Traditional Chinese medicine composition as well as preparation method and application thereof

Abstract

The invention relates to a traditional Chinese medicine composition as well as a preparation method and application thereof. The traditional Chinese medicine composition is prepared from the following medicinal materials: radix scutellariae, fructus forsythiae, radix isatidis, cortex phellodendri and semen oroxyli. The traditional Chinese medicine composition has analgesic, anti-inflammatory, bacteriostatic or antipyretic effects, and especially has curative effects on upper respiratory tract infection, pharyngitis, laryngitis, amygdalitis and angina.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and particularly to a traditional Chinese medicine composition, a preparation method thereof and an application thereof. Background Art

[0002] Acute upper respiratory tract infection is a general term for acute inflammations of the nasal cavity, pharynx or larynx. It includes common cold, viral pharyngitis, laryngitis, herpangina, pharyngoconjunctival fever, bacterial pharyngo-tonsillitis, etc. Although these diseases are mostly self-limiting, their incidence rates are relatively high. Among them, 70% - 80% are caused by viruses, including rhinovirus, coronavirus, adenovirus, influenza and parainfluenza viruses, respiratory syncytial virus, echovirus, coxsackievirus, etc. Another 20% - 30% of upper respiratory tract infections are caused by bacteria. The elderly, the young, the weak, those with low immune function or those suffering from chronic respiratory diseases are susceptible. Clinically, there is still no specific medicine for the treatment of acute upper respiratory tract infection. At present, traditional Chinese medicine preparations for treating acute upper respiratory tract infection mostly use drugs with bitter-cold properties for clearing heat and relieving the exterior, such as Reyanling Mixture, Shuanghuanglian Oral Liquid, Anti-virus Oral Liquid, etc. People with weak and cold constitutions are prone to adverse reactions such as diarrhea and stomach cold. Sometimes the patient has intermingled cold and heat, and it is not easy to judge wind-cold or wind-heat to administer medicine symptomatically, thus affecting the curative effect. Therefore, there are few drugs related to specific syndrome types and combined with syndrome differentiation and treatment. Summary of the Invention

[0003] Acute upper respiratory tract infection belongs to the category of "exogenous febrile diseases" in traditional Chinese medicine, corresponding to diseases such as "common cold", "acute throat obstruction", "acute aphonia", "acute tonsillitis" in traditional Chinese medicine. Through long-term clinical research, the inventor of the present invention found that the key pathogenesis of acute throat obstruction is "wind-heat attacking from above, simultaneous disease of the lung and stomach". Regarding the relationship between the throat obstruction and the lung and stomach, "Zhang's Medical General" once said, "The two orifices of the throat and pharynx come from the same cavity, with different functions. The throat is in front and is responsible for exhalation, and the pharynx is behind and is responsible for swallowing; the throat is firm and hollow, connecting to the root of the lung, being the path of qi, responsible for exhalation but not inhalation; the pharynx is soft and hollow, connecting to the root of the stomach, being the path of food, responsible for inhalation but not exhalation." Among them, (1) the throat belongs to the lung system, the hand taiyin lung meridian enters the lung, follows the meridian through the throat, and the throat is the passage of lung qi. The lung is a metal organ, governing qi and respiration. "The Experience Book of Sores and Ulcers, Volume 1" said, "The throat corresponds to the qi of heaven and is the connection of the lung"; (2) the pharynx belongs to the stomach system, and "General Treatise on the Holy Relief, Volume 60, Throat Disorders" said, "The throat and pharynx are produced from the qi of the lung and stomach, mainly responsible for ventilating qi, water and grains, being the path of stomach qi, so it is the connection of the stomach."

[0004] Based on clinical experience and traditional Chinese medicine theory, the inventor of the present invention believes that the key pathogenesis of acute upper respiratory tract infection with symptoms such as fever and sore throat is "exogenous wind-heat, simultaneous disease of the lung and stomach", and it is often related to the constitution of latent heat. Therefore, in the clinical treatment of acute upper respiratory tract infection, the inventor is good at using the main formula compatibility idea of "relieving exterior and interior simultaneously, treating the lung and stomach together". The inventor of the present invention screened out easily available, low-cost and easily industrialized medicinal materials from many Chinese medicinal materials as the raw materials of the traditional Chinese medicine composition of the present invention.

[0005] On the one hand, the present invention provides a traditional Chinese medicine composition, which is prepared from the following medicinal materials: Scutellaria baicalensis, Forsythia suspensa, Isatis indigotica, Phellodendron amurense, and Oroxylum indicum. The inventor of the present invention found that the traditional Chinese medicine composition uses Forsythia suspensa to relieve exterior syndrome with pungent and cool nature, and combines with Scutellaria baicalensis to relieve exterior syndrome and clear interior heat together. With Isatis indigotica added to clear heat and detoxify, and reduce inflammation and swelling, it is very effective for acute tonsillitis. On this basis, adding Phellodendron amurense not only strengthens the effect of clearing heat and detoxifying, but also is good at clearing and expelling latent heat; in addition, adding Oroxylum indicum not only improves the effect of clearing the lung and relieving sore throat, but also takes into account relieving cough and resolving phlegm, soothing the liver and regulating the stomach, and also has curative effect on acute attack of chronic pharyngitis. Through repeated clinical practice, the traditional Chinese medicine composition of the present invention has obvious improvement in symptoms such as tonsil enlargement for acute upper respiratory tract infection.

[0006] In the traditional Chinese medicine composition provided by the present invention, forsythia suspensa and scutellaria baicalensis are used as the monarch drugs. Among them, forsythia suspensa is cool in nature, bitter and pungent in taste, and belongs to the lung, heart, and small intestine meridians. It has the functions of dispersing wind-heat for pungent-cool exterior-relieving, clearing heat and detoxifying for dissipating swelling and nodules. In ancient times, those with excessive heat in the upper jiao and stagnant heat in the middle jiao must choose it. At the same time, forsythia suspensa is also the "sacred medicine for sores". "Shennong Ben Cao Jing" states that it "treats cold and heat, carbuncles and ulcers, heat accumulation, scrofula and tuberculosis". Modern pharmacological research shows that in addition to antioxidant activity, antibacterial activity, anti-inflammatory activity, antiviral activity, antipyretic and analgesic activity, neuroprotective effect, prevention of ototoxicity, etc., forsythia suspensa also has the effects of antiemetic, liver protection, and stomach regulation. It is commonly used for wind-heat colds, the initial stage of warm diseases, or when warm heat enters the nutrient system, with symptoms such as high fever, restlessness, thirst, coma, macules, sore throat, and carbuncles and ulcers. Scutellaria baicalensis is cold in nature and bitter in taste, and belongs to the lung, gallbladder, spleen, large and small intestine meridians. It has the functions of clearing heat and drying dampness, purging fire and detoxifying. As Li Dongyuan said: "For treating lung heat like being burned by fire, with restlessness, thirst, and being more severe during the day, a decoction of scutellaria baicalensis alone is suitable." "Compendium of Materia Medica" states that it "treats wind-heat, damp-heat headache, running piglet heat pain, cough with lung heat, lung abscess, throat odor, and various hemorrhages". This shows that scutellaria baicalensis is good at clearing heat pathogens in the upper jiao and can also clear damp-heat in the liver and gallbladder. Pharmacological research shows that scutellaria baicalensis has various pharmacological effects such as antipyretic and anti-inflammatory, anti-microbial, anti-tumor, free radical scavenging, antioxidant, liver protection, anti-ulcer activity, and immune regulation. It is commonly used for fever, restlessness, thirst, cough with lung heat, diarrhea with dysentery, heat strangury, jaundice, and carbuncles and ulcers. Secondly, isatis root and phellodendron amurense are used as the ministerial drugs. Among them, isatis root is bitter and cold in taste, and belongs to the heart, liver, and stomach meridians. It has the functions of clearing heat and detoxifying, cooling blood and dissipating nodules, and relieving sore throat and swelling. "Compendium of Materia Medica Readily Understood" once said: "It can enter the blood aspect of the liver and stomach, and its functions are just clearing heat, detoxifying, preventing epidemic diseases, and killing insects." Pharmacological research shows that isatis root not only has antiviral and antibacterial and anti-inflammatory effects, but also can improve the body's immunity and has a certain anti-tumor effect. It is mainly used for treating viral infectious diseases, and has significant effects on influenza, acute pharyngitis, epidemic encephalitis B, chronic pharyngitis, herpes simplex keratitis, herpes zoster, nephrotic hematuria, chickenpox, etc. Phellodendron amurense is bitter and cold in taste, and belongs to the kidney and bladder meridians. It can clear heat and dry dampness, purge fire and detoxify. "Shennong Ben Cao Jing" states that it "treats heat accumulation in the five zang-organs and the intestines and stomach, jaundice, intestinal hemorrhoids; stops diarrhea and dysentery, vaginal discharge in women with red and white color, and erosion sores due to yin injury." "Introduction to Medicine" says that it "can treat red eyes, rosacea, throat obstruction, carbuncles, breast abscess, and umbilical sores." This shows that phellodendron amurense can not only clear damp-heat in the lower jiao, but is also good at dispelling latent heat, which fits the pathogenesis characteristics of often having latent heat in the lung and stomach in patients with recurrent upper respiratory tract infections. Modern pharmacological research shows that phellodendron amurense has effects such as antibacterial, antifungal, antiviral, and other pathogenic microorganism resistance, anti-arrhythmia, blood pressure lowering, inhibition of cellular immune response, anti-gastrointestinal ulcer, and blood sugar lowering. It is commonly used for damp-heat diarrhea, jaundice, heat strangury, hemorrhoids and fistulas, steaming bone fever, rubella itching, and sores and ulcers. Finally, oroxylum indicum is used as the assistant and guiding drug. Oroxylum indicum is cool in nature, bitter, sweet, light in texture, and enters the lung, liver, and stomach meridians. It has the functions of clearing the lung and relieving sore throat, relieving cough and resolving phlegm, soothing the liver and regulating the stomach."Modern Practical Chinese Medicine" states that it "relieves cough, treats whooping cough and dry bronchitis", and "Chinese Medicine Dictionary" states that it "clears lung heat, benefits the throat, treats acute and chronic bronchitis, sore throat, and tonsillitis". "Chinese Pharmacopoeia" records that it "clears the lung, soothes the throat, soothes the liver and stomach, and is used for cough due to lung heat and liver-stomach qi pain". It is commonly used for cough due to lung heat, aphonia due to throat obstruction, liver-stomach qi pain, and non-healing of sore openings. It is particularly suitable for acute and chronic pharyngitis and laryngeal cough.

[0007] Therefore, for the traditional Chinese medicine composition of the present invention, when various herbs are combined, the whole formula relieves both exterior and interior syndromes, treats both the lung and stomach simultaneously, and jointly exerts the effects of dispersing wind and heat, clearing heat and detoxifying, and relieving swelling and pain in the throat. Thus, various symptoms can be alleviated, and the compatibility is precise. Therefore, it is suitable for those with acute throat obstruction belonging to the pattern of wind-heat attacking from above and co-pathology of the lung and stomach.

[0008] The selection of the herbs and the ratio of each raw material drug of the traditional Chinese medicine composition of the present invention are also obtained through the theory of compatibility of traditional Chinese medicine, the results of pharmacodynamic experiments, and the summary of clinical experience.

[0009] In some embodiments, the traditional Chinese medicine composition of the present invention is prepared from the following herbs in parts by weight: Scutellaria baicalensis Georgi 5 - 15 parts, Forsythia suspensa (Thunb.) Vahl 8 - 20 parts, Isatis indigotica Fortune 8 - 21 parts, Phellodendron amurense Rupr. 2 - 10 parts, and Oroxylum indicum (L.) Kurz 2 - 10 parts.

[0010] In some embodiments, the traditional Chinese medicine composition of the present invention is prepared from the following herbs in parts by weight: Scutellaria baicalensis Georgi 8 - 12 parts, Forsythia suspensa (Thunb.) Vahl 10 - 15 parts, Isatis indigotica Fortune 12 - 18 parts, Phellodendron amurense Rupr. 4 - 8 parts, and Oroxylum indicum (L.) Kurz 4 - 8 parts.

[0011] In some embodiments, for the traditional Chinese medicine composition of the present invention, the dosage of Scutellaria baicalensis Georgi is 8 parts, 9 parts, 10 parts, 11 parts, or 12 parts.

[0012] In some embodiments, for the traditional Chinese medicine composition of the present invention, the dosage of Forsythia suspensa (Thunb.) Vahl is 10 parts, 11 parts, 12 parts, 13 parts, 14 parts, or 15 parts.

[0013] In some embodiments, for the traditional Chinese medicine composition of the present invention, the dosage of Isatis indigotica Fortune is 12 parts, 13 parts, 14 parts, 15 parts, 16 parts, 17 parts, or 18 parts.

[0014] In some embodiments, for the traditional Chinese medicine composition of the present invention, the dosage of Phellodendron amurense Rupr. is 4 parts, 5 parts, 6 parts, 7 parts, or 8 parts.

[0015] In some embodiments, for the traditional Chinese medicine composition of the present invention, the dosage of Oroxylum indicum (L.) Kurz is 4 parts, 5 parts, 6 parts, 7 parts, or 8 parts.

[0016] In some embodiments, the traditional Chinese medicine composition of the present invention is prepared from the following herbs in parts by weight: Scutellaria baicalensis Georgi 10 parts, Forsythia suspensa (Thunb.) Vahl 12 parts, Isatis indigotica Fortune 15 parts, Phellodendron amurense Rupr. 6 parts, and Oroxylum indicum (L.) Kurz 6 parts.

[0017] In some embodiments, the traditional Chinese medicine composition of the present invention is prepared from the following medicinal materials by weight: 8 parts of Scutellaria baicalensis, 10 parts of Forsythia suspensa, 12 parts of Isatis tinctoria, 4 parts of Phellodendron amurense, and 4 parts of Oroxylum indicum.

[0018] In some embodiments, the traditional Chinese medicine composition of the present invention is prepared from the following medicinal materials by weight: 12 parts of Scutellaria baicalensis, 15 parts of Forsythia suspensa, 18 parts of Isatis tinctoria, 8 parts of Phellodendron amurense, and 8 parts of Oroxylum indicum.

[0019] In some embodiments, the traditional Chinese medicine composition of the present invention is prepared from the following medicinal materials by weight: 10 parts of Scutellaria baicalensis, 12 parts of Forsythia suspensa, 15 parts of Isatis tinctoria, 8 parts of Phellodendron amurense, and 6 parts of Oroxylum indicum.

[0020] In an embodiment of the present invention, for the traditional Chinese medicine composition of the present invention, Oroxylum indicum can be replaced by Achyranthes aspera L. Achyranthes aspera L. is a herbaceous plant of the genus Achyranthes in the family Amaranthaceae; it has the effects of clearing heat and detoxifying, and diuresis, and is used to treat symptoms such as cold and fever, tonsillitis, diphtheria, epidemic parotitis, urinary system stones, and nephritis edema. Achyranthes aspera L. replacing Oroxylum indicum in the present invention has the medicinal effects described in the present invention, but is weaker than the prescription containing Oroxylum indicum in terms of the efficacy in acute conditions.

[0021] In a second aspect, the present invention provides a pharmaceutical composition containing the above traditional Chinese medicine composition. In an embodiment of the present invention, the pharmaceutical composition provided by the present invention comprises the above traditional Chinese medicine composition and a pharmaceutically acceptable carrier.

[0022] In an embodiment of the present invention, for the pharmaceutical composition provided by the present invention, the weight percentage of the traditional Chinese medicine composition can be 0.1 - 99.9%, preferably 30 - 70%.

[0023] In an embodiment of the present invention, the pharmaceutical composition provided by the present invention is made into a pharmaceutically acceptable preparation form or dosage form.

[0024] In an embodiment of the present invention, the pharmaceutical composition of the present invention is in the form of a unit - dose pharmaceutical preparation, and the unit - dose form refers to the unit of the preparation, such as each tablet of a tablet, each capsule of a capsule, each bottle of an oral liquid, each bag of a granule, etc.

[0025] In some embodiments, for the pharmaceutical composition of the present invention, the pharmaceutical preparation form can be any pharmaceutically acceptable dosage form, and these dosage forms include: tablets (such as sugar - coated tablets, film - coated tablets or enteric - coated tablets), capsules (such as hard capsules or soft capsules), oral solutions, buccal tablets, granules, pills, syrups, powders, plasters, pills, suspensions, powders, solution agents, injections, suppositories, ointments, patches, creams, sprays, drops or patches.

[0026] In some embodiments, in the pharmaceutical composition of the present invention, the pharmaceutically acceptable carrier is selected from one or more of the following substances: water, ethanol, propylene glycol, mannitol, sorbitol, dextrin, maltodextrin, sodium starch glycolate, sodium metabisulfite, sodium bisulfite, sodium thiosulfate, mercaptoacetic acid, vitamin C, disodium EDTA, calcium disodium EDTA, carbonates, acetates, phosphates of monovalent alkali metals or their aqueous solutions, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids (such as glycine, cysteine hydrochloride, or methionine, etc.), sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose or its derivatives, alginates, gelatin, polyvinylpyrrolidone, glycerol, polysorbates (such as polysorbate 20, polysorbate 60 or polysorbate 80), sorbitans (sorbitan laurate, sorbitan oleate, sorbitan palmitate or sorbitan stearate), agar, calcium carbonate, calcium bicarbonate, surfactants (such as sodium dodecyl sulfate), polyethylene glycols, cyclodextrins (such as α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin or hydroxypropyl-β-cyclodextrin, etc.), phospholipid materials, kaolin, talc, calcium stearate, magnesium stearate, etc.

[0027] The pharmaceutical composition of the present invention is in the form of an oral solid dosage form and may contain common excipients as pharmaceutically acceptable carriers, such as binders, fillers, diluents, lubricants, disintegrants, colorants, flavoring agents and / or wetting agents. The tablets can be coated if necessary. Suitable fillers include dextrin, maltodextrin, cellulose and its derivatives, mannitol, lactose and other similar fillers. Suitable disintegrants include starch, polyvinylpyrrolidone, cellulose and its derivatives, starch derivatives, etc. and other similar disintegrants, such as sodium starch glycolate, sodium carboxymethylcellulose. Suitable lubricants include magnesium stearate, talc, calcium stearate, etc. Suitable pharmaceutically acceptable wetting agents include sodium dodecyl sulfate, etc. Suitable binders include ethanol solutions, starch paste, water, etc. The pharmaceutical composition of the present invention in solid oral form can be prepared by common methods such as mixing, filling, granulating, tabletting, etc. Repeated mixing can distribute the traditional Chinese medicine composition in the pharmaceutical composition.

[0028] The pharmaceutical composition of the present invention is in the form of an oral liquid preparation, for example, it can be an aqueous or oily suspension, solution, emulsion, syrup or elixir, or it can be a dry product that can be reconstituted with water or other suitable carriers before use. Such liquid preparations may contain conventional excipients as pharmaceutically acceptable carriers, such as suspending agents, for example, sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate or hydrogenated edible fat; emulsifying agents, for example, lecithin, sorbitan monooleate or gum arabic; non-aqueous carriers (which may include edible oils), for example, almond oil, coconut oil, propylene glycol or ethanol; preservatives, for example, methyl paraben or propyl paraben or sorbic acid; and if necessary, may contain conventional flavoring agents, fragrances or coloring agents.

[0029] The pharmaceutical composition of the present invention is in the form of an injection. The prepared liquid unit dosage form contains the traditional Chinese medicine composition of the present invention and a sterile carrier. Depending on the carrier and concentration, this traditional Chinese medicine composition can be dissolved. The preparation of the solution is usually by dissolving the traditional Chinese medicine composition in a carrier, filtering and sterilizing it before filling it into a suitable vial or ampoule, and then sealing it.

[0030] In some embodiments, the pharmaceutical composition of the present invention is a capsule, granule, tablet, dripping pill, oral solution, syrup, injection or ointment, etc.

[0031] In some embodiments, the pharmaceutical composition of the present invention is an oral solid preparation (such as a capsule, granule or tablet), which includes one or more of a flavoring agent, a binder, a disintegrant, a filler, a lubricant, a coloring agent, and a coating agent; preferably, the oral solid preparation is a granule.

[0032] In some embodiments, the flavoring agent in the pharmaceutical composition of the present invention is selected from one or more of sucrose, stevioside, aromatic syrup, sodium cyclamate, stevia sugar, sodium saccharin, protein sugar, xylitol, sorbitol, high fructose, aspartame, sucralose and citric acid; preferably sucralose.

[0033] In some embodiments, the addition amount of the flavoring agent is 0.1-0.4% of the total mass of the pharmaceutical composition, preferably 0.2-0.4%.

[0034] In some embodiments, the binder in the pharmaceutical composition of the present invention is selected from one or more of water, hydroxypropyl methylcellulose, starch paste or ethanol solution.

[0035] In some embodiments, the binder in the pharmaceutical composition of the present invention is selected from water or an ethanol solution, and the concentration of the ethanol solution is 50 - 95% (volume ratio). In the granulation preparation process, the amount of the binder is appropriate and is adjusted according to the state of the soft material. The soft material is required to form a ball when held and disperse when pinched. Water or ethanol will be removed during the particle drying process.

[0036] In some embodiments, the filler in the pharmaceutical composition of the present invention is selected from one or more of dextrin, microcrystalline cellulose, lactose, starch, pregelatinized starch, powdered sugar, mannitol, sorbitol, and maltodextrin. Preferably, the filler is maltodextrin. The mass ratio of the filler to the traditional Chinese medicine composition is (0.5 - 3.0):1; preferably (1.0 - 2.0):1.

[0037] In some embodiments, the disintegrant in the pharmaceutical composition of the present invention is selected from one or more of cross-linked polyvinylpyrrolidone, sodium carboxymethyl cellulose, starch, sodium carboxymethyl starch, hydroxypropyl starch, and low-substituted hydroxypropyl cellulose. The addition amount of the disintegrant is 0 - 2% of the total mass of the pharmaceutical composition.

[0038] In some embodiments, the lubricant in the pharmaceutical composition of the present invention is selected from one or more of magnesium stearate, calcium stearate, stearic acid, talc powder, colloidal silica, and polyethylene glycol. Optionally, the addition amount of the lubricant is 0 - 1% of the total mass of the pharmaceutical composition. Preferably, the polyethylene glycol is in solid form, such as polyethylene glycol 4000, polyethylene glycol 6000, etc. Preferably, the addition amount of the lubricant is 0 - 1% of the total mass of the pharmaceutical composition.

[0039] In a third aspect, the present invention provides a preparation method of the above traditional Chinese medicine composition. The preparation method includes the following steps: weighing the above 5 herbs (Scutellaria baicalensis, Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Oroxylum indicum, or Scutellaria baicalensis, Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Achyranthes aspera), decocting with water, filtering, and concentrating and / or drying the filtrate.

[0040] In some embodiments, the preparation method of the above traditional Chinese medicine composition provided by the present invention includes the following steps: weighing Scutellaria baicalensis extract, Forsythia suspensa extract, Isatis tinctoria extract, Phellodendron amurense extract, and Oroxylum indicum extract, or weighing Scutellaria baicalensis extract, Forsythia suspensa extract, Isatis tinctoria extract, Phellodendron amurense extract, and Achyranthes aspera extract; and mixing them. In some embodiments, the extract can adopt a preparation process of decocting with water, filtering, concentrating, and / or drying.

[0041] In some embodiments, the preparation method of the above traditional Chinese medicine composition provided by the present invention further includes an ethanol precipitation step for the filtrate, and the ethanol precipitation step is after the water decocting step.

[0042] In some embodiments, the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention comprises the following steps: Weigh the above 5 kinds of medicinal materials (Scutellaria baicalensis, Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Oroxylum indicum, or Scutellaria baicalensis, Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Achyranthes aspera), decoct with water 1 - 3 times, each time for 0.5 - 3 hours, filter, and concentrate and / or dry the filtrate. Optionally, decoct with 6 - 15 times the amount of water (referring to the total weight of the 5 kinds of medicinal materials, the same hereinafter).

[0043] In some embodiments, decoct three times. For the first time, add 8 - 15 times the amount of water, decoct for 1 - 2 hours, and filter; for the second time, add 6 - 12 times the amount of water, decoct for 0.5 - 2 hours, and filter; for the third time, add 6 - 12 times the amount of water, decoct for 0.5 - 2 hours, and filter; combine the filtrates of the three times; concentrate the filtrate to obtain a clear extract, and that's it.

[0044] In some embodiments, for the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention, among them, the above 5 kinds of medicinal materials can also be fed in the following way, where 4 kinds of medicinal materials including Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Oroxylum indicum (or Achyranthes aspera) are fed first, and Scutellaria baicalensis is added after decocting until the water boils; optionally, the temperature at which the water boils is 80 - 100 °C.

[0045] In some embodiments, the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention comprises the following steps: For the first time, add 8 - 15 times the amount of water to 4 kinds of medicinal materials including Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Oroxylum indicum (or Achyranthes aspera), decoct until the water boils and then add Scutellaria baicalensis, decoct for 1 - 2 hours, and filter; for the second time, add 6 - 12 times the amount of water, decoct for 0.5 - 2 hours, and filter; for the third time, add 6 - 12 times the amount of water, decoct for 0.5 - 2 hours, and filter; combine the filtrates of the three times, and concentrate the filtrate to obtain a clear extract, and that's it.

[0046] In some embodiments, the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention comprises the following steps: For the first time, add 10 times the amount of water to 4 kinds of medicinal materials including Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Oroxylum indicum (or Achyranthes aspera), decoct until the water boils and then add Scutellaria baicalensis, decoct for 1.5 hours, and filter; for the second time, add 8 times the amount of water, decoct for 1 hour, and filter; for the third time, add 8 times the amount of water, decoct for 1 hour, and filter; combine the filtrates of the three times, and concentrate the filtrate to obtain a clear extract, and that's it.

[0047] In some embodiments, the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention comprises the following steps: For the first time, add 8 - 15 times the amount of water to 4 kinds of medicinal materials including Forsythia suspensa, Isatis tinctoria, Phellodendron amurense, and Oroxylum indicum (or Achyranthes aspera), decoct until the water boils and then add Scutellaria baicalensis, decoct for 1 - 2 hours, and filter; for the second time, add 6 - 12 times the amount of water, decoct for 0.5 - 2 hours, and filter; combine the filtrates of the two times, and concentrate the filtrate to obtain a clear extract, and that's it.

[0048] In some embodiments, the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention comprises the following steps: adding 12 times the amount of water to Forsythia suspensa, Isatis indigotica, Phellodendron amurense, and Oroxylum indicum, or Forsythia suspensa, Isatis indigotica, Phellodendron amurense, and Achyranthes aspera for the first time, decocting until the water boils, then adding Scutellaria baicalensis, decocting for 2 hours, and filtering; adding 10 times the amount of water for the second time, decocting for 1 hour, and filtering; combining the filtrates of the two times, concentrating the filtrate to obtain a clear extract, and that's it.

[0049] In some embodiments, for the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention, the filtration is carried out by hot filtration. Optionally, the temperature of the hot filtration is 30-85°C, preferably 50-80°C. This preparation method can avoid the crystallization of active ingredients such as berberine and the decrease in transfer rate, and can also enable the filtrate to be concentrated within a short time, ensuring the stability of the contents of forsythoside A and berberine. Because when concentrating at high temperature for a long time, the contents of forsythoside A and berberine tend to decrease.

[0050] In some embodiments, the inventors found that the concentration temperature has a great influence on the contents of the active ingredients of the traditional Chinese medicine composition of the present invention, such as forsythoside A, phillyrin, berberine, oroxylin A, and baicalin. When concentrating under reduced pressure in a short time, the concentration temperature has little influence on the transfer rate of the above-mentioned active ingredients. However, with the prolongation of high temperature and concentration time, the contents of forsythoside A and berberine tend to decrease at 80°C and 90°C. Therefore, the concentration temperature is related to the sample amount. When the sample amount is small, it can be concentrated to the required relative density within a short time. During industrial production, it can be selected to start concentrating when the temperature ≤ 80°C. For example, ≤ 75°C, ≤ 70°C.

[0051] Normally, the relative density of the reduced-pressure concentration of the traditional Chinese medicine clear extract is generally higher than 1.20. The present inventors found that the relative density of the clear extract has a great influence on the yield of the solid content of the clear extract, and also found that when the relative density of the clear extract of the traditional Chinese medicine composition of the present invention is 1.16 at 50-65°C, the solid content rate is significantly reduced by about 20% compared with that at 1.10. Therefore, in some embodiments, for the preparation method of the above-mentioned traditional Chinese medicine composition provided by the present invention, the relative density of the clear extract at 50-65°C is 1.01 to 1.15, and it can be selected from 1.01, 1.02, 1.03, 1.04, 1.05, 1.06, 1.07, 1.08, 1.09, 1.10, 1.11, 1.12, 1.13, 1.14, 1.15. The present invention also found that when the relative density of the clear extract of the present invention is greater than 1.10, the texture of the clear extract is relatively viscous, the fluidity is poor, and when the density of the clear extract is high, there will be large losses and wall sticking when transferring the clear extract. Therefore, it can be selected to concentrate to a relative density not higher than 1.10.

[0052] In some embodiments, the method for preparing the above-mentioned traditional Chinese medicine composition provided by the present invention optionally includes the step of drying the clear extract into powder. The drying methods include but are not limited to spray drying method, vacuum drying method, freeze drying method, etc. In some embodiments, for example, when the relative density of the clear extract is greater than 1.10, the spray drying method can be used to avoid the loss caused by the transfer of the clear extract.

[0053] In some embodiments, the drying in the present invention is the spray drying method; for the spray drying, the inlet air temperature is 100-160 °C, and 100 °C, 110 °C, 120 °C, 130 °C, 140 °C, 150 °C, 160 °C can be selected; preferably 130-150 °C; preferably, the moisture content of the dry extract powder obtained by spraying is ≤5.0%.

[0054] In some embodiments, the present invention provides a method for preparing the pharmaceutical composition, which includes mixing the above-mentioned traditional Chinese medicine composition with a pharmaceutically acceptable carrier to prepare the pharmaceutical composition.

[0055] In some embodiments, the pharmaceutical composition of the present invention is a granule, and the granule is prepared by wet granulation method, dry granulation or one-step granulation method.

[0056] In some embodiments, the granule of the present invention is prepared by wet granulation.

[0057] In some embodiments, the pharmaceutical composition is a granule, and its preparation method includes wet granulation of the above-mentioned traditional Chinese medicine composition with one or more of a flavoring agent, a binder, a disintegrant, a filler, a lubricant, a coloring agent, and a coating agent, and drying to obtain the granule.

[0058] In some embodiments, the pharmaceutical composition is a granule, and its preparation method includes taking the above-mentioned traditional Chinese medicine composition and a flavoring agent and a filler, adding them to a wet mixing granulator for stirring and mixing, adding an appropriate amount of binder to make a soft material, granulating, and drying until the moisture content of the granule is ≤5.0%, preferably drying until the moisture content of the granule is ≤4.0%.

[0059] In the third aspect, the present invention provides the use of the above-mentioned traditional Chinese medicine composition or its pharmaceutical composition in the preparation of a drug for at least one of analgesia, anti-inflammatory, antibacterial, antiviral, antitussive and expectorant, and antipyretic effects.

[0060] In some embodiments, the present invention provides the use of the above-mentioned traditional Chinese medicine composition or its pharmaceutical composition in the preparation of a drug for preventing and / or treating one or more of the following diseases, and the diseases are selected from exogenous wind-heat, syndrome of exuberant heat in the lung and stomach; or the diseases are selected from upper respiratory tract infection; or the diseases are selected from exogenous wind-heat, upper respiratory tract infection with syndrome of exuberant heat in the lung and stomach. Preferably, the upper respiratory tract infection or the upper respiratory tract infection with exogenous wind-heat and syndrome of exuberant heat in the lung and stomach includes pharyngitis, laryngitis, tonsillitis, angina, etc.

[0061] In some embodiments, the upper respiratory tract infection or the upper respiratory tract infection of wind-heat attacking exterior and exuberant heat in lung and stomach syndromes is selected from acute diseases or the acute exacerbation period of chronic diseases. Optionally, the disease is selected from one or more of acute pharyngitis, acute laryngitis, acute tonsillitis, and the acute exacerbation period of patients with chronic pharyngitis.

[0062] In some embodiments, the disease includes colds with symptoms such as fever, sore throat, cough, and / or yellow phlegm.

[0063] The traditional Chinese medicine composition or its pharmaceutical composition provided by the present invention can be administered by oral, injection, coating, etc. Moreover, the dosage and frequency of administration can be determined according to the specific conditions of the subject and the degree of the disease.

[0064] Compared with the prior art, the present invention achieves the following technical effects:

[0065] The inventors screened out the easily obtained, low-cost, and industrially easy-to-implement medicinal materials Oroxylum indicum and Forsythia suspensa from numerous traditional Chinese medicinal materials. Most importantly, they can be combined with Scutellaria baicalensis and Isatis indigotica to synergistically exert the curative effect of treating upper respiratory tract infections. The inventors surprisingly found that the traditional Chinese medicine composition of the present invention has a better acute effect, especially obvious for cough caused by the upper respiratory tract. The extraction process of the present invention can fully extract the active ingredients, such as the high transfer rate of baicalin, oroxylin A, berberine, forsythoside A, and phillyrin, and at the same time, the yield of solid content is also high, and the active ingredients are stable. This process also meets the production efficiency of industrialization and energy conservation and efficiency improvement.

[0066] Other features and advantages of the present application will be described in the following specification, and, in part, will be obvious from the specification, or will be understood by implementing the present application. Other advantages of the present application can be achieved and obtained through the solutions described in the specification. Detailed Embodiments

[0067] The embodiments of the present invention will be described in detail below in conjunction with the examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. Those not specified in the examples are carried out under conventional conditions or the conditions recommended by the manufacturer. The original drugs, reagents, or instruments not specified by the manufacturer are all conventional products that can be obtained through commercial purchase or can be prepared according to the existing technology.

[0068] Example 1

[0069] A traditional Chinese medicine composition is composed of the raw medicinal materials Scutellaria baicalensis Georgi 374.0 g, Forsythia suspensa (Thunb.) Vahl 444.4 g, Isatis indigotica Fortune 555.6 g, Phellodendron amurense Rupr. 222.2 g, and Oroxylum indicum (L.) Kurz 222.2 g. First, 4 kinds of medicinal materials are put into an extraction tank in the order of Phellodendron amurense Rupr., Oroxylum indicum (L.) Kurz, Forsythia suspensa (Thunb.) Vahl, and Isatis indigotica Fortune, 12 times the amount of water of the total amount of medicinal materials is added, heated to a temperature of 90 ± 5 °C, Scutellaria baicalensis Georgi is put in, and extracted for 2.0 hours. The water decoction is filtered while it is hot, and the filtrate is collected. Then, 10 times the amount of water of the total amount of medicinal materials is added for the second time, decocted and extracted for 1.0 hour, the water decoction is filtered, and the filtrate is collected. The filtrates are combined. The filtrate is concentrated under reduced pressure at ≤ 75 °C to a relative density of 1.04 - 1.08 at 50 - 60 °C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 140 °C to obtain 550 g of dry paste powder with a water content of ≤ 5.0%.

[0070] Example 2

[0071] A traditional Chinese medicine composition is composed of the medicinal materials Scutellaria baicalensis Georgi 800 g, Forsythia suspensa (Thunb.) Vahl 1000 g, Isatis indigotica Fortune 1200 g, Phellodendron amurense Rupr. 400 g, and Oroxylum indicum (L.) Kurz 400 g. According to the extraction process of Example 1, 1140 g of dry paste powder is prepared with a water content of ≤ 5.0%.

[0072] Example 3

[0073] A traditional Chinese medicine composition is composed of the medicinal materials Scutellaria baicalensis Georgi 1200 g, Forsythia suspensa (Thunb.) Vahl 1500 g, Isatis indigotica Fortune 1800 g, Phellodendron amurense Rupr. 800 g, and Oroxylum indicum (L.) Kurz 800 g. According to the extraction process of Example 1, 1830 g of dry paste powder is prepared with a water content of ≤ 5.0%.

[0074] Example 4

[0075] A traditional Chinese medicine composition is composed of the medicinal materials Scutellaria baicalensis Georgi 1000 g, Forsythia suspensa (Thunb.) Vahl 1200 g, Isatis indigotica Fortune 1500 g, Phellodendron amurense Rupr. 800 g, and Oroxylum indicum (L.) Kurz 600 g. According to the extraction process of Example 1, 1428 g of dry paste powder is prepared with a water content of ≤ 5.0%.

[0076] Example 5

[0077] A traditional Chinese medicine composition is composed of the medicinal materials Scutellaria baicalensis Georgi 500 g, Forsythia suspensa (Thunb.) Vahl 800 g, Isatis indigotica Fortune 800 g, Phellodendron amurense Rupr. 200 g, and Oroxylum indicum (L.) Kurz 200 g. According to the extraction process of Example 1, 700 g of dry paste powder is prepared with a water content of ≤ 5.0%.

[0078] Example 6

[0079] A traditional Chinese medicine composition is composed of 374.0 g of Scutellaria baicalensis Georgi, 444.4 g of Forsythia suspensa (Thunb.) Vahl, 555.6 g of Isatis tinctoria L., 222.2 g of Phellodendron amurense Rupr., and 222.2 g of Oroxylum indicum (L.) Kurz. First, 4 kinds of medicinal materials are put into an extraction tank in the order of Phellodendron amurense Rupr., Oroxylum indicum (L.) Kurz., Forsythia suspensa (Thunb.) Vahl, and Isatis tinctoria L., 12 times the total amount of the medicinal materials of water is added, heated to a temperature of 90 ± 5 °C, Scutellaria baicalensis Georgi is put in, and decocted for 2 hours. The water decoction is filtered while it is hot, and the filtrate is collected; for the second time, 10 times the total amount of the medicinal materials of water is added, decocted for 1 hour, the water decoction is filtered, and the filtrate is collected. For the third time, 10 times the total amount of the medicinal materials of water is added, decocted for 1 hour, the water decoction is filtered, and the filtrate is collected. The filtrates are combined. The filtrate is concentrated under reduced pressure at 80 °C to a relative density of 1.04 - 1.08 at 50 - 60 °C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 150 °C to obtain 581 g of dry paste powder, and the moisture content ≤ 5.0%.

[0080] Example 7

[0081] A traditional Chinese medicine composition is composed of 374.0 g of Scutellaria baicalensis Georgi, 444.4 g of Forsythia suspensa (Thunb.) Vahl, 555.6 g of Isatis tinctoria L., 222.2 g of Phellodendron amurense Rupr., and 222.2 g of Oroxylum indicum (L.) Kurz. First, 4 kinds of medicinal materials are put into an extraction tank in the order of Phellodendron amurense Rupr., Oroxylum indicum (L.) Kurz., Forsythia suspensa (Thunb.) Vahl, and Isatis tinctoria L., 8 times the total amount of the medicinal materials of water is added, heated to a temperature of 90 ± 5 °C, Scutellaria baicalensis Georgi is put in, and decocted for 2 hours. The water decoction is filtered while it is hot, and the filtrate is collected; for the second time, 6 times the total amount of the medicinal materials of water is added, decocted for 1 hour, the water decoction is filtered, and the filtrate is collected. For the third time, 6 times the total amount of the medicinal materials of water is added, decocted for 1 hour, the water decoction is filtered, and the filtrate is collected. The filtrates are combined. The filtrate is concentrated under reduced pressure at 75 °C to a relative density of 1.04 - 1.08 at 50 - 60 °C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 130 °C to obtain 567 g of dry paste powder, and the moisture content ≤ 5.0%.

[0082] Example 8

[0083] A traditional Chinese medicine composition is composed of 30.0 kg of Scutellaria baicalensis Georgi, 36.0 kg of Forsythia suspensa (Thunb.) Vahl, 45.0 kg of Isatis tinctoria L., 18.0 kg of Phellodendron amurense Rupr., and 18.0 kg of Oroxylum indicum (L.) Kurz. First, 4 kinds of medicinal materials are put into an extraction tank in the order of Phellodendron amurense Rupr., Oroxylum indicum (L.) Kurz., Forsythia suspensa (Thunb.) Vahl, and Isatis tinctoria L., 10 times the total amount of the medicinal materials of water is added, heated to a temperature of 90 ± 5 °C, Scutellaria baicalensis Georgi is put in, and decocted for 2 hours. The water decoction is filtered while it is hot, and the filtrate is collected; for the second time, 8 times the total amount of the medicinal materials of water is added, decocted for 1 hour, the water decoction is filtered, and the filtrate is collected. For the third time, 8 times the total amount of the medicinal materials of water is added, decocted for 1 hour, the water decoction is filtered, and the filtrate is collected. The filtrates are combined. The filtrate is concentrated under reduced pressure at ≤ 75 °C to a relative density of 1.04 - 1.08 at 50 - 60 °C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 160 °C to obtain 44.7 kg of dry paste powder, and the moisture content ≤ 5.0%.

[0084] Example 9

[0085] A traditional Chinese medicine composition is composed of 30.0 kg of Scutellaria baicalensis Georgi, 36.0 kg of Forsythia suspensa (Thunb.) Vahl, 45.0 kg of Isatis tinctoria L., 18.0 kg of Phellodendron amurense Rupr., and 18.0 kg of Oroxylum indicum (L.) Kurz. First, 4 kinds of medicinal materials are put into the extraction tank in the order of Phellodendron amurense Rupr., Oroxylum indicum (L.) Kurz., Forsythia suspensa (Thunb.) Vahl, and Isatis tinctoria L., 10 times the amount of water of the total amount of medicinal materials is added, heated to 90 ± 5 °C, Scutellaria baicalensis Georgi is put in, and extracted for 2.0 hours. The water decoction is filtered while it is hot, and the filtrate is collected. Second, 8 times the amount of water of the total amount of medicinal materials is added, and decocted and extracted for 1.0 hour. The water decoction is filtered, and the filtrate is collected. The filtrates are combined. The filtrate is concentrated under reduced pressure at ≤ 75 °C to a relative density of 1.04 - 1.08 at 50 - 60 °C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 120 °C to obtain 41.5 kg of dry paste powder with a moisture content of ≤ 5.0%.

[0086] Example 10

[0087] A traditional Chinese medicine composition is composed of 374.0 g of Scutellaria baicalensis Georgi, 444.4 g of Forsythia suspensa (Thunb.) Vahl, 555.6 g of Isatis tinctoria L., 222.2 g of Phellodendron amurense Rupr., and 222.2 g of Oroxylum indicum (L.) Kurz. First, the 5 kinds of medicinal materials are put into the extraction tank, 10 times the amount of water of the total amount of medicinal materials is added, and extracted for 2.0 hours. The water decoction is filtered while it is hot, and the filtrate is collected. Second, 8 times the amount of water of the total amount of medicinal materials is added, and decocted and extracted for 1.0 hour. The water decoction is filtered, and the filtrate is collected. The filtrates are combined. The filtrate is concentrated under reduced pressure at ≤ 75 °C to a relative density of 1.04 - 1.08 at 60 - 65 °C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 140 °C to obtain 509 g of dry paste powder with a moisture content of ≤ 5.0%.

[0088] Example 11

[0089] A traditional Chinese medicine composition is composed of 300.0 g of Scutellaria baicalensis Georgi, 360.0 g of Forsythia suspensa (Thunb.) Vahl, 450.0 g of Isatis tinctoria L., 180.0 g of Phellodendron amurense Rupr., and 180.0 g of Oroxylum indicum (L.) Kurz. First, the 5 kinds of medicinal materials are put into the extraction tank, 10 times the amount of water of the total amount of medicinal materials is added, and decocted for 1.5 hours. The water decoction is filtered while it is hot, and the filtrate is collected; Second, 8 times the amount of water of the total amount of medicinal materials is added, and decocted for 1 hour. The water decoction is filtered, and the filtrate is collected. Third, 8 times the amount of water of the total amount of medicinal materials is added, and decocted for 1 hour. The water decoction is filtered, and the filtrate is collected. The filtrates are combined. The filtrate is concentrated under reduced pressure at 70 °C to a relative density of 1.08 - 1.10 at 60 - 65 °C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 140 °C to obtain 441 g of dry paste powder with a moisture content of ≤ 5.0%.

[0090] Example 12

[0091] A traditional Chinese medicine composition is composed of 300.0 g of Scutellaria baicalensis Georgi, 360.0 g of Forsythia suspensa (Thunb.) Vahl, 450.0 g of Isatis indigotica Fortune, 180.0 g of Phellodendron amurense Rupr., and 180.0 g of Oroxylum indicum (L.) Kurz. First, put the 5 kinds of medicinal materials into an extraction tank, add 10 times the amount of water of the total amount of medicinal materials, decoct for 1.5 hours, filter the water decoction while it is hot, and collect the filtrate; for the second time, add 8 times the amount of water of the total amount of medicinal materials, decoct for 1 hour, filter the water decoction, and collect the filtrate; for the third time, add 8 times the amount of water of the total amount of medicinal materials, decoct for 1 hour, filter the water decoction, and collect the filtrate, and then combine the filtrates. The filtrate is concentrated under reduced pressure at ≤70°C to a relative density of 1.15 at 60 - 65°C to obtain a clear paste, and spray drying is adopted with an inlet air temperature of 110°C to obtain 367 g of dry paste powder with a moisture content of ≤5.0%.

[0092] Examples 13 - 24 Tablets

[0093] Respectively take the dry extract powders of Examples 1 - 12, add 70% w / w microcrystalline cellulose, 4% w / w sodium carboxymethyl starch, and 0.5% w / w magnesium stearate (calculated based on the mass of the pharmaceutical composition being 100%), mix evenly, and press tablets to obtain tablets.

[0094] Examples 25 - 36 Oral Liquids

[0095] Respectively dissolve the dry extract powders of Examples 1 - 12 in water, let it stand overnight, add 0.5% w / w sodium benzoate and 1% w / w Tween 80 (calculated based on the mass of the pharmaceutical composition being 100%), mix well, add water to 1000 mL, stir evenly, boil, refrigerate, filter, adjust the pH to 6 - 7, package, and sterilize to obtain oral liquids.

[0096] Examples 37 - 48 Drop Pills

[0097] Respectively weigh twice the mass of polyethylene glycol (the polyethylene glycol includes polyethylene glycol 6000 and polyethylene glycol 4000 with a mass ratio of 3:1), heat and melt it, add it to the dry extract powders of Examples 1 - 12, stir evenly, drop it into dimethyl silicone oil coolant, wash the pills, dry, and select the pills to obtain drop pills.

[0098] Examples 49 - 60 Granules

[0099] Respectively add 50 g of the dry extract powders of Examples 1 - 12, 50 g of maltodextrin, and 0.2 g of sucralose into a wet granulator for stirring and mixing, add an appropriate amount of 90 - 95% ethanol solution to make soft materials, granulate, and stop drying when the moisture content reaches 4.0% to obtain granules.

[0100] Example 61

[0101] Take 50 g of the dry extract powder from Example 1, 100 g of dextrin, and 0.3 g of sucralose, add them to a wet granulating mixer for stirring and mixing, add an appropriate amount of 92 - 95% ethanol solution to make a soft material, granulate, and dry at 65°C. Stop drying when the moisture content drops to 4.0%, and the granule agent is obtained.

[0102] Example 62

[0103] Take 200 g of the dry extract powder from Example 1, 160 g of dextrin, and 0.9 g of sucralose, add them to a wet granulating mixer for stirring and mixing, add an appropriate amount of 90% ethanol solution to make a soft material, granulate, and dry at 80°C until the moisture content of the granules ≤ 4.0%. Stop drying, and the granule agent is obtained.

[0104] Example 63

[0105] Take 200 g of the dry extract powder from Example 1, 200 g of lactose, and 1.0 g of sucralose, add them to a wet granulating mixer for stirring and mixing, add an appropriate amount of 90% ethanol solution to make a soft material, granulate, and dry at 65°C until the moisture content of the granules ≤ 4.0%. Stop drying, and the granule agent is obtained.

[0106] Example 64

[0107] Take 50 g of the dry extract powder from Example 1, 48 g of dextrin, 2 g of cross-linked polyvinylpyrrolidone, and 0.2 g of sucralose, add them to a wet granulating mixer for stirring and mixing, add an appropriate amount of 95% ethanol solution to make a soft material, granulate, and dry at 70°C until the moisture content of the granules ≤ 4.0%. Stop drying, and the granule agent is obtained.

[0108] Example 65

[0109] Take 50 g of the dry extract powder from Example 1, 50 g of maltodextrin, and 0.2 g of sucralose, add them to a wet granulating mixer for stirring and mixing, add an appropriate amount of 95% ethanol solution to make a soft material, granulate, and dry at 70°C until the moisture content of the granules ≤ 4.0%. Stop drying, and the granule agent is obtained.

[0110] Example 66

[0111] Take 400 g of the dry extract powder from Example 1, 586.5 g of maltodextrin, 2.5 g of sucralose, and 1 g of citric acid, add them to a wet granulating mixer for stirring and mixing, add an appropriate amount of 95% ethanol solution to make a soft material, granulate, and dry at 65°C until the moisture content of the granules ≤ 4.0%. Stop drying, and the granule agent is obtained.

[0112] Example 67

[0113] Replace the oroxylum indicum in Example 1 with achyranthes bidentata, and keep the others unchanged.

[0114] Test Example 1

[0115]

Test Materials

[0116] Test drug The traditional Chinese medicine composition (dry extract powder of Example 1) of the present invention was provided by Jiangsu Longfengtang Traditional Chinese Medicine Co., Ltd., Yangzijiang Pharmaceutical Group, batch number: 21041411, and each gram of dry extract powder contains 4.13 g of crude drug content.

[0117] Positive control drugs Dexamethasone acetate tablets, Zhejiang Xianju Pharmaceutical Co., Ltd., batch number: 200421. Ibuprofen granules, Harbin Pharmaceutical Group Shiyitang Pharmaceutical Factory, batch numbers: 1906607, 2003611. Aspirin effervescent tablets, AstraZeneca Pharmaceutical Co., Ltd., batch number: 1908221.

[0118] Dose design The clinically intended dose of the traditional Chinese medicine composition of the present invention is 49 g of crude drug content per day. According to the equivalent dose conversion based on the body surface area ratio of animals and humans, the clinically equivalent dose for rats is 4.41 g of crude drug / kg, which is set as the medium dose. The high, medium, and low doses for rats are 8.82, 4.41, and 2.21 g of crude drug / kg respectively; the clinically equivalent dose for mice is 6.37 g of crude drug / kg, and the experimental doses for mice are 25.48, 12.74, 6.37, and 3.19 g of crude drug / kg.

[0119] Dexamethasone acetate tablets, the clinical daily dose is calculated based on 16 tablets, the specification is 0.75 mg per tablet, and according to the equivalent dose conversion based on the body surface area ratio of animals and humans, twice the clinically equivalent dose for rats is 2.16 mg / kg. Ibuprofen granules, the clinical daily dose is calculated based on 0.8 g, and according to the equivalent dose conversion based on the body surface area ratio of animals and humans, the clinically equivalent dose for mice is 0.10 g / kg, and twice the clinically equivalent dose for mice is 0.21 g / kg. Aspirin effervescent tablets, the clinical daily dose is calculated based on 2.0 g, and according to the equivalent dose conversion based on the body surface area ratio of animals and humans, the clinically equivalent dose for rats is 0.18 g / kg.

[0120] Animals SD rats, SPF grade, body weight 180 - 200 g; ICR mice, SPF grade, body weight 18 - 20 g; half male and half female, provided by Beijing Vital River Laboratory Animal Technology Co., Ltd., animal production license number: SCXK(Beijing)2016 - 0006. Raised in a barrier environment, experimental animal use license number: SYXK(Beijing)2019 - 0003.

[0121] Dosage and administration route The dosage for rats is 10 mL / kg, and the dosage for mice is 20 mL / kg. The gavage administration method is adopted.

[0122] Pseudomonas aeruginosa, strain number: 10104, batch number: 2a28-2; Staphylococcus aureus, strain number: 26003, batch number: 9a3-1; Escherichia coli, strain number: 44102, batch number: 3a33-1, purchased from the China National Center for Medical Bacterial Culture Collection, National Institutes for Food and Drug Control. Staphylococcus epidermidis, strain number: 12228, purchased from Zhengzhou Jingsiwei Chemical Industry Co., Ltd.

[0123] Reagent ammonia water, Beijing Chemical Works, batch number: 20180808; IL-6 ELISA Kit, WUHAN HUAMEIBIOTECH.,LTD, batch number: E13037834; TNF-α ELISA Kit, WUHAN HUAMEI BIOTECH.,LTD, batch number: E14037853; Evans blue, product of Solarbio, batch number: NO.619N041; Acetic acid (glacial acetic acid), Beijing Chemical Works, batch number: 20170401; Sodium chloride injection, Shijiazhuang No.4 Pharmaceutical Co., Ltd., batch number: 2008183203; Croton oil, MACKLIN, batch number: C10936730; Absolute ethanol, Sinopharm Chemical Reagent Co., Ltd., batch number: 20181210; Ether, Sinopharm Chemical Reagent Co., Ltd., batch number: 20181009; High-activity dry yeast, Angel Yeast Co., Ltd., production date: 2021 / 01 / 12; Nutrient agar medium, Beijing Aoboxing Biotechnology Co., Ltd., batch number: 20190418; Nutrient broth medium, Beijing Aoboxing Biotechnology Co., Ltd., batch number: 20190516.

[0124] Instruments: PL203 electronic balance, METTLER TOLEDO; Siemens ADVIA 2120 automatic hematology analyzer, Siemens, Germany; Toshiba TBA-120FR automatic biochemical analyzer; BioTek Epoch microplate reader, BioTek Instruments, Inc.; TP1020 automatic dehydrator, EG1140H paraffin embedding machine, DM 2500 biological microscope, Leica, Germany; HM355S automatic rotary microtome, Microm, Germany; XL5010 automatic staining machine, Autostainer, Germany.

[0125] 1. Acute pharyngitis experiment

[0126]

Test methods and results

[0127] Effect on the acute pharyngitis model of rats

[0128] Experimental method: Healthy SD rats of SPF grade, weighing 180 - 200 g, were randomly grouped by body weight into a normal control group and a model group. In the model group, 15% ammonia water was sprayed on the pharynx once in the morning and once in the afternoon, 3 presses each time with a laryngeal nebulizer, for 3 consecutive days. The normal control group was sprayed with an equal amount of pure water. On the 4th day, the model group was randomly divided into a model control group, high, medium, and low dose groups of the traditional Chinese medicine composition of the present invention (8.82, 4.41, 2.21 g crude drug / kg), and a positive control drug dexamethasone acetate tablet group, with 10 rats in each group, half male and half female. Each group was given drugs by gavage. The normal group and the model control group were given an equal volume of pure water (10 mL / kg body weight) by gavage once a day for 5 consecutive days. One hour after the last administration, the rats were anesthetized, and EDTAK2 anticoagulated blood and non - anticoagulated blood were taken. The anticoagulated blood was used for white blood cell counting and classification; the non - anticoagulated blood was centrifuged to separate serum, and an ELISA kit was used to measure the contents of inflammatory factors IL - 6 and TNF - α in the serum; the pharynx was taken and fixed in 10% formalin solution for pathological histological examination.

[0129] Experimental results

[0130] (1) Results of pathological histological examination of rat pharyngeal tissues

[0131] In the normal control group, there was no hyperkeratosis in the pharyngeal mucosa of rats, no hyperplasia, thickening of mucosal epithelial cells, no apoptosis of cells; there was no edema in the submucosal muscle tissue, no inflammation, no hypertrophy of glands, and the tissue structure was normal.

[0132] In the model control group, there was hyperkeratosis in the laryngeal and pharyngeal mucosa of rats, obvious hyperplasia and enlargement of mucosal epithelial cells, and apoptotic cells; there was inflammatory exudation in the submucosa, mainly lymphocytes, and de - nucleated mast cells, a small amount of eosinophils and neutrophilic segmented - nuclear cells; the submucosal lamina propria was congested and edematous, and the glands were enlarged; there was edema in the submucosal muscle layer, muscle cells were fractured, and there was a small amount of inflammation around.

[0133] In the high, medium, and low dose groups of the traditional Chinese medicine composition of the present invention and the positive drug dexamethasone acetate tablet group, the mucosal hyperplasia, hypertrophy, submucosal edema, inflammation and other lesions in the rat laryngeal and pharyngeal tissues were alleviated to varying degrees compared with the model control group. The results of the rank sum test showed that the high dose group of the traditional Chinese medicine composition of the present invention and the dexamethasone acetate tablet group could significantly alleviate the pharyngeal lesions, and there was a significant difference compared with the model control group. The results are shown in Table 1.

[0134] Table 1 Statistical table of microscopic pathological observations of laryngeal and pharyngeal tissues in acute pharyngitis model rats

[0135]

[0136]

[0137] Note: The rank sum test was performed by comparing each group with the model control group.

[0138] Appendix: Microscopic observation criteria

[0139] "-": No congestion or edema was observed in the pharyngeal mucosa of rats, no thickening of the mucosal epithelium was seen, no hypertrophy of the submucosal glands was observed, and the tissue structure was normal.

[0140] "+": No hyperplasia or edema was observed in the pharyngeal mucosal epithelium of rats, no thickening of the mucosal epithelium was seen, there was mild congestion under the mucosal epithelium, and no inflammation was observed.

[0141] "++": There was mild local hyperplasia in the pharyngeal mucosal epithelium of rats, congestion under the mucosal epithelium, and a small amount of inflammatory exudation.

[0142] "+++": There was hyperkeratosis and segmentation in the pharyngeal mucosal epithelium of rats, hyperplasia and thickening of the mucosal epithelial cells, swelling of the submucosal muscle layer, rupture of the muscle tissue, and a small amount of inflammation.

[0143] "++++": There was hyperkeratosis, hyperplasia of the epithelium, formation of rete pegs in the pharyngeal mucosal epithelium of rats, inflammatory exudation under the mucosal epithelium, hypertrophy of the glands, mainly lymphocytes, and a relatively extensive area of lobular nuclear lesions.

[0144] (2) Effects on white blood cell count and classification

[0145] Compared with the model control group, the NEUT (%) (percentage of neutrophils) in the high-dose and medium-dose groups of the traditional Chinese medicine composition of the present invention and the dexamethasone acetate tablet group were significantly increased, and the LYM (%) (percentage of lymphocytes) was significantly decreased, showing a significant difference compared with the model control group. The results are shown in Table 2.

[0146] Table 2 Effects of the traditional Chinese medicine composition of the present invention on white blood cell count and classification in the rat acute pharyngitis model ( ±SD)

[0147]

[0148] Note: Compared with the model control group * P<0.05, ** P<0.01;

[0149] WBC is white blood cell; NEUT is neutrophil; LYM is lymphocyte; MONO is monocyte; EOS is eosinophil; BASO is basophil.

[0150] (3) Effects on the content of inflammatory factors in rat serum

[0151] The content of IL-6 in the serum of the model control group was significantly higher than that of the normal group (P<0.01). The content of IL-6 in the serum of the high-dose (8.82 g crude drug / kg) of the traditional Chinese medicine composition of the present invention and the dexamethasone acetate tablet group was significantly lower than that of the model control group, showing a significant difference compared with the model control group. The results are shown in Table 3. The content of TNF-α in the serum was lower than the detection range (6.25 - 400 pg / mL) of the used ELISA kit.

[0152] Table 3 Effects of the traditional Chinese medicine composition of the present invention on inflammatory factors in the rat acute pharyngitis model ( ±SD)

[0153]

[0154] Note: Compared with the model control group, *P<0.05, **P<0.01.

[0155] 2. Anti-inflammatory experiment

[0156] 2.1 Effects on the increased permeability of peritoneal capillary vessels in mice induced by acetic acid

[0157] Test method: Take 50 healthy ICR mice, SPF grade, weighing 18 - 20 g. Randomly divide them into 5 groups according to body weight, namely the model control group, three dose groups of the traditional Chinese medicine composition of the present invention (12.74, 6.37, 3.18 g crude drug / kg), and the positive control drug ibuprofen granule group, with 10 mice in each group, half male and half female. Each group was given the corresponding drug by gavage once a day. The model control group was given the same volume of pure water (0.2 mL / 10 g body weight) by gavage for 3 consecutive days. 1 hour after the last dose, 0.1 mL / 10 g of 0.5% Evans blue solution was injected into the tail vein. 10 minutes later, 0.1 mL / 10 g of 0.8% acetic acid was injected into the abdominal cavity. Another 10 minutes later, 5 mL of normal saline injection was injected into the abdominal cavity. The mice were sacrificed, the abdomen was gently rubbed 50 times, the skin was cut open, the abdominal cavity fluid was aspirated with a pipette, centrifuged, and the absorbance of the supernatant was measured at a wavelength of 590 nm. The t-test was used for comparison between groups, and the inhibition rate was calculated.

[0158]

[0159] Test results: The three dose groups (12.74, 6.37, 3.18 g crude drug / kg) of the traditional Chinese medicine composition of the present invention showed an inhibitory trend on the increased permeability of peritoneal capillary vessels in mice induced by acetic acid, and the absorbance of their abdominal cavity fluid was lower than that of the model control group. The results are shown in Table 4.

[0160] Table 4 Effects of the traditional Chinese medicine composition of the present invention on the increased permeability of peritoneal capillary vessels ( ±SD) (administered for 3 days)

[0161]

[0162]

[0163] Note: Compared with the model control group, *P < 0.05, **P < 0.01.

[0164] 2.2 Effects on the increased permeability of peritoneal capillaries in mice induced by acetic acid (increasing the dosage and prolonging the administration days, and conducting repeated experiments)

[0165] Test method: Take 50 healthy ICR mice, SPF grade, weighing 18 - 20 g. Randomly divide them into 5 groups according to body weight, namely the model control group, three dosage groups of the traditional Chinese medicine composition of the present invention (25.48, 12.74, 6.37 g crude drug / kg), and the positive control drug ibuprofen granule group, with 10 mice in each group, half male and half female. Each group was intragastrically administered the corresponding drug once a day. The model control group was intragastrically administered the same volume of distilled water (0.2 mL / 10 g body weight) for 6 consecutive days. One hour after the last dose, 0.1 mL / 10 g of 0.5% Evans blue solution was injected into the tail vein. Five minutes later, 0.1 mL / 10 g of 0.8% acetic acid was injected into the abdominal cavity. Observe and record the number of writhing responses of the mice within 20 min after the injection of acetic acid. After the observation, 5 mL of normal saline injection was injected into the abdominal cavity, the mice were sacrificed, the abdomen was gently rubbed 50 times, the skin was cut open, the abdominal cavity fluid was aspirated with a pipette, centrifuged, and the absorbance of the supernatant was measured at a wavelength of 590 nm. Group - to - group comparison was performed by t - test, and the inhibition rate was calculated.

[0166]

[0167] Test results: The traditional Chinese medicine composition of the present invention at the dosages of 25.48 and 12.74 g crude drug / kg and the positive drug ibuprofen granule could significantly inhibit the increased permeability of peritoneal capillaries in mice induced by acetic acid. The absorbance of their abdominal cavity fluid was significantly lower than that of the model control group, showing a significant difference compared with the model control group, indicating that the traditional Chinese medicine composition of the present invention has an anti - inflammatory effect. The results are shown in Table 5.

[0168] Table 5 Effects of the traditional Chinese medicine composition of the present invention on the increased permeability of peritoneal capillaries ( ±SD) (administered for 6 days)

[0169]

[0170] Note: Compared with the model control group, *P < 0.05, **P < 0.01.

[0171] 2.3 Effects on ear swelling in mice induced by croton oil

[0172] Experimental method: 60 healthy ICR mice, SPF grade, weighing 18 - 20 g, were randomly divided into 5 groups according to body weight, namely the model control group, three dose groups of the traditional Chinese medicine composition of the present invention (25.48, 12.74, 6.37 g crude drug / kg), and the positive control drug ibuprofen granule group, with 10 mice in each group, half male and half female. Each group was given the corresponding drug by gavage once a day. The model control group was given the same volume of distilled water (0.2 mL / 10 g body weight) by gavage for 6 consecutive days. After administration, 70 μL of 3% croton oil was applied to both sides of the right ear of each mouse, and the left ear was used as a control. Four hours after inflammation induction, the mice were sacrificed, and both ears were cut along the auricle baseline. Ear pieces were punched out at the same position with an ear punch with a diameter of 8 mm, weighed on an electronic balance, and the weight difference between the left and right ear pieces (i.e., ear swelling value) was calculated. Group - to - group comparison was performed by t - test, and the inhibition rate was calculated.

[0173]

[0174] Experimental results: The traditional Chinese medicine composition of the present invention at doses of 25.48, 12.74, 6.37 g crude drug / kg and the positive drug ibuprofen granule could significantly reduce the ear swelling value of mice induced by croton oil, showing significant differences compared with the model control group, indicating that the traditional Chinese medicine composition of the present invention has anti - inflammatory effects. The results are shown in Table 6.

[0175] Table 6 Effects of the traditional Chinese medicine composition of the present invention on ear swelling of mice induced by croton oil ( ±SD)

[0176]

[0177] Note: Compared with the model control group, *P < 0.05, **P < 0.01.

[0178] 3. Analgesic experiment

[0179] 3.1 Effects on the analgesic response of mice induced by acetic acid

[0180] Experimental method: Grouping and drug administration were the same as in "2.2 Effects on the increased permeability of peritoneal capillaries of mice induced by acetic acid". One hour after the last dose, 0.1 mL / 10 g of 0.5% Evans blue solution was injected into the tail vein. Five minutes later, 0.1 mL / 10 g of 0.8% acetic acid was injected intraperitoneally. The number of writhing responses of mice within 20 min after injecting acetic acid was observed and recorded. Group - to - group comparison was performed by t - test, and the inhibition rate was calculated.

[0181] Experimental results: The number of writhing responses of the traditional Chinese medicine composition of the present invention at doses of 25.48, 12.74 g crude drug / kg and the positive drug ibuprofen granule was significantly lower than that of the model control group, showing significant differences compared with the model control group, indicating that the traditional Chinese medicine composition of the present invention has an inhibitory effect on the pain response of mice induced by acetic acid. The results are shown in Table 7.

[0182] Table 7 Effects of the traditional Chinese medicine composition of the present invention on acetic acid-induced pain response in mice( ±SD) (administered for 6 days)

[0183]

[0184] Note: Compared with the model control group, **P<0.01, *P<0.05

[0185] 3.2 Effects on acetic acid-induced pain response in mice (repeated experiment)

[0186] Test method: Take 60 healthy SPF-grade ICR mice, weighing 18-22 g. Randomly group them by body weight into a model control group, three dose groups of the traditional Chinese medicine composition of the present invention (12.74, 6.37, 3.18 g crude drug / kg), and a positive control drug ibuprofen granule group, with 10 mice in each group, half male and half female. Each group was given intragastric administration. The model control group was given an equal volume of pure water by gavage, once a day for 5 consecutive days. One hour after the last administration, 0.1 ml / 10 g of 0.8% acetic acid was injected intraperitoneally, and the typical writhing times (stretching the hind limbs, abdominal contraction, and twisting the body) of the mice within 20 min were observed. The t-test was used for comparison between groups, and the inhibition rate was calculated.

[0187]

[0188] Test results: The writhing times of the traditional Chinese medicine composition of the present invention at the dose of 12.74 g crude drug / kg and the positive drug ibuprofen granule were significantly lower than those of the model control group, with significant differences compared with the model control group, indicating that the traditional Chinese medicine composition of the present invention has an inhibitory effect on acetic acid-induced pain response in mice. The results are shown in Table 8.

[0189] Table 8 Effects of the traditional Chinese medicine composition of the present invention on acetic acid-induced pain response in mice( ±SD) (administered for 5 days)

[0190]

[0191]

[0192] Note: Compared with the model control group, **P<0.01, *P<0.05

[0193] 4. Rat antipyretic experiment

[0194] 4.1. Effects on yeast-induced fever in rats

[0195] Experimental method: Healthy SD rats, SPF grade, weighing 180 - 200 g, were selected. One day before the experiment, the rectal temperature of the animals was measured once a day for 4 days. 10 hours before the experiment, the animals were fasted. On the morning of the experimental day, the rectal temperature of the animals was measured twice as the basal rectal temperature. Pyrexia was induced by subcutaneous injection of 20% yeast solution (2 mL / 100 g) into the back. After 5 hours, the rectal temperature was measured. Those with an increase of more than 0.8 °C were used for the experiment. They were randomly divided into groups according to the increase in rectal temperature, namely the model control group, the high, medium, and low dose groups of the traditional Chinese medicine composition of the present invention (8.82, 4.41, 2.21 g crude drug / kg), and the positive control drug aspirin effervescent tablet group, with 10 rats in each group, half male and half female. Each group was given drugs by gavage. The model control group was given an equal volume of purified water (10 mL / kg body weight) by gavage. The rectal temperature was measured at 1, 2, 3, and 4 hours after drug administration. The difference between the rectal temperature measured at different times and the basal rectal temperature was used as an index of body temperature change, and statistical analysis was performed by t-test.

[0196] Experimental results: The results showed that the body temperature of rats increased to varying degrees after subcutaneous injection of yeast solution. Those with an increase of more than 0.8 °C were selected for the experiment. After gavage administration, the increase in body temperature of rats in each drug administration group was reduced to varying degrees compared with the model control group. The high dose group (8.82 g crude drug / kg) of the traditional Chinese medicine composition of the present invention could significantly inhibit the increase in body temperature of rats caused by yeast at 2 - 4 hours after drug administration, showing a significant difference compared with the model control group. The positive control drug aspirin effervescent tablet could significantly inhibit the increase in body temperature of rats caused by yeast within 4 hours after drug administration, indicating that the traditional Chinese medicine composition of the present invention has antipyretic effects. The results are shown in Tables 9 and 10.

[0197] Table 9 Effects of the traditional Chinese medicine composition of the present invention on yeast-induced fever in rats ( ±SD)

[0198]

[0199] Table 10 Effects of the traditional Chinese medicine composition of the present invention on yeast-induced fever in rats ( ±SD)

[0200]

[0201] Note: Compared with the model control group, *P < 0.05, **P < 0.01.

[0202] 5. In vitro antibacterial experiment

[0203] 5.1 In vitro antibacterial and bactericidal tests (liquid dilution method)

[0204] Experimental method

[0205] 1) One day before the experiment, each bacterium was inoculated into broth medium for enrichment culture overnight for 16 hours.

[0206] 2) During the experiment, take several 96-well cell culture plates, and first add 100 μL of broth medium per well.

[0207] 3) Add 100 μL of the drug sample per well to the first row of each plate, mix well, aspirate 100 μL and transfer it down to the second row, mix and transfer down in the same way, and repeat this process until the eighth dilution. After mixing, discard 100 μL per well. The concentration in the first row is 500 mg / mL, the second row is 250 mg / mL, and the concentrations in the third, fourth, fifth, sixth, seventh, and eighth rows are 125, 62.5, 31.2, 15.6, 7.8, and 3.9 mg / mL respectively.

[0208] 4) Turbidimetrically adjust each of the bacteria after enrichment to McFarland No. 1 tube (300 million bacteria / mL), then dilute it 100 times, aspirate 10 μL of each bacterium and add it to each row, with four columns added for each bacterium.

[0209] 5) Make positive controls and medium controls in parallel.

[0210] 6) Supplement 100 μL of broth per well to each plate.

[0211] 7) Place each plate in an incubator at 37 °C for 24 hours, observe the results under a microscope, and record the minimum inhibitory concentration (MIC).

[0212] 8) Aspirate 5 μL from each MIC well and transfer it to an agar culture plate, place it in an incubator at 37 °C for 24 hours, and observe whether there is bacterial growth to determine the minimum bactericidal concentration (MBC).

[0213] Test results

[0214] The in vitro antibacterial experiment shows that the extract of the traditional Chinese medicine composition of the present invention has antibacterial and bactericidal effects on the standard strains of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The results are shown in Table 11.

[0215] Table 11 Antibacterial test results of the traditional Chinese medicine composition of the present invention

[0216] Strain MIC (mg crude drug / mL) MBC (mg crude drug / mL) Staphylococcus aureus 114.58±24.33 125.00±0.00 Escherichia coli 125.00±0.00 166.67±61.55 Pseudomonas aeruginosa 57.29±12.16 62.50±0.00 Staphylococcus epidermidis 3.90±0.00 5.53±2.01

[0217]

Test conclusion

[0218] In summary, the pharmacodynamic experiment shows that the traditional Chinese medicine composition of the present invention can improve acute pharyngitis in rats and has anti-inflammatory, analgesic, antipyretic, and antibacterial effects.

[0219] Test Example II Efficacy study of the traditional Chinese medicine composition of the present invention in the treatment of acute pharyngitis (syndrome of exuberant heat in the lung and stomach)

[0220] I. Diagnostic criteria for acute pharyngitis

[0221] Formulated with reference to the "Clinical Research Guidelines for New Chinese Medicines in the Treatment of Acute Pharyngitis" in 2002 and the "Otolaryngology - Head and Neck Surgery - Ninth Edition" in 2018: Acute simple pharyngitis is an acute inflammation of the pharyngeal mucosa and submucosa, often involving the pharyngeal lymphoid tissue. This disease is equivalent to acute laryngeal obstruction in traditional Chinese medicine.

[0222] (1) Medical history: Both viral and bacterial infections can cause this disease. There are often inducing factors such as getting cold, overheating, getting wet, overexertion, excessive smoking and drinking, as well as various physical or chemical stimuli.

[0223] (2) Symptoms: Severe sore throat, aggravated by swallowing, dryness in the pharynx, excessive thirst and drinking, fever, headache, dry stools, and short and yellow urine.

[0224] (3) Examinations:

[0225] a) The pharyngeal mucosa is congested, with a bright red color.

[0226] b) The lymphoid follicles and lateral cords on the posterior pharyngeal wall are red and swollen, or there are scattered purulent spots on the pharyngeal mucosa.

[0227] c) The uvula and soft palate are red and swollen.

[0228] For diagnosis, there must be an acute onset, with some or all of the above symptoms, and one or more positive physical signs found in the examinations, then the diagnosis can be made.

[0229] II. TCM dialectical criteria for the syndrome of excessive heat in the lung and stomach

[0230] Formulated with reference to the "Diagnostic and Therapeutic Criteria for TCM Syndromes" in 2017:

[0231] Main symptoms: Sore throat, red and swollen pharynx.

[0232] Secondary symptoms: Cough, thick phlegm, thirst, fever, relatively dry stools, short and yellow urine.

[0233] Tongue and pulse: Red tongue, yellow coating, rapid and forceful pulse.

[0234] For diagnosis, the main symptoms are essential, and 2 secondary symptoms are required. Combining the tongue, pulse, and fingerprint, the syndrome can be differentiated.

[0235] III. Inclusion criteria

[0236] All the following criteria must be fully met for screening to be included in the trial

[0237] IV. Principles for excluding cases

[0238] All cases will be included in the analysis, and the specific treatment principles will be processed accordingly according to the population for data statistical analysis.

[0239] V. Treatment plan:

[0240] Sample size: 43 cases, including 20 cases in the Oroxylum indicum prescription group and 23 cases in the Achyranthes aspera prescription group.

[0241] Oroxylum indicum prescription group: Orally take the traditional Chinese medicine composition of Example 1 (containing 24.5 g of crude drug amount) twice a day.

[0242] Achyranthes aspera prescription group: Orally take the traditional Chinese medicine composition of Example 67 (orally containing 24.5 g of crude drug amount) twice a day.

[0243] VI. Concomitant medications

[0244] If the subject has other diseases and needs to continue taking medications or other treatment methods, they can continue to be used, but the usage and dosage before enrollment should be maintained as much as possible.

[0245] Prohibited concomitant treatments: Except for the prescribed medications, the following medications or therapies are prohibited during the trial.

[0246] (1) Antibacterial and antiviral drugs shall not be used;

[0247] (2) Traditional Chinese medicine decoctions, proprietary Chinese medicines, and western medicines that have a therapeutic effect on acute pharyngitis or are similar to the functional indications of the trial drug shall not be used, including various throat lozenges for clearing and benefiting the throat;

[0248] (3) Antipyretic and analgesic drugs other than those specified in the protocol shall not be used.

[0249] Course of treatment: 5 days

[0250] VII. Results of efficacy analysis

[0251] Table 12: Clinical efficacy observation

[0252]

[0253]

[0254] 7.1 Main efficacy indicators: Time to disappearance of sore throat, disappearance rate

[0255] All subjects had sore throat at enrollment. The average time to disappearance of sore throat was 61.16 h in the Oroxylum indicum prescription group and 75.24 h in the Achyranthes aspera prescription group. The time to disappearance of sore throat in the Oroxylum indicum prescription group was shorter than that in the Achyranthes aspera prescription group. The disappearance rates of sore throat in the Oroxylum indicum prescription group and the Achyranthes aspera prescription group were 85% and 87% respectively, and the disappearance rates were comparable.

[0256] 7.2 Secondary efficacy indicators: Single disappearance rates of fever, thirst, cough, and sticky sputum

[0257] The disappearance rate of fever could not be evaluated. The single disappearance rates of pharyngeal redness and swelling, thirst, cough, and sticky sputum in both groups were ≥80%.

[0258] VIII. Conclusion:

[0259] Both the Oroxylum indicum prescription and the Achyranthes aspera prescription are effective in treating acute pharyngitis, but the Oroxylum indicum prescription has an advantage over the Achyranthes aspera prescription in terms of the duration of sore throat.

[0260] As described above, it is only the preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention should be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the said claims.

Claims

1. A traditional Chinese medicine composition, which is prepared from the following medicinal materials: Scutellaria baicalensis, Forsythia suspensa, Isatis indigotica, Phellodendron amurense, and Oroxylum indicum.

2. The traditional Chinese medicine composition according to claim 1, which is prepared from the following medicinal materials in parts by weight: Scutellaria baicalensis 5 - 15 parts, Forsythia suspensa 8 - 20 parts, Isatis indigotica 8 - 21 parts, Phellodendron amurense 2 - 10 parts, and Oroxylum indicum 2 - 10 parts; Preferably, the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by weight: Scutellaria baicalensis 8 - 12 parts, Forsythia suspensa 10 - 15 parts, Isatis indigotica 12 - 18 parts, Phellodendron amurense 4 - 8 parts, and Oroxylum indicum 4 - 8 parts; Preferably, the traditional Chinese medicine composition is prepared from the following medicinal materials in parts by weight: Scutellaria baicalensis 10 parts, Forsythia suspensa 12 parts, Isatis indigotica 15 parts, Phellodendron amurense 6 parts, and Oroxylum indicum 6 parts; or, Scutellaria baicalensis 8 parts, Forsythia suspensa 10 parts, Isatis indigotica 12 parts, Phellodendron amurense 4 parts, and Oroxylum indicum 4 parts; or, Scutellaria baicalensis 12 parts, Forsythia suspensa 15 parts, Isatis indigotica 18 parts, Phellodendron amurense 8 parts, and Oroxylum indicum 8 parts; or, Scutellaria baicalensis 10 parts, Forsythia suspensa 12 parts, Isatis indigotica 15 parts, Phellodendron amurense 8 parts, and Oroxylum indicum 6 parts.

3. The traditional Chinese medicine composition according to claim 1 or 2, wherein, Oroxylum indicum is replaced by Achyranthes aspera L..

4. A pharmaceutical composition, which comprises the traditional Chinese medicine composition according to any one of claims 1 - 3 and a pharmaceutically acceptable carrier; Optionally, the pharmaceutical composition is a capsule, granule, tablet, dripping pill, oral solution, syrup, injection or ointment; Optionally, in the pharmaceutical composition, the traditional Chinese medicine composition accounts for 0.1 - 99.9% of the total mass of the pharmaceutical composition, preferably 30 - 70%; Optionally, the pharmaceutical composition is an oral solid preparation, which comprises one or more of a flavoring agent, a binder, a disintegrant, a filler, a lubricant, a coloring agent, and a coating agent; Optionally, the flavoring agent is selected from one or more of sucrose, stevioside, aromatic syrup, sodium cyclamate, stevia sugar, sodium saccharin, protein sugar, xylitol, sorbitol, high fructose, aspartame, sucralose, and citric acid; preferably, the addition amount of the flavoring agent is 0.1 - 0.4% of the total mass of the pharmaceutical composition; Optionally, the binder is selected from one or more of water, hydroxypropyl methylcellulose, starch paste, or ethanol solution; preferably, the ethanol concentration is 50 - 95% v / v; Optionally, the filler is selected from one or more of dextrin, microcrystalline cellulose, lactose, starch, pregelatinized starch, powdered sugar, mannitol, sorbitol, and maltodextrin; preferably, the mass ratio of the filler to the traditional Chinese medicine composition is (0.5 - 3.0):1; Optionally, the disintegrant is selected from one or more of cross-linked polyvinylpyrrolidone, sodium carboxymethyl cellulose, starch, sodium carboxymethyl starch, hydroxypropyl starch, and low-substituted hydroxypropyl cellulose; preferably, the addition amount of the disintegrant is 0 - 2% of the total mass of the pharmaceutical composition; Optionally, the lubricant is selected from one or more of magnesium stearate, calcium stearate, stearic acid, talc powder, colloidal silica, and polyethylene glycol; preferably, the addition amount of the lubricant is 0 - 1% of the total mass of the pharmaceutical composition.

5. The preparation method of the traditional Chinese medicine composition according to any one of claims 1 to 3, wherein, The preparation method comprises the following steps: weighing Scutellaria baicalensis Georgi, Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or weighing Scutellaria baicalensis Georgi, Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L.; decocting with water; filtering; concentrating and / or drying.

6. The preparation method according to claim 5, wherein, The preparation method includes: weighing Scutellaria baicalensis Georgi, Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or weighing Scutellaria baicalensis Georgi, Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L.; decocting with water 1-3 times, 0.5-3 hours each time, filtering, and concentrating and / or drying the filtrate; preferably, decocting with 6-15 times the amount of water.

7. The preparation method according to claim 5 or 6, wherein, The five medicinal materials of Scutellaria baicalensis Georgi, Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or Scutellaria baicalensis Georgi, Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L. are fed in the following manner, wherein the four medicinal materials of Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L. are fed first, and Scutellaria baicalensis Georgi is added after boiling; preferably, the boiling temperature of the water is 80-100 °C.

8. The preparation method according to claim 7, wherein, The preparation method comprises the following steps: adding 8-15 times the amount of water to the four medicinal materials of Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L., boiling, adding Scutellaria baicalensis Georgi, decocting for 1-2 hours, filtering; adding 6-12 times the amount of water for the second time, decocting for 0.5-2 hours, filtering; adding 6-12 times the amount of water for the third time, decocting for 0.5-2 hours, filtering; combining the filtrates of the three times, concentrating the filtrate to obtain a clear paste, and drying; Preferably, add 10 times the amount of water to the four medicinal materials of Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L., boil, add Scutellaria baicalensis Georgi, decoct for 1.5 hours, filter; add 8 times the amount of water for the second time, decoct for 1 hour, filter; add 8 times the amount of water for the third time, decoct for 1 hour, filter; combine the filtrates of the three times, concentrate the filtrate to obtain a clear paste, and drying; Alternatively, add 8-15 times the amount of water to the four medicinal materials of Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L., boil, add Scutellaria baicalensis Georgi, decoct for 1-2 hours, filter; add 6-12 times the amount of water for the second time, decoct for 0.5-2 hours, filter; combine the filtrates of the two times, concentrate the filtrate to obtain a clear paste, and that's it; Preferably, add 12 times the amount of water to the four medicinal materials of Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Oroxylum indicum, or Forsythia suspensa (Thunb.) Vahl, Isatis tinctoria L., Phellodendron amurense Rupr. and Achyranthes aspera L., boil, add Scutellaria baicalensis Georgi, decoct for 2 hours, filter; add 10 times the amount of water for the second time, decoct for 1 hour, filter; combine the filtrates of the two times, concentrate the filtrate to obtain a clear paste, and that's it; Optionally, the filtering is carried out by hot filtration; preferably, the temperature of the hot filtration is 30-85 °C, preferably 50-80 °C; Optionally, the relative density of the clear paste at 50-65 °C is 1.01 to 1.

15.

9. The preparation method of a pharmaceutical composition according to claim 4, wherein, The preparation method comprises the following steps: mixing the traditional Chinese medicine composition according to any one of claims 1-3 with a pharmaceutically acceptable carrier; Preferably, the pharmaceutical composition is a granule, and the preparation method includes subjecting the traditional Chinese medicine composition according to any one of claims 1-3 to wet granulation with one or more of a flavoring agent, a binder, a disintegrant, a filler, a lubricant, a colorant, and a coating agent, and drying to obtain the granule; preferably, the preparation method includes taking the traditional Chinese medicine composition according to any one of claims 1-3, adding a flavoring agent and a filler, stirring and mixing in a wet granulator, adding an appropriate amount of binder to form a soft material, granulating, and drying until the moisture content of the granule is ≤5.0%.

10. The traditional Chinese medicine composition according to any one of claims 1 to 3 or the pharmaceutical composition according to claim 4 is used in the preparation of a drug for at least one of analgesia, anti-inflammation, antibacterial, antiviral, antitussive and expectorant, and antipyretic; or, used in the preparation of a drug for preventing and / or treating one or more of the following diseases; Optionally, the diseases are selected from exogenous wind-heat, syndrome of exuberant heat in the lung and stomach; or the diseases are selected from upper respiratory tract infection; or the diseases are selected from exogenous wind-heat, upper respiratory tract infection with syndrome of exuberant heat in the lung and stomach; preferably, the upper respiratory tract infection or exogenous wind-heat, upper respiratory tract infection with syndrome of exuberant heat in the lung and stomach includes pharyngitis, laryngitis, tonsillitis, and angina; or the diseases include cold accompanied by symptoms such as fever, sore throat, cough, and / or yellow phlegm; More preferably, the upper respiratory tract infection or the upper respiratory tract infection with the syndrome of exogenous wind-heat and exuberant heat in the lung and stomach is selected from an acute disease or the acute attack stage of a chronic disease; optionally, the disease is selected from one or more of acute pharyngitis, acute laryngitis, acute tonsillitis, and the acute attack stage of patients with chronic pharyngitis.

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