Traditional Chinese medicine composition for preventing and treating recurrent respiratory tract infection as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for preventing and treating recurrent respiratory tract infection and a preparation method and application. The traditional Chinese medicine composition comprises the following raw materials: lonicerae flos, folium isatidis, dandelion, houttuynia cordata, astragalus membranaceus, bighead atractylodes rhizome, divaricate saposhnikovia root, ampelopsis grossedentata, pogostemon cablin, radix glehniae and pericarpium citri reticulatae. The preparation method comprises the following steps: mixing all the raw materials, adding water and decocting. The traditional Chinese medicine composition has the obvious effects of improving the immunity of the organism and resisting inflammation. Clinical curative effect observation shows that the traditional Chinese medicine composition can obviously reduce the morbidity frequency of children with recurrent respiratory tract infection (lung-spleen qi deficiency syndrome), shorten the disease course, and effectively improve the traditional Chinese medicine syndromes of the children, such as less complexion, less breath, laziness to speak, less appetite, hidrosis and the like. The compound is based on the theory of monarch, minister, assistant and guide in traditional Chinese medicine, all the components are matched with one another, and an excellent use effect is achieved. Good application prospects are realized.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for preventing and treating recurrent respiratory tract infections, and a preparation method and application thereof. Background Art

[0002] Recurrent respiratory infections (RRI) are chronic respiratory diseases characterized by repeated attacks exceeding a specific number of times per unit time. They are more common in children. Recurrent respiratory infections often worsen the pathological damage to the airways and lung tissues, and can even cause serious complications such as asthma, myocarditis, and kidney disease, severely impacting the patient's quality of life. The "Expert Consensus on the Integrated Prevention and Treatment of Recurrent Respiratory Infections in Children with Traditional Chinese and Western Medicine" states that the occurrence of RRI in children may be associated with improper care, specific physical conditions, premature birth, low birth weight, lack of breastfeeding, early daycare, large families, the presence of school-age siblings, maternal smoking during the perinatal and pregnancy periods, malnutrition, stress, fatigue, vaccination deficiencies, climate change, a humid environment, and feeding in the supine position.

[0003] Currently, clinical treatment for RRI focuses on causal anti-infective therapy during the acute phase, followed by symptomatic management based on the patient's symptoms. During the remission phase, key measures focus on enhancing immunity, including nutritional support, supplementation of trace elements such as calcium, iron, and zinc, and the use of immunomodulators. While these can control respiratory infections to a certain extent, they are not very effective in preventing recurrence. In particular, the excessive use of antibiotics can easily lead to increased bacterial resistance, making infection treatment more difficult.

[0004] Traditional Chinese Medicine considers recurrent respiratory tract infections to be categorized as "congenital colds" or "exogenous febrile illnesses." The pathogenesis is due to a deficiency of vital energy in the patient's constitution, a deficiency of the lungs and spleen qi, and a weakened exterior, making them susceptible to external pathogens. These pathogens attack the lungs' defenses, stagnate and transform into heat, and the lungs fail to function properly. The lungs govern qi and are connected to the skin and fur. Recurrent upper respiratory tract infections are primarily related to lung qi deficiency and a weakened exterior defense system. Children's bodies are delicate, their internal organs are not fully developed, their skin is thin, and their defenses are loose. Furthermore, deficiencies in the lungs, spleen, and kidneys weaken their defenses against external pathogens. Furthermore, they are unable to regulate their responses to cold and heat, allowing them to be attacked by the six external pathogens, whether through the mouth and nose or through the skin, which all affect the lungs and lead to recurrent respiratory tract infections. Adults who are susceptible to upper respiratory infections are often those who are already weak. The Jingyue Complete Works on Colds states, "When blood and qi gradually decline, pathogenic factors will easily invade." The Xizhu Book on the Origin and Development of Miscellaneous Diseases states, "Colds are lung diseases, caused by deficiency of vital qi and loose pores." Generally speaking, colds caused by a weak constitution result from a weakening of vital qi, which is unable to resist external pathogens. This leads to the weakening of vital qi and the conflict between the two. This leads to a cycle of illness, often protracted and difficult to cure, as the mother's illness spreads to the child. Traditional Chinese Medicine treatment often focuses on replenishing qi, strengthening the exterior, strengthening the spleen, and tonifying the kidneys.

[0005] For example, Chinese invention patent application CN109771606A discloses a Chinese medicine composition and Chinese medicine preparation suitable for treating acute and chronic respiratory bacterial and viral infections. The composition comprises the following raw materials in parts by weight: 10-20 parts of Astragalus, 5-15 parts of Codonopsis, 5-15 parts of Atractylodes macrocephala, 5-10 parts of Amomum villosum, 5-10 parts of Cuscuta australis, 5-15 parts of Poria, 6-12 parts of Fritillaria thunbergii, 5-15 parts of Gallnut, 8-15 parts of Isatis indigotica, 6-12 parts of Honeysuckle, 5-12 parts of Chrysanthemum indicum, 5-15 parts of Polygonum multiflorum, 6-15 parts of Sophora flavescens, 8 parts of Portulaca oleracea. The herb contains 5-15 parts of dandelion, 6-12 parts of isatis root, 5-10 parts of schisandra chinensis, 3-10 parts of houttuynia cordata, 8-12 parts of trifoliate needles, 6-10 parts of pulsatilla, 5-15 parts of andrographis paniculata, 8-12 parts of forsythia, 5-10 parts of senecio scabra, 10-15 parts of moutan bark, 6-12 parts of burdock fruit, 6-12 parts of coptis root, 10-15 parts of tongguangsan, and 8-15 parts of red peony root. It has minimal toxicity and side effects, a very low drug resistance rate, and minimal gastric irritation, making it suitable for all types of patients. It can be widely used to treat respiratory bacterial and viral infections and has a preventive effect.

[0006] Another Chinese invention patent application CN113144047A discloses a Chinese herbal formula for respiratory tract anti-inflammatory and antibacterial treatment, comprising 10-15 grams of isatis leaf, 10-15 grams of isatis root, 10-15 grams of honeysuckle, 10-15 grams of forsythia, 10-15 grams of dandelion, 6-12 grams of platycodon, 6-12 grams of apricot kernel, 15-30 grams of andrographis paniculata, 6-12 grams of chrysanthemum chinense, and 10-20 grams of houttuynia cordata, comprising the following steps: S1, preparing the formula herbs: isatis leaf, isatis root, Honeysuckle, Forsythia suspensa, Dandelion, Platycodon grandiflorum, Apricot kernel, Andrographis paniculata, Caulis sylvestris and Houttuynia cordata; S2, weighing and preparing Folium Isatidis, Radix Isatidis, Honeysuckle, Forsythia suspensa, Dandelion, Platycodon grandiflorum, Apricot kernel, Andrographis paniculata, Caulis sylvestris and Houttuynia cordata; S3, crushing and packaging the weighed and prepared medicinal materials; S4, decocting in water and taking orally. This Chinese medicine formula can treat upper respiratory tract infections and acute and chronic tracheitis caused by various reasons, and also has the effects of protecting the liver and promoting bile secretion, clearing away heat and improving eyesight, and resolving phlegm and moistening the lungs.

[0007] In recent years, the integration of traditional Chinese and Western medicine has shown significant advantages in treating this disease. However, some challenges remain in clinical application, such as poor taste, poor compliance, suboptimal efficacy, high incidence of adverse reactions, and complex taste. Therefore, there is an urgent clinical need to develop a traditional Chinese medicine preparation that is effective, safe, and palatable to children to prevent and treat recurrent respiratory infections. Summary of the Invention

[0008] In view of the deficiencies in the prior art, the present invention provides a traditional Chinese medicine composition for preventing and treating recurrent respiratory tract infections, as well as a preparation method and application thereof.

[0009] In order to achieve the purpose of the present invention, the technical solutions adopted are as follows: A traditional Chinese medicine composition for preventing and treating recurrent respiratory tract infections comprises the following raw materials: honeysuckle, isatis indigotica, dandelion, houttuynia cordata, astragalus, atractylodes macrocephala, siler, vine tea, patchouli, adenophora scutellariae and tangerine peel.

[0010] Furthermore, the Chinese medicine composition includes, by weight: 3-18 parts of honeysuckle, 6-18 parts of isatis indigotica, 6-18 parts of dandelion, 6-20 parts of houttuynia cordata, 6-30 parts of astragalus, 3-18 parts of atractylodes, 3-15 parts of siler, 3-30 parts of vine tea, 3-12 parts of patchouli, 3-15 parts of northern adenophora and 3-12 parts of dried tangerine peel.

[0011] Furthermore, the Chinese medicine composition includes, by weight: 5-15 parts of honeysuckle, 6-15 parts of isatis indigotica, 6-15 parts of dandelion, 6-15 parts of houttuynia cordata, 6-20 parts of astragalus, 3-15 parts of atractylodes, 3-10 parts of siler, 5-15 parts of vine tea, 5-12 parts of patchouli, 5-15 parts of northern adenophora and 3-10 parts of dried tangerine peel.

[0012] Furthermore, the Chinese medicine composition includes, by weight: 12 parts of honeysuckle, 12 parts of isatis indigotica, 12 parts of dandelion, 12 parts of houttuynia cordata, 9 parts of astragalus, 9 parts of atractylodes, 6 parts of siler, 9 parts of rattan tea, 9 parts of patchouli, 9 parts of northern adenophora and 6 parts of dried tangerine peel.

[0013] The second object of the present invention is to provide a method for preparing the Chinese medicine composition, which comprises mixing all raw materials and boiling them in water.

[0014] Furthermore, the amount of water added is 5-15 times the mass of all raw materials, and / or the number of decoctions is 1-3 times, the decoction time each time is 0.5-1.5 hours, and / or the decoction is filtered after decoction to obtain the decoction.

[0015] Furthermore, the preparation method further comprises concentrating the water decoction to obtain a thick paste.

[0016] The third object of the present invention is to provide a pharmaceutical preparation, characterized in that the raw materials of the pharmaceutical preparation include the traditional Chinese medicine composition and pharmaceutically acceptable excipients.

[0017] Furthermore, the dosage form of the pharmaceutical preparation is selected from oral preparations or injections, and the oral preparation is selected from mixtures, granules, capsules or tablets; when the oral preparation is selected from granules, the preparation method of the pharmaceutical preparation comprises adding the traditional Chinese medicine composition to pharmaceutically acceptable excipients, granulating by wet method, and then drying and granulating.

[0018] Another object of the present invention is to provide a use of the Chinese medicine composition or the Chinese medicine composition prepared by the preparation method or the pharmaceutical preparation in the preparation of drugs for preventing and treating recurrent respiratory tract infections, and / or enhancing the body's immune function, and / or anti-inflammatory drugs.

[0019] In some embodiments of the present invention, the Chinese medicine composition can be prepared into dosage forms such as pills, capsules, granules, oral liquids, powders, tablets, lozenges, and lozenges. Suitable pharmaceutical carriers in the art can be selected for different dosage forms.

[0020] The pharmaceutical carrier used can be a solid, liquid or gas. Examples of solid carriers include lactose, kaolin, sucrose, talc, gelatin, agar, pectin, gum arabic, magnesium stearate and stearic acid. Examples of liquid carriers include syrup, peanut oil, olive oil and water. Examples of gaseous carriers include carbon dioxide and nitrogen.

[0021] When preparing oral dosage compositions, any medium consistent with pharmaceutical formulation requirements can be used. For example, water, ethanol, oils, alcohols, flavoring agents, preservatives, colorants, and the like can be used to form oral liquid formulations, such as suspensions and solutions; while carriers, such as starches, sugars, microcrystalline cellulose, diluents, granulating agents, emulsifiers, lubricants, binders, and disintegrants can be used to form oral solid formulations, such as powders, capsules, and tablets. Tablets and capsules are preferred oral dosage units using solid pharmaceutical carriers due to their ease of administration. Tablets can be coated using standard aqueous or nonaqueous techniques.

[0022] Tablets containing the Chinese medicine composition of the present invention can be prepared by tableting or molding, and one or more auxiliary ingredients or adjuvants can be used. The active ingredient can be compressed into a free-flowing form (such as powder or granules) in a suitable machine, and can be prepared by mixing with a binder, lubricant, inert diluent, surfactant or dispersant. Molded tablets can be molded in a suitable machine, i.e., a powdered mixture moistened with an inert liquid diluent, preferably containing about 0.05 mg to about 5 g of active ingredient per tablet, and preferably containing about 0.05 mg to about 5 g of active ingredient per sachet or capsule. For example, a preparation intended for oral administration to humans may contain about 0.5 mg to about 5 g of active drug, mixed with an appropriate and convenient pharmaceutical carrier, which may account for about 5% to 95% of the total composition. Unit dosage forms typically contain about 1 mg to about 2 g of active ingredient, typically 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg, 500 mg, 600 mg, 800 mg or 1000 mg.

[0023] In addition to the above-mentioned carrier components, the above-mentioned pharmaceutical preparations may include (if applicable) one or more additional carrier components, such as diluents, buffers, flavoring agents, binders, surfactants, thickeners, lubricants, preservatives (including antioxidants), etc. In addition, other excipients, such as lactose, starch, cellulose derivatives, magnesium stearate, stearic acid, colorants and flavoring agents, etc., may be added, and the components containing the Chinese medicine composition of the present invention may also be prepared in the form of powder or concentrate.

[0024] In some embodiments, the pharmaceutical composition of the present invention is prepared in the form of an injection.

[0025] In some embodiments, the injection comprises a sterile solution.

[0026] In some embodiments, the present invention comprises at least one preservative. Examples of suitable preservatives that can be used include, but are not limited to, phenol, benzyl alcohol, m-cresol, methylparaben, propylparaben, butylparaben, chlorobutanol, thimerosal, phenylmercuric salts, and the like, or mixtures thereof.

[0027] The present invention comprises a pharmaceutically acceptable carrier, which comprises an aqueous carrier, such as water for injection. It may also comprise one or more pH adjusters, buffers, isotonic agents or chelating agents.

[0028] In one embodiment, the pH can be adjusted within the range by means of a pH adjusting agent such as sodium bicarbonate, lactic acid, hydrochloric acid, acetic acid, sodium hydroxide, etc. A buffer or buffer system can be used to maintain the pH within the desired range. Suitable buffers that can be used include, but are not limited to, lactate buffer, acetate buffer, citrate buffer, gluconate buffer, tartrate buffer, phosphate buffer, etc.

[0029] In a preferred embodiment, the osmotic pressure molarity can be adjusted with the help of an isotonic agent. Typical isotonic agents that can be used in sterile solutions include, but are not limited to, mannitol, sorbitol, sodium chloride, potassium chloride, lactose, sucrose, maltose, trehalose, dextrose, and mixtures thereof.

[0030] In a preferred embodiment, the sterile solution optionally contains a chelating agent, such as disodium EDTA, edetic acid, EDTA, and the like.

[0031] Terms and Claims of the Present Invention: The articles "a," "an," and "the" include plural referents unless expressly limited to one or more referents otherwise.

[0032] Unless otherwise expressly indicated, all ranges or ratios disclosed herein are to be understood to include any and all subranges or subratios contained therein. For example, a range or ratio stated as 1 to 30 is to be considered inclusive of any and all subranges or subratios, integers, decimals, or subranges or subratios comprised therein, between a minimum of 1 and a maximum of 30, and including any subranges or subratios, integers, decimals, or subranges or subratios comprised therein.

[0033] The terms "comprises," "includes," "have," "has," "may," "contain" and variations thereof are meant as open-ended conjunctions or terms that do not exclude the possibility of additional compositions or structures.

[0034] Compared with the prior art, the present invention has the following beneficial effects: (1) The Chinese medicine composition of the present invention is derived from the traditional famous prescription Yupingfeng Powder with additions to the heat-clearing and detoxifying preparation Jinye Baidu Granules, and is composed of eleven Chinese medicinal herbs: Tengcha, Honeysuckle, Folium Isatidis, Taraxacum, Herba Houttuyniae, Radix Astragali, Rhizoma Atractylodis Macrocephalae, Radix Saposhnikoviae, Radix Glehniae, Pogostemon Cablin, and Pericarpium Citri Reticulatae. Astragalus in the prescription is sweet and warm, and is good at tonifying the spleen and lungs, replenishing qi and strengthening the exterior, strengthening the internal qi, and enhancing the function of defending the body from external pathogens; Honeysuckle is fragrant and penetrating, dispersing pathogenic heat, lightening and clearing qi, clearing heat and detoxifying, and is good at dispersing pathogenic pathogens from the exterior of the body; when the two herbs are used together, Astragalus strengthens the body's health to help Honeysuckle expel pathogenic pathogens and prevent them from entering the body, while Honeysuckle with Astragalus dispersing pathogenic pathogens and detoxifying without damaging the body's health, so they are both monarch herbs.

[0035] The spleen is the mother of the lungs. Atractylodes macrocephala strengthens the spleen and replenishes Qi. A strong spleen allows earth to generate metal, and sufficient lung Qi strengthens the exterior and the defenses. Combined with Astragalus membranaceus, it tonifies the middle to replenish the source of Qi and blood, strengthening the spleen and stomach and flesh and skin, thereby preventing external invasion and internal transmission. Dandelion is a detoxifying agent, while Isatis indigotica cools blood and eliminates freckles, Houttuynia cordata specifically clears lung heat, and Tengcha clears heat and relieves sore throats. Combined with honeysuckle, these four herbs double their detoxifying power and enhance their heat-clearing effects. They can not only clear pathogenic heat from the Qi, preventing it from transforming into fire and generating toxicity, but also halt the progression of the disease, halting the pathogenic factors and eliminating the factors that cause Qi and Ying to transmit and transform. By dispelling lingering pathogens, they can interrupt the pathological process of "evil stagnation turning into heat." These five herbs are collectively referred to as ministerial herbs.

[0036] Saposhnikovia root is pungent and slightly warm, dispelling wind, relieving exterior symptoms, and overcoming dampness. When used with Astragalus root, they act as a tonic, attacking, dispersing, and astringing combination. Astragalus root can prevent Saposhnikovia root from astringing pathogenic factors, while Astragalus root can prevent Saposhnikovia root from damaging Wei Qi. They both tonify the middle and dissipate, combining dispersing and astringing properties. Patchouli root is pungent and warm, dispelling dampness and harmonizing the middle, while its aromatic properties dispel turbidity. Tangerine peel regulates Qi and strengthens the spleen, drying dampness and resolving phlegm, promoting circulation and regulating Qi, relieving depression and relieving stagnation. It protects the gastrointestinal tract from the harmful effects of cold and dampness, while also aiding the spleen and stomach in digestion and metabolism, taking into account the fact that the spleen is the foundation of acquired health. Children often have "excess yang and insufficient yin," so Adenophora australis nourishes yin, clears the lungs, benefits the stomach, and promotes fluid production, preventing the depletion of yin by pungent and warm herbs. All of these herbs serve as adjuvants.

[0037] The entire formula is pungent and warm, sweet and cold, employing multiple approaches, including tonifying Qi and strengthening the exterior, clearing heat and detoxifying, and nourishing Yin and benefiting the lungs. These methods collectively address the pathogenesis of recurrent respiratory infections characterized by "deficiency of the body's vital energy and retention of pathogenic factors." They tonify the Qi of the lungs and spleen to ward off external pathogens, while clearing heat and toxins from the lung meridian to dispel internal pathogens. Taking into account the specific constitutions of children, this formula prioritizes both the vital energy and the expelling of pathogenic factors. When tonifying vital energy combined with expelling pathogenic factors, these tonifying factors do not stagnate, preventing the harmful effects of trapping the enemy within. Expelling pathogenic factors combined with tonifying vital energy are even more potent, clearing heat and detoxifying without harming vital energy, eliminating internal concerns. Warming the middle while clearing, tonifying the middle while eliminating, combining cold and warming, mutually reinforcing, allowing vital energy to flourish and expelling pathogenic factors. This is a truly appropriate remedy for individuals suffering from external infections.

[0038] (2) The Chinese medicine composition of the present invention has significant effects on improving the body's immunity and anti-inflammatory effects. Animal experimental studies have found that it can promote the development of immune organs (spleen and thymus) in normal mice, enhance humoral immune function (IgG, IgM, IgA), and effectively inhibit lipopolysaccharide-induced inflammatory damage.

[0039] (3) Clinical efficacy observations showed that the Chinese medicine composition of the present invention can significantly reduce the number of recurrent respiratory tract infections (lung and spleen qi deficiency syndrome) in children, shorten the course of the disease, and effectively improve TCM symptoms such as pale complexion, shortness of breath, laziness, poor appetite, and excessive sweating. The compound is based on the TCM theory of monarch, minister, assistant, and envoy, and the various components work together to achieve excellent results.

[0040] (4) In addition, the composition of the present invention has a good taste, no bad smell, high compliance among children, no serious adverse reactions in clinical practice, and a mild medicinal property. It can be used as both a preventive and a therapeutic drug, thus filling a gap in the market. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 The results of plasma TNF-α, IL-6, and IL-1β determination in mice of each group were shown. Compared with the model group, *p<0.05, **p<0.01, ***p<0.001, ****p<0.0001.

[0042] Figure 2 Representative H&E staining images of the main organs (heart, liver, spleen, lung, and kidney) of mice in each group. DETAILED DESCRIPTION

[0043] The present invention will be further described below in conjunction with specific embodiments. The following raw materials are all commercially available conventional raw materials.

[0044] Example 1 This embodiment provides a pharmaceutical composition, wherein the raw materials of the pharmaceutical composition are, by weight, 12 parts of honeysuckle, 12 parts of isatis indigotica, 12 parts of dandelion, 12 parts of houttuynia cordata, 9 parts of astragalus, 9 parts of atractylodes, 6 parts of siler, 9 parts of rattan tea, 9 parts of patchouli, 9 parts of northern adenophora, and 6 parts of dried tangerine peel.

[0045] The preparation method is: (1) Prepare the raw materials according to their weight; mix the raw materials, add 10 times the volume of water and boil twice, each time for 1 hour, and filter to obtain the decoction; (2) Combine the decoctions and concentrate to obtain a thick paste with a relative density of 1.20-1.28 at 60°C, which is set aside.

[0046] Example 2 This embodiment provides a pharmaceutical composition, in which the raw materials of the pharmaceutical composition are, by weight, 3 parts of honeysuckle, 6 parts of isatis indigotica, 6 parts of dandelion, 6 parts of houttuynia cordata, 6 parts of astragalus, 3 parts of atractylodes, 3 parts of siler, 3 parts of rattan tea, 3 parts of patchouli, 3 parts of northern adenophora, and 3 parts of dried tangerine peel.

[0047] The preparation method is: (1) Prepare the raw materials according to their weight; mix the raw materials, add 15 times the volume of water, and boil for 1.5 hours, then filter to obtain the decoction; (2) After concentration, a thick paste with a relative density of 1.20-1.28 at 60°C is obtained and set aside.

[0048] Example 3 This embodiment provides a pharmaceutical composition, in which the raw materials of the pharmaceutical composition are, by weight, 18 parts of honeysuckle, 18 parts of isatis indigotica, 18 parts of dandelion, 20 parts of houttuynia cordata, 30 parts of astragalus, 18 parts of atractylodes, 15 parts of siler, 30 parts of vine tea, 12 parts of patchouli, 15 parts of northern adenophora, and 12 parts of dried tangerine peel.

[0049] The preparation method is: (1) Prepare the raw materials according to their weight; mix the raw materials, add 8 times the volume of water and boil for 1 hour, filter, add 5 times the volume of water to the residue and boil for 0.5 hour, filter, add 5 times the volume of water to the residue and boil for 0.5 hour, filter, and combine the filtrates to obtain a decoction; (2) After concentration, a thick paste with a relative density of 1.20-1.28 at 60°C is obtained and set aside.

[0050] Example 4 This embodiment provides a granule, the raw materials of which are the same as those in Example 1.

[0051] The preparation method is as follows: 0.1% of the weight of the flavoring agent sucralose and 150% of the filler dextrin are added to the thick paste prepared in Example 1, and wet granulation is performed. After the granulation is completed, the granules are dried, granulated, and packaged to obtain granules.

[0052] Example 5 This embodiment provides a granule, the raw materials of which are the same as those in Example 1.

[0053] The preparation method is as follows: 0.1% of the weight of sucralose as a flavoring agent and 200% of the weight of dextrin as a filler are added to the thick paste prepared in Example 1, and wet granulation is performed. After the granulation is completed, the granules are dried, granulated, and packaged to obtain granules.

[0054] Example 6 This embodiment provides a granule, the raw materials of which are the same as those in Example 1.

[0055] The preparation method is as follows: 0.1% of the flavoring agent sucralose and 50% of the filler dextrin are added to the thick paste prepared in Example 1, mixed, dried, and crushed to prepare a dry paste powder, which is then granulated by a wet method. After the granulation is completed, the granules are dried, granulated, and packaged to obtain granules.

[0056] Example 7 This embodiment provides a Chinese medicine oral solution (decoction). The raw materials, calculated by weight, are: 12g of honeysuckle flower, 12g of isatis indigotica leaf, 12g of dandelion, 12g of houttuynia cordata, 9g of astragalus root, 9g of atractylodes macrocephala, 6g of siler, 9g of vine tea, 9g of patchouli, 9g of northern adenophora, and 6g of dried tangerine peel.

[0057] Preparation method: (1) Mix the above raw materials; (2) Add 10 times the weight of water, soak for 0.5 hours, decoct for 1 hour, and pour out the liquid; then add 8 times the weight of water, decoct for 1 hour, and pour out the liquid; combine the two liquids, concentrate to 180 ml, add 0.1% sucralose to correct the taste, and package into 30 ml / bag to obtain the traditional Chinese medicine solution (decoction) for detoxification.

[0058] Comparative Example 1 (lack of Jinyebaidu) Compared with Example 1, the raw materials are different and the medicinal flavor of Jinye Baidu Granules is removed: honeysuckle, isatis indigotica, dandelion and houttuynia cordata. The details are as follows: Calculated by weight, the components include 9 parts of astragalus, 9 parts of atractylodes, 6 parts of siler, 9 parts of vine tea, 9 parts of patchouli, 9 parts of northern adenophora and 6 parts of dried tangerine peel.

[0059] The preparation method is: (1) Prepare the raw materials according to their weight; mix the raw materials, add 10 times the volume of water and boil twice, each time for 1 hour, and filter to obtain the decoction; (2) Combine the decoctions and concentrate to obtain a thick paste with a relative density of 1.20-1.28 at 60°C, which is set aside.

[0060] Comparative Example 2 (missing jade screen group) The difference between this comparative example and Example 1 is that the raw materials are different, and the astragalus, siler and atractylodes in Yupingfeng powder are removed, specifically as follows: By weight, the components include 12 parts of honeysuckle, 12 parts of isatis indigotica, 12 parts of dandelion, 12 parts of houttuynia cordata, 9 parts of vine tea, 9 parts of patchouli, 9 parts of northern adenophora and 6 parts of dried tangerine peel.

[0061] The preparation method is: (1) Prepare the raw materials according to their weight; mix the raw materials, add 10 times the volume of water and boil twice, each time for 1 hour, and filter to obtain the decoction; (2) Combine the decoctions and concentrate to obtain a thick paste with a relative density of 1.20-1.28 at 60°C, which is set aside.

[0062] Comparative Example 3 (Group lacking adjuvant drugs) The difference between this comparative example and Example 1 is that the components are different, and the adjuvant drugs Saposhnikovia divaricata, Patchouli, Glehnia littoralis and Tangerine peel in the prescription are removed, specifically as follows: In parts by weight, the components include 12 parts of honeysuckle, 12 parts of isatis indigotica, 12 parts of dandelion, 12 parts of houttuynia cordata, 9 parts of astragalus, 9 parts of atractylodes, and 9 parts of rattan tea.

[0063] The preparation method is: (1) Prepare the raw materials according to their weight; mix the raw materials, add 10 times the volume of water and boil twice, each time for 1 hour, and filter to obtain the decoction; (2) Combine the decoctions and concentrate to obtain a thick paste with a relative density of 1.20-1.28 at 60°C, which is set aside.

[0064] Effect experiment example: Experimental Example 1: Effect of the Chinese medicine composition of the present invention on the immunity of normal mice Twenty-five male SPF Balb / c mice (8 weeks old) were randomly divided into five groups (n = 5) after one week of adaptive feeding: a normal group, a Guwei Jiedu group (Example 1), a Jinye Baidu group (Comparative Example 1), a Yupingfeng group (Comparative Example 2), and a Zuoshiyao group (Comparative Example 3). Mice in the Guwei Jiedu, Jinye Baidu, Yupingfeng, and Zuoshiyao groups were gavaged with the corresponding drug at a dose equivalent to 21 g / kg of the decoction piece. The normal group received an equal amount of saline by gavage once daily for seven consecutive days. After the last dose, the mice were fasted overnight. The next day, the mice were anesthetized, weighed, and blood was collected from their orbits. The blood samples were stored on ice. The mice were then euthanized, and their spleens and thymuses were removed, washed with saline, dried, and weighed. The spleen and thymus indices were calculated. Blood samples were centrifuged at 4500 rpm for 10 min at 4°C to separate plasma, and the levels of IgG, IgM, and IgA in plasma were detected by ELISA. The spleen index and thymus index results of mice are shown in Table 1 , and the plasma IgG, IgM, and IgA levels are shown in Table 2 .

[0065] Table 1 Spleen index and thymus index of mice (Mean ± SEM, n = 5)

[0066] Compared with the normal group,* p <0.05.

[0067] Compared with the normal group, the spleen index and thymus index of mice in the Guweijiedu group, the Jinyebaidu deficiency group, the Yupingfeng deficiency group and the Zuoshiyao deficiency group were increased to varying degrees, among which the Guweijiedu group was significantly increased ( p <0.05, p <0.05 vs normal group).

[0068] Table 2 Plasma IgG, IgM, and IgA assay results in mice (Mean ± SEM, n = 5)

[0069] Note: Compared with the normal group, * p <0.05,** p <0.01.

[0070] The results in Table 2 show that plasma immunoglobulin levels (IgG, IgM, and IgA) in mice in the Guwei Jiedu, Jinye Baidu, Yupingfeng, and Zuoshiyao groups were all elevated compared with those in the normal control group. Among them, the Guwei Jiedu group had the highest plasma IgG, IgM, and IgA levels. These results suggest that Guwei Jiedu positively regulates the development of immune organs (spleen and thymus) and humoral immune function (IgG, IgM, and IgA) in normal mice, validating its overall immune-boosting effect.

[0071] Experimental Example 2: Effects of the composition of the present invention on inflammation model mice Thirty-five male SPF Balb / c mice (8 weeks old) were randomly divided into seven groups (n = 5) after one week of adaptive feeding: a normal group, a model group, a Guwei Jiedu group (Example 1 group), a Jinye Baidu group (Comparative Example 1 group), a Yupingfeng group (Comparative Example 2 group), a Zuoshiyao group (Comparative Example 3 group), and a dexamethasone group (positive drug group). Mice in the Guwei Jiedu, Jinye Baidu, Yupingfeng, and Zuoshiyao groups were gavaged with the corresponding drug at a dose equivalent to 21 g / kg of the decoction piece. The dose was equal across all groups. Mice in the dexamethasone group were intravenously injected with 5 mg / kg dexamethasone sodium phosphate solution, while mice in the normal and model groups were gavaged with an equal volume of normal saline. The drugs were administered once daily for seven consecutive days.

[0072] 0.5 hours after the last dose, LPS (5 mg / kg) was injected intraperitoneally in all groups except the normal control group, which received an equal volume of saline. 24 hours after injection, mice were anesthetized, and blood was collected from the orbital cavity and stored on ice. Mice were then euthanized, and the heart, liver, spleen, lung, and kidney were excised, washed with saline, dried, and fixed in 4% paraformaldehyde for hematoxylin and eosin (H&E) staining. Blood samples were centrifuged at 4500 rpm for 10 minutes at 4°C, and plasma was separated. Plasma levels of TNF-α, IL-1β, and IL-6 were measured by ELISA.

[0073] TNF-α, IL-1β and IL-6 levels are shown in Figure 1 .

[0074] The results showed that after LPS stimulation, the levels of inflammatory factors such as TNF-α, IL-1β and IL-6 in the plasma of mice in the model group were significantly increased (p<0.0001, p<0.0001, p<0.0001 vs the normal group), while in the experimental group with drug intervention, the levels of TNF-α, IL-1β and IL-6 in the plasma of mice were decreased, and the decrease was more obvious in the Guwei Jiedu group, and was comparable to that of the positive drug dexamethasone group.

[0075] The H&E staining results of the main organs of mice (heart, liver, spleen, lung and kidney) are shown in Figure 2 .

[0076] Results showed that compared to the normal control group, the model group mice exhibited varying degrees of inflammatory infiltration in the heart, liver, spleen, lungs, and kidneys, displaying typical inflammatory features, indicating a successful inflammatory model. Furthermore, compared to the model group, the Guwei Jiedu group, the Jinye Baidu group, the Yupingfeng group, the adjuvant-deficient group, and the dexamethasone group showed improved inflammatory infiltration in major organs, with the Guwei Jiedu group demonstrating the greatest efficacy. These results demonstrate that Guwei Jiedu effectively inhibits inflammatory damage.

[0077] Experimental Example 3: Clinical trial of the Chinese medicine composition of the present invention Research subjects: A total of 98 children with recurrent respiratory tract infections who visited the pediatric outpatient clinic of our hospital from January 2024 to April 2025 were selected and randomly divided into a control group and an experimental group. There were 48 cases in the control group, including 25 males and 23 females, aged 2 to 10 years, with an average age of 4.73±1.09 years; there were 50 cases in the experimental group, including 26 males and 24 females, aged 2 to 11 years, with an average age of 5.12±1.26 years.

[0078] Diagnostic criteria: Western medicine diagnostic criteria refer to the criteria defined in the "Clinical Concepts and Management Principles of Recurrent Respiratory Tract Infections" and the 2017 edition of the "Expert Consensus on the Clinical Diagnosis, Treatment and Management of Recurrent Respiratory Tract Infections in Children." The criteria for recurrent respiratory tract infection are shown in Table 3.

[0079] Table 3 Criteria for determining recurrent respiratory tract infection

[0080] The TCM syndrome differentiation standards are formulated with reference to the 2024 edition of the "Guidelines for TCM Diagnosis and Treatment of Recurrent Respiratory Tract Infections in Children" and the spleen and lung qi deficiency syndrome standards in the "TCM Pediatrics": recurrent exogenous infections, sallow complexion, thin body, loose muscles, poor appetite, excessive sweating, easy sweating when moving, fear of wind when sweating, fatigue, shortness of breath and laziness to speak, irregular bowel movements, pale tongue, thin white fur, weak pulse, and pale fingerprints.

[0081] Inclusion criteria: Meet the diagnostic criteria of Western medicine and the criteria of traditional Chinese medicine differentiation of syndromes; 2-14 years old, regardless of gender; informed consent of the patients.

[0082] Exclusion criteria: RRTIs caused by congenital or organic lesions; primary immunodeficiency, HIV infection, and other immune system diseases; systemic use of immunomodulators, inhibitors, etc. before diagnosis; and concurrent serious chronic diseases of other systems.

[0083] Withdrawal and Dropout Criteria: Subjects who meet the inclusion criteria but fail to complete the trial for some reason are considered dropouts. This includes both voluntary withdrawal and researcher-determined withdrawal.

[0084] Treatment options: Control group: Yupingfeng Granules (Guangdong Global Pharmaceutical Co., Ltd. of Sinopharm Group, national medicine standard number Z10930036, specification: 5g / bag), 3 times a day, 1 bag each time.

[0085] Test group: oral solution (decoction) of Chinese medicine prepared in Example 5, taken once in the morning and evening, 30 ml each time.

[0086] Treatment course: 2 weeks for both groups. Follow-up was conducted for 6 months after treatment, and the frequency, type, and course of the disease were recorded.

[0087] Observation indicators: 1) Efficacy assessment: Markedly effective: The number of respiratory tract infections in children decreased by more than 75% within 6 months. Effective: The number of respiratory tract infections in children within 6 months decreased by >25% and ≤75% compared with the previous period; Ineffective: The number of respiratory tract infections in children within 6 months decreased by ≤25% compared with the previous period.

[0088] Total effective rate = (number of markedly effective + effective) cases / total number of cases × 100%.

[0089] 2) TCM syndrome score: The grading and quantification of symptoms and signs were formulated with reference to the Guidelines for the Diagnosis and Treatment of Common Diseases in Pediatrics of Traditional Chinese Medicine (2012) and the Technical Guidelines for the Clinical Design and Evaluation of Clinical Trials of New Traditional Chinese Medicine Drugs for Recurrent Respiratory Tract Infections in Children. The specific grading and quantification standards of traditional Chinese medicine symptoms and signs are shown in Table 4.

[0090] Table 4 Quantitative standards for grading TCM symptoms and signs

[0091] 3) Statistical analysis results GraphPad Prism 8.0 software was used for statistical analysis and comparison before and after treatment. p <0.05 was considered statistically significant. The results of the treatment effects of the two groups are shown in Table 5. The total effective rate of the experimental group was higher than that of the control group, and the difference was statistically significant ( p <0.05).

[0092] Table 5 Comparison of treatment effects between the two groups

[0093] Compared with the control group, * p <0.05.

[0094] The results of the comparison of TCM syndrome scores between the two groups of children are shown in Table 6. Before treatment, there was no statistically significant difference in TCM syndrome scores between the two groups of children ( p >0.05); After 2 weeks of treatment, the TCM syndrome scores of the two groups were lower than before treatment, and the TCM syndrome scores of the experimental group were lower than those of the control group, with statistically significant differences ( p <0.05), see Table 6.

[0095] Table 6 Comparison of TCM syndrome scores between the two groups of children (mean ± SD)

[0096] Compared with the group before treatment, * p <0.05, ** p <0.01, **** p <0.0001; compared with the control group after treatment, ## p <0.01, #### p <0.0001.

[0097] During clinical treatment of the present invention, the composition of Example 1, 2 or 3 is used according to the specific conditions of the patient, and all of them can achieve good efficacy in treating recurrent respiratory tract infections in children.

[0098] The above detailed description is a specific description of one feasible embodiment of the present invention. This embodiment is not intended to limit the patent scope of the present invention. Any equivalent implementation or modification that does not depart from the present invention should be included in the scope of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for preventing and treating recurrent respiratory tract infections, characterized in that: The raw materials of the traditional Chinese medicine composition include honeysuckle, isatis indigo leaf, dandelion, houttuynia cordata, astragalus, atractylodes macrocephala, siler, vine tea, patchouli, adenophora scutellariae and tangerine peel.

2. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition comprises, by weight, 3-18 parts of honeysuckle, 6-18 parts of isatis indigotica, 6-18 parts of dandelion, 6-20 parts of houttuynia cordata, 6-30 parts of astragalus, 3-18 parts of atractylodes, 3-15 parts of siler, 3-30 parts of vine tea, 3-12 parts of patchouli, 3-15 parts of northern adenophora and 3-12 parts of dried tangerine peel.

3. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition comprises, by weight, 5-15 parts of honeysuckle, 6-15 parts of isatis indigotica, 6-15 parts of dandelion, 6-15 parts of houttuynia cordata, 6-20 parts of astragalus, 3-15 parts of atractylodes, 3-10 parts of siler, 5-15 parts of vine tea, 5-12 parts of patchouli, 5-15 parts of northern adenophora and 3-10 parts of dried tangerine peel.

4. The Chinese medicine composition according to claim 1, characterized in that The Chinese medicine composition comprises, by weight, 12 parts of honeysuckle, 12 parts of isatis indigotica, 12 parts of dandelion, 12 parts of houttuynia cordata, 9 parts of astragalus, 9 parts of atractylodes, 6 parts of siler, 9 parts of rattan tea, 9 parts of patchouli, 9 parts of northern adenophora and 6 parts of dried tangerine peel.

5. A method for preparing the traditional Chinese medicine composition according to any one of claims 1 to 4, characterized in that: The method comprises mixing all the raw materials, adding water and boiling.

6. The preparation method according to claim 5, characterized in that The amount of water added is 5-15 times the mass of all raw materials, and / or the number of decoctions is 1-3 times, the decoction time each time is 0.5-1.5 hours, and / or the decoction is filtered after decoction to obtain the decoction.

7. The preparation method according to claim 6, characterized in that The preparation method further comprises concentrating the water decoction to obtain a thick paste.

8. A pharmaceutical preparation, characterized in that The raw materials of the pharmaceutical preparation include the traditional Chinese medicine composition according to any one of claims 1 to 4 and pharmaceutically acceptable excipients.

9. The pharmaceutical preparation according to claim 8, characterized in that The dosage form of the pharmaceutical preparation is selected from oral preparations or injections, and the oral preparation is selected from mixtures, granules, capsules or tablets; when the oral preparation is selected from granules, the preparation method of the pharmaceutical preparation comprises adding the traditional Chinese medicine composition to pharmaceutically acceptable excipients, granulating by wet method, and then drying and granulating.

10. Use of the traditional Chinese medicine composition according to any one of claims 1 to 4, or the traditional Chinese medicine composition prepared by the preparation method according to any one of claims 5 to 7, or the pharmaceutical preparation according to claim 8 or 9 in the preparation of drugs for preventing and treating recurrent respiratory tract infections, and / or enhancing immune function, and / or anti-inflammatory drugs.

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