Traditional Chinese medicine composition for treating sphagitis and application thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating sphagitis. The traditional Chinese medicine composition comprises the following components in parts by weight: 12-18 parts of barbed skullcap herb, 12-18 parts of henry clematis root, 8-12 parts of solidago decurrens, 8-12 parts of fineleaf schizonepeta herb, 8-12 parts of small leaf swallowwort herb, 3-6 parts of solanum lyratum thunb and 3-6 parts of divaricate saposhnikovia root. The preparation method comprises the following steps: adding water into the formula medicines, decocting for 2-3 times, adding 8-12 times of water each time, decocting for 1-3 hours, combining decoctions, filtering, and concentrating the filtrate into extract with the relative density of 1.05-1.15. The traditional Chinese medicine composition is unique in formula, has a synergistic effect among the formulas, can be used for treating sphagitis, and is obvious in curative effect, quick in effect and free of toxic and side effects. The traditional Chinese medicine composition disclosed by the invention has a particularly remarkable effect on treating the throat pain caused by sphagitis, and the throat pain basically disappears after the traditional Chinese medicine composition is taken for 3-4 hours.

Description

Technical Field

[0001] The present invention relates to the field of Chinese medicine compositions, and in particular to a Chinese medicine composition for treating pharyngitis and application thereof. Background Art

[0002] Pharyngitis is a non-specific inflammation of the throat. It is a general term for inflammation caused by various microorganisms infecting the throat. It is a common inflammatory disease in clinical practice, mainly divided into acute pharyngitis and chronic pharyngitis. Acute pharyngitis is manifested by sore throat, hoarseness, cough and other symptoms. Chronic pharyngitis is mainly manifested by symptoms such as foreign body sensation in the throat, itchy throat, and dry throat. Modern medical clinical investigations and studies have shown that pharyngitis is mostly caused by viral or bacterial infection, and may also be caused by environmental pollution, chemical plant stimulation, diet and other physical and chemical factors, and long speaking time. Clinical symptoms are mostly manifested as pain in the throat, mucosal congestion and edema, dryness and foreign body sensation, which seriously affect the patient's normal activities such as eating and speaking.

[0003] At present, Western medicine mainly uses oral medications in clinical practice, combined with spray, local atomization treatment and other methods, which can temporarily relieve the patient's throat discomfort, but it is easy to relapse after treatment, resulting in a waste of medical resources, and also increasing the psychological and economic pressure on patients.

[0004] From the traditional Chinese medicine point of view, pharyngitis is "throat congestion" and the disease is located in the throat. It is a mixture of real and virtual, and the causes and pathogenesis are complex and changeable. There are internal damage to the lungs, spleen, and kidneys, and external causes such as wind, heat, dampness, phlegm, blood stasis, and depression. It should nourish the spleen and stomach, nourish the lungs and kidneys, soothe the liver and relieve depression, and clear the heart and reduce fire.

[0005] After searching, many formulas have been 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 tangerine peel, 40-60 milliliters of vinegar, 100 grams of water, 5-8 grams of licorice, 11-15 grams of Chuan Pu, 10-15 grams of Su Geng, 5-10 grams of Trichosanthes, 8-14 grams of Scrophularia, 12-15 grams of Bean Root, 8-10 grams of Arisaema, 8-10 grams of Two Peony Roots, 5-10 grams of Platycodon, and 5-10 grams of Bombyx Batryticatus.

[0006] CN109125589A discloses a Chinese medicine composition for treating pharyngitis, comprising Radix Isatidis, Kumquat Peel, Radix Sophorae Tonkinensis, Radix Ophiopogonis, Platycodon Grandiflorum, Licorice, Houttuynia Cordata, Flos Lonicerae, Cortex Moutan, Fritillariae Chuanxiong, Taraxacum Herba and Chrysanthemum.

[0007] The Chinese medicine compositions of the above formulas each have advantages and disadvantages. It is of great significance to develop a new Chinese medicine composition for treating pharyngitis and its application. Summary of the invention

[0008] In view of the deficiencies in the prior art, the object of the present invention is to provide a Chinese medicine composition for treating pharyngitis and its application. The Chinese medicine composition of the present invention has a unique formula, a synergistic effect between the formulas, obvious curative effect, quick effect, and no toxic side effects. The Chinese medicine composition of the present invention is particularly effective in treating throat pain caused by pharyngitis, and the throat pain basically disappears 3-4 hours after taking the medicine.

[0009] The technical solution of the present invention is: A traditional Chinese medicine composition for treating pharyngitis is composed of the following traditional Chinese medicine components in parts by weight: 12-18 parts of Scutellaria barbata, 12-18 parts of Herba Cibotii, 8-12 parts of Solidago asiatica, 8-12 parts of Schizonepeta tenuifolia, 8-12 parts of Glechoma longituba, 3-6 parts of Bletilla striata, and 3-6 parts of Saposhnikovia divaricata.

[0010] Preferred scheme 1, the Chinese medicinal components are calculated by weight: 15 parts of Scutellaria barbata, 15 parts of Psoralea corylifolia, 10 parts of Solidago asiatica, 10 parts of Schizonepeta tenuifolia, 10 parts of Microphylla scabra, 5 parts of Bletilla striata, and 5 parts of Saposhnikovia divaricata.

[0011] Preferred solution 2, the Chinese medicinal components are calculated by weight: 18 parts of Scutellaria barbata, 18 parts of Psoralea corylifolia, 12 parts of Solidago asiatica, 12 parts of Schizonepeta tenuifolia, 12 parts of Microphylla scabra, 6 parts of Bletilla striata, and 6 parts of Saposhnikovia divaricata.

[0012] The present invention also provides a method for preparing the Chinese medicine composition for treating pharyngitis: all the prescription drugs are decocted with water for 2-3 times, decocting for 1-3 hours with 8-12 times the amount of water each time, combining the decoctions, filtering, and concentrating the filtrate to a relative density of 1.05-1.15 to obtain the Chinese medicine composition of the present invention.

[0013] The preferred preparation method is to decoct all the above-mentioned prescription drugs twice with water, the first time with 10-12 times the amount of water and decoct for 2-3 hours, the second time with 8-10 times the amount of water and decoct for 1-3 hours, combine the decoctions, filter, and concentrate the filtrate to an extract with a relative density of 1.05-1.15 (50℃-60℃).

[0014] Furthermore, the Chinese medicine composition is made into one of tablets, granules, pills, capsules, decoctions and oral liquids, and the method of preparing it into different dosage forms is an existing method.

[0015] The invention also provides application of the traditional Chinese medicine composition in preparing medicines for pharyngitis.

[0016] Further preferred is the use of the traditional Chinese medicine composition in the preparation of drugs for acute and chronic pharyngitis.

[0017] The formula compatibility principle of the present invention is as follows: Scutellaria barbata: pungent, bitter, cold in nature; enters the lungs and liver, has the effects of clearing away heat and detoxification, dispersing blood stasis and stopping bleeding, and diuresis and swelling. It is mainly used to treat heat-toxic carbuncle and sore throat.

[0018] Xuelikai: Clematis unifolia, a plant of the Ranunculaceae family Clematis henryi Oliver's root or leaf. It tastes spicy and bitter, and is warm in nature. It has the effects of promoting qi and blood circulation, and antibacterial and anti-inflammatory.

[0019] Solidago: spicy and bitter in taste, cool in nature; has the effects of dispelling wind and heat, detoxifying and reducing swelling.

[0020] Schizonepeta: spicy in taste, slightly warm in nature; enters the lung and liver meridians; has the effects of dispelling wind and relieving exterior symptoms, clearing rashes and eliminating sores, and stopping bleeding.

[0021] Small Leaf Green: It is the whole herb of the orchid family, such as the large spotted leaf orchid, small spotted leaf orchid, large flower spotted orchid or velvet leaf spotted leaf orchid. It tastes sweet, spicy and has a neutral nature. It has the effects of nourishing the kidney and replenishing qi, clearing away heat and detoxifying wind-heat.

[0022] Solanum lycopersicum: bitter, slightly cold in nature. Enters the liver and stomach meridians; has the effects of clearing away heat and detoxifying, promoting dampness and reducing swelling, and anti-cancer.

[0023] Saposhnikovia divaricata: spicy, sweet, slightly warm in nature; enters the bladder, liver, and spleen; has the effects of dispelling wind and relieving exterior symptoms, eliminating dampness and relieving pain, and stopping spasms.

[0024] In the formula of the present invention, Scutellaria barbata is pungent and cold in taste, good at clearing away heat and detoxifying, and removing blood stasis; Psoralea corylifolia is pungent and cold in taste, clearing away heat and detoxifying, removing phlegm and relieving cough, promoting qi and activating blood circulation, and relieving pain; the two medicines work together to clear away heat and detoxify, promote qi and activate blood circulation, and relieve high fever, cough, and sore throat, and are the main medicine. Schizonepeta and Saposhnikovia divaricata are pungent and slightly warm in taste, and assist the main medicine in dispelling wind and heat, and dispersing the evil of wind and heat in the upper part of the body. The two are compatible with each other, and the medicinal effect is moderate, warm but not dry, and can relieve the exterior and dissipate wind, while restraining the harsh nature of the main and ministerial drugs; they are the ministerial drugs. Goldenrod clears heat and detoxifies, dispels wind-heat; Small Leaf Green moistens the lungs and relieves cough, promotes qi and blood circulation, reduces swelling and detoxifies; White Sage: clears heat and detoxifies, promotes dampness and reduces swelling; the three herbs work together to assist the monarch and minister herbs in clearing heat and detoxifying, promoting qi and blood circulation and reducing swelling; at the same time, the throat is connected to the lungs and stomach, and the kidney meridians are located above the throat. Small Leaf Green belongs to the lung and kidney meridians, and has the effects of moistening the lungs and relieving coughs, nourishing the kidneys and replenishing qi, promoting qi and blood circulation, reducing swelling and detoxifying, so as to prevent throat diseases from spreading to the lungs and kidneys. All the herbs are used together to treat sore throat, hoarseness, dry throat, itchy throat, and throat discomfort.

[0025] The Scutellaria barbata and Psoralea corylifolia are the main drugs, the Schizonepeta tenuifolia and Saposhnikovia divaricata are the secondary drugs, and the Solidago asiatica, Glehnia littoralis and Scutellaria baicalensis are the adjuvant drugs. The weight ratio of the main drug to the secondary drug is preferably 2-3 times, and the weight ratio of the main drug to the adjuvant drug is preferably 1-1.5 times. Within this ratio range, the synergistic effect of the drugs is better exerted and the efficacy is more significant.

[0026] Compared with the prior art, the advantages of the present invention are: 1. Clinical use results show that the patients treated with the Chinese medicine composition of the present invention have rapid improvement in symptoms of sore throat, and the effective rate after clinical treatment can reach more than 90%. The effect of treating pharyngitis is obvious, the effect is fast, and the adverse reaction is low.

[0027] 2. The results of pharmacological experiments show that the Chinese medicine composition of the present invention can alleviate the degeneration and necrosis of the mucosal epithelial cells and glands in the throat of pharyngitis model animals, reduce the infiltration of inflammatory cells in the throat, and also has significant analgesic and anti-nonspecific inflammatory effects, indicating that the composition of the present invention has a significant therapeutic effect on pharyngitis.

[0028] 3. The results of toxicity tests on rats with a single oral administration of the Chinese medicine composition of the present invention and repeated oral administration for 6 consecutive months showed that the test substance did not cause acute toxic reactions in rats, and repeated administration toxicity tests did not cause chronic toxic reactions, indicating that the Chinese medicine composition of the present invention is highly safe and has no toxic side effects.

[0029] 4. The Chinese medicine composition of the present invention is in line with the "monarch, minister, assistant and envoy" theory of traditional Chinese medicine. The combination of various medicines can clear away heat and detoxify, relieve sore throat and pain, and have antibacterial and anti-edema effects.

[0030] The detailed structure of the present invention is further described below in conjunction with the accompanying drawings and specific implementation methods. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 The results of the effects of ZHT01 and ZHT03 on the pathological changes of pharyngeal tissue in the acute pharyngitis model (HE staining, ×200), where: A: sham operation group; B: model control group; C: Jinsang Sanjie pills group; D: ZHT01 low-dose group; E: ZHT01 medium-dose group; F: ZHT01 high-dose group; G: ZHT03 high-dose group. DETAILED DESCRIPTION Example 1

[0032] A traditional Chinese medicine composition for treating pharyngitis: measured by weight: 15 parts of Scutellaria barbata, 15 parts of Psoralea corylifolia, 10 parts of Solidago asiatica, 10 parts of Schizonepeta tenuifolia, 10 parts of Microphylla scabra, 5 parts of Bletilla striata, and 5 parts of Saposhnikovia divaricata.

[0033] Preparation method: All the formulated drugs are decocted twice with water, decocted for 2 hours with 12 times the amount of water for the first time and decocted for 2 hours with 10 times the amount of water for the second time, the decoctions are combined, filtered, and the filtrate is concentrated to an extract with a relative density of 1.05 to 1.15 (50°C-60°C) to obtain the Chinese medicine composition of Example 1 (hereinafter referred to as ZHT01). Example 2

[0034] A traditional Chinese medicine composition for treating pharyngitis: measured by weight: 18 parts of Scutellaria barbata, 18 parts of Psoralea corylifolia, 12 parts of Solidago asiatica, 12 parts of Schizonepeta tenuifolia, 12 parts of Microphylla scabra, 6 parts of Bletilla striata, and 6 parts of Saposhnikovia divaricata.

[0035] Preparation method: All the prescription drugs are decocted twice with water, the first time with 10 times the amount of water and decocted for 2 hours, the second time with 12 times the amount of water and decocted for 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℃), to obtain the Chinese medicine composition of Example 2 (hereinafter referred to as ZHT02) Contrast

[0036] A Chinese medicine composition: calculated by weight: 14 parts of snow prickly ash, 9 parts of schizonepeta tenuifolia, 9 parts of microphylla scutellariae, 4 parts of white smilax china, and 4 parts of siler.

[0037] Preparation method: All the formula drugs are decocted twice with water, decocted for 2 hours with 12 times the amount of water for the first time and decocted for 2 hours with 10 times the amount of water for the second time, the decoctions are combined, filtered, and the filtrate is concentrated to an extract with a relative density of 1.05-1.15 (50℃-60℃) to obtain the comparative Chinese medicine composition (hereinafter referred to as ZHT03).

[0038] Example 3 Single-dose toxicity test in rats

[0039] 80 SD rats, half male and half female, were randomly divided into 4 groups according to sex and weight, namely blank control group (distilled water), ZHT01 group (cumulative dose of 108g crude drug / kg), ZHT02 group (cumulative dose of 108g crude drug / kg), and ZHT03 group (cumulative dose of 108g crude drug / kg), with 20 rats in each group. Before the experiment, the rats were fasted but not watered for about 16 hours, and then distilled water and ZHT01 extract solution, ZHT02 extract solution, and ZHT03 extract solution were orally gavaged at a volume of 20mL / kg, and the drug was administered twice on the day of administration (6 hours between the two administrations, and fasting but not watered between the two administrations). The poisoning manifestations and characteristics of the animals in each group, the occurrence and recovery time of toxic reactions, and the death of the animals were closely observed and recorded within 0 to 4 hours after administration, and then observed twice a day, once in the morning and once in the afternoon, for 14 consecutive days. The animals were weighed before administration on the day of administration and on the 4th, 7th, 10th and 14th days after administration, and the weight changes and deaths of the animals were recorded.

[0040] Test results: After two administrations within 24 hours, the Chinese medicine compositions of Example 1, Example 2 and the comparative formula showed no obvious acute toxicity reaction and had no obvious effect on the weight gain of the rats. No obvious abnormalities were found in the gross observation of the surface and section of each organ after the test.

[0041] Experimental conclusion: Under the experimental conditions, the maximum tolerated dose (MTD) of ZHT01 extract solution for rats administered orally was greater than 108 g crude drug / kg.

[0042] The method is the same as above. Under the experimental conditions, the maximum tolerated dose (MTD) of ZHT02 extract solution for rats administered orally was greater than 108 g crude drug / kg.

[0043] The method is the same as above. Under the experimental conditions, the maximum tolerated dose (MTD) of ZHT03 extract solution for rats administered orally was greater than 108 g crude drug / kg.

[0044] Example 4 Six-month repeated administration toxicity test in rats 520 SD rats were randomly divided into 13 groups according to sex and weight, with 40 animals in each group. The experiment was divided into blank control group, ZHT01 low-dose group (10g crude drug / kg), ZHT01 medium-dose group (20g crude drug / kg), ZHT01 high-dose group (40g crude drug / kg), ZHT02 low-dose group (10g crude drug / kg), ZHT02 medium-dose group (20g crude drug / kg), ZHT02 high-dose group (40g crude drug / kg), ZHT03 low-dose group (10g crude drug / kg), ZHT03 medium-dose group (20g crude drug / kg), and ZHT03 high-dose group (40g crude drug / kg). The drug was administered by gavage at a volume of 15mL / kg for 26 consecutive weeks. At the end of the middle administration period (the 13th week of the week) and the end of the recovery period (the 30th week of the week), 130 rats were dissected as planned, and at the end of the final administration period (the 26th week of the week), 260 rats were dissected as planned, half of them were male and half were female. The examination items include: general clinical observation; measurement of body weight, food intake, and water intake; urine routine, hematology, blood biochemistry, coagulation and electrolyte tests, and ophthalmological examination; organ coefficient measurement; and histopathological examination.

[0045] Test results: General clinical observations: During the dosing and recovery observation periods, no abnormalities related to drug toxicity were found in the appearance signs, behavioral activities, and general conditions of animals in the ZHT01, ZHT02, and ZHT03 dose groups compared with the blank control group during the same period.

[0046] Body weight: During the experimental period, there was no significant effect on the weight gain of rats in the ZHT01, ZHT02, and ZHT03 dose groups compared with the blank control group during the same period.

[0047] Food intake and water intake: There were no obvious abnormal changes in food intake and water intake related to the test substance in the ZHT01, ZHT02 and ZHT03 dose groups.

[0048] Hematological examination: There were no toxicologically significant changes in the hematological parameters of the ZHT01, ZHT02 and ZHT03 dose groups compared with the blank control group during the same period.

[0049] Blood biochemical examination: There was no toxicologically significant change in the blood biochemical indexes of each dose group of ZHT01, ZHT02 and ZHT03 compared with the blank control group during the same period.

[0050] Coagulation examination: There was no toxicologically significant change in the coagulation indexes of each dose group of ZHT01, ZHT02 and ZHT03 compared with the blank control group during the same period. The results showed that ZHT01, ZHT02 and ZHT03 had no significant effect on the coagulation indexes of rats.

[0051] Electrolyte examination: There was no toxicologically significant change in the electrolyte indexes of the ZHT01, ZHT02, and ZHT03 dose groups compared with the blank control group during the same period. The results showed that ZHT01 had no significant effect on the electrolyte indexes of rats.

[0052] Urinalysis examination: There was no toxicologically significant change in urine routine indexes of ZHT01, ZHT02 and ZHT03 groups compared with the blank control group during the same period.

[0053] Bone marrow examination: Peripheral blood examination revealed no abnormalities related to drug toxicity, so the bone marrow smear was not observed under a microscope.

[0054] Ophthalmological examination: No obvious abnormalities were found in the ophthalmological examinations of the ZHT01, ZHT02, ZHT03 dose groups and the blank control group.

[0055] Organ coefficients: Compared with the blank control group during the same period, no toxicologically significant changes were observed in the organ coefficients of the ZHT01, ZHT02, and ZHT03 dose groups. The results showed that ZHT01, ZHT02, and ZHT03 had no significant effects on the organ coefficients of rats.

[0056] Gross anatomy and pathological examination: No significant differences were found in the high-dose groups of ZHT01, ZHT02, and ZHT03 when the animals were dissected at the middle, end, and recovery stages of drug administration compared with the blank control group during the same period, and no pathological changes of toxicological significance were found.

[0057] Experimental conclusion: Under the experimental conditions, SD rats were orally gavaged with ZHT01, ZHT02, and ZHT03 for 6 consecutive months, and the no-observed-toxicity-effect dose (NOAEL) was 40 g crude drug / kg.

[0058] The method was the same as above. SD rats were orally gavaged with ZHT02 for 6 consecutive months, and the no-observed-toxicity-effect level (NOAEL) was 40 g crude drug / kg.

[0059] The method was the same as above. SD rats were orally gavaged with ZHT03 for 6 consecutive months, and the no-observed-toxicity-effect level (NOAEL) was 40 g crude drug / kg.

[0060] Example 5 Efficacy test data: Experiment 1 Effects on the rat acute pharyngitis (chemical method) model

[0061] 1 Experimental methods 1.1 Modeling, grouping and drug administration 70 SPF SD rats with qualified quarantine, weighing 163.1-191.4g, half male and half female, were randomly divided into 7 groups according to sex and weight, with 10 animals in each group, namely sham operation group, model control group, Jinsang Sanjie pill group (1.1g / kg), low-dose group of ZHT01 (0.7g crude drug / kg), medium-dose group of ZHT01 (2.1g crude drug / kg), high-dose group of ZHT01 (6.3g crude drug / kg), and high-dose group of ZHT03 (6.3g crude drug / kg). Except for the sham operation group, the animals in the other groups were smeared with 2.5% ammonia water on the throat with a sterile cotton swab (modeling in the morning), once a day for 7 consecutive days. The sham operation group was smeared with normal saline on the throat in the same way. Before administration, the drugs were prepared into corresponding concentrations with pure water. At the same time as modeling, each group of animals was gavaged with corresponding drug solution at 10 mL / kg every afternoon, once a day, for 7 consecutive days. The sham operation group and the model control group were gavaged with equal volumes of pure water.

[0062] 1.2 Detection indicators (1) Cough detection: One hour after the last administration, 10% ammonia solution was used to induce cough in rats, and a cough-inducing instrument was used to detect the number of coughs and cough latency of rats in each group within 5 minutes.

[0063] (2) Histopathological examination: On the day after the last administration, animals in each group were selected and euthanized by bleeding from the abdominal aorta after inhalation anesthesia with isoflurane (1-4% for induction of anesthesia, 0.25-2% for maintenance of anesthesia). The throat tissues were dissected and fixed in 10% neutral formalin solution, embedded in paraffin, sliced, and stained with HE. The pathological changes of the throat tissues were observed under a microscope, and the scores were based on mucosal congestion, vascular dilation and serous exudation, mucosal inflammatory cell infiltration, and mucosal swelling and thickening. The specific scoring criteria are as follows: no obvious abnormality, scored as "0"; mild, scored as "1"; moderate, scored as "2"; severe, scored as "3".

[0064] 2 Experimental Results 2.1 Effect on cough sensitivity As shown in Table 1, compared with the sham operation group, the cough latency of rats in the model control group was significantly shortened ( P≤ 0.01), the number of coughs increased significantly ( P ≤ 0.01). Compared with the model control group, the cough latency of rats in the ZHT01 medium-dose, high-dose and ZHT03 high-dose groups was significantly prolonged after administration ( P ≤ 0.01), the number of coughs was significantly reduced ( P ≤ 0.05 or P ≤ 0.01). Compared with the model control group, the cough latency of the rats in the Jinsang Sanjie Pills group was significantly prolonged after administration ( P ≤ 0.01), the number of coughs was significantly reduced ( P ≤ 0.05). Compared with the Jinsang Sanjie Pills group, the cough frequency in the medium and high dose groups of ZHT01 was significantly reduced ( P ≤0.05). Compared with the high-dose group of ZHT03, the cough frequency in the medium- and high-dose groups of ZHT01 was significantly reduced ( P ≤ 0.05).

[0065]

[0066] Note: Compared with sham operation group ++ P ≤ 0.01; compared with the model control group ** P ≤ 0.01, * P ≤ 0.05; compared with the Jinsang Sanjie Pills group # P ≤ 0.05; compared with the high-dose ZHT03 group & P ≤ 0.05.

[0067] 2.2 Effects on pathological changes in pharyngeal and laryngeal tissues As shown in Table 2 and Figure 1 As shown in the figure, compared with the sham operation group, the pharyngeal mucosal congestion, mucosal inflammatory cell infiltration, mucosal swelling and thickening scores and comprehensive scores of the model control group were significantly increased ( P ≤ 0.01). Compared with the model control group, mucosal congestion, mucosal inflammatory cell infiltration, mucosal swelling and thickening, and comprehensive scores 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 mucosal congestion score and comprehensive score of the Jinsang Sanjie Pills group were significantly reduced ( P ≤ 0.05). Compared with the Jinsang Sanjie Pills group, the comprehensive score of the high-dose ZHT01 group was significantly reduced ( P ≤ 0.05). Compared with the high-dose ZHT03 group, the mucosal inflammatory cell infiltration and comprehensive score in the high-dose ZHT01 group were significantly reduced (P ≤ 0.05).

[0068]

[0069] Note: Compared with sham operation group ++ P ≤ 0.01; compared with the model control group * P ≤ 0.05, ** P ≤ 0.01; compared with the Jinsang Sanjie Pills group # P ≤ 0.05; compared with the high-dose ZHT03 group & P ≤ 0.05.

[0070] Experiment 2 In vitro antibacterial effect By using the agar diffusion method (punch method), Staphylococcus aureus, Pseudomonas aeruginosa, hemolytic Streptococcus and Streptococcus pneumoniae were inoculated in culture plates containing 100 mg / mL ZHT01 and ZHT03 extract solutions, and the diameters of the inhibition zones in the plates were measured. By 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 Streptococcus and Streptococcus pneumoniae, and the bacterial growth in the test tubes was observed. The highest dilution of the drug at which no bacterial or fungal growth was observed was taken as the minimum inhibitory concentration (MIC) of the drug.

[0071] The results showed that the MICs of cefixime against standard strains of hemolytic streptococci and pneumococci, 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 greater than those of standard strains, indicating that standard strains were more sensitive to the antibacterial effects of cefixime and gentamicin. ZHT01 and ZHT03 had certain inhibitory effects on standard strains and clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, hemolytic streptococci, and pneumococci, and the inhibitory effects of ZHT01 on standard strains and clinical isolates of the above four bacteria were stronger than those of ZHT03.

[0072]

[0073] Experiment 3: Anti-nonspecific inflammatory effect 60 ICR male mice, weighing 18.5-22.6g, were randomly divided into 6 groups according to their weight, namely blank control group, aspirin group (0.23g / kg), ZHT01 low (1.0g crude drug / kg), medium (3.0 crude drug / kg), high (9.0g crude drug / kg) dose groups, and ZHT03 high dose group (9.0g crude drug / kg), with 10 animals in each group. Before administration, the drugs were prepared with pure water to the corresponding concentrations, and each group of mice was gavaged with the corresponding dose of drug solution at 20mL / kg, once a day, for 7 consecutive days, and the blank control group was gavaged with an equal volume of pure water. 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 killed 30 minutes later, and both ears were cut along the baseline of the auricle. A 6-mm diameter puncher was used to punch out discs at the same position of the left and right ears. The weights of the left and right ears were weighed, and the degree of swelling was calculated as the right ear weight - the left ear weight.

[0074] The results showed that, as shown in Table 4, compared with the blank control group, the swelling 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 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 of mice in the aspirin group was significantly reduced ( P ≤ 0.05).

[0075]

[0076] Note: Compared with the blank control group * P ≤ 0.05, ** P ≤ 0.01.

[0077] Experiment 4: Analgesia 60 SPF ICR mice, half male and half female, weighing 20.4-26.1g, were randomly divided into 6 groups according to body weight, 10 mice in each group, namely blank control group, aspirin group (0.23g / kg), ZHT01 low (1.0g crude drug / kg), medium (3.0 crude drug / kg), high (9.0g crude drug / kg) dose groups, and ZHT03 high dose group (9.0g crude drug / kg), with 10 animals in each group. Before administration, the drugs were prepared into corresponding concentrations with pure water, and each group of mice was given the corresponding dose of drug solution by gavage at 20mL / kg, once a day, for 7 consecutive days, and the blank control group was given an equal volume of pure water by gavage.

[0078] The results showed that, as shown in Table 5, compared with the blank control group, the writhing latency of mice in the medium and high dose groups of ZHT01 was prolonged ( P ≤ 0.05 or P≤ 0.01), the number of writhing times of mice in the low, medium and high dose groups of ZHT01 were significantly reduced ( P ≤0.01). Compared with the blank control group, the writhing latency of mice in the aspirin group was significantly prolonged, the number of writhing reactions was significantly reduced, and the writhing reaction inhibition rate reached 77.78%. Compared with the high-dose ZHT03 group, the writhing latency of mice in the medium- and high-dose ZHT01 groups was prolonged, and the number of writhing reactions of mice in the medium- and high-dose ZHT01 groups was significantly reduced.

[0079]

[0080] Note: Compared with the blank control group* P ≤ 0.05,** P ≤ 0.01.

[0081] Experiment 5 Effects on the experimental rabbit chronic pharyngitis model induced by chemical injury 1 Experimental methods 1.1 Modeling, grouping and drug administration A total of 64 experimental rabbits weighing 2.0-3.0 kg, half male and half female, were selected as the sham operation group, and the remaining 54 animals were selected as the model group. The animals in the model group were smeared with 2.5% ammonia water on the throat with a sterile cotton swab once a day for 21 consecutive days, and 0.5 mL of turpentine was injected under the throat mucosa on the 8th day to replicate the chronic pharyngitis model; the animals in the sham operation group were smeared and injected with 0.9% sodium chloride injection in the same way. On the 22nd day, two animals were randomly selected from the model group and the sham operation group, respectively, and anesthetized by injecting 20% ​​ulanose 800 mg / kg into the ear vein, and euthanized by bleeding from the femoral artery, and histopathological examination was performed to determine whether the model was successful. According to histopathological examination, the model group experimental rabbits had mucosal epithelial hyperplasia in the pharynx and larynx in the form of spikes, vascular dilation and hyperplasia, obvious infiltration of a large number of inflammatory cells, and a large number of secretory granules in the cytoplasm of the submucosal glandular cells, which confirmed that the experimental rabbit chronic pharyngitis model was successfully replicated. 48 model experimental rabbits were selected and randomly divided into 6 groups according to gender and weight, namely, model control group, Jinsang Sanjie pill group (1.1g / kg), test substance ZHT01 low-dose group (0.7g crude drug / kg), ZHT01 medium-dose group (2.1g crude drug / kg), ZHT01 high-dose group (6.3g crude drug / kg), ZHT03 high-dose group (6.3g crude drug / kg), 8 rabbits in each group. Before daily administration, the test substance dry extract and Jinsang Sanjie pill were prepared into corresponding concentrations of liquid with distilled water. Each group of experimental rabbits was given the corresponding drug solution by gavage at 10mL / kg, once a day, for 14 consecutive days. The model control group and the sham operation group were given an equal volume of distilled water by gavage.

[0082] 1.2 Detection indicators (1) Gross observation of pharyngeal tissues: One hour after the last administration, rabbits in each group were anesthetized by intra-auricular injection of 20% urea and rats were anesthetized by intraperitoneal injection of 2% sodium pentobarbital 40 mg / kg. The rats were euthanized by exsanguination and autopsied to obtain pharyngeal and laryngeal tissues, which were divided into four grades according to their color, surface gloss, amount of secretions, degree of congestion, and degree of swelling. Grade 1: the pharyngeal (or laryngeal) tissue is light red, with a moist and shiny surface, no secretions, no congestion or swelling, and is awarded 1 point; Grade 2: the pharyngeal (or laryngeal) mucosa has poor gloss, with a small amount of secretions and mild congestion, and is awarded 2 points; Grade 3: the pharyngeal (or laryngeal) tissue is dark red with poor gloss, with less secretions, congestion and mild swelling, and is awarded 3 points; Grade 4: the pharyngeal (or laryngeal) tissue is dark red, dull, with more secretions accumulated, and obvious congestion and swelling, and is awarded 4 points.

[0083] (2) Histopathological examination of pharynx and larynx: One hour after the last administration, rabbits in each group were anesthetized by intraauricular injection of 20% urea and rats were anesthetized by intraperitoneal injection of 2% sodium pentobarbital 40 mg / kg. The animals were euthanized by exsanguination and dissected. The pharynx and larynx tissues were obtained, fixed with formalin, embedded in paraffin, sectioned, stained with HE, and observed under a microscope. The histopathological changes of the pharynx (or larynx) were scored according to the mucosa and lamina propria layer, glandular structure, and inflammatory cells.

[0084] 2 Experimental Results 2.1 Impact on the gross observation score of pharyngeal tissue As shown in Table 6, the pharynx and larynx of the rabbits in the sham operation group were shiny and moist, without obvious congestion and swelling; the pharynx and larynx tissues 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 operation group ( P ≤ 0.01). Compared with the model control group, the macroscopic observation scores of the pharynx and larynx of the 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 of the Jinsang Sanjie Pills experimental rabbits were significantly reduced ( P ≤ 0.01). Compared with the Jinsang Sanjie Pills 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). Compared with the high-dose ZHT03 group, the macroscopic observation scores of the pharynx and larynx of the experimental rabbits in the high-dose ZHT01 group were significantly reduced ( P ≤ 0.05).

[0085]

[0086] Note: Compared with the blank control group ++P ≤ 0.01; compared with the model control group** P ≤ 0.01; compared with the Jinsang Sanjie Pills group # P ≤ 0.05, ## P ≤ 0.01; compared with the high-dose ZHT03 group & P ≤ 0.05.

[0087] 2.2 Effects on pathological changes in throat tissue As shown in Table 7, compared with the sham operation group, the scores of pharyngeal mucosa and lamina propria, glandular structure, inflammatory cell pathology score and comprehensive score of the model control group were significantly increased ( 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 structure 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 Jinsang Sanjie Pills group were significantly reduced ( P ≤ 0.05). Compared with the Jinsang Sanjie Pills group, the pathological score and comprehensive score of the pharyngeal glandular structure in the high-dose ZHT01 group were significantly reduced ( P ≤ 0.05 or P ≤ 0.01).

[0088] 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 glandular structures in the high-dose ZHT01 group were significantly reduced.

[0089]

[0090] Note: Compared with sham operation group + P ≤ 0.05, ++ P ≤ 0.01; compared with the model control group* P ≤ 0.05,** P ≤ 0.01; compared with the Jinsang Sanjie Pills group# P ≤ 0.05,## P ≤ 0.01.

[0091] Example 6 Clinical experience study on the use of the Chinese medicine composition of the present invention in treating pharyngitis at the onset stage This study aims to explore the clinical efficacy and safety of the ZHT001 drug group (the Chinese medicine composition of the present invention) in the treatment of pharyngitis attacks, and to provide new ideas and evidence for clinical treatment.

[0092] Study purpose: To evaluate the effect of ZHT001 drug group treatment on the improvement of clinical symptoms of patients with pharyngitis exacerbation; to observe the safety of ZHT001 treatment in patients with pharyngitis exacerbation.

[0093] Protocol Design: Randomized, double-blind, placebo-controlled study.

[0094] Case selection criteria: The diagnostic criteria of Western medicine refer to the "Otorhinolaryngology Head and Neck Surgery" as follows: 1) Medical history: history of upper respiratory tract infection such as acute tonsillitis or acute rhinitis.

[0095] 2) Symptoms: including dry throat, sore throat or pain when swallowing, accompanied by chills and fever, thirst, loss of appetite (poor appetite) and heaviness and pain in the body.

[0096] TCM diagnosis and scoring to be determined: Inclusion criteria: Meet the above diagnostic and differentiation criteria; 2) Age 18-70 years old; 3) Disease duration ≤ 48 hours; 4) 4 points ≤ pharyngeal pain visual analogue scale (VAS) score ≤ 7 points; Those who voluntarily become subjects and sign to agree to complete the treatment.

[0097] Exclusion criteria: 1) Body temperature>38.0℃; 2) Peripheral blood leukocyte count > 10 × 10^9 / L at the first visit; 3) Other Chinese and Western medicines (such as Chinese medicine preparations, glucocorticoids, non-steroidal anti-inflammatory drugs, etc.) have been used to treat acute pharyngitis during this illness; 4) Examination confirms that pharyngitis is caused by measles, scarlet fever, influenza, infectious mononucleosis, agranulocytosis, leukemia, etc.; 5) Liver function impairment [alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 times the upper limit of normal value], renal insufficiency [creatinine (Cr) > upper limit of normal value]; 6) Patients with serious primary diseases of cardiovascular, cerebrovascular, liver, kidney, endocrine or hematopoietic system, or mental illness; 7) Women who are pregnant or preparing to become pregnant (except those who want to terminate the pregnancy) or breastfeeding; 8) Known history of allergy to the components of the test drug; 9) Participating in other drug clinical trials.

[0098] Exit Criteria ① During the study, if the subjects develop comorbidities or complications that may make them unsuitable for continued participation in the study, the clinical investigators will be stopped based on the doctor's judgment; ② During the study, if the patient's condition worsens or a serious adverse event may occur or has occurred, the clinical study will be stopped according to the doctor's judgment, and those whose condition worsens will be treated as invalid cases; ③ In clinical research, if the subjects are unwilling to continue the clinical research and request to withdraw from the clinical research, the clinical research will be stopped based on the doctor's judgment.

[0099] Treatment options Example 1 Group: ZHT001 Chinese medicine composition, the Chinese medicine components are calculated by weight: Scutellaria barbata 15g, Psoralea corylifolia 15g, Solidago asiatica 10g, Nepeta tenuifolia 10g, Microphylla scabrae 10g, Sophora flavescens 5g, Saposhnikovia divaricata 5g. The above-mentioned prescription medicine is decocted twice with water, the first time with 10 times the amount of water, decocted for 2 hours, the second time with 10 times the amount of water, decocted for 2 hours, the decoction is combined, filtered, and the Chinese medicine decoction of the present invention is obtained, which is divided into 2 portions, one dose per day, taken twice a day, morning and evening. Drink for 3 consecutive days.

[0100] 2. Drug control group: Yinhuang oral liquid, oral liquid, each bottle contains 10 ml, national medicine standard number Z36020687 "Pharmacopoeia of the People's Republic of China" 2010 edition Part 1, usage: 10 ml at a time, 3 times a day.

[0101] A total of 120 participants with pharyngitis exacerbation were selected, with 60 participants in each group.

[0102] Observation indicators Efficacy indicators include: 1) VAS score of pharyngeal pain.

[0103] 2) Efficacy of TCM syndrome: According to the efficacy judgment standard formulated in the "Guidelines for Clinical Research of New Chinese Medicines (Trial)", the main symptoms include sore throat, dry and burning throat, and pharyngeal mucosal congestion, and the scoring standard is: 0 points for none, 2 points for mild, 4 points for moderate, and 6 points for severe. Secondary symptoms include hoarseness, dysphagia, fever, aversion to wind, headache, and cough with yellow sputum, and the scoring standard is: 0 points for none, 1 point for mild, 2 points for moderate, and 3 points for severe. The efficacy is judged as follows: Recovery: Symptoms and signs disappear or almost disappear, and the symptom score reduction rate is ≥95%.

[0104] Markedly effective: symptoms and signs are significantly improved, with the reduction rate of syndrome scores ≥70% but <95%.

[0105] Effective: Symptoms and signs have improved, and the reduction rate of syndrome scores is ≥30% but <70%.

[0106] Ineffective: There is no significant improvement in symptoms and signs, or they may even worsen, and the reduction rate of symptom scores is less than 30%.

[0107] The calculation formula for the total effective rate of TCM syndrome is: (number of cured patients + number of markedly effective patients + number of effective patients) / total number of patients.

[0108] Total number of cases × 100%. The SF-36 scale covers 8 dimensions and a total of 36 items, each with a corresponding score. The score of each dimension is the sum of the scores of all items in that dimension. According to the scale scoring method, the weighted scores of each item are added together to obtain the final score, with a total score ranging from 35 to 144 points. A low score means a poor quality of life, while a high score means a better quality of life.

[0109] Observation period The treatment duration is 4 days.

[0110] Statistical methods Statistical methods: SPSS16.0 statistical software was used for data collection and analysis. The t-test was used for comparison of quantitative data, and the x2 test was used for comparison of counting data. P<0.05 indicated statistical significance.

[0111] Experimental Results

[0112]

[0113] The research results show that both the control group 1 and the example 1 group have good therapeutic effects on pharyngitis, and the total effective rate of the example 1 group is 93.33%.

[0114] Safety evaluation: No adverse events occurred during the trial, and the trial was safe and reliable.

[0115] Typical cases of rapid relief of sore throat: A Chinese medicine composition for treating pharyngitis, wherein the Chinese medicine components are calculated by weight as follows: 15g of Scutellaria barbata, 15g of Psoralea corylifolia, 10g of Solidago asiatica, 10g of Nepeta tenuifolia, 10g of Microphylla scabra, 5g of Sophora flavescens, and 5g of Saposhnikovia divaricata. The above-mentioned prescription drugs are decocted with water twice, decocted for 2 hours with 10 times the amount of water for the first time, and decocted for 2 hours with 10 times the amount of water for the second time, the decoctions are combined, filtered, and the Chinese medicine decoction of the present invention is obtained, which is divided into 2 portions, and taken once a day, twice a day, in the morning and evening.

[0116] Typical case 1, Mr. Wei, 50 years old, suffered from severe sore throat, hoarseness, inability to swallow, and obvious sore throat after drinking water. After taking anti-inflammatory drugs for several days without any effect, he took the decoction of the Chinese medicine composition of Example 1 of the present invention, 2 doses per day, divided into morning and evening. After taking it once, about 4 hours later, the hoarseness was significantly improved, and the sore throat almost completely disappeared. After continuing to take it for 4 days, all symptoms disappeared and he was cured.

[0117] Typical case 2, Ms. Shen, 29 years old, suffered from severe sore throat. Examination showed that the tonsils were inflamed, red and swollen, the throat was obviously painful, and the voice was hoarse. She then took the decoction of the Chinese medicine composition of Example 1 of the present invention, one dose per day, twice a day, morning and evening, and once at night. The sore throat basically disappeared on the morning of the second day, and she continued to take it for 3 days and recovered.

[0118] Typical case 3, Xie Moumou, female, 49 years old, suffered from severe sore throat due to cold, and had a "razor throat". She then took the Chinese medicine composition decoction of Example 1 of the present invention, one dose per day, divided into morning and evening. After taking it once, about 4 hours later, the pain of sore throat was significantly relieved. After taking 6 doses, she recovered.

[0119] The above is a specific implementation mode of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field, within the technical scope disclosed by the present invention, can make equivalent replacements or changes according to the technical solutions and concepts of the present invention, which should be covered by the protection scope of the claims of the present invention.

Claims

1. A Chinese medicine composition for treating pharyngitis, characterized in that: The invention is composed of the following traditional Chinese medicine components in parts by weight: 12-18 parts of Scutellaria barbata, 12-18 parts of Psoralea corylifolia, 8-12 parts of Solidago asiatica, 8-12 parts of Schizonepeta tenuifolia, 8-12 parts of Microphylla scabra, 3-6 parts of Bletilla striata and 3-6 parts of Saposhnikovia divaricata.

2. A Chinese medicine composition for treating pharyngitis according to claim 1, characterized in that: The Chinese medicinal components are calculated by weight as follows: 15 parts of Scutellaria barbata, 15 parts of Psoralea corylifolia, 10 parts of Solidago asiatica, 10 parts of Schizonepeta tenuifolia, 10 parts of Glechoma longituba, 5 parts of Bletilla striata, and 5 parts of Saposhnikovia divaricata.

3. A Chinese medicine composition for treating pharyngitis according to claim 1, characterized in that: The Chinese medicinal components are calculated by weight as follows: 18 parts of Scutellaria barbata, 18 parts of Psoralea corylifolia, 12 parts of Solidago asiatica, 12 parts of Schizonepeta tenuifolia, 12 parts of Microphylla scabra, 6 parts of Bletilla striata, and 6 parts of Saposhnikovia divaricata.

4. A Chinese medicine composition for treating pharyngitis according to any one of claims 1 to 3, characterized in that: The above-mentioned prescription medicine is decocted with water for 2-3 times, each time adding 8-12 times the amount of water and decocting 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 medicine composition of the present invention.

5. A Chinese medicine composition for treating pharyngitis according to claim 4, characterized in that: The above-mentioned prescription medicine is decocted with water twice, the first time adding 10-12 times the amount of water and decocting for 2-3 hours, the second time adding 8-10 times the amount of water and decocting for 1-3 hours, combining the decoctions, filtering, and concentrating the filtrate to a relative density of 1.05-1.15 to obtain the Chinese medicine composition of the present invention.

6. A Chinese medicine composition for treating pharyngitis according to any one of claims 1 to 3, characterized in that: The above-mentioned prescription medicine is decocted with water for 2-3 times, and 8-12 times the amount of water is added each time for decocting for 1-3 hours. The decoctions are combined and filtered to obtain the Chinese medicine composition decoction of the present invention.

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

8. Use of the Chinese medicine composition according to any one of claims 1 to 7 in the preparation of pharyngitis medicines.

9. The use according to claim 7, characterized in that: The Chinese medicine composition is used in preparing medicines for acute and chronic pharyngitis.

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