A traditional Chinese medicine composition containing bovine gallstones, a pharmaceutical preparation and application

Abstract

The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition containing ox gall, a pharmaceutical preparation and application, the present application provides a traditional Chinese medicine composition containing ox gall, which has the effects of clearing heat and resolving toxins, cooling liver and resolving lung, dispersing wind and relieving pain, and the preparation has a wide range of uses, the preparation method of the composition provided by the present application is easy to operate, and through years of production practice accumulation, the quality of the obtained product is stable and controllable, and the product is used for preparing drugs for treating liver and lung heat accumulation, wind and fire disturbance, dizziness, oral and nasal sores, wind and fire toothache, sudden eye inflammation, skin itching and other diseases in clinic, and has a wide application value.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a traditional Chinese medicine composition containing bezoar, pharmaceutical preparations, and applications. Background Technology

[0002] Modern medicine considers symptoms such as liver and lung heat accumulation, wind-fire disturbance, dizziness, sores in the mouth and nose, toothache due to wind-fire, acute conjunctivitis, and itchy skin to be an inflammatory reaction or an external manifestation of an inflammatory reaction. Treatment typically involves medications with antipyretic, anti-inflammatory, analgesic, sedative, and anticonvulsant effects. These medications have a strong inhibitory effect on various pathogenic microorganisms that cause inflammation, such as antibiotics and antipyretic analgesics. However, with the development of modern society, there is a problem of antibiotic abuse, and antipyretic analgesics have strict indications and numerous side effects. Traditional Chinese medicine (TCM), on the other hand, refers to medicines unique to traditional Chinese medicine. With the advancement of modern science and technology, the efficacy of more and more TCM herbs has been affirmed, and their safety has been guaranteed, making them highly practical.

[0003] For example, Chinese patent document CN106177146A discloses a Niuhuang Shangqing Pill, which is made from the following raw materials in the indicated weight ratios: 15-25 parts artificial bezoar, 290-310 parts peppermint, 390-410 parts chrysanthemum, 150-170 parts schizonepeta, 150-170 parts angelica dahurica, 150-170 parts chuanxiong rhizome, 490-510 parts gardenia, 150-170 parts rhubarb, 90-110 parts phellodendron bark, 490-510 parts scutellaria baicalensis, and 790-810 parts rhubarb. The formula contains 490-510 parts of Forsythia suspensa, 150-170 parts of Paeonia lactiflora, 490-510 parts of Angelica sinensis, 630-650 parts of Rehmannia glutinosa, 150-170 parts of Platycodon grandiflorus, 90-110 parts of Glycyrrhiza uralensis, 790-810 parts of Gypsum fibrosum, and 90-110 parts of Borneol. However, this traditional Chinese medicine composition focuses more on clearing heat and has a poor effect on inflammatory reactions, with a long treatment period. Therefore, establishing a traditional Chinese medicine composition that is simple to prepare, easy to use, and has a good therapeutic effect on inflammation has become an urgent technical problem to be solved. Summary of the Invention

[0004] Therefore, the purpose of this invention is to establish a traditional Chinese medicine composition and pharmaceutical preparation that is simple to prepare, easy to use, and has a good therapeutic effect on inflammation.

[0005] This invention discloses a traditional Chinese medicine composition containing bezoar. By weight, the composition comprises: 12-36 parts rhubarb, 18-54 parts scutellaria baicalensis, 6-18 parts white peony root, 1.5-4.5 parts uncaria rhizome, 3-9 parts saposhnikovia root, 18-54 parts platycodon root, 6-18 parts dioscorea opposita, 1.5-4.5 parts clove, 1.5-4.5 parts cinnamon, 3-9 parts licorice root, 6-18 parts realgar, 0.0375-0.1125 parts bezoar, 0.75-2.25 parts cinnamon, 0.75-2.25 parts borneol, 0.75-2.25 parts menthol, and 0.01875-0.05625 parts musk.

[0006] The musk is artificial musk, and the bezoar is artificial bezoar.

[0007] Further, by weight, the traditional Chinese medicine composition comprises: 24 parts rhubarb, 36 parts scutellaria baicalensis, 12 parts white peony root, 3 parts uncaria rhizome, 6 parts saposhnikovia root, 36 parts platycodon root, 12 parts yam, 3 parts clove, 3 parts cinnamon, 6 parts licorice root, 12 parts realgar, 0.075 parts artificial bezoar, 1.5 parts cinnabar, 1.5 parts borneol, 1.5 parts menthol, and 0.0375 parts artificial musk.

[0008] Further, by weight, the traditional Chinese medicine composition comprises: 12 parts rhubarb, 18 parts scutellaria baicalensis, 6 parts white peony root, 1.5 parts uncaria rhizome, 3 parts saposhnikovia root, 18 parts platycodon root, 6 parts yam, 1.5 parts clove, 1.5 parts cinnamon bark, 3 parts licorice root, 6 parts realgar, 0.0375 parts artificial bezoar, 0.75 parts cinnamon, 0.75 parts borneol, 0.75 parts menthol, and 0.01875 parts artificial musk.

[0009] Furthermore, by weight, the raw materials include: 36 parts rhubarb, 54 parts scutellaria baicalensis, 18 parts white peony root, 4.5 parts uncaria rhizome, 9 parts saposhnikovia root, 54 parts platycodon root, 18 parts yam, 4.5 parts clove, 4.5 parts cinnamon, 9 parts licorice root, 18 parts realgar, 0.1125 parts artificial bezoar, 2.25 parts cinnamon, 2.25 parts borneol, 2.25 parts menthol, and 0.05625 parts artificial musk.

[0010] Furthermore, the Chinese medicine composition is a composition obtained by pulverizing each raw material; or an extract obtained by mixing each raw material and then extracting it using conventional extraction methods or by extracting it separately using conventional extraction methods; or the effective portion obtained by refining and purifying the extract.

[0011] Furthermore, the conventional extraction method includes one or more of the following: maceration extraction, decoction extraction, reflux extraction, percolation extraction, ultrasonic extraction, and steam distillation; the extraction solvent includes water, 20-95 wt% ethanol solution, or pure ethanol; the purification process includes one or more of the following: water extraction and alcohol precipitation, extraction, silica gel column separation, and macroporous resin column separation.

[0012] The present invention also provides a pharmaceutical preparation comprising the traditional Chinese medicine composition containing bezoar as described in any of the above claims, and further comprising pharmaceutically acceptable excipients.

[0013] The pharmaceutical preparation is a pill, tablet, capsule, powder, mixture, or granule; and / or, the pharmaceutically acceptable excipient is selected from at least one of the following pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, stabilizers, flow aids, flavoring agents, preservatives, coating materials, fragrances, anti-adhesives, pH adjusters, buffers, plasticizers, surfactants, diluents, polymeric framework materials, and film-forming materials.

[0014] In some embodiments, the excipients are selected from at least one of starch, dextrin, microcrystalline cellulose, purified water, ethanol, magnesium stearate, talc, white sugar, lemon yellow, celery powder, and honey.

[0015] In some embodiments, the pharmaceutical formulation is a tablet, and the excipients of the tablet include at least one of fillers, lubricants, and binders.

[0016] In some preferred embodiments, the filler is selected from at least one of starch, lactose, dextrin, and microcrystalline cellulose. More preferably, the mass ratio of the filler to the traditional Chinese medicine composition is 25-190:70-250.

[0017] In some preferred embodiments, the lubricant is selected from at least one of magnesium stearate and talc. More preferably, the mass percentage of the lubricant added to the pharmaceutical formulation is 3-8%.

[0018] In some preferred embodiments, the adhesive is at least one of starch paste, ethanol solution, and polyvinylpyrrolidone. The starch paste is an aqueous solution of starch dissolved or swollen with water, and the starch content is 5-8 wt%.

[0019] This invention provides a method for preparing a pharmaceutical preparation, which uses any of the above-described traditional Chinese medicine compositions containing bezoar as the active component, adds conventional excipients, and prepares the preparation according to conventional processes.

[0020] Furthermore, the pharmaceutical preparation is a tablet, and the method for preparing the tablet includes the following steps:

[0021] (1) Take rhubarb, scutellaria baicalensis, white peony root, uncaria, saposhnikovia divaricata, platycodon grandiflorus, yam, clove, cinnamon and licorice, grind them into powder and mix them or mix them and then grind them into fine powder;

[0022] (2) Take the mixed fine powder and mix it with bezoar, cinnabar and realgar, add a binder, make it into granules and dry it;

[0023] (3) Take the dried granules from step (2) and mix them with borneol, menthol and musk, and press them into tablets to obtain the product.

[0024] The method for preparing a pharmaceutical formulation provided in certain preferred embodiments includes the following steps:

[0025] (1) Take rhubarb, scutellaria baicalensis, white peony root, uncaria, saposhnikovia divaricata, platycodon grandiflorus, yam, clove, cinnamon, and licorice. After pulverizing, mix them or after mixing, and pulverize them through an 80-120 mesh sieve to make a fine mixed powder. Take cinnabar and realgar, pulverize them, and sieve them through an 80-120 mesh sieve to make cinnabar powder and realgar powder respectively. According to the equal increment method, take musk and mix it with 0.8-2 times the amount of the fine mixed powder to obtain musk mixed powder.

[0026] (2) Take the remaining fine powder, cinnabar powder, realgar powder and filler, mix them together, add binder, make granules, dry them, and obtain mixed granules;

[0027] (3) Melt camphor and peppermint with ethanol, then mix with mixed granules, musk powder and lubricant, and press into tablets to obtain the product.

[0028] The method for preparing a pharmaceutical formulation provided in certain preferred embodiments includes the following steps:

[0029] (1) Take rhubarb, scutellaria baicalensis, white peony root, uncaria rhizome, saposhnikovia root, platycodon root, yam, clove, cinnamon, and licorice root, grind them into powder and mix them or grind them into powder and pass them through an 80-120 mesh sieve to make a fine mixed powder; take cinnabar and realgar, grind them into powder and pass them through an 80-120 mesh sieve to make cinnabar powder and realgar powder respectively; take musk and mix it with part of the fine mixed powder according to the equal increment method to obtain musk mixed powder;

[0030] (2) Take the remaining fine powder, cinnabar powder, realgar powder and filler, mix them together, add binder, make granules, dry them, and obtain mixed granules;

[0031] (3) Melt borneol and peppermint with ethanol and then mix with some of the mixed particles to obtain borneol and peppermint granule powder; take musk mixed powder and mix with some of the mixed particles to obtain musk granule powder;

[0032] (4) Take borneol granules, musk granules, and the remaining mixed granules and lubricant, mix them together, and compress them into tablets.

[0033] Furthermore, in step (1), the musk is mixed with 0.8-5 times the amount of mixed particles, where multiples refer to the ratio of the mass of the mixed fine powder to the mass of the musk.

[0034] Further, in step (3), borneol and peppermint are mixed with 0.8-5 times the amount of mixed granules; the multiple refers to the ratio of the mass of the mixed granules to the sum of the masses of borneol and peppermint.

[0035] Furthermore, in step (3), the musk mixed powder is mixed with 0.8-5 times the amount of mixed particles, where multiples refer to the ratio of the mass of the mixed particles to the mass of the musk mixed powder.

[0036] The present invention also provides the use of any of the above-mentioned bezoar-containing traditional Chinese medicine compositions, or any of the above-mentioned bezoar-containing pharmaceutical preparations, or the bezoar-containing pharmaceutical preparations prepared by the above-mentioned preparation method in the preparation of drugs, wherein the drugs have at least one of the following uses: (1) inhibiting or eliminating inflammatory reactions; (2) inhibiting or eliminating edema; (3) inhibiting capillary permeability; (4) inhibiting or eliminating at least one of the following symptoms: liver and lung heat accumulation, wind-fire disturbance, dizziness, sores in the mouth and nose, toothache due to wind-fire, acute conjunctivitis and itchy skin.

[0037] Furthermore, the inflammatory response is an acute or chronic inflammatory response; and / or, the swelling is caused by an acute inflammatory response.

[0038] The liver belongs to the wood element and its orifice is the eyes. Its meridian connects to the eye system and intersects at the vertex. The liver is a rigid organ, storing blood. It is yin in nature but yang in function, and it governs the free flow of qi and prefers smooth circulation. When liver qi cannot flow smoothly, it becomes stagnant and transforms into fire. When fire moves, yang loses its concealment and becomes excessive in the upper body. The lungs belong to the metal element and their orifice is the nose. In the body, they manifest as skin and hair. The lungs govern the dispersing and descending of qi, dispersing fluids and reducing fire. When liver qi stagnates and transforms into fire, wood fire attacks metal. Liver fire travels along the lung meridian and emerges from its orifice, causing nosebleeds and nasal sores. The liver opens to the eyes; when liver heat causes yang to rise, liver fire flares upward, disturbing the sensory orifices and causing dizziness and conjunctivitis. Excessive lung heat causes wind and fire to disturb the upper body, resulting in sores in the mouth and nose, and itchy skin. Excessive liver fire easily attacks the stomach; stomach fire flares upward, causing toothache and loose teeth. The traditional Chinese medicine composition provided by this invention selects raw materials that clear heat and detoxify, calm the liver and subdue yang, benefit the throat and improve eyesight, dispel wind and unblock the meridians and relieve pain, so as to relieve the ailments of the head, eyes, mouth and nose caused by the accumulation of heat in the liver and lungs and the disturbance of wind and fire.

[0039] The technical solution of this invention has the following advantages:

[0040] 1. The present invention provides a traditional Chinese medicine composition containing bezoar. Bezoar, rhubarb, and scutellaria baicalensis clear heat and detoxify, cool the liver and purge the lungs, promote bowel movements and clear heat, serving as the principal herbs. Realgar is used as the assistant herb to detoxify and reduce swelling; white peony root nourishes yin and softens the liver; and uncaria calms the liver and subdues yang, assisting the principal herbs in cooling the liver. Together, they treat dizziness, acute conjunctivitis, and headaches. Saposhnikovia divaricata is pungent and dispersing, relieves pain, dispels wind and relieves itching; and Platycodon grandiflorus is pungent and bitter, clears the lungs and benefits the throat, relieving sores in the mouth and nose, toothache due to wind-heat, and itchy skin. The adjuvant herbs are: Borneol and menthol, being pungent, bitter, and cold in nature, clear heat, relieve pain, purge fire, detoxify, and improve eyesight. Cinnabar, sweet, cold, and heavy in nature, clears heat, detoxifies, calms the mind, and soothes the nerves. Dioscorea opposita, sweet, neutral, and moistening in nature, nourishes qi and yin to replenish qi and fluids depleted by excessive heat. Cloves, cinnamon, and musk, being pungent, warm, and fragrant, can invigorate blood circulation, regulate menstruation, reduce swelling, and relieve pain to treat sores and carbuncles. They also help to counteract the excessive coldness of other ingredients, allowing licorice to remain sweet and neutral, clear heat, detoxify, relieve spasms and pain, and harmonize the effects of all the other ingredients. When combined in a specific ratio, these herbs work together to clear heat, detoxify, cool the liver and lungs, dispel wind, and relieve pain. They can significantly inhibit inflammatory responses and suppress, alleviate, or eliminate symptoms.

[0041] 2. The bezoar-containing pharmaceutical preparations provided by this invention, with the addition of conventional excipients and the production of clinically acceptable formulations using conventional processes, are scientifically sound, easy to operate, and have a wide range of applications. Among them, the tablets (also known as Bezoar Detoxification Tablets) are the result of years of production practice, with a mature preparation method, stable and controllable product quality, high and uniform content of active ingredients, and small batch-to-batch differences. In addition, they have achieved significant clinical efficacy in treating liver and lung heat, wind-heat disturbance, dizziness, sores in the mouth and nose, toothache due to wind-heat, acute conjunctivitis, and itchy skin, and have broad application value. Detailed Implementation

[0042] Example 1

[0043] This embodiment provides a traditional Chinese medicine composition containing bezoar, with the following formula: 24g rhubarb, 36g scutellaria baicalensis, 12g white peony root, 3g uncaria rhizome, 6g saposhnikovia root, 36g platycodon root, 12g yam, 3g clove, 3g cinnamon bark, 6g licorice root, 12g realgar, 0.075g artificial bezoar, 1.5g cinnamon, 1.5g borneol, 1.5g menthol, and 0.0375g artificial musk.

[0044] This embodiment also provides a Niuhuang Jiedu tablet and its preparation method, the preparation method including the following steps:

[0045] (1) Weigh out 24g of rhubarb, 36g of scutellaria baicalensis, 12g of white peony root, 3g of uncaria rhizome, 6g of saposhnikovia root, 36g of platycodon root, 12g of yam, 3g of clove, 3g of cinnamon, and 6g of licorice root. Grind these ten ingredients into a fine powder, pass through a 100-mesh sieve, and mix them evenly to make a fine powder mixture of the ten ingredients. Weigh out 1.5g of cinnabar and 12g of realgar, and grind them into an extremely fine powder by water-milling, then pass through a 100-mesh sieve.

[0046] (2) Weigh 0.075 g of artificial bezoar, 1.5 g of menthol, 1.5 g of borneol and 0.0375 g of artificial musk and store them separately; grind according to the equal increment method, mix 0.0375 g of artificial musk with 0.0375 g of the ten-herb mixed fine powder to make artificial musk mixed powder; grind the remaining ten-herb mixed fine powder with the above artificial bezoar, cinnabar, realgar and 80 g of starch, mix evenly and add 7 wt% starch paste, granulate by wet method, dry the wet granules at 70℃, granulate and make fine powder granules;

[0047] (3) Borneol and menthol are dissolved in an appropriate amount of ethanol and then poured into 3 grams of fine granules and mixed to make borneol-menthol granules; artificial musk mixed powder is mixed with 0.075 grams of fine granules to make artificial musk granules; after mixing borneol-menthol granules and artificial musk granules, they are mixed with the remaining fine granules, and then 0.5% magnesium stearate (the mass of magnesium stearate accounts for 0.5% of the total mass of the mixture formed after adding magnesium stearate) is added, mixed, and pressed into 1000 tablets. The shape of the Niuhuang Jiedu tablet is concave, and the punch and die are used. Coat with sugar, and you're done.

[0048] Example 2

[0049] This embodiment provides a traditional Chinese medicine composition containing bezoar, the formula of which is as follows:

[0050] Rhubarb 12g, Scutellaria baicalensis 18g, Paeonia lactiflora 6g, Uncaria rhynchophylla 1.5g, Saposhnikovia divaricata 3g, Platycodon grandiflorus 18g, Dioscorea opposita 6g, Clove 1.5g, Cinnamomum cassia 1.5g, Glycyrrhiza uralensis 3g, Realgar 6g, Artificial bezoar 0.0375g, Cinnamon 0.75g, Borneol 0.75g, Menthol 0.75g, Artificial musk 0.01875g.

[0051] This embodiment also provides a Niuhuang Jiedu tablet and its preparation method, the preparation method including the following steps:

[0052] (1) Weigh out 12g of rhubarb, 18g of scutellaria baicalensis, 6g of white peony root, 1.5g of uncaria rhizome, 3g of saposhnikovia root, 18g of platycodon root, 6g of yam, 1.5g of clove, 1.5g of cinnamon, and 3g of licorice root according to the selected weight. Grind the ten herbs into a fine powder, pass through a 100-mesh sieve, mix evenly, and make a fine powder mixture of the ten herbs. Weigh out 0.75g of cinnabar and 6g of realgar, grind them into an extremely fine powder, and pass through a 100-mesh sieve.

[0053] (2) Weigh 0.0375 g of artificial bezoar, 0.75 g of menthol, 0.75 g of borneol and 0.01875 g of artificial musk and store them separately; grind them according to the equal increment method, mix 0.01875 g of artificial musk with 0.01875 g of the ten-herb mixed fine powder to make artificial musk mixed powder; grind the remaining ten-herb mixed fine powder with the above artificial bezoar, cinnabar, realgar and 25 g of dextrin and 41 g of starch, mix evenly and add 100 g of 6wt% starch paste, granulate by wet method, dry the wet granules at 70℃, granulate and make fine powder granules;

[0054] (3) Borneol and menthol are dissolved in an appropriate amount of ethanol and then poured into 5 grams of fine granular powder and mixed evenly to make borneol-menthol granular powder; artificial musk mixed powder is mixed with 0.1 grams of fine granular powder to make artificial musk granular powder; after mixing borneol-menthol granular powder and artificial musk granular powder, it is mixed with the remaining fine granular powder, and then 0.5% magnesium stearate is added, mixed evenly, and pressed into 1000 tablets. The shape of the Niuhuang Jiedu tablet is concave, and the punch and die are used. Coat with sugar, and you're done.

[0055] Example 3

[0056] This embodiment provides a traditional Chinese medicine composition containing bezoar, with the following formula: 36g rhubarb, 54g scutellaria baicalensis, 18g white peony root, 4.5g uncaria rhizome, 9g saposhnikovia root, 54g platycodon root, 18g yam, 4.5g clove, 4.5g cinnamon bark, 9g licorice root, 18g realgar, 0.1125g artificial bezoar, 2.25g cinnamon, 2.25g borneol, 2.25g menthol, and 0.05625g artificial musk.

[0057] This embodiment also provides a Niuhuang Jiedu tablet and its preparation method, the preparation method including the following steps:

[0058] (1) Weigh out 36g of rhubarb, 54g of scutellaria baicalensis, 18g of white peony root, 4.5g of uncaria rhizome, 9g of saposhnikovia root, 54g of platycodon root, 18g of yam, 4.5g of clove, 4.5g of cinnamon, and 9g of licorice root according to the selected weight. Grind the ten herbs into a fine powder, pass through a 100-mesh sieve, mix evenly, and make a fine powder mixture of the ten herbs. Weigh out 2.25g of cinnabar and 18g of realgar, grind them into an extremely fine powder by water-milling, and pass through a 100-mesh sieve.

[0059] (2) Weigh 0.1125 g of artificial bezoar, 2.25 g of menthol, 2.25 g of borneol and 0.05625 g of artificial musk and store them separately; grind them according to the equal increment method, mix 0.05625 g of artificial musk with 0.05625 g of the ten-herb mixed fine powder to make artificial musk mixed powder; grind the remaining ten-herb mixed fine powder with the above artificial bezoar, cinnabar, realgar and 75 g of dextrin, mix evenly, add 100 g of 8wt% starch paste, granulate by wet method, dry the wet granules at 70℃, granulate and make fine powder granules;

[0060] Borneol and menthol are dissolved in an appropriate amount of ethanol and then added to 5 grams of fine granular powder, mixed well to make borneol-menthol granular powder; artificial musk mixed powder is mixed with 0.1 grams of fine granular powder to make artificial musk granular powder; borneol-menthol granular powder and artificial musk granular powder are mixed well, then mixed with the remaining fine granular powder, magnesium stearate is added, mixed well, and pressed into 1000 tablets. The shape of the Niuhuang Jiedu tablets is deeply concave, and the punch is used for die-cutting. Coat with sugar, and you're done.

[0061] Example 4

[0062] This embodiment provides a traditional Chinese medicine composition containing bezoar, with the following formula: 36g rhubarb, 54g scutellaria baicalensis, 18g white peony root, 4.5g uncaria rhizome, 9g saposhnikovia root, 54g platycodon root, 18g yam, 4.5g clove, 4.5g cinnamon bark, 9g licorice root, 18g realgar, 0.1125g artificial bezoar, 2.25g cinnamon, 2.25g borneol, 2.25g menthol, and 0.05625g artificial musk.

[0063] This embodiment discloses a Niuhuang Jiedu Pill and its preparation method, the preparation method including the following steps:

[0064] (1) Weigh out 36g of rhubarb, 54g of scutellaria baicalensis, 18g of white peony root, 4.5g of uncaria rhizome, 9g of saposhnikovia root, 54g of platycodon root, 18g of yam, 4.5g of clove, 4.5g of cinnamon, and 9g of licorice root according to the selected weight. Grind the ten herbs into a fine powder, pass through a 100-mesh sieve, mix evenly, and make a fine powder mixture of the ten herbs. Weigh out 2.25g of cinnabar and 18g of realgar, grind them into an extremely fine powder by water-milling, and pass through a 100-mesh sieve.

[0065] (2) Weigh out 0.1125g of artificial bezoar, 2.25g of menthol, 2.25g of borneol and 0.05625g of artificial musk and store them separately; grind them according to the equal increment method, and mix 0.05625g of artificial musk with 0.05625g of the ten-herb mixed fine powder to make artificial musk mixed powder;

[0066] (3) Mix the remaining ten herbs into a fine powder and mix with the above-mentioned artificial bezoar, cinnabar and realgar. Pass the mixture through a 100-mesh sieve to obtain a mixture. Add 30% refined honey and 80ml water to the mixture. Dissolve borneol and menthol in an appropriate amount of ethanol and add them to the mixture. Make pills and prepare water-honey pills.

[0067] Experiment Example 1: Effect of Niuhuang Jiedu Tablets on Xylene-Induced Acute Ear Swelling in Mice 1. Experimental Objective

[0068] The effect of Niuhuang Jiedu tablets of the present invention on the degree of ear swelling in mice was observed through an acute inflammatory response experiment induced by xylene in mice, and the effect of Niuhuang Jiedu tablets on inhibiting acute inflammatory response was evaluated.

[0069] 2. Test materials

[0070] 2.1 Tested drugs

[0071] Niuhuang Jiedu Tablets of the present invention: Prepared according to the method of Example 1. Niuhuang Jiedu Tablets of the prior art: Provided by Beijing Tongrentang Science & Technology Development Co., Ltd. Pharmaceutical Factory, batch number: 15120408. Bamyl Aspirin Effervescent Tablets, provided by AstraZeneca Pharmaceuticals Co., Ltd., batch number: 1408008.

[0072] 2.2 Reagents

[0073] Xylene, 500 ml / bottle, Beijing Chemical Plant, batch number: 20101207.

[0074] 2.3 Experimental animals and feeding conditions

[0075] 60 ICR male mice, SPF grade, weighing 10 - 12 g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., license number: SCXK(Beijing)2012 - 0001, certificate number: No:11400700091111.

[0076] The experimental animals were housed in a SPF - grade animal room, illuminated by fluorescent lamps with a 12 - h light - dark cycle, free access to water and food, temperature 22℃±2℃, humidity 40 - 70%RH.

[0077] 2.4 Test instruments

[0078] Sartorious BT 124S electronic precision balance, Sartorius Scientific Instruments Co., Ltd.;

[0079] Hepu corneal trephine: 8 mm in diameter.

[0080] 3. Test methods

[0081] 3.1 Drug preparation<​​​​​​​​​​​​​​​​After 3 days of acclimatization, the mice were randomly divided into 6 groups of 10 mice each according to their body weight. These groups were the model group, the aspirin group, the Niuhuang Jiedu tablet group, and the high, medium, and low dose Niuhuang Jiedu tablet groups of Example 1.

[0088] 3.3 Administration method

[0089] Mice in each group were administered the tested drugs orally via gavage. The high, medium, and low dose groups of the Niuhuang Jiedu tablets were given doses of 1.146 g / kg, 0.573 g / kg, and 0.2865 g / kg, respectively; the aspirin group received a dose of 0.9 g / kg. The Niuhuang Jiedu tablets group received a dose of 364.5 mg / kg, and the model group received an equal volume of distilled water.

[0090] The oral administration volume was 0.2 ml / 10 g body weight for mice.

[0091] 3.4 Test Methods

[0092] Mice in each group were administered the tested drug via gavage once daily for 5 consecutive days. Forty minutes after the last administration, 0.05 ml of xylene was applied to both sides of the left ear of each mouse (0.025 ml on each side) to induce inflammation. Sixty minutes after inflammation, the mice were sacrificed, and ear flaps were punched at the same location on both auricles using an 8 mm punch. The flaps were weighed using an electronic analytical balance, and the difference in weight between the left and right ear flaps was the degree of swelling. The auricle swelling rate and inhibition rate were calculated for each treatment group.

[0093] Auricular swelling rate (%) = (Weight of left auricle - Weight of right auricle) / Weight of right auricle × 100%

[0094] Auricular swelling inhibition rate (%) = (Mean auricular swelling in the model group - Mean auricular swelling in the treatment group) / Mean auricular swelling in the model group × 100%

[0095] 4. Statistical Methods

[0096] Experimental data are expressed as mean ± standard deviation. The data were first tested for homogeneity of variance. For data with homogeneity of variance, One-Way ANOVA was used to compare between groups; for data with unequal variance, the t' test was used to compare between groups.

[0097] 5. Test Results

[0098] The results showed that the aspirin group and the high and medium dose groups of Niuhuang Jiedu tablets (Example 1) significantly reduced the ear swelling degree of xylene-induced acute inflammatory response in mice, with significant differences compared with the model group (P<0.001, 0.01, 0.05, 0.05, respectively). The aspirin group and the high, medium, and low dose groups of Niuhuang Jiedu tablets (Example 1) all reduced the ear swelling rate of xylene-induced acute inflammatory response in mice to varying degrees, with significant differences compared with the model group (P<0.001, 0.001, 0.001, 0.05, respectively). These results indicate that the Niuhuang Jiedu tablets of this invention can significantly reduce the degree and rate of acute ear swelling in mice induced by xylene, and have a good inhibitory effect on acute inflammatory response. The results are shown in Table 1 below.

[0099] Table 1. Effect of Niuhuang Jiedu tablets on xylene-induced acute ear swelling model in mice (Example 1).

[0100]

[0101] Compared with the model group, *p<0.05; **p<0.01; ***p<0.001.

[0102] Experiment Example 2: Effect of Niuhuang Jiedu Tablets on Peritoneal Capillary Permeability in Mice

[0103] 1. Experimental Objective

[0104] The effect of Niuhuang Jiedu tablets described in Example 2 on acetic acid-induced Evans blue permeation in the peritoneal cavity of mice was observed by a mouse peritoneal capillary permeability test, and the inhibitory effect of Niuhuang Jiedu tablets described in Example 2 on capillary permeability of acute inflammatory response was evaluated.

[0105] 2. Test materials

[0106] 2.1 Test Drug:

[0107] The Niuhuang Jiedu tablets of the present invention were prepared according to the method of Example 2.

[0108] The existing technology for Niuhuang Jiedu tablets is provided by Beijing Tongrentang Technology Development Co., Ltd. Pharmaceutical Factory, batch number: 15120408.

[0109] Dexamethasone acetate tablets, Tianjin Pharmaceutical Group Xinzheng Co., Ltd., batch number: 140421.

[0110] 2.2 Reagents:

[0111] Evans Blue, Sigma, CAS NO 314-13-6.

[0112] 2.3 Laboratory animals and their husbandry

[0113] 72 ICR mice, with 36 males and 36 females, SPF grade, weighing 18 - 22 g, were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., with the license number: SCXK(Beijing)2012 - 0001 and the certificate number: No:11400700095492.

[0114] The experimental animals were housed in a SPF - grade animal room with fluorescent lighting, a 12 - hour light - dark cycle, free access to water and food, at a temperature of 22℃ ± 2℃ and a humidity of 40 - 70%RH.

[0115] 2.4 Test instruments

[0116] Multiskan Mk3 microplate reader, manufacturer: Thermo Fisher Scientific (Shanghai) Instrument Co., Ltd.

[0117] Sartorious BT 124S electronic precision balance, Sartorius Scientific Instruments (Beijing) Co., Ltd. <着

[0118] 3. Test methods

[0119] 3.1 Dosage setting

[0120] (1) Niuhuang Jiedu Tablets described in Example 2

[0121] The high - dose, medium - dose and low - dose groups were respectively given doses of 1.2 g / kg, 0.6 g / kg, and 0.3 g / kg, with a total of three dose groups.

[0122] (2) Dexamethasone acetate

[0123] Each tablet of this product contains 0.75 mg of the main ingredient dexamethasone acetate. Dosage and administration: Oral, the initial dose for adults is 1 - 4 tablets once, 2 - 4 times a day. In this study, calculated based on 12 mg / day for an adult with a body weight of 60 kg, the human dosage is 0.2 mg / kg, and the equivalent dose for mice is 1.8 mg / kg.

[0124] (3) Niuhuang Jiedu Tablets group

[0125] According to the dosage and administration instructions of Niuhuang Jiedu Tablets, oral, 3 tablets once, 2 - 3 times a day, the core weight of each tablet is 0.27 g. In this experiment, calculated based on the adult daily dosage of 2.43 g for an adult with a body weight of 60 kg, the human dosage is 40.5 mg / kg, and the equivalent dose for mice is 0.3645 g / kg.

[0126] 3.2 Drug preparation

[0127] Niuhuang Jiedu Tablets described in Example 2: Prepared into suspensions with concentrations of 5.73%, 2.865% and 1.4325% respectively using distilled water;

[0128] Dexamethasone: Prepared as a 0.009% suspension with distilled water.

[0129] Niuhuang Jiedu Tablets: Prepared as a 1.8225% suspension with distilled water.

[0130] All of the above medications should be prepared and used immediately.

[0131] 3.3 Animal Experiment Grouping

[0132] After 3 days of acclimatization, the mice were randomly divided into 6 groups of 12 mice each according to their body weight. The groups were the model group, the dexamethasone group, the Niuhuang Jiedu tablet group, and the high, medium and low dose groups of Niuhuang Jiedu tablets as described in Example 2.

[0133] 3.4 Administration method

[0134] Mice in each group were administered the tested drugs orally via gavage. Specifically, the high, medium, and low dose groups of Niuhuang Jiedu tablets described in Example 2 were administered at doses of 1.2 g / kg, 0.6 g / kg, and 0.3 g / kg, respectively; the dexamethasone group was administered at a dose of 1.8 mg / kg. The Niuhuang Jiedu tablet group was administered at a dose of 364.5 mg / kg, and the model group was given an equal volume of distilled water.

[0135] The oral administration volume was 0.2 ml / 10 g body weight for mice.

[0136] 3.5 Test Methods

[0137] After 3 days of acclimatization, mice in each group were administered the tested drug by gavage once daily for 5 consecutive days. 60 minutes after the last administration, each mouse was injected intravenously with 0.1 ml / 10 g of 0.5% Evans blue saline solution, followed by 0.2 ml / mouse of 0.8% glacial acetic acid. Twenty minutes later, the mice were euthanized by cervical dislocation, and 4 ml of saline was injected intraperitoneally. After gently massaging the abdomen, the abdominal skin and muscle were cut open, and 1 ml of the liquid was collected. The mixture was centrifuged at 3000 rpm for 15 minutes, and the supernatant was measured at 540 nm for absorbance.

[0138] 4. Statistical Methods

[0139] Experimental data are expressed as mean ± standard deviation. The data were first tested for homogeneity of variance. For data with homogeneity of variance, One-Way ANOVA was used to compare between groups; for data with unequal variance, the t' test was used to compare between groups.

[0140] 5. Test Results

[0141] The results showed that the dexamethasone group, Niuhuang Jiedu Tablets group and the high, medium and low dose groups of Niuhuang Jiedu Tablets described in Example 2 could all inhibit the increased permeability of peritoneal capillary vessels in mice caused by acetic acid to varying degrees, and there were significant differences compared with the model group (P<0.01, 0.01, 0.05, 0.05 respectively). The results are shown in the following table.

[0142] Table 2 Effects of Niuhuang Jiedu Tablets in Example 2 on the permeability of peritoneal capillary vessels in mice

[0143] Group Dosage (mg / kg) N Absorbance(SD) Model group -- 12 0.210±0.062 Dexamethasone group 1.80 12 <![CDATA[0.152±0.055 * ]]> Niuhuang Jiedu Tablets 364.5 12 <![CDATA[0.119±0.048 *** ]]> Example 2: High-dose group of Niuhuang Jiedu tablets 1200.00 12 <![CDATA[0.152±0.046 * ]]> Example 2: Medium-dose group of Niuhuang Jiedu tablets 600.00 12 <![CDATA[0.122±0.034 *** ]]> Example 2: Low-dose group of Niuhuang Jiedu tablets 300.00 12 <![CDATA[0.155±0.045 * ]]>

[0144] Compared with the model group, *P<0.05; **P<0.01; ***P<0.001

[0145] Experimental Example 3 Effects of Niuhuang Jiedu Tablets on the formation of cotton ball granulomas in rats

[0146] 1. Test purpose

[0147] Through the chronic inflammatory reaction test of cotton ball granulomas in rats, observe the effects of Niuhuang Jiedu Tablets described in Example 3 on the formation of cotton ball granulomas in rats, and evaluate the effect of Niuhuang Jiedu Tablets described in Example 3 in inhibiting chronic inflammatory reactions.

[0148] 2. Test materials

[0149] Niuhuang Jiedu Tablets of the present invention: Prepared according to the method of Example 3. Dexamethasone acetate tablets, Xinzheng Co., Ltd., Tianjin Pharmaceutical Group, batch number: 1400421. Niuhuang Jiedu Tablets of the prior art: Provided by Beijing Tongrentang Technology Development Co., Ltd. Pharmaceutical Factory, batch number: 15120408.

[0150] 2.2 Reagents:

[0151] Penicillin sodium for injection, North China Pharmaceutical Co., Ltd., batch number: F4041101.

[0152] [[ID=Z4]]2.3 Experimental animals and feeding conditions

[0153] 60 SD rats, male, SPF grade, weighing 60-80 g, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd., license number: SCXK(Beijing)2012-0001, certificate number: No: 11400700098874.

[0154] The experimental animals were housed in an SPF-grade animal room, illuminated by fluorescent lamps, with a 12-hour light-dark cycle, free access to water and food, temperature 22°C±2°C, and humidity 40-70%RH.

[0155] 2.4 Test instruments

[0156] Sartorious BT 124S electronic precision balance, Sartorious Scientific Instruments Ltd.;

[0157] DHG-9140A Electric Heating Constant Temperature Drying Oven, Shanghai Yiheng Technology Co., Ltd.

[0158] 3. Test Methods

[0159] 3.1 Dosage setting

[0160] (1) The Niuhuang Jiedu tablets described in Example 3

[0161] In Example 3, the high, medium, and low dose groups of Niuhuang Jiedu tablets were administered at doses of 1.146 g / kg, 0.573 g / kg, and 0.2865 g / kg, respectively, for a total of three dose groups.

[0162] (2) Dexamethasone acetate

[0163] Each tablet contains 0.75 mg of the main ingredient, dexamethasone acetate. Dosage and administration: Oral administration. The initial adult dose is 1-4 tablets, 2-4 times daily. This study calculated a dose of 12 mg / day for an adult weighing 60 kg, resulting in a human dose of 0.2 mg / kg, equivalent to an effective dose of 1.2 mg / kg in rats.

[0164] (3) Niuhuang Jiedu Tablets

[0165] According to the instructions for use and dosage of Niuhuang Jiedu tablets, the dosage is 3 tablets orally, 2-3 times a day. The core weight of each tablet is 0.27g. In this experiment, the daily adult dose was calculated based on 2.43g and the adult weight was 60kg. The human dose was 40.5mg / kg, which is equivalent to 243mg / kg for rats.

[0166] 3.2 Drug Preparation

[0167] The Niuhuang Jiedu tablets described in Example 3 were prepared into mixed solutions with concentrations of 7.64%, 3.82%, and 1.91% using distilled water.

[0168] Dexamethasone acetate: Prepare a 12% mixed solution with distilled water.

[0169] Niuhuang Jiedu tablets: Prepare a 2.43% mixed solution with distilled water.

[0170] All of the above medications should be prepared and used immediately.

[0171] 3.3 Animal Experiment Methods and Grouping

[0172] 60 male SD rats, weighing 180 - 200 g, were adaptively fed for 4 days, then anesthetized by intraperitoneal injection of 10% chloral hydrate. 20 mg of high-pressure sterilized cotton balls (each cotton ball added with 1 mg of sodium penicillin in 0.1 ml and dried in an oven at 60°C) were implanted subcutaneously in the left and right groin of each rat. After surgery, the rats were randomly divided into 6 groups of 10 each, namely the model group, dexamethasone group, Niuhuang Jiedu Tablet group, and the high, medium, and low-dose groups of Niuhuang Jiedu Tablets described in Example 3. From the day after surgery, the animals in each group were intragastrically administered the corresponding drugs for 7 consecutive days, and the model group was given an equal volume of distilled water. On the 8th day, the animals were sacrificed, the cotton balls were removed together with the surrounding connective tissue, the adipose tissue was removed, and they were dried in an oven at 60°C for 24 hours and weighed. The weight obtained was subtracted from the original weight of the cotton ball to obtain the granuloma weight.

[0173] Granuloma weight = obtained weight - original weight of cotton ball

[0174] 3.3 Administration method

[0175] Each group of rats was intragastrically administered the test drugs. Among them, the high, medium, and low-dose groups of Niuhuang Jiedu Tablets described in Example 3 were given doses of 1.146 g / kg, 0.573 g / kg, and 0.2865 g / kg respectively; the dexamethasone group was given a dose of 1.2 mg / kg. The Niuhuang Jiedu Tablet group was given a dose of 0.3645 g / kg, and the model group was given an equal volume of distilled water.

[0176] The intragastric administration volume was 1 ml / 100 g body weight of rats.

[0177] Four. Statistical method

[0178] The experimental data were expressed as mean ± standard deviation (x ± s). The data were first subjected to a homogeneity of variance test. If the variances were homogeneous, the One-Way ANOVA method was used for comparison between groups; if the variances were not homogeneous, the t’ test was used for comparison between groups.

[0179] 5. Test results

[0180] The results showed that the dexamethasone group, Niuhuang Jiedu Tablet group, and each administration group of Niuhuang Jiedu Tablets described in Example 3 could all inhibit the formation of cotton ball granuloma in rats to varying degrees. Compared with the model group, there were significant differences in the dexamethasone group, Niuhuang Jiedu Tablet group, and the high, medium, and low-dose groups of Niuhuang Jiedu Tablets described in Example 3 (P < 0.0001, 0.05, 0.05, 0.05, 0.05 respectively). The results are shown in Table 3 below.

[0181] Table 3 Effect of Niuhuang Jiedu Tablets in Example 3 on the formation of cotton ball granuloma in rats

[0182] Group Dosage (mg / kg) N Dry weight of cotton ball granuloma (mg) Model group -- 10 43.70±10.98 Dexamethasone group 1.20 10 20.35±15.25*** Niuhuang Jiedu Tablets 243 10 34.00±8.02* Example 3: High-dose group of Niuhuang Jiedu tablets 800.4 9 28.80±12.31* Example 3: Medium-dose group of Niuhuang Jiedu tablets 400.2 10 31.80±8.26* Example 3: Low-dose group of Niuhuang Jiedu tablets 200.1 9 31.45±12.67*

[0183] Compared with the model group, *p<0.05; **p<0.01; ***p<0.001.

[0184] Obviously, the above embodiments and experimental examples are merely illustrative and not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. The use of a traditional Chinese medicine composition containing bezoar in the preparation of a drug for inhibiting or eliminating acute inflammatory reactions, characterized in that, The preparation method of the traditional Chinese medicine composition is as follows: (1) Weigh out 24 parts of rhubarb, 36 parts of scutellaria, 12 parts of white peony root, 3 parts of uncaria, 6 parts of saposhnikovia root, 36 parts of platycodon root, 12 parts of yam, 3 parts of clove, 3 parts of cinnamon and 6 parts of licorice root, grind the ten ingredients into fine powder, pass through a 100-mesh sieve, mix evenly, and make a fine powder of the ten ingredients; weigh out 1.5 parts of cinnabar and 12 parts of realgar, grind them into very fine powder by water-milling, and pass through a 100-mesh sieve; (2) Weigh 0.075 parts of artificial bezoar, 1.5 parts of menthol, 1.5 parts of borneol and 0.0375 parts of artificial musk and store them separately; grind according to the equal incremental method, mix 0.0375 parts of artificial musk with 0.0375 parts of the ten-herb mixed fine powder to make artificial musk mixed powder; grind the remaining ten-herb mixed fine powder with the above artificial bezoar, cinnabar, realgar and 80 parts of starch, mix evenly and add 7wt% starch paste, wet granulation, dry the wet granules at 70℃, granulate and make fine powder granules; (3) After dissolving borneol and menthol in an appropriate amount of ethanol, pour them into 3 parts of fine granules and mix well to make borneol and menthol granules; mix artificial musk mixed powder with 0.075 parts of fine granules to make artificial musk granules; mix borneol and menthol granules and artificial musk granules, then mix with the remaining fine granules, add 0.5% magnesium stearate, mix well, and press into 1000 tablets. The shape of the Niuhuang Jiedu tablet is concave, the punch and die are φ10.5mm, and it is coated with sugar.

2. The use according to claim 1, characterized in that, The traditional Chinese medicine composition containing bezoar and pharmaceutically acceptable excipients are used to prepare a pharmaceutical preparation containing bezoar.

3. The use according to claim 2, characterized in that, The pharmaceutical preparation is a pill, tablet, capsule, powder, mixture, or granule; and / or, the pharmaceutically acceptable excipient is selected from at least one of the following pharmaceutically acceptable solvents, solubilizers, cosolvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, stabilizers, flow aids, flavoring agents, preservatives, coating materials, fragrances, anti-adhesives, pH adjusters, buffers, plasticizers, surfactants, diluents, polymeric framework materials, and film-forming materials.

4. The use according to claim 2, characterized in that, The pharmaceutical preparation is a tablet, and the excipients of the tablet include at least one of fillers, lubricants and binders; The filler is selected from at least one of starch, lactose, dextrin and microcrystalline cellulose; The lubricant is selected from at least one of magnesium stearate and talc; The adhesive is at least one of starch paste, ethanol solution, and polyvinylpyrrolidone.

5. The use according to claim 2, characterized in that, The pharmaceutical preparation containing bezoar is prepared by adding conventional excipients and conventional processes to the aforementioned traditional Chinese medicine composition containing bezoar as the active component.

6. The use according to any one of claims 2 to 5, characterized in that, The pharmaceutical preparation is a tablet, and the preparation method of the tablet includes the following steps: (1) Take rhubarb, scutellaria, white peony root, uncaria, saposhnikovia root, platycodon root, yam, clove, cinnamon and licorice, grind them into powder and mix them or grind them into powder to make a fine powder; (2) Take the mixed fine powder and mix it with bezoar, cinnabar and realgar, add the binder, make it into granules and dry; (3) Take the dried granules from step (2), mix them with borneol, menthol, and musk, and compress them into tablets to obtain the product; or, (1) Take rhubarb, scutellaria, white peony root, uncaria, saposhnikovia root, platycodon root, yam, clove, cinnamon, and licorice root, grind them into powder and mix them or grind them into powder and pass them through an 80-120 mesh sieve to make a fine mixed powder; take cinnabar and realgar, grind them into powder and pass them through an 80-120 mesh sieve to make cinnabar powder and realgar powder respectively; according to the equal increment method, take musk and mix it with 0.8-2 times the amount of the fine mixed powder to obtain musk mixed powder; (2) Take the remaining fine powder, cinnabar powder, realgar powder and filler, mix them, add binder, make granules, dry them, and obtain mixed granules; (3) Melt camphor and menthol with ethanol, then mix with mixed granules, musk powder, and lubricant, and compress into tablets to obtain the product; or, (1) Take rhubarb, scutellaria, white peony root, uncaria, saposhnikovia root, platycodon root, yam, clove, cinnamon, and licorice root, grind them into powder and mix them or grind them into powder and pass them through an 80-120 mesh sieve to make a fine mixed powder; take cinnabar and realgar, grind them into powder and pass them through an 80-120 mesh sieve to make cinnabar powder and realgar powder respectively; according to the equal increment method, take musk and mix it with 0.8-2 times the amount of the fine mixed powder to obtain musk mixed powder; (2) Take the remaining fine powder, cinnabar powder, realgar powder and filler, mix them, add binder, make granules, dry them, and obtain mixed granules; (3) Melt borneol and peppermint with ethanol and then mix with some of the mixed particles to obtain borneol and peppermint granule powder; take musk mixed powder and mix with some of the mixed particles to obtain musk granule powder; (4) Take borneol granules, musk granules, and the remaining mixed granules and lubricant, mix them together, and compress them into tablets to obtain the product.

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