A traditional Chinese medicine composition for treating laryngopharyngitis and application thereof

Abstract

The application provides a traditional Chinese medicine composition for treating pharyngolaryngitis, and components and proportions of the traditional Chinese medicine composition are as follows: half branch 12-18 parts, snow 12-18 parts, one branch 8-12 parts, schizonepeta 8-12 parts, small leaf green 8-12 parts, white 3-6 parts, and wind 3-6 parts. A preparation method is as follows: the above formula medicines are decocted with water for 2-3 times, 8-12 times of water is added each time, decoction is carried out for 1-3 hours, the decoction is combined, filtration is carried out, and the filtrate is concentrated to the relative density of 1.05-1.15 of the extract. The traditional Chinese medicine composition has a unique formula, a synergistic effect is generated between the formula, can be used for treating pharyngolaryngitis, has obvious curative effect, and has fast effect and no toxic side effect. The traditional Chinese medicine composition has particularly remarkable effect in treating pharyngolaryngitis caused by pharyngeal pain, and pharyngeal pain basically disappears after 3-4 hours of medicine taking.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine compositions, specifically to a traditional Chinese medicine composition for treating pharyngitis and its application. Background Technology

[0002] Pharyngitis, a nonspecific inflammation of the pharynx, is a general term for inflammation caused by various microbial infections of the throat. It is a common inflammatory disease in clinical practice, mainly divided into acute and chronic pharyngitis. Acute pharyngitis manifests as sore throat, hoarseness, and cough. Chronic pharyngitis mainly presents as a foreign body sensation in the throat, itching, and dryness. Modern medical clinical research shows that pharyngitis is mostly caused by viral or bacterial infections, but may also be caused by environmental pollution, chemical plant irritation, dietary factors, and prolonged speaking. Clinical symptoms often include throat pain, mucosal congestion and edema, dryness, and a foreign body sensation, severely affecting patients' normal activities such as eating and speaking.

[0003] Currently, Western medicine mainly uses oral medications in clinical practice, combined with sprays, local nebulization and other methods, which can relieve patients' throat discomfort in a short time. However, relapse is common after treatment, leading to a waste of medical resources and increasing the psychological and economic pressure on patients.

[0004] Traditional Chinese medicine views pharyngitis as "throat obstruction," with the disease location in the throat. It involves a mixture of deficiency and excess, and its etiology and pathogenesis are complex and varied. Internally, it is caused by deficiency of the lungs, spleen, and kidneys, while externally, it is often caused by wind, heat, dampness, phlegm, blood stasis, and stagnation. The treatment should focus on tonifying the spleen and stomach, nourishing the lungs and kidneys, soothing the liver and relieving stagnation, and clearing the heart and reducing fire.

[0005] A search revealed numerous formulas disclosed in existing patents. For example, CN109602826A discloses a traditional Chinese medicine for treating pharyngitis and its preparation process. The main ingredients of the traditional Chinese medicine formula are 13 grams of olive, 10-15 grams of dried tangerine peel, 40-60 ml of vinegar, 100 grams of water, 5-8 grams of licorice, 11-15 grams of magnolia bark, 10-15 grams of perilla stem, 5-10 grams of trichosanthes root, 8-14 grams of scrophularia root, 12-15 grams of senna root, 8-10 grams of arisaema, 8-10 grams of peony root, 5-10 grams of platycodon root, and 5-10 grams of silkworm.

[0006] CN109125589A discloses a traditional Chinese medicine composition for treating pharyngitis, comprising Isatis root, tangerine peel, Sophora root, Ophiopogon root, Platycodon root, licorice, Houttuynia cordata, honeysuckle, peony bark, Fritillaria cirrhosa, dandelion, and chrysanthemum.

[0007] Each of the above-mentioned traditional Chinese medicine compositions has its own advantages and disadvantages. Developing a new traditional Chinese medicine composition for treating pharyngitis and its application is of great significance. Summary of the Invention

[0008] To address the shortcomings of existing technologies, the purpose of this invention is to provide a traditional Chinese medicine composition for treating pharyngitis and its application. The traditional Chinese medicine composition of this invention has a unique formula, with synergistic effects between the ingredients, resulting in significant and rapid efficacy without toxic side effects. The traditional Chinese medicine composition of this invention is particularly effective in treating sore throat caused by pharyngitis; the sore throat essentially disappears 3-4 hours after administration.

[0009] The technical solution of this invention is:

[0010] A traditional Chinese medicine composition for treating pharyngitis, comprising the following traditional Chinese medicine components in parts by weight: 12-18 parts of Scutellaria barbata, 12-18 parts of Saussurea involucrata, 8-12 parts of Solidago virgaurea, 8-12 parts of Schizonepeta tenuifolia, 8-12 parts of Clematis armandii, 3-6 parts of Solanum lyratum, and 3-6 parts of Saposhnikovia divaricata.

[0011] Preferred Scheme 1, wherein the Chinese herbal components are in the following proportions by weight: 15 parts of Scutellaria barbata, 15 parts of Saussurea involucrata, 10 parts of Solidago virgaurea, 10 parts of Schizonepeta tenuifolia, 10 parts of Clematis armandii, 5 parts of Solanum lyratum, and 5 parts of Saposhnikovia divaricata.

[0012] Preferred Scheme 2, wherein the Chinese herbal components are in the following proportions by weight: 18 parts of Scutellaria barbata, 18 parts of Saussurea involucrata, 12 parts of Solidago virgaurea, 12 parts of Schizonepeta tenuifolia, 12 parts of Solanum lyratum, and 6 parts of Saposhnikovia divaricata.

[0013] The present invention also provides a method for preparing the traditional Chinese medicine composition for treating pharyngitis: all the prescription drugs are decocted with water 2-3 times, each time with 8-12 times the amount of water and decocted for 1-3 hours, the decoctions are combined, filtered, and the filtrate is concentrated to a relative density of 1.05-1.15 to obtain the traditional Chinese medicine composition of the present invention.

[0014] The preferred preparation method involves decocting all the above-mentioned formulation drugs twice with water. The first decoction is made with 10-12 times the amount of water for 2-3 hours, and the second decoction is made with 8-10 times the amount of water for 1-3 hours. The decoctions are combined, filtered, and the filtrate is concentrated to an extract with a relative density of 1.05-1.15 (50℃-60℃).

[0015] Furthermore, the method for preparing the traditional Chinese medicine composition into one of the following dosage forms—tablets, granules, pills, capsules, decoctions, and oral liquids—is an existing method.

[0016] This invention also provides the application of traditional Chinese medicine compositions in the preparation of pharyngitis drugs.

[0017] Furthermore, the use of the traditional Chinese medicine composition in the preparation of drugs for acute and chronic pharyngitis is preferred.

[0018] The formulation compatibility principle of this invention is as follows:

[0019] Scutellaria barbata: Pungent, bitter, and cold in nature; it belongs to the lung and liver meridians and has the effects of clearing heat and detoxifying, removing stasis and stopping bleeding, and inducing diuresis and reducing swelling. It is mainly used to treat heat-toxic carbuncles and swelling, and sore throat.

[0020] Hedyotis herb: It is the root or leaf of Clematis henryi Oliv. of the Ranunculaceae family. Pungent, bitter, and warm in nature; it has the effects of promoting qi and activating blood circulation, antibacterial and anti-inflammatory. Clematis henryi Oliver.

[0021] Solidago virgaurea: Pungent, bitter, and cool in nature; it has the effects of dispersing wind and clearing heat, detoxifying and reducing swelling.

[0022] Schizonepeta tenuifolia: Pungent, slightly warm in nature; it belongs to the lung and liver meridians; it has the effects of expelling wind and relieving the exterior, promoting eruption and resolving carbuncles, and stopping bleeding.

[0023] Little Green Leaf: It is the whole herb of Goodyera schlechtendaliana Reichb. f., Goodyera repens (L.) R. Br., Goodyera biflora (Lindl.) Hook. f. or Goodyera velutina Maxim. of the Orchidaceae family. Sweet, pungent, and neutral in nature; it has the effects of tonifying the kidney and replenishing qi, clearing heat and detoxifying wind-heat.

[0024] Solanum lyratum Thunb.: Bitter, slightly cold in nature. It belongs to the liver and stomach meridians; it has the effects of clearing heat and detoxifying, promoting diuresis and reducing swelling, and anti-cancer.

[0025] Saposhnikovia divaricata: Pungent, sweet, slightly warm in nature; it belongs to the bladder, liver, and spleen meridians; it has the effects of expelling wind and relieving the exterior, eliminating dampness and relieving pain, and stopping convulsions.

[0026] In the formula of the present invention, Scutellaria barbata is pungent, bitter, and cold, and is good at clearing heat and detoxifying, removing stasis; Hedyotis herb is pungent, bitter, and cool, clearing heat and detoxifying, resolving phlegm and relieving cough, promoting qi and activating blood circulation, and relieving pain; the two herbs together play the roles of clearing heat and detoxifying, promoting qi and activating blood circulation, relieving high fever, cough, and sore throat, and are the monarch drugs. Schizonepeta tenuifolia and Saposhnikovia divaricata are pungent and slightly warm, assisting the monarch drugs to disperse wind and clear heat, and expelling the pathogenic factors of wind-heat in the upper jiao. The two are used in combination, with milder药力, warm but not dry, relieving the exterior and dispersing wind, and at the same time restricting the drastic nature of the monarch and ministerial drugs; they are the ministerial drugs. Solidago virgaurea clears heat and detoxifies, disperses wind and heat; Little Green Leaf moistens the lung and relieves cough, promotes qi and activates blood circulation, reduces swelling and detoxifies; Solanum lyratum Thunb.: Clears heat and detoxifies, promotes diuresis and reduces swelling; the three herbs together assist the monarch and ministerial drugs to clear heat and detoxify, promote qi and activate blood circulation and reduce swelling; at the same time, the throat connects to the lung and stomach below, and the kidney meridian ascends along the pharynx. Little Green Leaf belongs to the lung and kidney meridians, and has the effects of moistening the lung and relieving cough, tonifying the kidney and replenishing qi, promoting qi and activating blood circulation, reducing swelling and detoxifying, so as to prevent the spread of throat diseases to the lung and kidney. All the herbs are used together to treat sore throat, hoarseness, dryness and itching of the throat, and discomfort in the pharynx.

[0027] The above-mentioned Scutellaria barbata and Hedyotis herb are the monarch drugs, the above-mentioned Schizonepeta tenuifolia and Saposhnikovia divaricata are the ministerial drugs, and the above-mentioned Solidago virgaurea, Little Green Leaf and Solanum lyratum Thunb. are the adjuvant drugs. The weight ratio of the monarch drug to the ministerial drug is preferably 2 - 3 times, and the weight ratio of the monarch drug to the adjuvant drug is preferably 1 - 1.5 times. Within this ratio range, the synergistic effect of the drugs is better and the medicinal effect is more significant.

[0028] Compared with the prior art, the advantages of the present invention are:

[0029] 1. Clinical use has proven that patients treated with the herbal composition of this invention experience rapid improvement in sore throat symptoms. The clinical efficacy rate after treatment can reach over 90%, demonstrating significant and rapid effects in treating pharyngitis with low adverse reactions.

[0030] 2. Pharmacological experimental results show that the traditional Chinese medicine composition of the present invention can reduce the degeneration and necrosis of pharyngeal mucosal epithelial cells and glands in pharyngeal model animals, reduce the infiltration of inflammatory cells in the larynx, and also has significant analgesic and anti-non-specific inflammatory effects, suggesting that the composition of the present invention has a significant therapeutic effect on pharyngitis.

[0031] 3. The toxicity test results of rats after single-dose and repeated oral administration of the traditional Chinese medicine composition of the present invention for 6 consecutive months showed that the test substance did not cause acute toxicity in rats, and the repeated administration toxicity test did not cause chronic toxicity, indicating that the traditional Chinese medicine composition of the present invention has high safety and no toxic side effects.

[0032] 4. The traditional Chinese medicine composition of the present invention conforms to the theory of "principal, assistant, adjuvant and guide" in traditional Chinese medicine. When the various medicines in this formula are used together, they can clear heat and detoxify, soothe the throat and relieve pain, and fight bacteria and reduce swelling.

[0033] The detailed structure of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0034] Figure 1 The results of the effects of ZHT01 and ZHT03 on the pathological changes of pharyngeal tissue in an acute pharyngitis model (HE staining, ×200) are shown in the figure. A: sham operation group; B: model control group; C: Jin Sang San Jie Wan group; D: low-dose ZHT01 group; E: medium-dose ZHT01 group; F: high-dose ZHT01 group; G: high-dose ZHT03 group. Detailed Implementation Example 1

[0035] A traditional Chinese medicine composition for treating pharyngitis: by weight: 15 parts of Scutellaria barbata, 15 parts of Saussurea involucrata, 10 parts of Solidago virgaurea, 10 parts of Schizonepeta tenuifolia, 10 parts of Clematis armandii, 5 parts of Solanum lyratum, and 5 parts of Saposhnikovia divaricata.

[0036] Preparation method: Add water to all the formula drugs and decoct twice. Add 12 times the amount of water for the first decoction and decoct for 2 hours. Add 10 times the amount of water for the second decoction and decoct for 2 hours. Combine the decoctions, filter, and concentrate the filtrate to an extract with a relative density of 1.05 to 1.15 (50℃-60℃) to obtain the traditional Chinese medicine composition of Example 1 (hereinafter referred to as ZHT01). Example 2

[0037] A traditional Chinese medicine composition for treating pharyngitis: by weight: 18 parts of Scutellaria barbata, 18 parts of Saussurea involucrata, 12 parts of Solidago virgaurea, 12 parts of Schizonepeta tenuifolia, 12 parts of Clematis armandii, 6 parts of Solanum lyratum, and 6 parts of Saposhnikovia divaricata.

[0038] Preparation method: All the ingredients in the formula are decocted twice with water. The first decoction is decocted with 10 times the amount of water for 2 hours, and the second decoction is decocted with 12 times the amount of water for 3 hours. The decoctions are combined, filtered, and the filtrate is concentrated to an extract with a relative density of 1.05 to 1.15 (50℃-60℃) to obtain the traditional Chinese medicine composition of Example 2 (hereinafter referred to as ZHT02).

[0039] Comparison

[0040] A traditional Chinese medicine composition: by weight: 14 parts of snow fungus, 9 parts of schizonepeta, 9 parts of dandelion, 4 parts of solanum lyratum, and 4 parts of saposhnikovia divaricata.

[0041] Preparation method: Add water to all the formula drugs and decoct twice. Add 12 times the amount of water for the first decoction and decoct for 2 hours. Add 10 times the amount of water for the second decoction and decoct for 2 hours. Combine the decoctions, filter, and concentrate the filtrate to an extract with a relative density of 1.05 to 1.15 (50℃-60℃) to obtain the Chinese medicine composition of the comparative formula (some texts will be referred to as ZHT03 in the following text).

[0042] Example 3: Single-dose toxicity test in rats

[0043] Eighty SD rats, half male and half female, were randomly divided into four groups according to sex and weight: a blank control group (distilled water), the ZHT01 group (cumulative dose of 108g crude drug / kg), the ZHT02 group (cumulative dose of 108g crude drug / kg), and the ZHT03 group (cumulative dose of 108g crude drug / kg), with 20 rats in each group. Before the experiment, the rats were fasted for approximately 16 hours but allowed free access to water. Then, they were administered distilled water and ZHT01, ZHT02, and ZHT03 extract solutions orally at a volume of 20mL / kg, respectively. Administered twice on the day of administration (6 hours apart, with fasting but free access to water between administrations). The animals were closely and carefully observed and recorded for 0–4 hours after administration, noting the characteristics of poisoning, the onset and recovery time of toxic reactions, and mortality. Observations were then conducted twice daily, once in the morning and once in the afternoon, for 14 consecutive days. Animals were weighed on the day of administration, before administration, and on days 4, 7, 10, and 14 after administration. Changes in animal weight and mortality were recorded.

[0044] Experimental Results: After two administrations within 24 hours to rats, no obvious acute toxic reactions were observed in the herbal compositions of Example 1, Example 2, and the comparative formula, and there was no significant effect on the weight gain of the rats. No obvious abnormalities were observed on the surface and cut surfaces of any organs after the experiment.

[0045] Experimental conclusion: Under the conditions of this experiment, the maximum tolerated dose (MTD) of rats orally administered ZHT01 extract solution was greater than 108 g crude drug / kg.

[0046] The method was the same as above. Under the conditions of this experiment, the maximum tolerated dose (MTD) of rats orally administered ZHT02 extract solution was greater than 108 g crude drug / kg.

[0047] The method was the same as above. Under the conditions of this experiment, the maximum tolerated dose (MTD) of rats orally administered ZHT03 extract solution was greater than 108 g crude drug / kg.

[0048] Example 4: Repeated-dose toxicity test in rats over 6 months

[0049] Five hundred and twenty SD rats were randomly divided into 13 groups (n=40 per group) according to sex and body weight. The experiment included a blank control group, a low-dose ZHT01 group (10g crude drug / kg), a medium-dose ZHT01 group (20g crude drug / kg), a high-dose ZHT01 group (40g crude drug / kg), a low-dose ZHT02 group (10g crude drug / kg), a medium-dose ZHT02 group (20g crude drug / kg), a high-dose ZHT02 group (40g crude drug / kg), a low-dose ZHT03 group (10g crude drug / kg), a medium-dose ZHT03 group (20g crude drug / kg), and a high-dose ZHT03 group (40g crude drug / kg). The rats were administered the drug via gavage at a volume of 15mL / kg for 26 consecutive weeks. At the end of the mid-treatment period (weekend of week 13) and the end of the recovery period (weekend of week 30), 130 rats were dissected as planned. At the end of the final treatment period (weekend of week 26), 260 rats (half male and half female) were dissected as planned. The examination items include: general clinical observation; measurement of weight, food intake, and water intake; routine urine test, hematology, blood biochemistry, coagulation and electrolyte tests, ophthalmological examination; organ coefficient measurement; and histopathological examination.

[0050] Experimental results:

[0051] General clinical observation: During the administration and recovery periods, no abnormalities related to drug toxicity were observed in the appearance, behavior, and general condition of animals in the ZHT01, ZHT02, and ZHT03 dosage groups compared with the blank control group.

[0052] Body weight: During the experiment, the weight gain of rats in each of the ZHT01, ZHT02, and ZHT03 dose groups was not significantly affected compared with the blank control group.

[0053] Food and water intake: No significant abnormal changes in food and water intake related to the test substance were observed in the ZHT01, ZHT02, and ZHT03 dosage groups.

[0054] Hematological examination: Compared with the blank control group, no toxicologically significant changes were observed in the hematological parameters of each dose group of ZHT01, ZHT02 and ZHT03.

[0055] Blood biochemistry tests: Compared with the blank control group, no toxicologically significant changes were observed in the blood biochemistry indicators of each dose group of ZHT01, ZHT02, and ZHT03.

[0056] Coagulation test: Compared with the blank control group, no toxicologically significant changes were observed in the coagulation indicators of each dose group of ZHT01, ZHT02, and ZHT03. The results indicate that ZHT01, ZHT02, and ZHT03 have no significant effect on the coagulation indicators of rats.

[0057] Electrolyte test: Compared with the blank control group, no toxicologically significant changes were observed in the electrolyte indicators of each dose group of ZHT01, ZHT02 and ZHT03. The results indicate that ZHT01 has no significant effect on the electrolyte indicators of rats.

[0058] Urinalysis: Compared with the blank control group, no toxicologically significant changes were observed in the urinalysis indicators of each dose group of ZHT01, ZHT02, and ZHT03.

[0059] Bone marrow examination: Peripheral blood tests showed no abnormalities related to drug toxicity, therefore the bone marrow smear was not examined under a microscope.

[0060] Ophthalmological examination: No obvious abnormalities were found in the ophthalmological examinations of the ZHT01, ZHT02, ZHT03 dose groups and the blank control group.

[0061] Organ coefficient: Compared with the blank control group, no toxicologically significant changes were observed in the organ coefficients of each dose group of ZHT01, ZHT02, and ZHT03. The results indicate that ZHT01, ZHT02, and ZHT03 had no significant effect on the organ coefficients of rats.

[0062] Gross anatomy and pathological examination: Animals in the high-dose groups ZHT01, ZHT02, and ZHT03 who were dissected during the middle, end, and recovery periods of drug administration showed no significant differences compared with the blank control group at the same time point, and no pathological changes of toxicological significance were found.

[0063] Experimental conclusion: Under the conditions of this experiment, the no-observed toxicity level (NOAEL) of SD rats after oral administration of ZHT01, ZHT02, and ZHT03 for 6 consecutive months was 40 g crude drug / kg.

[0064] The method was the same as above. SD rats were orally administered ZHT02 for 6 consecutive months. The no obvious toxic effect dose (NOAEL) was 40g crude drug / kg.

[0065] The method was the same as above. SD rats were orally administered ZHT03 for 6 consecutive months. The no obvious adverse reaction level (NOAEL) was 40 g crude drug / kg.

[0066] Example 5: Efficacy test data:

[0067] Experiment 1 Effects on a rat model of acute pharyngitis (chemical method)

[0068] 1 Experimental Methods

[0069] 1.1 Modeling, grouping, and drug administration

[0070] Seventy qualified SPF-grade SD rats, weighing 163.1–191.4 g, with half males and half females, were randomly divided into seven groups of ten animals each, according to sex and weight. These groups were: sham-operated group, model control group, Jin Sang San Jie Wan group (1.1 g / kg), low-dose ZHT01 group (0.7 g crude drug / kg), medium-dose ZHT01 group (2.1 g crude drug / kg), high-dose ZHT01 group (6.3 g crude drug / kg), and high-dose ZHT03 group (6.3 g crude drug / kg). Except for the sham-operated group, all other groups had 2.5% ammonia solution applied to the throat with sterile cotton swabs (modeling in the morning) once daily for seven consecutive days. The sham-operated group underwent the same procedure with saline solution applied to the throat. Before administration, the drug was prepared into the corresponding concentration using pure water. At the same time as the model was established, each group of animals was given the corresponding drug solution by gavage at 10 mL / kg every afternoon, once a day for 7 consecutive days. The sham surgery group and the model control group were given the same volume of pure water by gavage.

[0071] 1.2 Detection Indicators

[0072] (1) Cough detection: 1 hour after the last administration, rats were induced to cough with 10% ammonia solution. The number of coughs and the cough latency of each group of rats within 5 minutes were detected using a cough-inducing and asthma-inducing instrument.

[0073] (2) Histopathological examination: On the day following the last administration, animals in each group were selected and euthanized by exsanguination of the abdominal aorta after inhalation anesthesia with isoflurane (1-4% for induction anesthesia, 0.25-2% for maintenance anesthesia). Pharyngeal tissue was dissected, fixed in 10% neutral formalin solution, embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and observed under a microscope for histopathological changes in the pharynx. The scores were based on mucosal congestion, vasodilation and serous exudation, mucosal inflammatory cell infiltration, and mucosal swelling and thickening. The specific scoring criteria are as follows: no obvious abnormalities, scored as "0"; mild, scored as "1"; moderate, scored as "2"; severe, scored as "3".

[0074] 2. Experimental Results

[0075] 2.1 Effect on cough sensitivity

[0076] As shown in Table 1, compared with the sham-operated group, the cough latency of rats in the model control group was significantly shortened ( P ≤ 0.01), the frequency of coughing increased significantly ( P ≤ 0.01). Compared with the model control group, the cough latency period was significantly prolonged in rats in the medium- and high-dose ZHT01 groups and the high-dose ZHT03 group after administration ( P ≤ 0.01), significantly reduced the number of coughs ( P ≤ 0.05 or P ≤ 0.01). Compared with the model control group, the cough latency period of rats in the Jin Sang San Jie Wan group was significantly prolonged after administration ( P ≤ 0.01), significantly reduced the number of coughs ( P ≤ 0.05). Compared with the Jin Sang San Jie Wan group, the number of coughs was significantly reduced in the medium and high dose groups of ZHT01 ( P ≤0.05). Compared with the high-dose ZHT03 group, the number of coughs was significantly reduced in the medium- and high-dose ZHT01 groups. P ≤ 0.05).

[0077]

[0078] Note: Compared with the sham surgery group ++ P ≤ 0.01; compared with the model control group ** P ≤ 0.01, * P ≤ 0.05; compared with Jin Sang San Jie Wan group # P ≤ 0.05; compared with the high-dose ZHT03 group & P ≤ 0.05.

[0079] 2.2 Effects on pathological changes in pharyngeal and laryngeal tissues

[0080] As shown in Table 2 and Figure 1 As shown, compared with the sham surgery group, the model control group showed significantly increased scores for pharyngeal mucosal congestion, mucosal inflammatory cell infiltration, mucosal swelling and thickening, and overall score. P ≤ 0.01). Compared with the model control group, the medium and high dose groups of ZHT01 showed significantly reduced mucosal hyperemia, mucosal inflammatory cell infiltration, mucosal swelling and thickening, and comprehensive score. P ≤ 0.05 or P ≤ 0.01). Compared with the model control group, the mucosal congestion score and comprehensive score of Jin Sang San Jie Wan group were significantly reduced ( P≤ 0.05). Compared with the Jin Sang San Jie Wan group, the comprehensive score of the ZHT01 high-dose group was significantly reduced ( P ≤ 0.05). Compared with the high-dose ZHT03 group, the high-dose ZHT01 group showed significantly reduced mucosal inflammatory cell infiltration and overall score. P ≤ 0.05).

[0081]

[0082] Note: Compared with the sham surgery group ++ P ≤ 0.01; compared with the model control group * P ≤ 0.05, ** P ≤ 0.01; compared with Jin Sang San Jie Wan group # P ≤ 0.05; compared with the high-dose ZHT03 group & P ≤ 0.05.

[0083] Experiment 2 In vitro antibacterial effect

[0084] Using the agar diffusion method (perforation method), Staphylococcus aureus, Pseudomonas aeruginosa, hemolytic streptococci, and Streptococcus pneumoniae were inoculated into culture plates containing 100 mg / mL ZHT01 and ZHT03 extract solutions, respectively, and the diameter of the inhibition zone in the plate was measured. Using the test tube dilution method, different concentrations of ZHT01 and ZHT03 extract solutions were added to test tubes containing standard strains and clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, hemolytic streptococci, and Streptococcus pneumoniae, respectively, and the bacterial growth in the test tubes was observed. The highest dilution of the drug in which no bacterial or fungal growth was observed was taken as the minimum inhibitory concentration (MIC) of the drug.

[0085] The results showed that the MICs of cefixime against standard strains of hemolytic streptococci and Streptococcus pneumoniae, and the MICs of gentamicin against standard strains of Staphylococcus aureus and Pseudomonas aeruginosa, were consistent with those reported in the literature. The MICs of cefixime and gentamicin against clinical isolates of the above four bacteria were higher than those against the standard strains, indicating that the standard strains were more sensitive to the antibacterial effects of cefixime and gentamicin. ZHT01 and ZHT03 all showed some inhibitory effects on standard and clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, hemolytic streptococci, and Streptococcus pneumoniae, with ZHT01 showing stronger inhibitory effects than ZHT03 against both standard and clinical isolates of these four bacteria.

[0086]

[0087] Experiment 3: Anti-nonspecific inflammatory effects

[0088] Sixty male ICR mice, weighing 18.5–22.6 g, were randomly divided into six groups according to their weight: a blank control group, an aspirin group (0.23 g / kg), and low (1.0 g crude drug / kg), medium (3.0 g crude drug / kg), and high (9.0 g crude drug / kg) dose groups of ZHT01, and a high-dose group of ZHT03 (9.0 g crude drug / kg), with 10 animals in each group. Before administration, the drugs were prepared to the appropriate concentrations using pure water. Mice in each group were administered the corresponding dose of drug solution by gavage at a dose of 20 mL / kg once daily for 7 consecutive days. The blank control group was administered an equal volume of pure water by gavage. One hour after the last administration, 50 μL of xylene was applied to the right ear of each group of mice to induce inflammation, while the left ear was not applied as a control. The mice were sacrificed 30 minutes later, and both ears were cut off along the auricle baseline. A circular piece was punched out from the same part of the left and right ears using a 6 mm diameter punch. The weight of the left and right ears was weighed, and the degree of swelling was calculated as the weight of the right ear minus the weight of the left ear.

[0089] The results, as shown in Table 4, indicated that compared with the blank control group, the swelling degree of mice in the low, medium, and high dose groups of ZHT01 was significantly reduced. P ≤ 0.05 or P ≤ 0.01), and the swelling degree of mice in the high-dose ZHT01 group was significantly lower than that in the high-dose ZHT03 group. Compared with the blank control group, the swelling degree of mice in the aspirin group was significantly lower ( P ≤ 0.05).

[0090]

[0091] Note: Compared with the blank control group * P ≤ 0.05, ** P ≤ 0.01.

[0092] Experiment 4: Analgesic effect

[0093] Sixty SPF-grade ICR mice (half male and half female, weighing 20.4–26.1 g) were randomly divided into six groups of ten mice each: a blank control group, an aspirin group (0.23 g / kg), and three dose groups of ZHT01 (low (1.0 g crude drug / kg), medium (3.0 g crude drug / kg), and high (9.0 g crude drug / kg) and ZHT03 high-dose group (9.0 g crude drug / kg). Before administration, the drugs were prepared to the appropriate concentrations using pure water. Mice in each group were administered the corresponding dose of the drug solution by gavage at a dose of 20 mL / kg once daily for seven consecutive days. The blank control group was administered an equal volume of pure water by gavage.

[0094] The results, as shown in Table 5, indicated that compared with the blank control group, the writhing latency of mice in both the medium and high dose groups of ZHT01 was prolonged. P≤ 0.05 or P ≤ 0.01), the number of writhing movements in mice in the low, medium, and high dose groups of ZHT01 was significantly reduced ( P ≤0.01). Compared with the blank control group, the latency of writhing response in mice in the aspirin group was significantly prolonged, the number of writhing responses was significantly reduced, and the inhibition rate of writhing response reached 77.78%. Compared with the high-dose ZHT03 group, the latency of writhing response in mice in the medium- and high-dose ZHT01 groups was prolonged, and the number of writhing responses in mice in the medium- and high-dose ZHT01 groups was significantly reduced.

[0095]

[0096] Note: Compared with the blank control group* P ≤ 0.05, ** P ≤ 0.01.

[0097] Experiment 5 Effects on a rabbit model of chronic pharyngitis induced by chemical injury

[0098] 1 Experimental Methods

[0099] 1.1 Modeling, grouping, and drug administration

[0100] Sixty-four rabbits, weighing 2.0–3.0 kg (half male and half female), were used in the experiment. Ten animals were selected as the sham-operated group, and the remaining 54 animals were selected as the model group. In the model group, animals were treated with a sterile cotton swab dipped in 2.5% ammonia solution applied to the pharynx once daily for 21 consecutive days. On day 8, 0.5 mL of turpentine oil was injected submucosally into the pharyngeal mucosa of each animal to replicate the chronic pharyngitis model. Animals in the sham-operated group underwent the same treatment with 0.9% sodium chloride injection. On day 22, two animals were randomly selected from each group (model and sham-operated) for anesthesia via the marginal ear vein (800 mg / kg of 20% ursodeoxycholic acid), followed by exsanguination via the femoral artery for euthanasia. Histopathological examination was then performed to determine the success of the model. Histopathological examination revealed that the pharynx and larynx of the model rabbits showed mucosal epithelial hyperplasia with nail-like projections, vascular dilation and proliferation, significant infiltration of inflammatory cells, and numerous secretory granules in the cytoplasm of submucosal glandular cells, confirming the successful replication of the chronic pharyngitis model in the rabbits. Forty-eight model rabbits were randomly divided into six groups according to sex and weight: a model control group, a Jin Sang San Jie Wan group (1.1 g / kg), a low-dose ZHT01 group (0.7 g crude drug / kg), a medium-dose ZHT01 group (2.1 g crude drug / kg), a high-dose ZHT01 group (6.3 g crude drug / kg), and a high-dose ZHT03 group (6.3 g crude drug / kg), with eight rabbits in each group. Before daily administration, the dry extract of the test substance and Jin Sang San Jie Wan were prepared into solutions of the appropriate concentration using distilled water. Each group of experimental rabbits was given the corresponding drug solution by gavage at a dose of 10 mL / kg, once a day for 14 consecutive days. The model control group and the sham-operated group were given the same volume of distilled water by gavage.

[0101] 1.2 Detection Indicators

[0102] (1) Gross observation of pharyngeal tissue: 1 hour after the last administration, rabbits in each group were anesthetized by intravenous injection of 20% ursothione, and rats were anesthetized by intraperitoneal injection of 40 mg / kg sodium pentobarbital. They were then euthanized by exsanguination, dissected, and pharyngeal and laryngeal tissues were taken. Based on the color, surface gloss, amount of secretions, degree of congestion, and degree of swelling of the pharyngeal and laryngeal tissues, they were divided into 4 grades. Grade 1: The pharyngeal (or laryngeal) tissue is pale red, moist, and shiny, with no secretions, congestion, or swelling, scoring 1 point; Grade 2: The pharyngeal (or laryngeal) mucosa has poor luster, with a small amount of secretions and mild congestion, scoring 2 points; Grade 3: The pharyngeal (or laryngeal) tissue is dark red, with poor luster, a small amount of secretions, congestion, and mild swelling, scoring 3 points; Grade 4: The pharyngeal (or laryngeal) tissue is dark red, dull, with a large amount of accumulated secretions, and obvious congestion and swelling, scoring 4 points.

[0103] (2) Histopathological examination of the pharynx and larynx: 1 hour after the last administration, rabbits in each group were anesthetized by intravenous injection of 20% ursotose in the ear margin, and rats were anesthetized by intraperitoneal injection of 40 mg / kg sodium pentobarbital. They were then euthanized by exsanguination, dissected, and pharyngeal and laryngeal tissues were taken. The tissues were fixed in formalin, embedded in paraffin, sectioned, stained with hematoxylin and eosin (HE), and observed under a microscope. Histopathological changes of the pharynx and larynx (or laryngeal) tissues were scored according to the mucosa and lamina propria, glandular structure, and inflammatory cells.

[0104] 2. Experimental Results

[0105] 2.1 Impact on Gross Observation Scores of Pharyngeal Tissues

[0106] As shown in Table 6, the pharynx and larynx of the rabbits in the sham-operated group were shiny and moist, with no obvious congestion or swelling; the pharynx and larynx of the model control group were dark red, with more secretions, obvious congestion and swelling, and the gross observation score was significantly higher than that of the sham-operated group. P ≤ 0.01). Compared with the model control group, the gross observation scores of the pharynx and larynx of experimental rabbits in the low, medium, and high dose groups of ZHT01 and the high dose group of ZHT03 were significantly reduced ( P ≤ 0.01). Compared with the model control group, the gross observation scores of the pharynx and larynx in the rabbits treated with Jin Sang San Jie Wan were significantly reduced ( P ≤ 0.01). Compared with the Jin Sang San Jie Wan group, the gross observation scores of the pharynx and larynx of the experimental rabbits in the ZHT01 high-dose group were significantly reduced ( P ≤ 0.05). Compared with the high-dose ZHT03 group, the gross observation scores of the pharynx and larynx of the experimental rabbits in the high-dose ZHT01 group were significantly reduced ( P ≤ 0.05).

[0107]

[0108] Note: Compared with the blank control group ++ P ≤ 0.01; compared with the model control group** P ≤ 0.01; compared with Jin Sang San Jie Wan group # P ≤ 0.05, ## P ≤ 0.01; compared with the high-dose ZHT03 group & P ≤ 0.05.

[0109] 2.2 Effects on pathological changes in pharyngeal tissues

[0110] As shown in Table 7, compared with the sham surgery group, the model control group showed significantly increased scores in pharyngeal mucosa and lamina propria, glandular structure, inflammatory cell pathology, and overall score. P≤ 0.05 or P ≤ 0.01). Compared with the model control group, the pathological scores and comprehensive scores of the pharyngeal mucosa, lamina propria, and glandular structures in the medium and high dose groups of ZHT01 were significantly reduced ( P ≤ 0.05 or P ≤ 0.01); compared with the model control group, the pathological scores and comprehensive scores of the pharyngeal mucosa and lamina propria in the Jin Sang San Jie Wan group were significantly reduced ( P ≤ 0.05). Compared with the Jin Sang San Jie Wan group, the ZHT01 high-dose group showed a significant decrease in both the pathological score and the comprehensive score of the pharyngeal gland structure. P ≤ 0.05 or P ≤ 0.01).

[0111] Compared with the model control group, the pathological scores and comprehensive scores of the pharyngeal mucosa and lamina propria in the high-dose ZHT03 group were significantly reduced. Compared with the high-dose ZHT03 group, the pathological scores and comprehensive scores of the pharyngeal gland structure in the high-dose ZHT01 group were significantly reduced.

[0112]

[0113] Note: Compared with the sham surgery group + P ≤ 0.05, ++ P ≤ 0.01; compared with the model control group* P ≤ 0.05, ** P ≤ 0.01; compared with Jin Sang San Jie Wan group # P ≤ 0.05, ## P ≤ 0.01.

[0114] Example 6: Clinical experience study of the traditional Chinese medicine composition of the present invention in treating acute pharyngitis.

[0115] This study aims to explore the clinical efficacy and safety of the ZHT001 drug group (the traditional Chinese medicine composition of the present invention) in treating acute pharyngitis, and to provide new ideas and evidence for clinical treatment.

[0116] Study Objective: To evaluate the effect of ZHT001 treatment on improving clinical symptoms in patients with acute pharyngitis; and to observe the safety of ZHT001 treatment in patients with acute pharyngitis.

[0117] Study design: Randomized, double-blind, placebo-controlled study.

[0118] Case selection criteria:

[0119] The diagnostic criteria in Western medicine are based on the following information from "Otorhinolaryngology Head and Neck Surgery":

[0120] 1) Medical history: History of upper respiratory tract infection such as acute tonsillitis or acute rhinitis.

[0121] 2) Symptoms: These include dry throat, sore throat or pain when swallowing, accompanied by chills and fever, thirst, loss of appetite (loss of appetite), and heaviness and pain in the body.

[0122] Traditional Chinese Medicine diagnosis and scoring to be determined:

[0123] Inclusion criteria:

[0124] It meets the above diagnostic and syndrome differentiation criteria;

[0125] 2) Age 18-70 years old;

[0126] 3) The duration of illness is ≤48 hours;

[0127] 4) A score of 4 or less ≤ a visual analog scale (VAS) score for sore throat ≤ a score of 7;

[0128] Those who voluntarily become test subjects and sign a consent form to guarantee completion of the treatment.

[0129] Exclusion criteria:

[0130] 1) Body temperature>38.0℃;

[0131] 2) Peripheral blood leukocyte count > 10 × 10^9 / L at the first visit;

[0132] 3) Other Chinese and Western medicines used to treat acute pharyngitis during this illness (such as Chinese herbal preparations, glucocorticoids, nonsteroidal anti-inflammatory drugs, etc.) were used.

[0133] 4) Examination confirmed that the pharyngitis was caused by measles, scarlet fever, influenza, infectious mononucleosis, agranulocytosis, leukemia, etc.

[0134] 5) Liver function impairment [alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 times the upper limit of normal], renal insufficiency [creatinine (Cr) > upper limit of normal];

[0135] 6) Patients with serious primary diseases of the cardiovascular, cerebrovascular, liver, kidney, endocrine, or hematopoietic systems, or those with mental illness;

[0136] 7) Pregnant women or women planning to become pregnant (except those who request termination of pregnancy) and breastfeeding women;

[0137] 8) Known history of allergy to any component of the investigational drug;

[0138] 9) Currently participating in other drug clinical trials.

[0139] Exit Criteria

[0140] ① If a participant develops comorbidities or complications during the study period, they may be deemed unsuitable to continue participating in the study, and the clinical study may be discontinued based on the doctor's judgment;

[0141] ② If, during the study, a patient's condition worsens or a serious adverse event may occur or has already occurred, the clinical study will be discontinued based on the doctor's judgment. Patients whose condition worsens will be treated as invalid cases.

[0142] ③ In clinical studies, some subjects are unwilling to continue the clinical study and request to withdraw from the clinical study, or the clinical study is stopped based on the doctor's judgment.

[0143] Treatment plan

[0144] Example 1: ZHT001 Traditional Chinese Medicine Composition, wherein the traditional Chinese medicine components by weight are: 15g of Scutellaria barbata, 15g of Saussurea involucrata, 10g of Solidago virgaurea, 10g of Schizonepeta tenuifolia, 10g of Clematis armandii, 5g of Solanum lyratum, and 5g of Saposhnikovia divaricata. The above-mentioned herbs are decocted twice with water. The first decoction is decocted with 10 times the amount of water for 2 hours, and the second decoction is decocted with 10 times the amount of water for 2 hours. The decoctions are combined, filtered, and the resulting traditional Chinese medicine decoction is divided into two portions. One dose is taken daily, twice a day, in the morning and evening. This is continued for 3 days.

[0145] 2. Drug control group: Yinhuang oral liquid, oral liquid, 10 ml per bottle, National Drug Approval Number Z36020687, Pharmacopoeia of the People's Republic of China 2010 Edition, Part I, Usage: 10 ml each time, 3 times a day.

[0146] 120 participants with acute pharyngitis were selected for the study, with 60 people in each group.

[0147] Observation indicators

[0148] Therapeutic indicators include:

[0149] 1) VAS score for sore throat.

[0150] 2) Efficacy Evaluation Based on Traditional Chinese Medicine Syndromes: According to the efficacy evaluation criteria established in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs (Trial Implementation)," primary symptoms include sore throat, dry and burning throat, and pharyngeal mucosal congestion. The scoring criteria are: 0 points for none, 2 points for mild, 4 points for moderate, and 6 points for severe. Secondary symptoms include hoarseness, difficulty swallowing, fever, aversion to wind, headache, and yellow phlegm cough. The scoring criteria are: 0 points for none, 1 point for mild, 2 points for moderate, and 3 points for severe. The efficacy evaluation is as follows:

[0151] Cure: Symptoms and signs disappear or basically disappear, and the syndrome score reduction rate is ≥95%.

[0152] Significant effect: Symptoms and signs are significantly improved, and the reduction rate of syndrome score is ≥70% but <95%.

[0153] Effective: Symptoms and signs have improved, and the reduction rate of syndrome score is ≥30% but <70%.

[0154] Ineffective: Symptoms and signs show no significant improvement or even worsen, and the syndrome score reduction rate is <30%.

[0155] The formula for calculating the overall effective rate of TCM syndromes is: (number of cured patients + number of patients with significant improvement + number of patients with effective results) / total number of patients.

[0156] The total number of cases is multiplied by 100%. The SF-36 scale covers 8 dimensions and 36 items, each with a corresponding score. The score for each dimension is the sum of the scores of all items within that dimension. According to the scale's scoring method, the weighted scores of each item are added together to obtain the final score, with the total score ranging from 35 to 144. A low score indicates a poorer quality of life, while a high score indicates a better quality of life.

[0157] Observation period

[0158] The treatment lasts for 4 days.

[0159] Statistical methods

[0160] Statistical methods: SPSS 16.0 statistical software was used for data processing and analysis in this study. The t-test was used to compare continuous data, and the chi-square test was used to compare categorical data. P < 0.05 was considered statistically significant.

[0161] Experimental results

[0162]

[0163] The results showed that both the control group 1 and the example group 1 had good therapeutic effects on pharyngitis, and the total effective rate of the example group 1 was 93.33%.

[0164] Safety evaluation: No adverse events occurred during the test, indicating that the test was safe and reliable.

[0165] Typical cases of quickly relieving sore throat:

[0166] A traditional Chinese medicine composition for treating pharyngitis, wherein the medicinal components, by weight, are: 15g of Scutellaria barbata, 15g of Saussurea involucrata, 10g of Solidago virgaurea, 10g of Schizonepeta tenuifolia, 10g of Clematis armandii, 5g of Solanum lyratum, and 5g of Saposhnikovia divaricata. The above-mentioned medicinal ingredients are decocted twice with water. The first decoction is decocted with 10 times the amount of water for 2 hours, and the second decoction is decocted with 10 times the amount of water for 2 hours. The decoctions are combined, filtered, and the resulting decoction is divided into two portions. One dose is taken daily, twice a day, in the morning and evening.

[0167] Typical Case 1: Mr. Wei, 50 years old, suffered from severe sore throat, hoarseness, inability to eat, and significant throat pain upon drinking water. He took anti-inflammatory drugs for several days without effect. He then took the traditional Chinese medicine decoction of Example 1 of this invention, two doses per day, divided into morning and evening doses. After taking it once, about 4 hours later, his hoarseness improved significantly, and the sore throat almost completely disappeared. He continued to take it for 4 days, and all symptoms disappeared, and he recovered completely.

[0168] Typical Case 2: Ms. Shen, 29 years old, suffered from severe sore throat. Examination revealed tonsillitis and swelling, significant sore throat, and hoarseness. She then took the herbal decoction of Example 1 of this invention, one dose per day, divided into two doses in the morning and evening. The sore throat basically disappeared on the morning of the second day. She continued to take it for 3 days and recovered completely.

[0169] Typical Case 3: Ms. Xie, 49 years old, suffered from severe sore throat due to wind-cold, and her voice was like a knife. She then took the decoction of traditional Chinese medicine composition of Example 1 of this invention, one dose per day, divided into two doses in the morning and evening. After taking it once, about 4 hours later, the sore throat pain was significantly reduced. After taking it for 6 more doses, she recovered completely.

[0170] The above description is a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and concept of the present invention, should be covered within the scope of protection of the claims of the present invention.

Claims

1. A traditional Chinese medicine composition for treating pharyngitis, characterized in that, It is made from the following Chinese herbal ingredients in parts by weight: 12-18 parts of Scutellaria barbata, 12-18 parts of Saussurea involucrata, 8-12 parts of Solidago virgaurea, 8-12 parts of Schizonepeta tenuifolia, 8-12 parts of Clematis armandii, 3-6 parts of Solanum lyratum, and 3-6 parts of Saposhnikovia divaricata. Add water to the above-mentioned weight proportions of Chinese herbs and decoct 2-3 times, adding 8-12 times the amount of water each time and decocting for 1-3 hours. Combine the decoctions, filter, and obtain the Chinese herbal composition.

2. The traditional Chinese medicine composition for treating pharyngitis according to claim 1, characterized in that, The Chinese herbal components, by weight, are: 15 parts of Scutellaria barbata, 15 parts of Saussurea involucrata, 10 parts of Solidago virgaurea, 10 parts of Schizonepeta tenuifolia, 10 parts of Clematis armandii, 5 parts of Solanum lyratum, and 5 parts of Saposhnikovia divaricata.

3. The traditional Chinese medicine composition for treating pharyngitis according to claim 1, characterized in that, The Chinese herbal components, by weight, are: 18 parts of Scutellaria barbata, 18 parts of Saussurea involucrata, 12 parts of Solidago virgaurea, 12 parts of Schizonepeta tenuifolia, 12 parts of Clematis armandii, 6 parts of Solanum lyratum, and 6 parts of Saposhnikovia divaricata.

4. A traditional Chinese medicine composition for treating pharyngitis according to any one of claims 1-3, characterized in that, Add water to the above-mentioned weight proportions of Chinese herbal medicine and decoct 2-3 times, adding 8-12 times the amount of water each time and decoct for 1-3 hours. Combine the decoctions, filter, and concentrate the filtrate to a relative density of 1.05-1.15 to obtain the Chinese herbal medicine composition.

5. The traditional Chinese medicine composition for treating pharyngitis according to claim 4, characterized in that, The above-mentioned weight proportions of Chinese herbal medicine are decocted twice with water. For the first decoction, 10-12 times the amount of water are added and the decoction is decocted for 2-3 hours. For the second decoction, 8-10 times the amount of water are added and the decoction is decocted for 1-3 hours. The decoctions are combined, filtered, and the filtrate is concentrated to a relative density of 1.05-1.15 to obtain the Chinese herbal medicine composition.

6. A traditional Chinese medicine composition for treating pharyngitis according to any one of claims 1-3, characterized in that, The traditional Chinese medicine composition may be prepared into any one of the following: tablets, granules, pills, capsules, decoctions, and oral liquids.

7. The use of the traditional Chinese medicine composition according to any one of claims 1-6 in the preparation of a medicine for treating pharyngitis.

8. The application according to claim 7, characterized in that, The application of the traditional Chinese medicine composition in the preparation of drugs for treating acute and chronic pharyngitis.

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