricum formula, it has higher therapeutic efficiency and wider applicability to most populations, effectively relieving symptoms of rhinitis patients and is suitable for treating various types of rhinitis. On the other hand, the improved compound Xanthium sibiricum herbal composition of the present invention uses common medicinal materials as raw materials, which are inexpensive and easy to find, effectively reducing the economic burden on patients. It can be used to prepare a variety of different dosage forms, and the preparation process is simple and suitable for large-scale industrial production. Attached Figure Description

[0038] Figure 1a A schematic diagram of the overall distribution of 5hmC expression levels before gene therapy in patients who responded to and did not respond to treatment with Compound Xanthium sibiricum Formula.

[0039] Figure 1b Volcano plot showing the differential gene distribution before gene therapy in patients who responded to and did not respond to treatment with Compound Xanthium sibiricum Formula.

[0040] Figure 1c Heatmap of differential gene distribution before gene therapy for patients who responded to and did not respond to treatment with Compound Xanthium sibiricum Formula. Figure 1d PPI network diagram of differentially expressed genes in 5 hmC before treatment in patients who responded to and did not respond to Compound Xanthium sibiricum Formula.

[0041] Figure 1e This is a schematic diagram showing the regulatory function of key genes on rhinitis progression after KEGG enrichment analysis of the differentially expressed genes.

[0042] Figure 1f This diagram illustrates the difference in expression levels of the core targets of allergic rhinitis identified during treatment with Compound Xanthium sibiricum Decoction in patients who responded to the treatment and those who did not.

[0043] Figure 1g This is a schematic diagram illustrating the specificity and accuracy of predicting the efficacy of Compound Xanthium sibiricum Formula based on target expression levels.

[0044] Figure 2a Heatmap showing the 5hmC difference before and after treatment in patients who did not respond to treatment with Compound Xanthium sibiricum Formula.

[0045] Figure 2b This diagram illustrates the changes in gene expression levels at key sites of allergic rhinitis before and after treatment in patients who did not respond to treatment with Compound Xanthium sibiricum Formula.

[0046] Figure 2c Volcano plot showing the differential gene distribution before and after treatment in patients who responded to treatment with Compound Xanthium sibiricum Formula.

[0047] Figure 2d A schematic diagram illustrating the difference in PDE4D expression levels at a key site for rhinitis progression before and after treatment in patients who responded to treatment with Compound Xanthium sibiricum Formula.

[0048] Figure 2e A schematic diagram illustrating the difference in PDE4D expression levels at a key site for rhinitis progression before and after treatment in patients who did not respond to treatment with Compound Xanthium sibiricum Formula.

[0049] Figure 3 This is a schematic diagram illustrating the use of modified traditional Chinese medicine to identify targets related to allergic rhinitis based on 5hmc-Seal and to locate key targets based on the TCM database.

[0050] Figure 4a This is a schematic diagram showing the changes in body weight (mean ± SD, n = 10) of mice in each group of allergic rhinitis model mice during treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0051] Figure 4b This is a schematic diagram of the behavioral scores (mean±SD, n=10) of mice with allergic rhinitis in each group before treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0052] Figure 4c This is a schematic diagram of the behavioral scores (mean±SD, n=10) of mice with allergic rhinitis in each group on the eighth day of treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0053] Figure 4d This is a schematic diagram of the behavioral scores (mean±SD, n=10) of mice with allergic rhinitis in each group on the ninth day of treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0054] Figure 4e This is a schematic diagram of the behavioral scores (mean±SD, n=10) of mice with allergic rhinitis in each group on the tenth day of treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0055] Figure 5aThis is a schematic diagram showing the number of sneezes (mean ± SD, n = 10) in each group of allergic rhinitis model mice before treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0056] Figure 5b This is a schematic diagram showing the number of sneezes (mean ± SD, n = 10) in each group of mice with allergic rhinitis on the eighth day of treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0057] Figure 5c This is a schematic diagram showing the number of sneezes (mean ± SD, n = 10) in each group of mice with allergic rhinitis on the ninth day of treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0058] Figure 5d This is a schematic diagram showing the number of sneezes (mean ± SD, n = 10) in each group of mice with allergic rhinitis on the tenth day of treatment with the improved compound Xanthium sibiricum herbal composition of this invention.

[0059] Figure 6 A schematic diagram illustrating the clinical efficacy of Compound Xanthium sibiricum Formula and the modified Compound Xanthium sibiricum Formula of this invention in treating patients with allergic rhinitis using the VAS scoring scale. Detailed Implementation

[0060] To better understand the content of this invention, a detailed description will be provided in conjunction with the accompanying drawings and embodiments.

[0061] Pharmacological description of the improved compound Xanthium sibiricum herbal composition of this invention

[0062] Compound Xanthium Fruit Formula (Compound Xanthium Fruit Tablets) is used to clear the lungs and moisten dryness, and to open the nasal passages. It is indicated for symptoms such as nasal congestion, runny nose, headache, and dry throat caused by damp-heat. The original formula focuses on clearing the lungs and moistening dryness. Mulberry leaf clears the lung collaterals, and reed rhizome clears the heat from the lung meridian, serving as the chief ingredients. Xanthium fruit disperses wind-dampness, opens the nasal passages, and relieves symptoms such as nasal congestion caused by damp-heat. Platycodon root is pungent and bitter, opens the lung qi, and also has a soothing effect on the throat, relieving symptoms such as dry throat and itchy throat. Licorice root harmonizes the other herbs. The five herbs work together to clear the lungs, moisten dryness, and open the nasal passages.

[0063] Clinical studies of patients treated with Compound Xanthium sibiricum Formula (CXS) identified key differentially expressed genes related to the treatment by combining key genes for the progression of rhinitis with 5hmC differentially expressed genes. Intersection analysis of the target genes in the Compound Xanthium sibiricum Formula database and 5hmC differentially expressed genes revealed 17 drug-related differentially expressed genes and 727 differentially expressed genes outside the intersection. PPI network analysis of the 17 differentially expressed genes in the intersection revealed targets related to inflammation and immunity. For the genes outside the intersection, PPI network analysis was performed using key 5hmC differentially expressed genes related to efficacy, revealing key targets outside the drug intersection. These targets, including GSK3B, PDE4D, and S100A12, were screened and are closely related to immune system regulation.

[0064] Based on in-depth exploration of key targets, relevant traditional Chinese medicines were sought. For patients who responded to treatment, GSK3B, PDE4D, and S100A12 were significantly downregulated after treatment. In patients who did not respond to treatment, there was no significant difference in the expression levels of GSK3B, PDE4D, and S100A12 before and after treatment. This indicates that the original compound Xanthium sibiricum formula has insufficient ability to regulate relevant targets, which is a defect in the original formula when applied to the treatment of allergic rhinitis.

[0065] Network pharmacology analysis revealed that the targets of GSK3B, PDE4D, and S100A12 correspond to the traditional Chinese medicines Atractylodes lancea, Morus alba leaves, Sophora flavescens, Morus alba root bark, and Rabdosia rubescens. Among them, the modified traditional Chinese medicines Morus alba root bark, Sophora flavescens, and Rabdosia rubescens have a strong regulatory effect on GSK3B, PDE4D, and S100A12. The key components, morin M and matrine, have IC50 values ​​≤10μM for the targets. Through joint analysis of 5hmC and the compound Xanthium sibiricum target database, it is speculated that Atractylodes lancea, Morus alba leaves, Sophora flavescens, Morus alba root bark, and Rabdosia rubescens, together with the traditional compound Xanthium sibiricum targets, form a new formula to improve treatment.

[0066] This paper presents an improved compound Xanthium sibiricum formula (a modified compound Xanthium sibiricum herbal composition) based on traditional Chinese medicine theory and network pharmacology. The principal herb is Xanthium sibiricum, which has the effects of clearing nasal passages and dispersing wind-cold, making it a key herb for treating sinusitis. The assistant herbs are two pairs: mulberry leaf and mulberry bark, and sophora flavescens and lingzhi, whose main functions are clearing the lungs and detoxifying, respectively. Traditional Chinese medicine believes that "the lungs open into the nose" and "the lungs and large intestine are internally and externally related," therefore, the formula emphasizes the adjustment of the body's systems; nasal diseases are treated by addressing the lungs, and lung diseases by regulating the large intestine. Mulberry leaf, mulberry bark, and lingzhi enter the lung meridian, while sophora flavescens enters the large intestine meridian. In the assistant herb formulation, the ratio of clearing the lungs to clearing the large intestine is approximately 3:1. Although allergic rhinitis is located in the nasal cavity, it also possesses certain characteristics of the five evils: phlegm, dampness, toxins, and blood stasis, resulting in a lingering and difficult-to-cure condition. Mulberry leaves and mulberry bark both enter the lung meridian and are essential medicines for clearing the lungs, promoting blood circulation, and resolving phlegm. Sophora flavescens, in addition to its detoxifying, dampness-removing, antibacterial, and insecticidal effects, also has the function of resolving dampness and reducing turbidity. Rabdosia rubescens has the effect of clearing the lungs and detoxifying; it is also known as "blood-breaking herb" and has a certain effect of promoting blood circulation and unblocking the meridians. The adjuvant medicine is reed rhizome, which moistens the lungs and generates fluids, counteracting the drying nature of the principal medicine, Xanthium sibiricum, and also has the effect of clearing the lungs and purging fire. The guiding medicines are Platycodon grandiflorus and Atractylodes lancea. Platycodon grandiflorus acts as the "boat" for all medicines, carrying them upwards, while licorice harmonizes the other medicines, tonifies qi and strengthens the middle jiao, together pushing the medicinal power to the affected area, achieving the effect of clearing and moistening the lungs and opening the nasal passages.

[0067] Sequencing of patients with allergic rhinitis and network pharmacology study of the modified compound Xanthium sibiricum herbal composition of this invention for the treatment of allergic rhinitis

[0068] Using 5hmC-Seal sequencing technology, changes in plasma cfDNA epigenetic markers in patients with allergic rhinitis before and after treatment with Compound Xanthium sibiricum Formula were detected. Significant markers of allergic rhinitis disease progression and differences in marker levels after treatment were identified. Potential drug targets for UC treatment behind these markers were screened. Molecular subtyping studies of the efficacy differences of Compound Xanthium sibiricum Formula were conducted. Based on network pharmacology screening, additional ingredients were added to construct a novel modified Compound Xanthium sibiricum Formula (a modified Compound Xanthium sibiricum herbal composition) for anti-allergic rhinitis. This study provides support for the efficacy basis of the modified Compound Xanthium sibiricum Formula in treating allergic rhinitis.

[0069] 1.1 Sample Collection

[0070] Plasma samples were collected from 132 patients with allergic rhinitis and 100 healthy individuals. The 132 allergic rhinitis patients included 70 patients before treatment with Compound Xanthium sibiricum Formula (37 of whom responded to subsequent treatment and 33 did not respond to subsequent treatment), and 62 patients after treatment with Compound Xanthium sibiricum Formula.

[0071] Blood samples (8 mL each) were collected from 132 patients with allergic rhinitis upon admission and diagnosis. Plasma separation was performed within 24 hours to collect plasma samples. Additionally, blood samples were collected from 100 healthy individuals, and plasma separation was performed within 24 hours to collect plasma samples. The specific steps included: a first centrifugation at 1350g, 4°C for 12 min, carefully removing the pale yellow supernatant and transferring it to a 2 mL DNase-free sterile EP tube to avoid contamination of the white blood cell layer; a second centrifugation at 1350g, 4°C for 5 min, carefully removing the supernatant and transferring it to a 2 mL DNase-free sterile EP tube to remove any remaining red blood cells; and a third centrifugation at 1350g, 4°C for 5 min, carefully removing the supernatant and transferring it to a 2 mL DNase-free sterile centrifuge tube to obtain approximately 4 mL of plasma. The collected plasma was labeled and stored at -80°C for later use.

[0072] 1.2 Extraction of plasma DNA

[0073] Using the Quick-CfDNA Serum and Plasma Kit (ZYMO Kit), 8-10 ng of plasma CfDNA was extracted from the plasma samples prepared in step 1.1.

[0074] 1.3 End-completing the CfDNA and ligating it to the sequencing adapter.

[0075] Prepare a reaction mixture (total volume 24 μL) containing 20 μL cfDNA, 2.8 μL end-repair & A-tail buffer, and 1.2 μL end-repair & A-tail enzyme mixture according to the KAPA HyperPlus library preparation kit instructions. Incubate at 20 °C for 30 min, then at 65 °C for 30 min. Prepare the following ligation reaction mixture in a 0.5 mL hypoadsorption EP tube: 2 μL nuclease-free water, 12 μL ligation buffer, and 4 μL DNA ligase. Add 2 μL sequencing adapter to 18 μL of the ligation reaction mixture, mix, and add to 24 μL of the reaction sample. Incubate at 20 °C for 4 h. Purify the reaction product using a DNA Clean & Concentrator 5 (ZYMO) purification kit, eluting with 20 μL of elution buffer to obtain the final DNA ligation sample.

[0076] 1.4 5hmC marker

[0077] Prepare a 4 μL labeling reaction mixture: 1 μL 50 μM UDP-N3-Glu 1 μL LBGT enzyme (NEB) and 2 μL HEPES buffer (pH 8.0, final concentration 50 mM). Add the 4 μL labeling mixture to 20 μL of DNA ligation sample. Incubate the mixture at 37°C for 2 hours. Remove the mixture and purify the reaction product using the DNA Clean & Concentrator 5 (ZYMO) purification kit to obtain 30 μL of purified DNA. Then, add 1 μL LDBCOPEG4-biotin (Click Chemistry Tools) to the 30 μL purified DNA, incubate at 37°C for 1 hour, and purify the reaction product using the DNA Clean & Concentrator 5 (ZYMO) purification kit to obtain 30 μL of purified labeled product.

[0078] 1.5 5hmC enrichment

[0079] First, prepare the binding magnetic beads as follows: Take 2.5 μL of Dynabeads (Invitrogen) and add 100 μL of washing buffer (5 mM Tris (pH 7.5), 1 M NaCl, and 0.02% Tween 20), mix well by pipetting, place on a 1.5 mL magnetic rack, and wash the binding magnetic beads three times with 100 μL of washing buffer. Finally, add 32 μL of binding buffer (10 mM Tris (pH 7.5), 2 M NaCl, and 0.04% Tween 20) and mix well. Then, add the purified labeled product obtained in the above steps to the magnetic bead mixture and mix in a rotary mixer for 30 min to ensure complete binding. Finally, wash the magnetic beads five times with 100 μL of washing buffer (5 mM Tris (pH 7.5), 1 M NaCl, and 0.02% Tween 20), centrifuge to remove the supernatant, and add 23.8 μL of RNase-free water.

[0080] 1.6 PCR amplification

[0081] Add 25 μL of 2X PCR master mix and 1.25 μL of PCR primers (total volume 50 μL) to the final system of the above steps, and amplify according to the temperature and conditions of the PCR reaction cycle: purify the amplification product with AmpureXP beads to obtain the final 5 hmC library, and determine the library concentration using Qubit 3.0.

[0082] 1.7 High-throughput sequencing was performed on the 5hmC library after quality control.

[0083] The obtained 5hmC libraries were subjected to quality control using the Fragment Analyzer TN fully automated capillary electrophoresis system to determine the size of DNA fragments and the presence of impurities; concentrations were determined by qPCR. The quality-controlled sequencing libraries were mixed at the same concentration and sequenced using an Illumina NextSeg500 sequencing kit (High Output Kit v2, 75 cycles), with a sequencing throughput of 1.5 Gb per sample and a sequencing band size of 75 bp.

[0084] 1.8 Alignment of raw sequence data

[0085] Each raw FASTQ sequencing dataset was first trimmed for low-quality data using Trimmomatic software, then aligned to the human genome hg19 using Bowtie2 software. MACS software was used to identify read peaks containing 5hmC, with the following parameters: effective genome size = 2.72e+09; tag size = 38; bandwidth = 100; model fold = 10; P-value cutoff = 1.00e-05. Peak information from plasma CFDNA of patients who responded to treatment and those who did not was filtered, with each peak appearing in at least 10 samples. Peaks were then called to generate counts files. DEse2 software was used to compare the 5hmC peak regions with reads greater than 50 from the counts files of different samples. Differentially regulated biomarkers of 5hmC were then selected based on log2FoldChange >= 1 and p-value < 0.01. Further GO analysis was performed on differentially expressed biomarkers of 5hmC upregulation using the ClueGO (version 2.5.5) and uePedia (version 1.5.5) plugins of Cytoscape software (version 3.7.2) (parameters used: Medium Network Specificity, Bonferroni step-down pV Correction, Two-sided hypergeometric test) to identify signaling pathways closely related to the development and treatment of allergic rhinitis, thereby identifying potential drug targets. Counts data from patients who responded to and did not respond to the compound Xanthium sibiricum treatment were analyzed for difference, and differentially expressed biomarkers of 5hmC were selected based on log2FoldChange>=1 and p-value<0.01. Further GO analysis using Cytoscape software revealed signaling pathways associated with the progression of allergic rhinitis and the efficacy of the compound Xanthium sibiricum formula in the GO analysis results of 5hmC upregulation biomarkers.

[0086] 1.9 Construction of an improved compound Xanthium sibiricum formula based on target and network pharmacology

[0087] Based on clinical cohort screening to identify key targets and traditional Chinese medicine (TCM) theories, and combined with network pharmacology technology, the compound Xanthium sibiricum formula was modified. Based on the TDM-CT and ETCM databases, TCMs that inhibit key sites of rhinitis were retrieved and added. Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http: / / lsp.nwu.edu.cn / tcmsp.php), the TCM name was entered in the "Herbname" field to retrieve relevant TCM entries for each ingredient in the compound Xanthium sibiricum formula. Molecular information was then obtained, including the chemical component ID and molecular name (Mol ID, Molecule Name), oral bioavailability (OB), and drug-likeness (DL). Active ingredients of the compound Xanthium sibiricum formula and potential modified TCMs were screened using OB ≥ 30% and DL ≥ 0.18 as criteria, and an improved formula was constructed.

[0088] 1.10 Efficacy Validation of Modified Compound Xanthium sibiricum Formula Based on Network Pharmacology

[0089] Based on the screening of key targets in clinical cohorts, a modified compound Xanthium sibiricum formula was developed. Using 5hmc-seal sequencing to obtain the target of action against allergic rhinitis, Cytoscape 3.7.2 software was used to obtain the "active ingredient-target" regulatory network of compound Xanthium sibiricum formula in the treatment of allergic rhinitis, in order to verify the effectiveness of the new formula.

[0090] Studies have shown that the expression level of 5hmC in patients with rhinitis is higher than that in healthy controls, and the higher 5hmC expression level in patients is related to their inflammatory and immune status (e.g., Figure 1a (As shown). A 5hmC-Seal sequencing study of rhinitis patients treated with Compound Xanthium sibiricum Formula revealed that the expression of the 5hmC markers S100A12, PDE4D, and GSK3B genes in rhinitis patients who did not respond to Compound Xanthium sibiricum Formula treatment was significantly upregulated before treatment compared to patients who responded to the treatment (e.g., ...). Figure 1b , Figure 1c (As shown). Functional analysis of key genes and related genes such as S100A12, PDE4D, and GSK3B showed that these gene loci significantly affect cell chemotaxis and neutrophil-related immune signaling pathways, regulating the occurrence and progression of allergic rhinitis (e.g., Figure 1d , Figure 1e (As shown). The study results showed that patients who did not respond to treatment with Compound Xanthium sibiricum Formula had high expression of related genes, which further aggravated their allergic reactions and led to the progression of rhinitis.

[0091] Further 5hmC-Seal studies of rhinitis patients before and after treatment with Compound Xanthium sibiricum showed that the expression levels of key gene markers such as S100A12, PDE4D, and GSK3B were significantly reduced after treatment in patients who responded to Compound Xanthium sibiricum treatment (e.g., Figure 1f , Figure 2c , Figure 2d As shown), the expression level did not change significantly in the ineffective treatment group (e.g. Figure 2a , Figure 2b , Figure 2e As shown in the figure, a further 5hmC-Seal study before and after treatment of patients with rhinitis who responded to and did not respond to the treatment with Compound Xanthium sibiricum Formula showed that S100A12, PDE4D and GSK3B play key roles in the occurrence and progression of rhinitis.

[0092] Based on the expression levels of biomarkers such as S100A12, PDE4D, and GSK3B, the efficacy of Compound Xanthium sibiricum Formula in treating allergic rhinitis can be predicted relatively well. The AUC values ​​of the expression levels of key biomarkers for the diagnostic accuracy and specificity of Compound Xanthium sibiricum Formula in treating allergic rhinitis ranged from 0.95 to 0.99, indicating that the functions of the selected key targets in inflammation and immune regulation are significantly correlated with the occurrence and progression of allergic rhinitis and the efficacy of Compound Xanthium sibiricum Formula in treating allergic rhinitis (e.g., Figure 1g (As shown).

[0093] Based on this, network pharmacology studies using the TCMSP database showed that adding traditional Chinese medicines such as Atractylodes lancea, dried ginger, Sophora flavescens, Rabdosia rubescens, and Morus alba root bark—which inhibit key sites of allergic rhinitis progression, to the compound Xanthium sibiricum formula can regulate the occurrence and progression of allergic rhinitis (e.g., ...). Figure 3 (As shown). Therefore, the selected traditional Chinese medicines were used to modify the compound Xanthium sibiricum formula to prepare an improved compound Xanthium sibiricum formula (improved compound Xanthium sibiricum traditional Chinese medicine composition), and the results were verified.

[0094] Preparation of oral formulations of modified compound Xanthium sibiricum herb composition

[0095] Example 1

[0096] A traditional Chinese medicine oral preparation for treating allergic rhinitis, by weight, is composed of the following raw materials: 9 parts of Xanthium sibiricum, 15 parts of Morus alba leaf, 15 parts of Phragmites communis rhizome, 9 parts of Platycodon grandiflorus, 3 parts of Glycyrrhiza uralensis, 7 parts of Atractylodes lancea, 7 parts of Zingiber officinale, 9 parts of Sophora flavescens, 9 parts of Rabdosia rubescens, and 9 parts of Morus alba root bark. Its active ingredients are prepared from a decoction of the raw materials.

[0097] The preparation method of this oral Chinese medicine preparation includes the following steps: Mixing the raw materials in an extraction tank at a weight ratio of 1:10 (raw materials to water), soaking for 1 hour; heating and extracting for 1 hour at a temperature of 90°C, repeating the extraction twice, and filtering to obtain the extract. For example, approximately 92g of the above-mentioned medicinal materials are decocted in water to prepare an extract (approximately 1000ml). The extract is then concentrated in a multi-effect energy-saving evaporation and concentration device to a volume of 400mL, which is Example 1 of the modified compound Xanthium sibiricum decoction.

[0098] Example 2

[0099] A traditional Chinese medicine oral preparation for treating allergic rhinitis, by weight, is composed of the following raw materials: 5 parts Xanthium sibiricum, 7 parts Morus alba leaves, 7 parts Phragmites communis rhizome, 4 parts Platycodon grandiflorus, 1 part Glycyrrhiza uralensis, 3 parts Atractylodes lancea, 3 parts Zingiber officinale, 4 parts Sophora flavescens, 4 parts Rabdosia rubescens, and 4 parts Morus alba root bark. Its active ingredients are prepared from a decoction of the raw materials.

[0100] The preparation method of this traditional Chinese medicine includes the following steps: The raw materials are mixed in an extraction tank at a weight ratio of 1:5 (raw materials to water), and soaked for 1 hour. The extraction time is 0.5 hours, and the heating temperature is 80℃. The extraction is repeated twice, and the extract is obtained by filtration. The extract is then concentrated in a multi-effect energy-saving evaporation and concentration device to a volume of 600 mL, which is Example 2 of the modified compound Xanthium sibiricum decoction.

[0101] Example 3

[0102] A traditional Chinese medicine oral preparation for treating allergic rhinitis, by weight, is composed of the following raw materials: 15 parts of Xanthium sibiricum, 22 parts of Morus alba leaf, 22 parts of Phragmites communis rhizome, 14 parts of Platycodon grandiflorus, 5 parts of Glycyrrhiza uralensis, 11 parts of Atractylodes lancea, 11 parts of Zingiber officinale, 14 parts of Sophora flavescens, 14 parts of Rabdosia rubescens, and 14 parts of Morus alba root bark. Its active ingredients are prepared from a decoction of the raw materials.

[0103] The preparation method of this traditional Chinese medicine includes the following steps: The raw materials are mixed in an extraction tank at a weight ratio of 1:10 (raw materials to water), and soaked for 2 hours. The extraction is then carried out at 100℃ for 2 hours. The extraction is repeated three times, and the extract is obtained by filtration. The extract is then concentrated in a multi-effect energy-saving evaporation and concentration device to a volume of 600 mL, which is Example 3 of the modified compound Xanthium sibiricum decoction.

[0104] Example 4

[0105] A traditional Chinese medicine oral preparation for treating allergic rhinitis, by weight, is composed of the following raw materials: 8 parts of Xanthium sibiricum, 11 parts of Morus alba leaf, 11 parts of Phragmites communis rhizome, 6 parts of Platycodon grandiflorus, 2 parts of Glycyrrhiza uralensis, 5 parts of Atractylodes lancea, 5 parts of Zingiber officinale, 6 parts of Sophora flavescens, 6 parts of Rabdosia rubescens, and 6 parts of Morus alba root bark. Its active ingredients are prepared from a decoction of the raw materials.

[0106] The preparation method of this traditional Chinese medicine includes the following steps: The raw materials are mixed in an extraction tank at a weight ratio of 1:10 (raw materials to water), and soaked for 2 hours. The extraction is then carried out at 100°C for 2 hours. The extraction is repeated three times, and the extract is obtained by filtration. The extract is then concentrated in a multi-effect energy-saving evaporation and concentration device to a volume of 600 mL, which is Example 4 of the modified compound Xanthium sibiricum decoction.

[0107] Therapeutic effect of modified compound Xanthium sibiricum herbal composition on a mouse model of rhinitis

[0108] The modified compound Xanthium sibiricum herbal composition of the present invention was used to prevent and treat allergic rhinitis, and a randomized controlled experiment on animal models was conducted to evaluate the pharmacological effects of the herbal composition.

[0109] Randomized controlled trial of pharmacological efficacy in animal models: Seventy BALB / c mice were randomly divided into a blank control group, a model group, a low-dose compound Xanthium sibiricum formula group, a high-dose compound Xanthium sibiricum formula group, a modified low-dose compound Xanthium sibiricum formula group, a modified high-dose compound Xanthium sibiricum formula group, and a positive control group (fluticasone propionate). Except for the control group, all other groups were sensitized by intraperitoneal injection of 200 μL of ovalbumin in aluminum hydroxide adjuvant solution, once every 7 days for a total of 3 times over 21 days. Starting on day 21 of modeling, 10 μL of 10% ovalbumin saline solution was administered intranasally for challenge, once daily for 7 days. Starting on day 28, 10 μL of 10% ovalbumin saline solution was continued intranasally for maintenance, once daily. The observation drug was administered concurrently during the maintenance period for 8 days. AR behavioral indicators in mice were continuously observed from the day of treatment.

[0110] Animal grouping, modeling, and drug administration: After 3 days of acclimatization, all mice were randomly divided into a control group and a drug group according to their body weight. The blank control group received no intervention, while the negative control and drug treatment groups underwent rhinitis modeling. Mice in the drug group received intraperitoneal injections of 200 μL of ovalbumin solution at fixed times on days 0, 7, and 14 of the modeling process, while the blank control group received the same volume of physiological saline. Seven days after the last sensitization (day 21 of modeling), mice in each group underwent nasal challenge drug administration once daily for 7 consecutive days. Each group received 10 μL of ovalbumin solution in each anterior nasal cavity using a pipette tip, for a total of 20 μL, to maintain sensitization.

[0111] Behavioral observation: After the last nasal stimulation on day 27, two observers who were not involved in the experiment immediately observed and recorded the behavioral performance of each group of mice within 5 minutes. The scoring criteria were based on the following mouse allergic rhinitis model assessment criteria table (Table 1). The results were obtained using a cumulative quantitative scoring method, and a total score ≥ 5 was considered a successful model establishment.

[0112] Table 1. Criteria for Evaluating Mouse Allergic Rhinitis Model

[0113]

[0114] Starting from day 28, the established mouse model of allergic rhinitis was treated with drugs once daily for 10 consecutive days. Following each daily administration, 20 μL of ovalbumin stimulation solution was continuously instilled into the nasal cavity to maintain the sensitization state in the mice. The blank control group continued to receive physiological saline instillation.

[0115] The treatment regimens for the drug-treated groups were as follows: Blank control group: no treatment received; Negative control group: no drug treatment received, but 300 μL of normal saline was administered by gavage; Positive control group: fluticasone propionate nasal spray was administered as a positive control, with a concentration of 0.25 μg / μL and a dosage of 0.52 μg, 2 μL instilled into each nostril, for a total of 4 μL; Experimental group 1: low-dose compound Xanthium sibiricum decoction administered by gavage, 300 μL each time; Experimental group 2: high-dose compound Xanthium sibiricum decoction administered by gavage, 600 μL each time; Experimental group 3: low-dose modified compound Xanthium sibiricum tablet decoction administered by gavage, 300 μL each time; Experimental group 4: high-dose modified compound Xanthium sibiricum tablet decoction administered by gavage, 600 μL each time.

[0116] After each nasal instillation of ovalbumin stimulation solution, two observers not involved in the experiment immediately observed and recorded four behavioral patterns in mice within 5 minutes: the number of times they scratched their nose, the number of times they sneezed, the amount of nasal discharge, and the severity of asthma. These results were compared with the initial data of the model to analyze the effect of the drug intervention. The medication was administered once daily for a total of 7 times.

[0117] Statistical methods: One-way ANOVA was performed using Prism 8, and multiple t-tests were used for intergroup comparisons.

[0118] Experimental results: Before the start of drug administration on day 28, the behavioral scores of all drug groups were greater than 5, indicating that the mouse allergic rhinitis model was successfully established (e.g., Figure 4b As shown in the figure), before treatment, there were no statistically significant differences in behavioral scores and body weight among the mice in each treatment group. During the treatment period, the body weight of mice in each group did not change significantly, indicating that the modified compound Xanthium sibiricum formula has good safety (as shown in the figure). Figure 4a (As shown).

[0119] Behavioral scores of mice were observed one week after drug administration to evaluate the efficacy of the treatment, from day 8 until the end of treatment. The rhinitis behavioral scores of the model mice in the rhinitis model group and the drug treatment group are shown in Table 2. Figures 4b to 4e .

[0120] Table 2. Behavioral rating scale of BALB / c mice at different time points after treatment (Mean±SD)

[0121]

[0122] In Table 2, time points are represented by the number of days of treatment (D0) or the number of treatments. Treatment began 4 weeks (D0) after the model was established and an allergic reaction was induced, with n=10. Compared with the rhinitis model group, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; compared with the positive control group, #P<0.05.

[0123] A comparison with the baseline behavioral scores on the day of treatment showed that, during the treatment course, the modified compound Xanthium sibiricum formula achieved a symptom improvement of nearly 60% (improvement rate of 57.14%) compared to the baseline behavioral scores by day 8, meeting the standard of significant efficacy. Furthermore, at the end of treatment, the symptom improvement rate approached 70%, far exceeding the original compound Xanthium sibiricum formula (Table 2).

[0124] At the end of the treatment course (D10), when neither the original formula nor the Western medicine treatment group could continue to significantly improve rhinitis symptoms, the modified compound Xanthium sibiricum formula showed significant differences from the model group in both the low-dose and medium-dose groups. It demonstrated a more significant therapeutic effect than the original compound Xanthium sibiricum formula and Western medicine treatment (fluticasone group), and could more thoroughly cure allergic rhinitis. The behavioral scores of the low-dose and high-dose groups of the modified compound Xanthium sibiricum formula were significantly lower than those of the negative control group at each observation time point. Figure 4b -e), and showed a significant advantage over the control group in reducing the number of sneezes in mice with rhinitis. Figure 5a -d).

[0125] On the 8th day of treatment, the sneezing and nasal itching symptoms of mice with allergic rhinitis in the modified compound Xanthium sibiricum treatment group showed significant improvement, indicating that the modified compound Xanthium sibiricum formula has a good therapeutic effect on allergic rhinitis in mice.

[0126] The results showed that during the treatment course, the rhinitis behavioral scores of mice in the positive control group, the compound Xanthium sibiricum formula group, and the modified compound Xanthium sibiricum formula group were significantly reduced at all time points, and rhinitis symptoms such as nose scratching and sneezing were significantly alleviated. During the treatment course, the high-dose group treated with the modified compound Xanthium sibiricum formula showed a significantly lower number of sneezes compared to the positive control group and the compound Xanthium sibiricum formula treatment group, indicating that the modified compound Xanthium sibiricum formula has better anti-allergic rhinitis efficacy than the compound Xanthium sibiricum formula and fluticasone propionate, a commonly used clinical drug for rhinitis.

[0127] Experimental Results: After OVA sensitization, the rhinitis behavioral scores of mice in both the model and treatment groups significantly increased, indicating successful induction of the rhinitis model. After drug treatment, the rhinitis behavioral scores of mice in the positive control group, the compound Xanthium sibiricum formula group, and the modified compound Xanthium sibiricum formula group were significantly reduced, and symptoms such as nose scratching and sneezing were significantly alleviated. During the treatment course, the high-dose modified compound Xanthium sibiricum formula group showed significantly lower sneezing frequency and rhinitis behavioral scores compared to the positive control group and the compound Xanthium sibiricum formula group, indicating that the modified compound Xanthium sibiricum formula has better anti-allergic rhinitis efficacy than compound Xanthium sibiricum formula and fluticasone propionate, a commonly used clinical rhinitis drug. Therefore, the modified compound Xanthium sibiricum formula has a significant ameliorative effect on the symptoms of allergic rhinitis in mice; the modified compound Xanthium sibiricum formula exerts its therapeutic effect on allergic rhinitis by inhibiting key pathways in the development of allergic rhinitis and suppressing the progression of the disease and related inflammation.

[0128] Application of the improved compound Xanthium sibiricum herbal composition

[0129] Seventy-seven patients with allergic rhinitis were selected as the study subjects and divided into a control group (70 cases) and an experimental group (7 cases) according to different treatment plans.

[0130] Inclusion criteria: Patients met the diagnostic criteria for allergic rhinitis in the "Guidelines for the Diagnosis and Treatment of Allergic Rhinitis"; had symptoms such as nasal congestion, nasal itching, runny nose, and sneezing; and had dark red nasal mucosa. Patients and their families voluntarily participated in the study.

[0131] Exclusion criteria: liver or kidney dysfunction; malignant tumors; respiratory diseases; altered mental status; inability to cooperate with medication or allergy to the investigational drug.

[0132] Treatment methods: The control group was treated with Compound Xanthium sibiricum Tablets, taken orally after meals, 7 tablets / time, twice a day. Experimental group 1 was treated with the prepared decoction of the traditional Chinese medicine composition described in Example 1 above, taken orally after meals, 200ml / time, twice a day. Both groups were treated for 3 weeks.

[0133] Clinical evaluation and symptom scoring: Symptom scores were evaluated in both groups before and after treatment. The VAS scale is currently the most commonly used scoring method internationally and is also a commonly used scale for assessing the severity of rhinitis symptoms. The method of use involves patients drawing lines on a 100mm long line, where 0 represents no symptoms and 100mm represents the most severe symptoms. Each symptom was categorized as mild (<30mm), moderate (30–70mm), or severe (>70mm).

[0134] Efficacy evaluation criteria: The VAS scale was used to evaluate the treatment effect based on the symptom score reduction rate. A reduction rate of 25%–90% was considered effective, and below 25% was considered ineffective. Reduction rate (%) = (Pre-treatment score - Post-treatment score) / Pre-treatment score; Treatment effectiveness rate (%) = (Number of cured cases + Number of significantly effective cases + Number of effective cases / Total number of cases) x 100%. Treatment results are shown in Table 3 and... Figure 6 As shown.

[0135] Table 3 Treatment Results

[0136]

[0137] Based on the comparison of treatment results shown in Table 3, compared with the widely recognized Compound Xanthium Formula, the modified Compound Xanthium Formula (modified Compound Xanthium Herbal Composition) with added ingredients can significantly improve the effectiveness of allergic rhinitis treatment by regulating the activity of PDE4D, GSK3B, and S100A12 targets, and has outstanding effect in treating allergic rhinitis.

[0138] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any variations or substitutions that can be easily conceived by those skilled in the art within the scope of the technology disclosed in the present invention should be included within the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be determined by the scope of the claims.

Claims

1. A modified compound Xanthium Chinese medicine composition for treating allergic rhinitis, characterized in that, The traditional Chinese medicine composition is prepared from the following raw materials in the following proportions by weight: Xanthium sibiricum 5-15 parts, mulberry leaf 7-22 parts, reed 7-22 parts, platycodon 4-14 parts, liquorice 1-5 parts, atractylodes 3-11 parts, dried ginger 3-11 parts, kudzu 4-14 parts, and white mulberry bark 4-14 parts.

2. The traditional Chinese medicine composition of claim 1, wherein, The traditional Chinese medicine composition is prepared from the following raw materials in the following proportions by weight: Xanthium sibiricum 9 parts, mulberry leaf 15 parts, reed 15 parts, platycodon 9 parts, liquorice 3 parts, atractylodes 7 parts, dried ginger 7 parts, kudzu 9 parts, and white mulberry bark 9 parts.

3. A traditional Chinese medicine oral preparation for treating allergic rhinitis, characterized in that, The traditional Chinese medicine composition of claim 1 or 2 is used to prepare a traditional Chinese medicine oral preparation.

4. The traditional Chinese medicine oral preparation according to claim 3, characterized in that, The traditional Chinese medicine oral preparation is a traditional Chinese medicine decoction.

5. A method for preparing a Chinese medicine oral preparation for treating allergic rhinitis, characterized in that, The traditional Chinese medicine composition of claim 1 or 2 is used to prepare a traditional Chinese medicine oral preparation.

6. The production method according to claim 5, wherein The method comprises the following steps: S1, mixing the traditional Chinese medicine composition of claim 1 or 2 to form a mixed raw material, soaking and performing a heating extraction operation, and filtering to obtain an extraction liquid; S2, performing a normal pressure concentration operation on the extraction liquid to obtain a traditional Chinese medicine decoction.

7. The production method according to claim 6, wherein The weight ratio of the traditional Chinese medicine composition to water in the mixed raw material is 1:5 to 1:

10.

8. The production method according to claim 6, wherein The step S1 comprises soaking the mixed raw material for 1 to 2 hours, heating and maintaining at 80 to 100°C for 0.5 to 2 hours for the heating extraction operation.

9. The production method according to claim 8, wherein The step S1 further comprises: The heating extraction operation is repeated 2 to 3 times.

10. The production method according to claim 6, wherein The step S2 comprises: The normal pressure concentration operation is performed on the extraction liquid to concentrate the volume of the extraction liquid to 1 / 3 of the original volume to obtain the traditional Chinese medicine decoction.

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