Traditional Chinese medicine composition for treating infantile cough as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention discloses a traditional Chinese medicine composition for treating infantile cough and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicines: pink reineckea herb, folium mori, cortex mori radicis, cortex lycii radicis, moutan bark, radix paeoniae alba, cicada slough, radix peucedani, honey-fried flos farfarae, honey-fried radix asteris, bulbus fritillariae cirrhosae, poria cocos, liquorice and the like, and is prepared by the following steps: adding water into twelve medicinal materials except the bulbus fritillariae cirrhosae, decocting, concentrating into clear paste, adding cane sugar and bulbus fritillariae cirrhosae fine powder, heating, concentrating and uniformly mixing. The prepared product has the effects of dispelling wind and ventilating lung, relieving cough and reducing sputum, and dispelling wind and relieving cough. Clinical application shows that after the product is used for treating children with cough, the cough, phlegm in throat, lung signs and the like of the children with cough are effectively improved, and no adverse reaction is reported in the process. The invention provides an effective and safe novel traditional Chinese medicine preparation for treating infantile cough. The medicine is worthy of popularization and application clinically.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to a traditional Chinese medicine composition for treating pediatric cough, and a preparation method and application thereof. Background Art

[0002] Cough is a common lung disease in children. It can be categorized as either exogenous or internal. It's similar to tracheitis and bronchitis in Western medicine and can occur year-round, but is more common in winter and spring. The younger the child, the higher the prevalence.

[0003] At present, the main method of Western medicine to treat children's cough is to use antibiotics, cough suppressants and other drugs to help children relieve symptoms. Among them, antibiotics can play a role in sterilization and anti-inflammation, effectively inhibit the reproduction of pathogens, alleviate infection symptoms, and thus relieve cough. However, long-term use of antibiotics may cause adverse reactions such as imbalance of intestinal flora and increased drug resistance. [1] Traditional Chinese medicine has unique advantages in treating children's cough. Recent studies have shown that a variety of traditional Chinese medicine preparations have multi-target effects such as relieving cough, resolving phlegm, relieving asthma, anti-inflammatory, anti-allergic, antibacterial, and antiviral. High-level evidence has been obtained for their use in treating children's cough. [2,3,4,5] .

[0004] The pathogenesis of pediatric cough is closely linked to the liver and lungs. When exogenous pathogens invade the body, they primarily target the lung defenses, causing lung qi to be constricted and qi flow to become stagnant. This leads to a failure of the lung's functions of dispersing and descending, and a breakdown of its functions of clearing and purifying. This causes lung qi to rise, resulting in cough. The lungs and liver are closely connected, with direct meridian connections and physiological functions that synergize in regulating the rise and fall of qi in the body. Whether liver or lung function is excessive or deficient, this ultimately leads to dysfunction of the lung's functions of dispersing and purifying, causing lung qi to rise and result in cough. Therefore, it is necessary to explore effective traditional Chinese medicine preparations for the treatment of pediatric cough to serve clinical needs. Summary of the Invention

[0005] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating children's cough.

[0006] Another object of the present invention is to provide a method for preparing a traditional Chinese medicine composition for treating cough in children.

[0007] Another object of the present invention is to provide a use of a traditional Chinese medicine composition in preparing medicine for treating cough in children.

[0008] In order to achieve the purpose of the present invention, the present invention adopts the following technical solutions and steps:

[0009] The pharmaceutical composition for treating cough in children according to the present invention is composed of the following raw materials in parts by weight: 125-140 parts of herba schisandrae, 125-140 parts of mulberry leaves, 125-140 parts of mulberry barks, 125-140 parts of lycium bark, 125-140 parts of moutan barks, 125-140 parts of white peony root, 70-90 parts of cicada slough, 125-140 parts of peucedanum peucedanum, 125-140 parts of honey coltsfoot flowers, 125-140 parts of honey aster, 35-45 parts of fritillaria cirrhosa, 125-140 parts of poria cocos, and 35-45 parts of liquorice.

[0010] Preferably, the pharmaceutical composition for treating cough in children of the present invention is composed of the following raw materials in parts by weight: 130-135 parts of lucky grass, 130-135 parts of mulberry leaves, 130-135 parts of mulberry bark, 130-135 parts of Lycium bark, 130-135 parts of peony bark, 130-135 parts of white peony root, 75-85 parts of cicada shell, 130-135 parts of peucedanum, 130-135 parts of honey coltsfoot flower, 130-135 parts of honey aster, 38-42 parts of Fritillaria cirrhosa, 130-135 parts of Poria cocos, and 38-42 parts of licorice.

[0011] Further preferably, the pharmaceutical composition for treating children's cough according to the present invention is composed of the following raw materials in parts by weight: 133 parts of lucky grass, 133 parts of mulberry leaves, 133 parts of mulberry bark, 133 parts of Lycium bark, 133 parts of peony bark, 133 parts of white peony root, 80 parts of cicada shell, 133 parts of peucedanum, 133 parts of honey coltsfoot flower, 133 parts of honey aster, 40 parts of Fritillaria cirrhosa, 133 parts of Poria cocos, and 40 parts of licorice.

[0012] Among them, Reineckea carnea (Andr.) Kunth., a perennial green herb belonging to the genus Reineckea in the Liliaceae family, is the whole herb with roots. Its nature and flavor are sweet and cooling. It has lung-clearing, cough-relieving, blood-regulating, and detoxifying properties. It is used to treat lung-heat cough, hematemesis, epistaxis, bloody stool, traumatic injuries, sores, conjunctivitis, and malnutrition. It primarily contains a variety of chemical components, including steroids, flavonoids, lignans, terpenes, and organic acids. In animal models of cough, expectoration, and inflammation, oral administration of Reineckea carnea total saponins at varying doses demonstrated significant antitussive and expectorant effects. It also significantly inhibited increased capillary permeability and xylene-induced auricular inflammation in mice.

[0013] Mulberry leaf: The dried leaves of Morus alba L., a plant of the Moraceae family, are sweet, bitter, and cold. They enter the lung and liver meridians. They dispel wind-heat, clear the lungs and moisten dryness, and clear the liver and improve eyesight. They are used to treat wind-heat colds, lung-heat and dry coughs, dizziness, headaches, and red and blurred vision. Mulberry leaf components primarily include polysaccharides, flavonoids, alkaloids, and Diels-Alder adducts. Modern pharmacological research has demonstrated that mulberry leaf possesses natural antidiabetic therapeutic properties, significantly suppressing postprandial hyperglycemia. 1-Deoxynojirimycin (1-DNJ), a component of mulberry leaf, is absorbed from the gastrointestinal mucosa and rapidly diffuses to the liver, where it inhibits α-glucosidase activity, hindering the binding of disaccharides such as sucrose and maltose to α-glucosidase, thereby reducing the amount of glucose entering the blood and lowering blood sugar levels. Research has shown that mulberry leaf also has anti-atherosclerotic, lipid-lowering, and cardioprotective effects. Numerous studies have demonstrated that, in addition to these therapeutic benefits, mulberry leaf also possesses antioxidant, antipyretic, analgesic, anti-inflammatory, and anti-tumor properties.

[0014] Morus alba bark (Mulberry bark) is the dried root bark of Morus alba L., a plant of the Moraceae family. It is sweet and cold in nature, and enters the Lung meridian. It has the effects of purging the lungs, relieving asthma, promoting diuresis, and reducing swelling. It is used to treat lung heat, asthma, cough, edema, oliguria, and puffiness of the face and skin. It primarily contains flavonoids, stilbenes, aromatic benzofuran derivatives, and coumarins, as well as N-containing sugars and steroids. The total flavonoids in Morus alba bark are the primary active anti-inflammatory and analgesic components. They significantly inhibit xylene-induced ear swelling in mice and acetic acid-induced increased capillary permeability, indicating that the total flavonoids in Morus alba bark possess certain peripheral analgesic and anti-inflammatory properties. Morus alba bark also exhibits multiple pharmacological effects, including antiviral, hypoglycemic, cardiovascular relaxation, anti-tumor, immunomodulatory, antioxidant, and hepatoprotective and cardioprotective properties. Its extracts exhibit potent pharmacological activities, including hypoglycemic, antiviral, anticancer, and anti-allergic effects.

[0015] Moutan bark is the dried root bark of Paeonia suffruticosa Andr. (Ranunculaceae). It has a bitter, pungent, and slightly cold taste. It enters the heart, liver, and kidney meridians. It has the effects of clearing heat, cooling blood, and promoting blood circulation and removing blood stasis. It is used to treat heat invading the blood, feverish toxicity causing rash, hematemesis and epistaxis, night fever and morning chills, anorexia and bone steaming, amenorrhea and dysmenorrhea, pain from falls and injuries, and carbuncles and sores. The main components of moutan bark are phenols and phenolic glycosides, monoterpenes and their glycosides, as well as triterpenes, sterols and their glycosides, flavonoids, organic acids, and coumarins. Moutan bark has certain pharmacological effects in lowering blood sugar, combating atherosclerosis, protecting the liver, enhancing immunity, and providing an anticonvulsant. In addition, peony bark also has antibacterial and anti-inflammatory effects. In vitro tests show that peony bark decoction has a strong inhibitory effect on Staphylococcus aureus, hemolytic Streptococcus, Escherichia coli, Shigella dysenteriae, Salmonella typhi, Salmonella paratyphi, Proteus, Pneumococcus, Vibrio cholerae, etc.

[0016] Rehmannia root bark: This product is the dried root bark of Lycium chinense Mill. or Lycium barbarum L., both of the Solanaceae family. It is sweet and cold in nature. It enters the lung, liver, and kidney meridians. It has the effects of cooling the blood, removing steam, clearing the lungs, and reducing internal heat. It is used for hot flashes due to yin deficiency, night sweats caused by bone steaming, cough due to lung heat, hemoptysis, epistaxis, and internal heat-induced thirst. It primarily contains alkaloids, organic acids, anthraquinones, and cyclic peptides. Modern pharmacological studies have shown that Rehmannia root bark has a hypoglycemic effect, increasing serum insulin and glycogen levels in diabetic rats. Its effect on promoting insulin secretion from pancreatic B cells is even greater than that of Astragalus root. Rehmannia root bark also has antihypertensive and antilipidemic, antipyretic, and antibacterial and antiviral activities.

[0017] White peony root: The dried root of Paeonia lactiflora Pall., a plant of the Ranunculaceae family. It has a bitter, sour, and slightly cold taste and enters the liver and spleen meridians. It nourishes blood and regulates menstruation, astringes yin and stops sweating, softens the liver and relieves pain, and calms liver yang. It is used for sallow complexion caused by blood deficiency, irregular menstruation, spontaneous sweating, night sweats, flank pain, abdominal pain, cramps in the limbs, headaches, and dizziness. Its main chemical components include monoterpenes and their glycosides, triterpenes, flavonoids and their glycosides, phenylethanoid glycosides, tannins, volatile oils, polysaccharides, and trace elements. Modern pharmacological studies have shown that paeoniflorin can reduce lactate dehydrogenase release, reduce intracellular Ca2+ overload, promote cell proliferation, and decrease caspase-3 protein expression. Total glucosides of white paeony have a bidirectional regulatory effect on the production of immune active substances and the proliferation of immune cells, which depends on the drug concentration and the immune status of the patient. In autoimmune reactions, it is mostly manifested as an inhibitory effect on immune active substances.

[0018] Honey Aster: The dried root and rhizome of Aster tataricus Lf., a plant of the Asteraceae family. It has a pungent, bitter, and warm nature. It enters the Lung meridian. It moistens the lungs, lowers Qi, and relieves phlegm and cough. It is used for coughs with excessive phlegm, new and chronic coughs, and hemoptysis caused by exertion. Its main chemical components include terpenes, peptides, coumarins, flavonoids, anthraquinones, and organic acids. It is primarily used to treat respiratory diseases such as cough, phlegm, and asthma. Modern pharmacological research has shown that Aster not only relieves cough and phlegm, promotes lung function, and relieves asthma, but also exhibits anti-tumor, antibacterial, antioxidant, and diuretic and laxative effects. In vitro antibacterial tests on ethanol and alkaloid extracts of Aster tataricus have demonstrated that the ethanol extract has strong antibacterial effects against Staphylococcus aureus, Pasteurella multocida, Escherichia coli, Streptococcus, and Salmonella. Quercetin and kaempferol are excellent antioxidants that can inhibit hemolysis of red blood cells, brain lipid peroxidation, and the generation of superoxide free radicals. In addition, emodin has anti-inflammatory and antibacterial effects as well as anti-tumor properties.

[0019] Honey coltsfoot flower: The dried flower buds of Tussilago farfara L., a plant of the Asteraceae family, are pungent, slightly bitter, and warm. They enter the Lung meridian. They moisten the lungs, promote qi circulation, and relieve cough and phlegm. They are used to treat new and chronic coughs, wheezing with phlegm, and hemoptysis caused by exertion. The chemical components of honey coltsfoot flower primarily include flavonoids, sesquiterpenes, triterpenes, phenolic acids, alkaloids, and volatile oils. The lung-moistening, cough-relieving, phlegm-resolving, and asthma-relieving effects of honey coltsfoot flower have been clinically recognized. Modern pharmacological research has shown that coltsfoot flower is effective in preventing and treating respiratory and digestive system diseases. A decoction of coltsfoot flower has a certain antispasmodic effect, consistent with its antitussive and antiasthmatic properties. Studies have shown that coltsfoot ketone and sedum alkaloids in coltsfoot flower significantly inhibit spasms in isolated guinea pig tracheal strips. Crude coltsfoot flower polysaccharides not only effectively inhibit the proliferation of cultured human leukemia K562 cells in vitro, but also inhibit the growth of lung cancer cells in a dose-dependent manner. Studies have shown that coltsfoot has anti-tumor effects, coltsfoot ketone can inhibit the proliferation of colon cancer cells, and also has a significant stimulating effect on the cardiovascular system.

[0020] Poria: It is the dried sclerotium of the Polyporaceae fungus Poria cocos (Schw.) Wolf. It is sweet, light and neutral. It enters the heart, lung, spleen and kidney meridians. It has the effects of promoting diuresis and dispelling dampness, strengthening the spleen and calming the mind. It is used to treat edema, oliguria, phlegm and fluid retention, dizziness and palpitations, spleen deficiency and poor appetite, loose stools and diarrhea, restlessness, palpitations and insomnia. Poria contains a variety of chemical components such as triterpenes, polysaccharides, sterols, and volatile oils, among which Poria polysaccharides and triterpenes are the main ones. Modern pharmacological research mainly includes: anti-tumor, immune regulation, effects on diabetes and related complications, regulation of lipid metabolism, kidney protection, cardioprotection, liver protection and other effects. Studies have found that pachymic acid has the effects of inhibiting the proliferation, migration, invasion and inducing apoptosis of human liver cancer cells (HepG2, SK-Hepl, SMMC-7721 cell lines), thereby inhibiting the occurrence and development of liver cancer. Poria polysaccharide can protect against acetaminophen-induced liver damage by activating the expression of CYP3A4 and NOS2 in hepatocytes. Poria polysaccharide can also protect mice from cyclophosphamide-induced intestinal mucosal damage by improving colon physiological status, reducing intestinal permeability, inhibiting epithelial cell apoptosis, and increasing intestinal mucosal immunity.

[0021] Peucedanum praeruptorum Dunn is the dried root of the Apiaceae plant. It is bitter, pungent, and slightly cold. It enters the Lung meridian. It has the effects of descending Qi, resolving phlegm, dispersing wind and clearing heat. It is used for wheezing due to phlegm-heat, coughing up thick yellow sputum, and coughing with excessive sputum due to wind-heat. Peucedanum praeruptorum Dunn primarily contains coumarins, volatile oils, chromones, polyacetylenes, lignins, and simple phenylpropane derivatives, with coumarins being the primary pharmacologically active ingredients. The coumarin compounds in Peucedanum praeruptorum Dunn exhibit potent cardiovascular pharmacological activity, with mechanisms manifested in the following: blocking calcium influx; inhibiting platelet aggregation; promoting potassium channel opening; and regulating myocardial action potentials. The effects of peucedanum praeruptorum Dunn on tracheal smooth muscle and myocardial cells have been extensively studied, demonstrating its ability to relax intestinal smooth muscle and act as a calcium antagonist. Peucedanum praeruptoside A is the main active ingredient in Peucedanum praeruptoside. It has strong cardiovascular pharmacological activity and protective effects on the cardiovascular system. It has anti-myocardial ischemia and heart failure effects, as well as vasodilation, hypotensive effects, inhibition of calcium influx, and reduced oxygen consumption. Furthermore, Peucedanum praeruptoside A can enhance phenol red secretion in the trachea of mice, indicating its expectorant properties.

[0022] Cicada sloughs are the skins shed by nymphs of the Cicadidae insect Cryptotympana pustulata Fabricius during eclosion. They are sweet and cold in nature. They enter the lung and liver meridians. They dispel wind-heat, relieve sore throats, clear rashes, brighten eyes, and relieve spasms. They are used to treat wind-heat colds, sore throats and hoarseness, persistent measles, itchy urticaria, red eyes with cataracts, convulsions, and tetanus. Cicada sloughs contain large amounts of chitin, protein, amino acids, organic acids, as well as phenols, flavonoids, steroids, sugars, oils, ethanolamine, and various trace elements. Both alcohol and water extracts of cicada sloughs have anticonvulsant effects. The amino acids in cicada sloughs have anticonvulsant pharmacological effects. Trace element analysis has revealed high levels of calcium and aluminum, which are associated with anticonvulsant effects. The alcohol extract of cicada slough can significantly reduce the spontaneous activity of normal mice, antagonize the excitatory effect of caffeine, and has a synergistic effect with pentobarbital, enhancing the hypnotic effect of pentobarbital. The alcohol extract of cicada slough also has strong antibacterial activity, and it is inferred that its anti-inflammatory effect is related to antibacterial activity. Cicada slough has a significant antiasthmatic effect in a histamine-induced asthma model, can stabilize mast cell degranulation, block the release of allergic mediators (such as histamine), inhibit allergic reactions and the degree of airway damage, thereby slowing airway inflammation and reducing airway hyperresponsiveness to prevent and treat bronchial asthma.

[0023] Fritillaria cirrhosa (D. Don), Fritillaria unibracteata (Hsiao et KCHsia), Fritillaria przewalskii Maxim., Fritillaria delavayi Franch., Fritillaria taipaiensis (P.Y. Li), or Fritillaria unibracteata (Hsiao et KCHsia) (var. wabuensis, SY Tang et S C Yue) (ZD Liu, S. Wang et S C Chen), all of the Liliaceae family. It has a bitter, sweet, and slightly cold flavor. It enters the Lung and Heart meridians. It clears heat and moistens the lungs, resolves phlegm and relieves cough, and dissipates stagnation and abscesses. It is used for lung-heat-induced dry cough, dry cough with scant sputum, yin deficiency-induced cough, blood-tinged sputum, scrofula, mastitis, and lung abscess. Fritillaria cirrhosa contains a wide variety of chemical components, including alkaloids, organic acids and their esters, nucleosides, sterols and their glycosides, polysaccharides, volatile oils, saponins, terpenes, and trace elements. Alkaloids found in Fritillaria cirrhosa, such as fritillin A, fritillin B, xibenin, xibenin N-oxide, cibenin alkaloids, isothuribitin A, and isothuribitin A N-oxide, can effectively prolong the cough latency period and reduce the frequency of coughing in mice. Peyrimidine from Fritillaria cirrhosa has a significant analgesic effect on nociceptive pain induced by acetic acid, formalin, or paclitaxel in mice.

[0024] Licorice: The dried roots and rhizomes of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., or Glycyrrhiza glabra L., all from the Leguminosae family. It has a sweet and neutral flavor and enters the Heart, Lung, Spleen, and Stomach meridians. It tonifies the spleen and replenishes Qi, clears away heat and toxins, relieves phlegm and cough, relieves pain, and harmonizes various medicinal herbs. It is used to treat spleen and stomach deficiency, fatigue, palpitations and shortness of breath, cough with sputum, cramps and pain in the abdomen and limbs, carbuncles, and sores, and to alleviate the toxicity and potency of drugs. Currently, licorice has been found to contain over 400 compounds, with high levels of triterpenoid saponins, flavonoids, and polysaccharides. Modern pharmacological studies have shown that the flavonoids in licorice have potent anti-inflammatory properties. Licorice extract significantly inhibits nigericin-induced activation of the NLRP3 inflammasome in primary mouse bone marrow macrophages. Jiang Miao et al. found that glycyrrhetinic acid has an anti-arrhythmic effect and can restore the decreased activity of myocardial Na+-K+-ATPase caused by aconitine. Wang Xiaoli et al. found that glycyrrhizin, glycyrrhizin polysaccharide, and glabridin can enhance the phagocytic ability of macrophages, promote the secretion of IL-1β, IL-6, IL-12, and TNF-α, and inhibit the secretion of IL-4, IL-10, and TGF-β.

[0025] In this prescription, the main medicines are mulberry leaves and auspicious grass. Mulberry leaves are sweet, bitter, and cold in nature. They enter the lung and liver meridians and can clear away heat from the lung meridian and relieve wind in the liver meridian. Auspicious grass is salty, pungent, and cold. It enters the liver and gallbladder meridians and can clear away heat and relieve cough. The two medicines together have the effects of dispersing wind-heat, moistening dryness and relieving cough; the assistant medicines are white peony root, red peony root bark, honey coltsfoot flower, honey aster, and Sichuan fritillary. White peony root and red peony root can soothe the liver and relieve heat, eliminate wind and relieve cough. Honey coltsfoot flower and honey aster moisten the lungs and resolve phlegm, promote lung function and relieve cough. Sichuan fritillary is bitter, sweet, and slightly cold. It enters the lung meridian and has the effects of nourishing yin and moistening the lungs, resolving phlegm and relieving cough; the adjuvant medicines are mulberry bark, rehmannia root bark, peucedanum chinense, cicada shell, and Poria. Mulberry bark, rehmannia root bark, peucedanum chinense, cicada shell are sweet and cold. They enter the lung and liver meridians and have the effects of dispersing wind-heat, dispelling wind, relieving spasm and relieving cough; licorice harmonizes the various medicines and serves as the guiding medicine. The whole prescription dispels wind and promotes lung function, relieves cough and resolves phlegm, eliminates wind and relieves cough, fully embodying the therapeutic principle of treating both the lungs and the liver.

[0026] The preparation method of the pharmaceutical composition of the present invention comprises the following steps:

[0027] S1, according to the formula, take the herbs of auspicious grass, mulberry leaves, white mulberry bark, Chinese wolfberry bark, peony bark, white peony root, cicada slough, peucedanum chinense, honey coltsfoot flower, honey aster, poria cocos, and licorice, add water and decoct three times, soak in water for 1 hour before the first decoction, decoct for 1 hour each time, filter, and concentrate the filtrate to a clear paste with a relative density of 1.18-1.22 at 60°C;

[0028] S2, taking Fritillaria cirrhosa according to the formula, crushing it into fine powder to obtain Fritillaria cirrhosa fine powder; then mixing the clear paste obtained in step S1 with the Fritillaria cirrhosa powder, adding an appropriate amount of sucrose, continuing to heat, concentrate, and mix to obtain.

[0029] The step S1 of the present invention is to add water and decoct three times: add water in an amount of 6-10 times the total amount of the medicinal materials for the first time, and add water in an amount of 4-8 times the total amount of the medicinal materials for the second and third times, and decoct for 0.5-1.5 hours each time.

[0030] Preferably, the step S1 of the present invention is performed by decocting the mixture three times: adding water in an amount of 8 times the total amount of the medicinal materials for the first time, and adding water in an amount of 6 times the total amount of the medicinal materials for the second and third times, and decocting the mixture for 1 hour each time.

[0031] The amount of sucrose added in the present invention is 40% of the mass of the clear paste.

[0032] The pharmaceutical composition of the present invention or the pharmaceutical composition prepared by the preparation method is used in preparing a pharmaceutical preparation for treating cough in children.

[0033] The pharmaceutical preparation of the present invention is a pharmaceutically acceptable preparation prepared by adding pharmaceutically acceptable excipients to a pharmaceutical composition, including a solid preparation or a liquid preparation.

[0034] The solid preparations of the present invention are granules, tablets, capsules and pills; the liquid preparations are decoctions and mixtures.

[0035] Beneficial effects of the present invention:

[0036] The pharmaceutical composition of the present invention significantly improved the clinical symptoms and signs of children with cough, with a total effective rate of 86.84%. Clinical symptom and sign scores were significantly higher after treatment than before treatment, with the difference being highly statistically significant (P < 0.001). The scores of each clinical symptom and sign between the treatment groups were significantly higher after treatment than before treatment, with the difference being highly statistically significant (P < 0.001). No adverse reactions were observed during the treatment. This is an effective and safe traditional Chinese medicine preparation for treating pediatric cough and is worthy of widespread clinical application. DETAILED DESCRIPTION

[0037] The present invention is described in detail below with reference to specific embodiments.

[0038] Example 1

[0039] Recipe: 133g of auspicious grass, 133g of mulberry leaves, 133g of mulberry bark, 133g of Rehmannia root bark, 133g of peony bark, 133g of white peony root, 80g of cicada shell, 133g of peucedanum, 133g of honey coltsfoot flower, 133g of honey aster, 40g of Fritillaria cirrhosa, 133g of Poria cocos, and 40g of licorice.

[0040] Example 2

[0041] Recipe: 140g of auspicious grass, 140g of mulberry leaves, 140g of mulberry bark, 140g of Rehmannia root bark, 140g of peony bark, 140g of white peony root, 90g of cicada shell, 140g of peucedanum, 140g of honey coltsfoot flower, 140g of honey aster, 45g of Fritillaria cirrhosa, 140g of Poria cocos, and 45g of licorice.

[0042] Example 3

[0043] Recipe: 125g of auspicious grass, 125g of mulberry leaves, 125g of mulberry bark, 125g of Rehmannia root bark, 125g of peony bark, 125g of white peony root, 70g of cicada shell, 125g of peucedanum, 125g of honey coltsfoot flower, 125g of honey aster, 35g of Fritillaria cirrhosa, 125g of Poria cocos, and 35g of licorice.

[0044] Example 4

[0045] Recipe: 130g of auspicious grass, 130g of mulberry leaves, 130g of mulberry bark, 130g of Rehmannia root bark, 130g of peony bark, 130g of white peony root, 85g of cicada shell, 130g of peucedanum, 130g of honey coltsfoot flower, 130g of honey aster, 38g of Fritillaria cirrhosa, 130g of Poria cocos, and 42g of licorice.

[0046] Example 5

[0047] Recipe: 135g of auspicious grass, 135g of mulberry leaves, 135g of mulberry bark, 135g of Rehmannia root bark, 135g of peony bark, 135g of white peony root, 75g of cicada shell, 135g of peucedanum, 135g of honey coltsfoot flower, 135g of honey aster, 42g of Fritillaria cirrhosa, 135g of Poria cocos, and 38g of licorice.

[0048] Example 6

[0049] Recipe: 133g of auspicious grass, 133g of mulberry leaves, 135g of mulberry bark, 135g of Rehmannia root bark, 130g of peony bark, 130g of white peony root, 80g of cicada shell, 130g of peucedanum, 135g of honey coltsfoot flower, 135g of honey aster, 40g of Fritillaria cirrhosa, 133g of Poria cocos, and 41g of licorice.

[0050] Example 7

[0051] Recipe: 133g of auspicious grass, 133g of mulberry leaves, 133g of mulberry bark, 133g of Rehmannia root bark, 130g of peony bark, 130g of white peony root, 80g of cicada shell, 130g of peucedanum, 130g of honey coltsfoot flower, 130g of honey aster, 38g of Fritillaria cirrhosa, 130g of Poria cocos, and 40g of licorice.

[0052] The formulations of Examples 1 to 7 are used in the following preparation methods.

[0053] Example 8

[0054] S1, according to the formula, take the medicinal materials of auspicious grass, mulberry leaves, white mulberry bark, Chinese wolfberry bark, peony bark, white peony root, cicada slough, peucedanum chinense, honey coltsfoot flower, honey aster, poria cocos, and licorice, add water and decoct three times, soak in water for 1 hour before the first decoction, add 8 times the total amount of medicinal materials in water for the first decoction, and add 6 times the total amount of medicinal materials in water for the second and third decoctions, decoct for 1 hour each time, filter, and concentrate the filtrate to a clear paste with a relative density of 1.18-1.22 at 60°C;

[0055] S2, taking Fritillaria cirrhosa according to the formula, crushing it into fine powder to obtain Fritillaria cirrhosa fine powder; then mixing the clear paste obtained in step S1 with the Fritillaria cirrhosa powder, and then adding 40% of sucrose in the amount of the clear paste, continuing to heat, concentrate, and mix to obtain.

[0056] Example 9

[0057] S1, according to the formula, take the medicinal materials of auspicious grass, mulberry leaves, white mulberry bark, Chinese wolfberry bark, peony bark, white peony root, cicada shell, peucedanum chinense, honey coltsfoot flower, honey aster, poria cocos, and licorice, add water and decoct three times, soak in water for 1 hour before the first decoction, add 10 times the total amount of medicinal materials in water for the first decoction, and add 8 times the total amount of medicinal materials in water for the second and third decoctions, decoct for 1.5 hours each time, filter, and concentrate the filtrate to a clear paste with a relative density of 1.18-1.22 at 60°C;

[0058] S2, taking Fritillaria cirrhosa according to the formula, crushing it into fine powder to obtain Fritillaria cirrhosa fine powder; then mixing the clear paste obtained in step S1 with the Fritillaria cirrhosa powder, and then adding 40% of sucrose in the amount of the clear paste, continuing to heat, concentrate, and mix to obtain.

[0059] Example 10

[0060] S1, according to the formula, take the medicinal materials of auspicious grass, mulberry leaves, white mulberry bark, Chinese wolfberry bark, peony bark, white peony root, cicada slough, peucedanum chinense, honey coltsfoot flower, honey aster, poria cocos, and licorice, add water and decoct three times, soak in water for 1 hour before the first decoction, add 6 times the total amount of water of the medicinal materials for the first decoction, and add 4 times the total amount of water of the medicinal materials for the second and third decoctions, decoct for 0.5 hour each time, filter, and concentrate the filtrate to a clear paste with a relative density of 1.18-1.22 at 60°C;

[0061] S2, taking Fritillaria cirrhosa according to the formula, crushing it into fine powder to obtain Fritillaria cirrhosa fine powder; then mixing the clear paste obtained in step S1 with the Fritillaria cirrhosa powder, and then adding 40% of sucrose in the amount of the clear paste, continuing to heat, concentrate, and mix to obtain.

[0062] In order to prove the feasibility and beneficial effects of the present invention, research tests were conducted, and some of the tests are excerpted as follows:

[0063] 1. Prescription composition and compatibility

[0064] This traditional Chinese medicine composition is a Xiaofeng Zhike paste, formulated by Professor Chen Zhu of Pediatrics. It consists of 13 Chinese herbs: jixiangcao (Chinese auspicious herb), mulberry leaves, white mulberry bark, lychee bark, peony bark, white peony root, cicada slough, peucedanum peucedanum, honey coltsfoot flower, honey aster, Fritillaria cirrhosa, Poria cocos, and liquorice. The formula contains no toxic herbs and is free of the 18 anti-incompatibility and 19 incompatibility contraindications.

[0065] The formula is extracted with water, added with Fritillaria cirrhosa powder, and made with sucrose as an auxiliary material. Except for the herb Jixiangcao, which complies with the 2003 edition of the "Quality Standards for Traditional Chinese Medicine and Ethnic Medicinal Materials in Guizhou Province", the other 12 Chinese herbal medicines in the formula all comply with the standards of Part I of the 2020 edition of the "Chinese Pharmacopoeia", and sucrose complies with the standards of Part IV of the 2020 edition of the "Chinese Pharmacopoeia". The composition and implementation standards of the preparation are shown in Table 1.

[0066] Table 1: Composition and implementation standards of Xiaofengzhike ointment prescription (1000g)

[0067]

[0068] 2. Preparation process

[0069] This prescription is a traditional Chinese medicine compound, used clinically in the form of a decoction. Based on traditional medication practices, the decoction is prepared using water extraction and concentration methods. The excipients used in the decoction are sugar or invert sugar, with honey, sucrose, and maltose being common. Considering that children are not suitable for honey and that suppliers of pharmaceutical-grade maltose are limited and expensive, this product uses sucrose as the final molding excipient. Based on research results, the basic process route is as follows: The thirteen medicinal slices above are ground into a fine powder for later use, and the remaining medicinal slices are boiled and extracted with water. The aqueous extract is concentrated to a relative density. Sucrose and sucrose powder are added to obtain a mixed paste. The mixture is then packaged and the final product is obtained.

[0070] 2.1 Determination of water absorption rate of medicinal slices

[0071] Weigh 1 / 2 of the clinical prescription amount of decoction pieces, add 10 times the amount of water to soak, soak for different time periods, filter, weigh the wet medicine weight (until the weight of the decoction pieces no longer increases), and determine the water absorption rate of the decoction pieces. The formula is as follows (see Table 2 for the results).

[0072]

[0073] mb—mass of the slices in the water-saturated state (g)

[0074] mg—mass of the slice in dry state (g)

[0075] Table 2 Investigation on water absorption rate of decoction pieces

[0076]

[0077] It can be seen from the table that the water absorption rate of the slices after soaking for 8 hours is about 1.9 times. Therefore, when adding water for decoction for the first time, the water absorption of the dry slices should be supplemented. To facilitate production calculations, add twice the amount of water for the slices when adding water for decoction for the first time.

[0078] 2.2 Determination of soaking time

[0079] Under the condition of meeting the water absorption rate of the medicinal slices, the influence of the soaking time on the paste yield of the prescription was examined. The total solid yield was used as the investigation index, and the soaking time with the greatest influence on the paste yield of the prescription was selected. The detailed results are shown in Tables 3 and 4.

[0080] 2.2.1 Sample preparation

[0081] Weigh the prescribed amount of slices and add 8 times the amount of water for the first time, and 6 times the amount for the second and third times. Considering that prolonged soaking of the decoction can easily breed bacteria and cause deterioration, and considering the feasibility of large-scale production, we designed samples with no soaking, soaking for 1 hour, 2 hours, and 4 hours. Decoction three times, 30 minutes each time, filter, and concentrate the filtrate to less than 100 mL. Cool and dilute to 100 mL with water. Set aside.

[0082] 2.2.2 Determination of paste yield

[0083] Referring to the extract determination method in 2201 of the General Chapter 4 of the 2020 edition of the Chinese Pharmacopoeia, accurately transfer 10 mL of the extract to an evaporating dish that has been dried to a constant weight, evaporate to dryness in a water bath, dry at 105°C for 3 hours, cool in a desiccator for 30 minutes, quickly and accurately weigh the weight, and calculate the paste rate by weighing. The formula is as follows.

[0084]

[0085] W is the weight of total solid matter in 10 mL of extract, and Wt is the total weight of the raw materials.

[0086] Table 3 Effect of soaking time on paste yield

[0087]

[0088] Table 4 Analysis of variance

[0089]

[0090] Conclusion: P=0.00095, P<0.05. The results show that soaking time has a significant effect on the paste yield, so we chose to soak for 1 hour before decocting.

[0091] 2.3. Extraction process conditions screening

[0092] 2.3.1 Determination of orthogonal factor levels

[0093] The main factors affecting water decoction are the number of decoctions, the amount of water added, and the decoction time. This experiment used these three factors as the investigation factors, each with three levels, to conduct a three-factor, three-level orthogonal experiment to screen the water extraction process conditions. The orthogonal factor levels are shown in Table 5.

[0094] Table 5 Levels of orthogonal factors of water extraction

[0095]

[0096] Note: For the first extraction, add twice as much water.

[0097] 2.3.2 Selection of evaluation indicators

[0098] We used a comprehensive scoring method to optimize the extraction process and calculated the comprehensive score of peucedanum praeruptorum content and paste yield, where the weight of content and paste yield was 0.5 each. The calculation formula is as follows:

[0099]

[0100] 2.3.3 Sample preparation

[0101] Weigh 9 pieces of decoction pieces according to the prescription ratio, and press L9(3 4 ) orthogonal test conditions for decoction extraction, filtration, combined extracts, and continued to concentrate to less than 100 mL, let cool, and add water to 100 mL.

[0102] 2.3.4 Determination of praeruptorin A content in aqueous extract

[0103] (1) Chromatographic conditions and system suitability test: Octadecylsilane bonded silica gel was used as the filler, methanol-water (75:25) was used as the mobile phase; the detection wavelength was 321 nm; the column temperature was 30°C. The theoretical plate number calculated based on the praeruptorin A peak was not less than 4000.

[0104] (2) Preparation of reference solution: Accurately weigh an appropriate amount of praeruptorin A reference solution, add methanol to dissolve it and prepare a solution containing 20 μg of praeruptorin A per 1 ml.

[0105] (3) Preparation of test solution: Concentrate the extract to 100 mL, take 10 mL and place it in a 25 mL volumetric flask. Add methanol to the mark, shake well, filter through a 0.45 μm microporous filter membrane, and use the filtrate as the test solution.

[0106] (4) Content Determination: Accurately pipette 10 μL of each test solution and reference solution into the chromatograph, record the peak area, and calculate the content. The results are shown in Tables 6 and 7.

[0107] 2.3.5 Determination of paste yield

[0108] Accurately transfer 10 mL of the extract to a constant-weight evaporating dish, evaporate to dryness in a water bath, dry at 105°C for 3 hours, cool in a desiccator for 30 minutes, quickly and accurately weigh, and calculate the paste yield using the following formula:

[0109]

[0110] W is the weight of total solid matter in 10 mL of extract, and Wt is the total weight of the raw materials.

[0111] Table 6L9(3 4 ) Orthogonal experimental design variance analysis results (n=2)

[0112]

[0113] Table 7 Variance analysis table of comprehensive score of water extraction orthogonal test

[0114]

[0115] Note: F 0.05 (2, 2) = 19.00, F 0.01 (2, 2) = 99.0

[0116] Result analysis: From the intuitive analysis results, we know that the influence of the three factors on the results is C>A>B, and we get the optimal conditions as A3B1C3; we take the blank column where the D factor is located as the error source, and perform variance analysis on the orthogonal design results. From the variance analysis results, we can see that there is no significant difference among the three factors. Considering that adding too much water will lead to a longer time for the final concentrated paste, extending the production cycle, combined with the comprehensive score and the actual situation of large-scale production, we chose the best combination as A3B1C3. We chose to decoct 3 times, each time for 60 minutes, and add water 6 times as the best extraction process. According to the results of previous studies, the medicinal pieces will absorb 2 times their own weight of water, so the extraction process we finally determined is to add 8 times water for the first decoction, 6 times water for the second and third times, and decoct for 60 minutes each time. The extract is filtered through a 100-mesh filter.

[0117] 2.3.6 Extraction process validation

[0118] According to the results of the orthogonal design experiment, three batches of samples were extracted, and the extract was concentrated to 100 mL. The extract yield and the content of praeruptorin A in the samples were determined. The verification test results are shown in Table 8.

[0119] Table 8 Extraction process validation test

[0120]

[0121] From the results in the above table, we can see that the verification test results are consistent with the orthogonal design optimization results, which shows that the water extraction process conditions are basically stable and can be used as water extraction process conditions.

[0122] 2.4. Preparation molding process research

[0123] 2.4.1 Investigation of the concentration level of the clear paste

[0124] Investigation of the Concentration of the Clear Paste: A batch of liquid medicine was extracted according to the preliminarily determined extraction process. Five 200 ml portions of the extract were collected and concentrated to varying degrees. The collection status of each portion was observed. After cooling, the volume of the concentrated liquid was measured and the relative density and the content of praeruptorin A were determined to determine the concentration of the clear paste. The results of the investigation of the concentration of the clear paste are shown in Table 9.

[0125] Table 9 Investigation results of the concentration degree of the clear paste

[0126]

[0127]

[0128] Summary: After a certain degree of concentration, the content of peucedanum praeruptorum in the sample did not decrease significantly; as the degree of concentration increased, the relative density of the solution increased, which not only made production difficult, but also when the relative density was too high, the clear paste was difficult to transfer. At the same time, a certain amount of space needed to be reserved for the subsequent addition of auxiliary materials. Therefore, the appropriate degree of concentration must be controlled. Therefore, we initially concentrated the extract to a clear paste with a relative density of 1.18 to 1.22 (60°C).

[0129] 2.4.2 Determination of the paste collection process

[0130] 2.4.3 Determination of excipient types

[0131] Decoctions require the addition of a certain amount of sugar or invert sugar to the clear paste, which not only increases the viscosity of the paste but also has an antibacterial effect. Commonly used sugars include honey, sucrose, maltose, and crystal sugar. However, with the implementation of the national policy on filing management of excipients, honey, sucrose, and maltose have all been filed. However, the price of maltose is too high. If used, it will greatly increase the finished product and thus increase the patient's medical expenses. Honey is not recommended for children, so we choose sucrose.

[0132] 2.4.4 Screening of sucrose dosage

[0133] The extract obtained from two clinically prescribed amounts of the decoction pieces was concentrated to approximately 120 g of a clear paste. The paste was weighed and the weight recorded. Sucrose in varying prescribed amounts was added, and heating and stirring were continued to dissolve the sucrose. Fritillaria cirrhosa powder (dispersed with a small amount of purified water) was then added and mixed thoroughly. Properties, taste, and ease of use were measured and observed. The results are shown in Table 10.

[0134] Table 10 Effect of sucrose dosage on the quality of mixed paste

[0135]

[0136] The above results show that increasing the amount of sucrose increases sweetness. However, excessive sucrose can affect the appearance of the preparation and easily generate foam during the process. Furthermore, considering that excessive sucrose may cause the paste to become sandy, we added 50g of sucrose to every two clinical prescriptions.

[0137] 2.5. Determination of pilot test prescription and process

[0138] 2.5.1 Composition of the formulation for pilot test batch confirmation

[0139] Based on the results of the pilot study, the pilot confirmation batch formula was determined. The medicinal ingredients and excipients are shown in Table 11.

[0140] Table 11: Small test batch prescription flavors and excipients (150g paste)

[0141]

[0142] 2.5.2 Pilot test preparation process

[0143] Based on the above pilot study results, the pilot test process was determined as follows: Crush the Fritillaria cirrhosae into a fine powder for the thirteen ingredients above. Decoction the remaining twelve ingredients three times with water, soaking for one hour the first time and then decocting for one hour each time. Filter and concentrate the filtrate to a clear paste with a relative density of 1.18-1.22 (at 60°C). Add 333g of sucrose and Fritillaria cirrhosae powder to every 830g of the paste, continue heating, concentrating, and mixing until 1000g is obtained.

[0144] 2.5.3 Small-scale confirmation test

[0145] Three batches of small-scale process verification were carried out based on the prescription and process confirmed by the small-scale test. The appearance, fluidity, taste, amount of clear paste and amount of mixed paste of the samples of the small-scale test verification batch were measured. The results are shown in Tables 12 to 13.

[0146] Table 12 Small-scale test batch yield

[0147]

[0148] Table 13 Inspection results of appearance characteristics of small-scale test batch samples

[0149]

[0150] Summary: The appearance and properties of the three batches of small-scale tests were consistent. Combined with the results of the small-scale tests and the verification batches, it was preliminarily determined that the product is a brown, thick, semi-fluid substance with a bitter and slightly sweet taste.

[0151] 2.6 Preliminary scale-up studies

[0152] In order to investigate the situation after the scale-up of the prescription process determined in the early small-scale test, the preparation prescription quantity was produced, the production situation after scale-up was preliminarily investigated, and the properties, identification, content, etc. of the paste were preliminarily evaluated. The results are shown in Table 14.

[0153] Table 14 Preliminary amplification results statistics

[0154]

[0155] Conclusion: The preliminary scale-up results showed that the mixed paste received had no significant difference from the small-scale test; there was no significant difference between batches of praeruptorin A, and the other quality test results had no significant difference from the small-scale test confirmation batch.

[0156] 2.7 Large Production

[0157] Based on the production capacity of our institute's production equipment and the expected usage within the institute, we set the large-scale production scale at 5,000 bags / batch, and produced three batches continuously to examine the feasibility of large-scale production.

[0158] 2.7.1 Sample production company information

[0159] This product is prepared by our hospital. The sample preparation unit information is shown in Table 15.

[0160] Table 15 Sample preparation unit information

[0161]

[0162] 2.7.2 Batch Prescription

[0163] Table 16: Batch prescription composition and implementation standards (5000 bags, specification 10g / bag)

[0164]

[0165] 2.7.3 Preparation process

[0166] The preparation process is as follows: sterilize Fritillaria cirrhosa → crush into fine powder → soak the remaining slices in 8 times water for 1 hour, decoct three times → concentrate the filtrate into a clear paste → add sucrose and Fritillaria cirrhosa powder → continue heating and concentrating → package.

[0167] 2.7.4 Main production equipment

[0168] The main production equipment involved in the production of this product includes multifunctional extraction tanks, concentration tanks, jacketed kettles, universal grinders, paste filling machines, etc. The main production equipment information is shown in Table 16.

[0169] Table 16 Main production equipment information

[0170]

[0171] 2.7.5 Summary of large production samples

[0172] According to the above large-scale production batch prescription and process parameters, three batches of 5,000 bags were produced continuously, and full inspection was carried out in accordance with the draft quality standards. The production status summary is shown in Table 17, and the quality status summary is shown in Table 18.

[0173] Table 17 Summary of production situation

[0174]

[0175] Table 18 Quality Inspection Summary

[0176]

[0177]

[0178] 2.8 Final process determination

[0179] According to the prescription, 133g of auspicious grass, 133g of mulberry leaves, 133g of mulberry bark, 133g of rehmannia root, 133g of peony bark, 133g of white peony root, 80g of cicada shell, 133g of peucedanum, 133g of honey coltsfoot flower, 133g of honey aster, 133g of poria, and 40g of liquorice were weighed and decocted three times with water. The medicines were soaked in water for 1 hour before the first decoction. 8 times the amount of water of the total amount of the medicinal materials was added for the first time, and 6 times the amount of water of the total amount of the medicinal materials was added for the second and third times. The medicines were decocted for 1 hour each time, filtered, and the filtrate was concentrated to a clear paste with a relative density of 1.18-1.22 at 60°C for later use; 40g of cirrhosa was weighed according to the prescription and crushed into fine powder; then 333g of sucrose (40% of the amount of the clear paste) and cirrhosa powder were added to every 830g of the clear paste, mixed, and continued to heat, concentrate, and mix to make a thick paste.

[0180] 3. Clinical Efficacy Verification

[0181] In order to verify the clinical efficacy, the present invention team conducted a clinical efficacy verification experiment on the finished product (Xiaofeng Zhike Cream) prepared according to the preparation method of Example 8 based on the formula of Example 1.

[0182] 3.1 Case Source:

[0183] The cases were all from outpatients and inpatients diagnosed with pediatric cough (cough) in the Department of Pediatrics of the Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, and they were also voluntary clinical researchers who joined this project.

[0184] 3.2 Collection Time

[0185] During the period 2019-2024.

[0186] 3.3 Diagnostic criteria

[0187] Refer to the Guiding Principles for Clinical Research of New Chinese Medicines [1] .

[0188] 3.3.1 Western medicine diagnostic criteria

[0189] 1) Medical history

[0190] It is more common in winter and spring, often caused by climate changes, and often has a history of colds before the onset of the disease.

[0191] 2) Symptoms

[0192] The main symptom is cough, which may be accompanied by sputum.

[0193] 3) Physical signs

[0194] Lung auscultation revealed rough breath sounds in both lungs, with dry rales or irregular coarse moist rales.

[0195] 4) Inspection

[0196] a. Routine blood count: The total white blood cell count is normal or low in patients with viral infection; the total white blood cell count and neutrophil count are increased in patients with bacterial infection.

[0197] bX-ray examination: Chest X-ray shows thickened and blurred lung markings and deepened hilar shadows.

[0198] c. Pathogenic examination: Abnormal sputum bacterial culture.

[0199] 3.3.2 Traditional Chinese Medicine Diagnostic Criteria

[0200] Wind-heat attacking the lungs

[0201] Main symptoms: yellow and sticky sputum, persistent cough, thirst and sore throat, difficult to cough up, and turbid nasal discharge;

[0202] Secondary symptoms: headache, aversion to wind, fever, and sweating;

[0203] Tongue appearance: Tongue pulse: Thin yellow tongue coating.

[0204] Pulse condition: floating and rapid pulse or floating purple fingerprints.

[0205] The diagnosis can be confirmed if the child has two main symptoms and one secondary symptom, or only one main symptom and two secondary symptoms; symptoms and main symptom scores are shown in Table 1.

[0206] Table 1 Symptoms and main symptom scores

[0207]

[0208]

[0209] 3.4 Inclusion criteria

[0210] (1) Meet the diagnostic standards of Western medicine.

[0211] (2) Meet the diagnostic criteria of TCM syndromes.

[0212] 3.5 Exclusion criteria

[0213] (1) Combined with abnormal liver and kidney function;

[0214] (2) allergic to the drugs used in this study;

[0215] (3) recent other related treatments; (4) the presence of bronchial asthma;

[0216] (5) Presence of congenital heart disease.

[0217] 4 Observation indicators

[0218] 4.1 Safety Observation

[0219] (1) General physical examination items

[0220] If adverse reactions occur, the clinical manifestations, time of occurrence, severity, symptomatic treatment methods and results should be recorded to objectively evaluate their safety.

[0221] 4.2 Efficacy Observation (Evaluation once before treatment and within 24 hours after treatment)

[0222] (1) Observe the relevant symptoms, tongue and pulse required by this test, and pay attention to the onset time and recovery time.

[0223] (2) Related symptoms: cough, fever, sputum, red throat, mental state, sleep, etc.

[0224] (3) Related physical signs: redness and swelling of tongue, pulse, and throat, etc.

[0225] 5. Efficacy evaluation

[0226] 5.1 Criteria for evaluating therapeutic efficacy

[0227] (1) Evaluation basis (refer to the Guiding Principles for Clinical Research of New Chinese Medicines (Edited by Zheng Xiaoyu, China Medical Science and Technology Press, 2002):

[0228] (2) Calculation method (Nimodipine method): (score before treatment - score after treatment) / score before treatment × 100%

[0229] (3) Evaluation criteria: ① Clinical control: disappearance of clinical symptoms and signs, with a score reduction of ≥95%. ② Markedly effective: significant improvement in clinical symptoms and signs, with a score reduction of ≥70% and <95%. ③ Effective: a score reduction of ≥30% and <70% in clinical symptoms and signs. ④ Ineffective: no significant improvement in clinical symptoms and signs, or a score reduction of less than 30%.

[0230] 6 Statistical processing

[0231] SPSS 26.0 software was used for statistical analysis of the data. Kolmogorov-Smirnov test was used to check the normal distribution of continuous variables, and the normal distribution of measurement data was tested using The paired sample t-test was used to compare the differences between the two groups before and after treatment, and P < 0.05 was considered to be statistically significant.

[0232] 7 Test results

[0233] 7.1 General Data Comparison

[0234] A total of 109 children were treated with Xiaofeng Zhike Ointment in this study, with an average observation time of 5 days. There were 62 males and 47 females. See Table 2.

[0235] Table 2 General data comparison

[0236]

[0237] The results are shown in Table 2. The treatment duration was 5 days. The scores after treatment were significantly relieved compared with those before treatment, and the difference was statistically significant (P < 0.01).

[0238] 7.2 Comprehensive efficacy

[0239] The total effective rate after treatment was 86.84%. See Table 3.

[0240] Table 3 Comparison of TCM symptoms efficacy after treatment (x 2 , n = 38)

[0241]

[0242] Using the nimodipine method: therapeutic index = {(total score before treatment - total score after treatment) / total score before treatment} × 100%

[0243] The therapeutic efficacy of Xiaofeng Zhike Paste: Oral Xiaofeng Zhike Paste has a cure rate of 34.21%, a marked efficacy rate of 39.47%, an effective rate of 13.16%, and an overall effective rate of 86.84%.

[0244] 7.3 Comparison of clinical symptom and sign scores between groups

[0245] Compared with before treatment, the clinical symptom and sign scores after treatment were significantly lower than those before treatment, indicating that the treatment was effective, and the difference was extremely statistically significant (P < 0.01). See Table 4.

[0246] Table 4 Comparison of clinical symptom and sign scores before and after treatment among patients in the two groups

[0247]

[0248] Note: Intra-group comparison: compared with before treatment, # P<0.01.

[0249] 7.4 Comparison of symptom scores between groups

[0250] Compared with before treatment, the scores of clinical symptoms and signs in the two groups after treatment were significantly lower than those before treatment, with extremely significant statistical differences (P < 0.01). See Table 5.

[0251] Table 5 Comparison of symptoms and signs before and after treatment between the two groups

[0252]

[0253] Note: Comparison of symptoms and signs within the same group: compared with before treatment, # P<0.01.

[0254] 8 Adverse reactions

[0255] No adverse reactions occurred during the treatment of the patients.

[0256] 9 Comprehensive efficacy analysis

[0257] The results of this study showed that Xiaofeng Zhike Paste can improve the symptoms and signs of children with cough, with an overall effective rate of 86.84%. This indicates that Xiaofeng Zhike Paste can significantly improve the clinical symptoms and signs of children with cough, and is an effective and safe traditional Chinese medicine preparation for treating pediatric cough, worthy of clinical promotion and application.

[0258] IV. Typical Cases

[0259] Typical Case 1

[0260] Wang XX, male, 4 years and 4 months old. Hospital number: 2436076. Admitted to the hospital on September 4, 2024, with a cough for 3+ days, worsening with fever for 5+ hours.

[0261] Symptoms on admission: Cough, paroxysmal, 3-4 coughs / time, especially at night, easy to wake up with coughing, sputum difficult to cough up, hoarseness, nasal congestion, runny nose, no fever, chills, no wheezing, shortness of breath, cyanosis, or dyspnea, no barking cough or crowing sound, no vomiting, no diarrhea, etc., mental state and sleep are normal since the onset of illness, bowel movements are 2-3 times / day, urination is normal, tongue is red, thin yellow fur, slippery pulse. Physical examination: clear mind, normal spirit, slightly congested pharynx, tonsil enlargement of degree I, no herpes or pus spots, coarse breath sounds in both lungs, a few fine moist rales are audible, no dry rales, heart and abdomen (-).

[0262] Diagnosis: Children's cough, wind-heat invading the lungs.

[0263] Diagnostic basis: formulated with reference to the "Traditional Chinese Medicine Industry Standards of the People's Republic of China·Traditional Chinese Medicine Disease Diagnosis and Efficacy Standards·Traditional Chinese Medicine Pediatric Disease Diagnosis and Efficacy Standards·Cough" (ZY / T001.1~001.9-94) issued by the State Administration of Traditional Chinese Medicine in 1994.

[0264] 1.1 It is more common in winter and spring and is often caused by climate changes.

[0265] 1.2 Most patients have a history of colds before becoming ill.

[0266] 1.3 Cough is the main clinical symptom.

[0267] 1.4 Lung auscultation: The breath sounds in both lungs are rough, or dry rales are heard.

[0268] 1.5 Blood examination: The total white blood cell count of patients with viral infection is normal or low; the total white blood cell count and neutrophil count of patients with bacterial infection are increased.

[0269] 1.6 X-ray examination: Not performed.

[0270] Supplementary blood tests: Complete blood count: white blood cell count 6.00 x 109 / L, neutrophil percentage 52.1%, lymphocyte percentage 36%, monocyte percentage 11.7%, neutrophil count 15.8 x 109 / L, hemoglobin 104 g / L, platelet count 326 x 109 / L, C-reactive protein: 1.37 mg / L. Based on the medical history, symptoms, signs, and supplementary tests, the diagnosis is considered established.

[0271] Treatment: 1 dose of Xiaofeng Zhike ointment, taken orally 3 times a day, for a total of 6 doses (2024-09-4 to 2024-9-9)

[0272] Efficacy: On the second day after admission, the patient was free of fever and had a slightly relieved cough, which was paroxysmal, about 3-4 times per time, especially at night. The patient had sputum that was difficult to cough up, accompanied by nasal congestion, runny nose, and hoarseness. The patient had no fever. Physical examination showed that the patient was clear-headed and in good spirits. The pharynx was slightly congested, the tonsils were I° enlarged, no herpes or pus spots were found, the breath sounds of both lungs were coarse, a small amount of fine moist rales were audible, and no dry rales were heard. The heart and abdomen were (-).

[0273] On the third day after admission, the patient's cough was significantly improved, and was paroxysmal, about 1-3 times / time, especially at night. He was easily awakened by coughing, and had sputum that was difficult to cough up, accompanied by runny nose and hoarseness. He had no aversion to cold or fever. Physical examination showed that he was clear-headed and in good spirits.

[0274] The pharynx was slightly congested, the tonsils were I° enlarged, no herpes or pus spots were seen, the breath sounds in both lungs were coarse, a small amount of coarse moist rales were audible, no dry rales were heard, and the heart and abdomen were (-).

[0275] On the 5th day after admission, the patient was examined and had occasional monotonic cough, but no nasal congestion, runny nose, or vomiting. Physical examination showed that the patient was alert and in good spirits, with no pharyngeal congestion, I° enlargement of the tonsils, no herpes or pus spots, coarse breath sounds in both lungs, no dry or wet rales, and heart and abdomen (-).

[0276] Efficacy assessment: Effective.

[0277] Typical Case 2

[0278] Liu XX, male, 6 years old. Hospital number: 2438285. Admitted to the hospital at 10:30 AM on September 15, 2024, due to a 20-day cough that worsened for 2 weeks.

[0279] Symptoms on admission: Cough, paroxysmal, 2-3 coughs / second, producing small amounts of sticky white sputum, particularly at night, accompanied by nasal congestion, runny nose, and sneezing. No wheezing, shortness of breath, fever, chills, cyanosis, or dyspnea. No barking cough or crowing sound at the end of a cough. No diarrhea. Poor mental state and sleep since onset. Appetite is acceptable. Constipation is dry and hard, occurring once a week. Urinary function is normal. No significant weight gain or loss in recent history. Physical examination: Temperature: 36.7°C, alert, poor mental state, no perioral cyanosis, pharyngeal congestion, I° tonsil enlargement, no exudate or herpes, negative triple sign. Coarse breath sounds bilaterally, with a few medium to fine moist rales and no dry rales. No abnormal abdominal or chest findings.

[0280] Diagnosis: Children's cough due to wind-heat attacking the lungs

[0281] Diagnosis is based on:

[0282] It was formulated with reference to the "Traditional Chinese Medicine Industry Standards of the People's Republic of China·Traditional Chinese Medicine Disease Diagnosis and Efficacy Standards·Traditional Chinese Medicine Pediatric Disease Diagnosis and Efficacy Standards·Cough" (ZY / T001.1~001.9-94) issued by the State Administration of Traditional Chinese Medicine in 1994.

[0283] 1.1 It is more common in winter and spring and is often caused by climate changes.

[0284] 1.2 Most patients have a history of colds before becoming ill.

[0285] 1.3 Cough is the main clinical symptom.

[0286] 1.4 Lung auscultation: The breath sounds in both lungs are rough, or dry rales are heard.

[0287] 1.5 Blood examination: The total white blood cell count of patients with viral infection is normal or low; the total white blood cell count and neutrophil count of patients with bacterial infection are increased.

[0288] 1.6 Chest CT examination (2024-9-14 Guiyang Maternal and Child Health Hospital): manifestations of bronchitis.

[0289] Auxiliary examination: blood routine: white blood cell count 9.31*109 / L, neutrophil percentage 56%, lymphocyte percentage 34%, neutrophil count 45*109 / L, hemoglobin 122g / L, platelet 281*109 / L, Mycoplasma pneumoniae (2024-9-4 Guiyang Wudang District Medical Community Hospital) IGM antibody (+). Combined with the medical history, symptoms, signs and auxiliary examinations, the diagnosis is considered to be established. Treatment: Xiaofeng Zhike ointment, 1 dose / day, orally, divided into 3 times / day, for a total of 5 doses (2024-09-15 to 2024-09-19)

[0290] Efficacy: On the second day of hospitalization, the patient occasionally coughed, with paroxysmal coughs of 2-3 times / time, especially at night. He could cough up white sputum, accompanied by nasal congestion and runny nose. He did not have shortness of breath or dyspnea, fever, chills, or convulsions. His spirits and sleep improved, and his urine output increased slightly. Physical examination showed clear consciousness, but poor spirits. He had a red tongue with a greasy yellow coating and a red pharynx. His tonsils were enlarged to the degree I, but no exudate or herpes was observed. The three-way sign was negative. His breath sounds were coarse in both lungs, with a few medium-fine moist rales and no dry rales. There were no abnormalities in the heart or abdomen.

[0291] On the fifth day after admission, the patient was examined for occasional monotonic coughs, but had no fever, barking coughs, or crowing sounds, and no vomiting or diarrhea. Physical examination revealed clear consciousness, good reflexes, a ruddy complexion, a pale red tongue with a thin white coating, a clear pharyngeal area, no tonsil enlargement, no herpes or pus-filled spots, and coarse breath sounds in both lungs, with no dry or wet rales. The patient was discharged.

[0292] Efficacy assessment: Effective.

[0293] Although the present invention has been described in detail above using general explanations, specific embodiments, and experiments, it will be apparent to those skilled in the art that modifications and improvements may be made based on the present invention. Therefore, such modifications and improvements, which do not depart from the spirit of the present invention, are intended to be within the scope of protection claimed herein.

[0294] References:

[0295] [1] Xiong Zhiqun, Luo Guiping. Observation on the efficacy of modified Sangjuyin combined with traditional Chinese medicine Fuxiongsan in the treatment of cough in children with wind-heat invading the lungs[J]. Hubei Journal of Traditional Chinese Medicine, 2020, 42(6): 35-36.

[0296] [2] Li Nan, Geng Shaoyi, Wang Xiaofang, et al. A randomized, open, parallel controlled, multicenter clinical observation on the efficacy and safety of Lianhua Qingke Tablets in the treatment of acute bronchitis with phlegm-heat obstructing the lungs in children[J]. Chinese Journal of Experimental Traditional Chinese Medicine, 2024, 30(10):90-94.

[0297] [3] Liu Kun, Ji Xiaohua, Cai Jianxin, et al. A multicenter, double-blind, randomized controlled study of Xiaoer Qingfei granules in the treatment of acute bronchitis with phlegm-heat obstructing the lungs in children[J]. Journal of Traditional Chinese Medicine, 2020, 61(17): 1530-1535+1546.

[0298] [4] Sun Xiangjuan, Chang Ke, Han Xinmin, et al. A multicenter randomized controlled clinical study on the treatment of acute bronchitis in children with Zibei Xuanfei syrup [J / OL]. World Traditional Chinese Medicine, 1-6 [2024-10-22].

[0299] [5] Li Meifang, Hu Siyuan, Niu Liqing, et al. Comprehensive clinical evaluation of Xiaoer Feire Kechuan oral liquid in the treatment of acute bronchitis (wind-heat attacking the lung syndrome) in children[J]. Drug Evaluation Research, 2024, 47(06): 1326-1336.

Claims

1. A pharmaceutical composition for treating cough in children, characterized in that: The invention is composed of the following raw materials in parts by weight: 125-140 parts of auspicious grass, 125-140 parts of mulberry leaves, 125-140 parts of mulberry bark, 125-140 parts of rehmannia root bark, 125-140 parts of moutan bark, 125-140 parts of white peony root, 70-90 parts of cicada shell, 125-140 parts of peucedanum chinense, 125-140 parts of honey coltsfoot flower, 125-140 parts of honey aster, 35-45 parts of cirrhosa, 125-140 parts of poria and 35-45 parts of liquorice.

2. The pharmaceutical composition according to claim 1, characterized in that The invention is composed of the following raw materials in parts by weight: 130-135 parts of auspicious grass, 130-135 parts of mulberry leaves, 130-135 parts of mulberry bark, 130-135 parts of rehmannia root bark, 130-135 parts of moutan bark, 130-135 parts of white peony root, 75-85 parts of cicada shell, 130-135 parts of peucedanum chinense, 130-135 parts of honey coltsfoot flower, 130-135 parts of honey aster, 38-42 parts of fritillaria cirrhosa, 130-135 parts of poria cocos and 38-42 parts of liquorice.

3. The pharmaceutical composition according to claim 2, characterized in that The invention is composed of the following raw materials in parts by weight: 133 parts of auspicious grass, 133 parts of mulberry leaves, 133 parts of mulberry bark, 133 parts of rehmannia root bark, 133 parts of peony bark, 133 parts of white peony root, 80 parts of cicada shell, 133 parts of peucedanum, 133 parts of honey coltsfoot flower, 133 parts of honey aster, 40 parts of fritillaria cirrhosa, 133 parts of poria cocos, and 40 parts of liquorice.

4. A method for preparing the pharmaceutical composition according to any one of claims 1 to 3, characterized in that: The steps include: S1, according to the formula, take the herbs of auspicious grass, mulberry leaves, white mulberry bark, Chinese wolfberry bark, peony bark, white peony root, cicada slough, peucedanum chinense, honey coltsfoot flower, honey aster, poria cocos, and licorice, add water and decoct three times, soak in water for 1 hour before the first decoction, decoct for 1 hour each time, filter, and concentrate the filtrate to a clear paste with a relative density of 1.18-1.22 at 60°C; S2, taking Fritillaria cirrhosa according to the formula, crushing it into fine powder to obtain Fritillaria cirrhosa fine powder; then mixing the clear paste obtained above with the Fritillaria cirrhosa fine powder, adding an appropriate amount of sucrose, continuing to heat, concentrate, and mix well to obtain.

5. The preparation method according to claim 4, characterized in that The step S1 is decocted three times with water added in an amount of 6-10 times the total amount of the medicinal materials for the first time, and water added in an amount of 4-8 times the total amount of the medicinal materials for the second and third times, and each decocting step is performed for 0.5-1.5 hours.

6. The preparation method according to claim 5, characterized in that The step S1 is to add water and decoct for three times: the first time, 8 times the amount of water of the total amount of the medicinal materials is added; the second and third times, 6 times the amount of water of the total amount of the medicinal materials are added; each time, decoction is for 1 hour.

7. The preparation method according to claim 4, characterized in that The added amount of sucrose is 40% of the amount of the clear paste.

8. Use of the pharmaceutical composition according to any one of claims 1 to 3 or the pharmaceutical composition prepared by the preparation method according to any one of claims 4 to 7 in preparing a pharmaceutical preparation for treating pediatric cough.

9. The use according to claim 8, characterized in that The pharmaceutical preparation is a pharmaceutical composition prepared by adding pharmaceutically acceptable excipients to a pharmaceutical composition to form a pharmaceutically acceptable preparation, including a solid preparation or a liquid preparation.

10. The use according to claim 9, characterized in that The solid preparations are granules, tablets, capsules, and pills; the liquid preparations are decoctions and mixtures.

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