Angong Niuhuang Pills and preparation method and application thereof

Abstract

The present invention provides an Angong Niuhuang Pill and a preparation method and application thereof, and relates to the technical field of traditional Chinese medicine. The preparation method of the present invention comprises the following steps: (1) Coptidis rhizome, Scutellaria baicalensis, Curcuma aromatica and Gardenia jasminoides are crushed to obtain a mixed powder A, with a particle size of D90=26-45 μm and D50=13-21 μm; (2) Pearl, cinnabar and realgar are treated with water to obtain a mixed powder B; (3) Bezoar and musk are crushed to obtain a mixed powder C; (4) Buffalo horn concentrated powder and borneol are crushed to obtain a mixed powder D, with a particle size of 80-120 mesh; (5) Mixing the mixed powder B, the mixed powder D, 40%-60% of the formula weight of the mixed powder A, and 20%-50% of the formula weight of the mixed powder C to obtain a honey pill core layer; and coating the remaining components on the surface of the honey pill core layer. The Angong Niuhuang Pill obtained by the preparation method of the present invention has a smooth and delicate surface, and has the remarkable effects of clearing away heat and detoxifying, and rapidly resisting convulsions.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and particularly relates to an Angong Niuhuang Pill and a preparation method and application thereof. Background Art

[0002] Traditional Chinese medicine believes that Angong means to make the heart settle in its palace. If the heat evil invades the pericardium, it will cause pericardial dysfunction, resulting in dangerous symptoms such as high fever, coma, delirium, convulsions, etc. Angong Niuhuang Pill has the effects of clearing away heat and detoxifying, calming the nerves and opening the orifices. It can be used to treat fever, evil entering the pericardium, high fever convulsions, coma, stroke coma, encephalitis, meningitis, toxic encephalopathy, cerebral hemorrhage, etc.

[0003] Angong Niuhuang Wan is composed of 11 herbs, including bezoar, turmeric, concentrated powder of buffalo horn, musk, pearl, gardenia, coptis root, scutellaria, cinnabar, realgar and borneol. It has the effects of clearing the heart and removing phlegm, awakening the mind and opening the orifices, and calming the nerves. From the perspective of the overall formula, the various ingredients in the traditional Angong Niuhuang Wan formula have a great influence on the effect. For example, if it contains volatile ingredients such as borneol and musk, if the pharmaceutical method is not appropriate, the activity of the effective ingredients will be reduced, affecting the efficacy of the medicine.

[0004] Chinese invention patent CN115137651A discloses a preparation process of Angong Niuhuang Wan drug powder, which comprises the following steps: (1) conventionally crushing four medicinal materials, namely, coptis root, gardenia, scutellaria baicalensis, and curcuma, into a mixed powder A of 40-60 mesh for standby use; (2) putting bezoar, buffalo horn concentrated powder, artificial musk, and borneol into a low-temperature vibration grinder and grinding at -20 to -15°C; adding cinnabar ultrafine powder, pearl ultrafine powder, and realgar ultrafine powder, and continuing to grind at -20 to -15°C to obtain a mixed powder B; (3) adding mixed powder A into the mixed powder B and continuing to grind and crush. Although the process described in the invention avoids the volatilization loss of heat-sensitive component drugs, the surface of Angong Niuhuang Wan prepared by conventionally mixing the powders is relatively rough, and the anticonvulsant effect still has a large room for improvement.

[0005] Chinese invention patent CN101579506A discloses an Angong Niuhuang preparation and its preparation method. The invention adopts ultrafine grinding technology to grind the raw material medicine, and then prepares the required dosage form according to conventional process; the prepared pills are soft and have a rough surface, and the heat-clearing, detoxifying and anticonvulsant effects are relatively low.

[0006] Chinese invention patent CN116617340A discloses an Angong Niuhuang Pill containing natural borneol and its preparation method, which includes the following raw materials by weight: 50-80 parts of artificial bezoar, 20-30 parts of storax, 40-60 parts of pearl, 50-80 parts of cinnabar, 60-90 parts of realgar, 50-120 parts of coptis root, 50-120 parts of scutellaria root, 50-120 parts of gardenia, 50-120 parts of curcuma and 10-20 parts of natural borneol, which is extracted from borneol camphor. The invention extracts the dextrorotatory borneol component in borneol camphor, and the prepared natural borneol has a high content of effective ingredients.

[0007] Chinese invention patent CN114712401A discloses a method for preparing pearl powder for Angong Niuhuang Wan, the steps are as follows: S1, pearl cleaning: add pearls and tofu wrapped in cloth into a sandwich pot, add water to it for steaming, take out the pearls, dry them in the sun, wash them, and dry them to obtain clean pearls; S2, low temperature crushing: crush the clean pearls at low temperature, sieve them, and obtain pearl coarse powder; S3, water-flying: put the pearl coarse powder and purified water into an electric mortar grinder for grinding, let it stand, and obtain the pearl coarse powder after water-flying; S4, drying and sieving: dry the pearl coarse powder after water-flying, sieve it, and obtain the pearl powder for Angong Niuhuang Wan. The pearl powder of this method can reach a fineness of 200 mesh, is off-white, has no flaky light spots, meets the quality requirements, and is easy to color evenly.

[0008] Therefore, the Angong Niuhuang Pills obtained by the existing crushing and mixing methods have a rough and uneven surface, and the efficacy of clearing away heat and detoxifying, and anticonvulsant needs to be improved. It is necessary to conduct in-depth research on the preparation method of Angong Niuhuang Pills, in order to obtain an Angong Niuhuang Pill product with efficient heat-clearing and detoxifying, rapid anticonvulsant effects, and a smooth and delicate surface. Summary of the invention

[0009] In view of the problems existing in the prior art, the present invention provides an Angong Niuhuang Pill and a preparation method and application thereof. The present invention further changes the grinding method and particle size of bezoar, buffalo horn concentrated powder, musk, borneol, coptis root, scutellaria baicalensis, curcuma, gardenia, pearl, cinnabar and realgar, so that the product has higher mixing uniformity, and the effects of clearing away heat and detoxifying and quickly resisting convulsion are significantly improved.

[0010] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0011] First, the present invention provides a method for preparing Angong Niuhuang Pills, comprising the steps of:

[0012] (1) Coptidis rhizome, Scutellaria baicalensis root, Curcuma aromatica and Gardenia jasminoides are ground to obtain mixed powder A; the particle size of the mixed powder A is D90=26-45 μm, and D50=13-21 μm;

[0013] (2) Pearl, cinnabar and realgar are subjected to water-water treatment to obtain a mixed powder B, wherein 95% of the particle size of the mixed powder B passes through a 100-150 mesh sieve;

[0014] (3) grinding bezoar and musk to obtain mixed powder C; the mixed powder C has a particle size of 325-450 mesh;

[0015] (4) Buffalo horn concentrated powder and borneol are mixed and crushed to obtain mixed powder D; the particle size of the mixed powder D is 80-120 mesh;

[0016] (5) Mix mixed powder B, mixed powder D, 40%-60% by weight of mixed powder A, and 20%-50% by weight of mixed powder C, add refined honey, stir at 400-600 rpm and 10-20° C. for 10-20 min, and make pills to obtain a honey pill core layer; coat the surface of the honey pill core layer with the remaining weight of mixed powder A and mixed powder C to obtain Angong Niuhuang Pills.

[0017] Preferably, in step (1), the particle size of the mixed powder A is D90=30-44 μm, D50=15-21 μm;

[0018] More preferably, the particle size of the mixed powder A is D90=38 μm, and D50=19 μm.

[0019] Preferably, step (1) is specifically as follows: intermittent ultrafine grinding of coptis root, scutellaria root, curcuma and gardenia, each grinding time is 20-30 minutes, the grinding is repeated 3-5 times, and the grinding temperature is 15-25°C to obtain mixed powder A.

[0020] Further preferably, step (1) is specifically as follows: coptis root, scutellaria root, curcuma and gardenia are coarsely ground into 80-150 mesh, and then intermittent ultrafine grinding is performed, each grinding time is 25 minutes, and the grinding is repeated 4 times at a grinding temperature of 20°C to obtain mixed powder A.

[0021] Preferably, in step (2), 95% of the particle size of the mixed powder B passes through a 110-140 mesh sieve.

[0022] More preferably, in step (2), 95% of the particle size of the mixed powder B passes through a 120-mesh sieve.

[0023] Preferably, step (2) is specifically as follows: pearl, cinnabar and realgar are subjected to water-water treatment at 10-20° C. to obtain mixed powder B.

[0024] Further preferably, step (2) specifically comprises: performing water-blasting treatment on pearl, cinnabar and realgar at 15±2° C. to obtain mixed powder B.

[0025] Preferably, in step (3), the particle size of the mixed powder C is 400 mesh.

[0026] Preferably, in step (3), the pulverization is intermittent low-temperature ultrafine pulverization, specifically: the pulverization temperature is 15-25°C, the pulverization time is 10-20 minutes each time, and the pulverization times are 6-10 times.

[0027] Further preferably, in step (3), the intermittent low-temperature ultrafine grinding is specifically as follows: the grinding temperature is 20° C., the grinding time is 15 min each time, and the number of grinding times is 8 times.

[0028] Preferably, in step (4), the particle size of the mixed powder D is 100 mesh.

[0029] Preferably, in step (4), the pulverization is intermittent low-temperature ultrafine pulverization, specifically: the pulverization temperature is 10-20°C, the pulverization time is 2-10 minutes each time, and the pulverization times are 1-4 times.

[0030] Further preferably, in step (4), the intermittent low-temperature ultrafine grinding is specifically as follows: the grinding temperature is 15°C, the grinding time is 5 minutes each time, and the grinding times are 2 times.

[0031] Preferably, step (5) is specifically as follows: mixing mixed powder B, mixed powder D, 45%-55% by weight of mixed powder A, and 25%-35% by weight of mixed powder C, adding refined honey, stirring at 450-550 rpm and 10-20° C. for 10-20 min, making pills to obtain a core layer of honey pills; then mixing the remaining weight of mixed powder A and mixed powder C with refined honey, coating the mixture on the surface of the core layer of honey pills, and obtaining Angong Niuhuang Pills.

[0032] Further preferably, step (5) is specifically as follows: mix mixed powder B, mixed powder D, 50% by weight of mixed powder A, and 30% by weight of mixed powder C, add refined honey, stir at 500 rpm and 15°C for 15 min, and make pills to obtain a core layer of honey pills; then mix the remaining weight of mixed powder A and mixed powder C with refined honey, and coat the mixture on the surface of the core layer of honey pills to obtain Angong Niuhuang Pills.

[0033] Preferably, in step (5), the amount of refined honey added is 1.0-1.5 times the mass of the raw material drug, and more preferably 1.25 times.

[0034] In the present invention, the musk is not limited to artificial musk or natural musk.

[0035] In the present invention, the bezoar is not limited to natural bezoar, cultured bezoar or in vitro cultured bezoar.

[0036] Then, the present invention provides an Angong Niuhuang Pill prepared by the above preparation method.

[0037] Preferably, the Angong Niuhuang Pills comprise the following raw materials, measured by weight: 50-150 parts of bezoar, 130-300 parts of buffalo horn concentrated powder, 18-32 parts of musk, 25-80 parts of pearl, 70-135 parts of cinnabar, 70-135 parts of realgar, 80-130 parts of coptis chinensis, 80-130 parts of scutellaria baicalensis, 80-130 parts of gardenia jasminoides, 80-130 parts of curcuma and 15-38 parts of borneol.

[0038] Further preferably, the Angong Niuhuang Pills comprise the following raw materials, measured by weight: 80-120 parts of bezoar, 165-250 parts of buffalo horn concentrated powder, 22-28 parts of musk, 40-65 parts of pearl, 90-115 parts of cinnabar, 90-115 parts of realgar, 90-120 parts of coptis chinensis, 90-120 parts of scutellaria baicalensis, 85-115 parts of gardenia jasminoides, 90-120 parts of curcuma and 20-29 parts of borneol.

[0039] More preferably, the Angong Niuhuang Pills comprise the following raw materials, measured by weight: 100 parts of bezoar, 200 parts of buffalo horn concentrated powder, 25 parts of musk, 50 parts of pearl, 100 parts of cinnabar, 100 parts of realgar, 100 parts of coptis chinensis, 100 parts of scutellaria baicalensis, 100 parts of gardenia jasminoides, 100 parts of curcuma and 25 parts of borneol.

[0040] Finally, the present invention provides the use of the Angong Niuhuang Pills in preparing medicines with heat-clearing, detoxicating and anticonvulsant effects.

[0041] Compared with the prior art, the present invention has the following beneficial effects:

[0042] 1. The present invention studies the preparation method of Angong Niuhuang Pills by controlling the grinding mode and particle size of each component, controls the particle size of different components, interacts with each other among the components with different particle sizes, and uses powders of different coarseness and fineness to prepare Angong Niuhuang Pills. The obtained Angong Niuhuang Pills have the effects of quickly clearing high fever and resisting convulsions.

[0043] 2. The present invention improves the preparation method of Angong Niuhuang Pills by first preparing a core layer of honey pills, and then coating the core layer of honey pills with part of mixed powder A and mixed powder C, so that each component can exert a rapid and lasting effect, further improving the efficacy.

[0044] 3. The present invention prepares mixed powder D by co-grinding buffalo horn concentrated powder and borneol, which can effectively retain the active ingredients in borneol; mixed powder D and mixed powder C interact with each other and have a significant therapeutic effect on febrile convulsions.

[0045] 4. The Angong Niuhuang Pills obtained by the preparation method of the present invention have suitable hardness, are non-sticky to the wall, and have a smooth and delicate surface. DETAILED DESCRIPTION

[0046] The following non-limiting examples can enable those skilled in the art to more fully understand the present invention, but do not limit the present invention in any way. The following content is merely an exemplary description of the scope of the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, which should also fall within the scope of the present invention.

[0047] When the embodiments give numerical ranges, it should be understood that, unless otherwise specified in the present invention, both endpoints of each numerical range and any numerical value between the two endpoints can be selected. Unless otherwise defined, all technical and scientific terms used in the present invention have the same meanings as those generally understood by those of ordinary skill in the art to which the present invention belongs.

[0048] The present invention is further described below by way of specific embodiments. The various chemical reagents used in the embodiments of the present invention are obtained through conventional commercial channels unless otherwise specified. The buffalo horn concentrated powder is purchased from Nanfeng Biochemical Co., Ltd., Xianyou County, Fujian Province, with the item number YWZ091B230501. Products from different manufacturers have no significant effect on the effect.

[0049] In the Angong Niuhuang Pills of the following embodiments, the raw material components are calculated by weight: 100 parts of bezoars, 200 parts of concentrated buffalo horn powder, 25 parts of musk, 50 parts of pearls, 100 parts of cinnabar, 100 parts of realgar, 100 parts of coptis root, 100 parts of scutellaria root, 100 parts of gardenia, 100 parts of curcuma and 25 parts of borneol. In the preparation process of Angong Niuhuang Pills, the amount of refined honey added is 1.25 times the mass of the raw material. The specification of each Angong Niuhuang Pill is 3g / pill.

[0050] Example 1

[0051] A preparation method of Angong Niuhuang Pills is:

[0052] (1) After the coptis root, scutellaria root, curcuma and gardenia were coarsely ground to 80-150 mesh, they were intermittently ultrafine ground, each time for 25 min, repeated 4 times, and the grinding temperature was 20°C to obtain mixed powder A;

[0053] The particle size of mixed powder A is D90=38μm, D50=19μm;

[0054] (2) Pearl, cinnabar and realgar are subjected to water-free treatment at 15±2°C to obtain mixed powder B;

[0055] 95% of the particle size of mixed powder B passed through a 120-mesh sieve;

[0056] (3) intermittent low-temperature ultrafine grinding of natural bezoar and musk, the grinding temperature is 20° C., the grinding time is 15 min each time, and the number of grinding times is 8 times to obtain mixed powder C, wherein the particle size of the mixed powder C is 400 mesh;

[0057] (4) Buffalo horn concentrated powder and borneol are mixed and subjected to intermittent low-temperature ultrafine grinding at a grinding temperature of 15° C., a grinding time of 5 min each time, and a grinding number of 2 times to obtain a mixed powder D, wherein the particle size of the mixed powder D is 100 mesh;

[0058] (5) Mixing mixed powder B, mixed powder D, 50% of the formula weight of mixed powder A, and 30% of the formula weight of mixed powder C, adding refined honey in an amount of 1.0 times the weight of the raw material drug, stirring at 500 rpm and 15°C for 15 min, and making pills to obtain a honey pill core layer; then mixing the remaining formula weight of mixed powder A and mixed powder C with the remaining refined honey, and coating the mixture on the surface of the honey pill core layer to obtain Angong Niuhuang Pills;

[0059] The mass of the refined honey is 1.25 times the mass of the raw material medicine.

[0060] Example 2

[0061] A preparation method of Angong Niuhuang Pills is:

[0062] (1) After the coptis root, scutellaria root, curcuma and gardenia were coarsely ground to 80-150 mesh, they were intermittently ultrafine ground for 20 min each time, repeated 5 times at a grinding temperature of 25°C to obtain mixed powder A;

[0063] The particle size of mixed powder A is D90=44μm, D50=21μm;

[0064] (2) Pearl, cinnabar and realgar are subjected to water-free treatment at 15±2°C to obtain mixed powder B;

[0065] 95% of the particle size of mixed powder B passed through a 140-mesh sieve;

[0066] (3) natural bezoar and musk are subjected to intermittent low-temperature ultrafine grinding at a grinding temperature of 15° C., each grinding time is 20 min, and the number of grinding times is 8 to obtain a mixed powder C, wherein the particle size of the mixed powder C is 450 mesh;

[0067] (4) Buffalo horn concentrated powder and borneol are mixed and subjected to intermittent low-temperature ultrafine grinding at a grinding temperature of 15° C., a grinding time of 5 min each time, and a grinding number of 2 times to obtain a mixed powder D, wherein the particle size of the mixed powder D is 100 mesh;

[0068] (5) Mixing mixed powder B, mixed powder D, 45% of the formula weight of mixed powder A, and 35% of the formula weight of mixed powder C, adding refined honey in an amount 1.0 times the weight of the raw material drug, stirring at 450 rpm and 10°C for 20 min, and making pills to obtain a honey pill core layer; then mixing the remaining formula weight of mixed powder A and mixed powder C with the remaining refined honey, and coating the mixture on the surface of the honey pill core layer to obtain Angong Niuhuang Pills;

[0069] The mass of the refined honey is 1.25 times the mass of the raw material medicine.

[0070] In this embodiment, the raw material components of Angong Niuhuang Pills are the same as those in Example 1.

[0071] Example 3

[0072] A preparation method of Angong Niuhuang Pills is:

[0073] (1) After the coptis root, scutellaria root, curcuma and gardenia were coarsely ground into 80-150 mesh, they were intermittently ultrafine ground for 30 min each time, and repeated 3 times at a grinding temperature of 15°C to obtain mixed powder A;

[0074] The particle size of mixed powder A is D90=30μm, D50=15μm;

[0075] (2) Pearl, cinnabar and realgar are subjected to water-free treatment at 15±2°C to obtain mixed powder B;

[0076] 95% of the particle size of mixed powder B passed through a 110-mesh sieve;

[0077] (3) natural bezoar and musk are subjected to intermittent low-temperature ultrafine grinding at a grinding temperature of 25° C., each grinding time is 10 min, and the number of grinding times is 8 to obtain a mixed powder C, wherein the particle size of the mixed powder C is 325 mesh;

[0078] (4) Buffalo horn concentrated powder and borneol are mixed and subjected to intermittent low-temperature ultrafine grinding at a grinding temperature of 15° C., a grinding time of 5 min each time, and a grinding number of 2 times to obtain a mixed powder D, wherein the particle size of the mixed powder D is 100 mesh;

[0079] (5) Mixing mixed powder B, mixed powder D, 55% of the formula weight of mixed powder A, and 25% of the formula weight of mixed powder C, adding refined honey in an amount of 1.0 times the weight of the raw material drug, stirring at 550 rpm and 20°C for 10 min, and making pills to obtain a honey pill core layer; then mixing the remaining formula weight of mixed powder A and mixed powder C with the remaining refined honey, and coating the mixture on the surface of the honey pill core layer to obtain Angong Niuhuang Pills;

[0080] The mass of the refined honey is 1.25 times the mass of the raw material medicine.

[0081] In this embodiment, the raw material components of Angong Niuhuang Pills are the same as those in Example 1.

[0082] Example 4

[0083] A preparation method of Angong Niuhuang Pills is:

[0084] (1) After the coptis root, scutellaria root, curcuma and gardenia were coarsely ground to 80-150 mesh, they were intermittently ultrafine ground for 30 min each time, repeated 5 times at a grinding temperature of 20°C to obtain mixed powder A;

[0085] The particle size of mixed powder A is D90=26μm, D50=13μm;

[0086] (2) Pearl, cinnabar and realgar are subjected to water-free treatment at 15±2°C to obtain mixed powder B;

[0087] 95% of the particle size of mixed powder B passes through a 150-mesh sieve;

[0088] (3) Cultivating bezoar and musk for intermittent low-temperature ultrafine grinding, the grinding temperature is 20° C., each grinding time is 15 min, the number of grinding times is 8, and mixed powder C is obtained, and the particle size of the mixed powder C is 400 mesh;

[0089] (4) Buffalo horn concentrated powder and borneol are mixed and subjected to intermittent low-temperature ultrafine grinding at a grinding temperature of 10° C., a grinding time of 10 min each time, and a grinding number of 2 times to obtain a mixed powder D, wherein the particle size of the mixed powder D is 80 mesh;

[0090] (5) Mixing mixed powder B, mixed powder D, 40% of the formula weight of mixed powder A, and 50% of the formula weight of mixed powder C, adding refined honey in an amount 1.0 times the weight of the raw material drug, stirring at 550 rpm and 20°C for 10 min, and making pills to obtain a honey pill core layer; then mixing the remaining formula weight of mixed powder A and mixed powder C with the remaining refined honey, and coating the mixture on the surface of the honey pill core layer to obtain Angong Niuhuang Pills;

[0091] The mass of the refined honey is 1.25 times the mass of the raw material medicine.

[0092] In this embodiment, the raw material components of Angong Niuhuang Pills are the same as those in Example 1.

[0093] Example 5

[0094] A preparation method of Angong Niuhuang Pills is:

[0095] (1) After the coptis root, scutellaria root, curcuma and gardenia were coarsely ground to 80-150 mesh, they were intermittently ultrafine ground for 20 min each time, and repeated 3 times at a grinding temperature of 20°C to obtain mixed powder A;

[0096] The particle size of mixed powder A is D90 = 45 μm, D50 = 21 μm;

[0097] (2) Pearl, cinnabar and realgar are subjected to water-free treatment at 15±2°C to obtain mixed powder B;

[0098] 95% of the particle size of mixed powder B passed through a 100-mesh sieve;

[0099] (3) Cultivating bezoar and musk in vitro and subjecting them to intermittent low-temperature ultrafine grinding, the grinding temperature is 20° C., the grinding time is 15 min each time, and the number of grinding times is 8 times to obtain a mixed powder C, wherein the particle size of the mixed powder C is 400 mesh;

[0100] (4) Buffalo horn concentrated powder and borneol are mixed and subjected to intermittent low-temperature ultrafine grinding at a grinding temperature of 15° C., a grinding time of 2 min each time, and a grinding number of 4 times to obtain a mixed powder D, wherein the particle size of the mixed powder D is 120 mesh;

[0101] (5) Mixing mixed powder B, mixed powder D, 60% of the formula weight of mixed powder A, and 20% of the formula weight of mixed powder C, adding refined honey in an amount of 1.0 times the weight of the raw material drug, stirring at 550 rpm and 20°C for 10 min, and making pills to obtain a honey pill core layer; then mixing the remaining formula weight of mixed powder A and mixed powder C with the remaining refined honey, and coating the mixture on the surface of the honey pill core layer to obtain Angong Niuhuang Pills;

[0102] The mass of the refined honey is 1.25 times the mass of the raw material medicine.

[0103] In this embodiment, the raw material components of Angong Niuhuang Pills are the same as those in Example 1.

[0104] Comparative Example 1

[0105] Angong Niuhuang Pills are prepared according to the method in the invention patent with publication number CN115137651A, specifically:

[0106] (1) The prescribed amount of four medicinal materials, namely, coptis root, gardenia, scutellaria baicalensis, and curcuma, are conventionally ground into a 50-mesh mixed powder A for later use; the mixed powder A can all pass through a 120-mesh standard sieve, and more than 95% can pass through a 150-mesh standard sieve;

[0107] (2) Add the prescribed amount of bezoar (natural bezoar), buffalo horn concentrated powder, artificial musk, and borneol into a low-temperature vibration grinder and grind at -17°C for 30 minutes; add the prescribed amount of cinnabar ultrafine powder, pearl ultrafine powder, and realgar ultrafine powder, and continue grinding at -17°C for 20 minutes to obtain a mixed powder B; all of the mixed powder B can pass through a standard sieve of 200 mesh, and more than 90% can pass through a standard sieve of 300 mesh;

[0108] (3) Add mixed powder A to mixed powder B, continue grinding and crushing for 8 minutes, and take out to obtain Angong Niuhuang Wan drug powder; the particles of mixed powder A are core particles, and mixed powder B is wrapped outside the core particles; Angong Niuhuang Wan drug powder is agglomerated under an optical microscope, and the powder composed of agglomerated particles can all pass through an 80-mesh standard sieve;

[0109] (4) According to the method recorded in the 2020 edition of the Chinese Pharmacopoeia, Angong Niuhuang Pills were prepared using refined honey.

[0110] In this comparative example, the formulation and dosage of each raw material component are the same as that in Example 1.

[0111] Comparative Example 2

[0112] Angong Niuhuang Pills were prepared according to the method described in Example 1 of the invention patent with publication number CN101579506A.

[0113] The prescription of Angong Niuhuang Wan is: 20g of bezoar (natural bezoar), 40g of concentrated buffalo horn powder, 5g of musk, 10g of pearl, 20g of cinnabar, 20g of realgar, 20g of coptis root, 20g of scutellaria root, 20g of gardenia, 20g of curcuma and 5g of borneol;

[0114] For the above 11 ingredients, cinnabar and realgar were separately ground into ultrafine powder (200 mesh); coptis root, scutellaria root, gardenia and curcuma were ground into coarse powder (100 mesh), mixed with bezoar, buffalo horn concentrated powder, musk and borneol, and ground in an ultrafine grinder at room temperature for 30 minutes to prepare an ultrafine drug composition; mixed with cinnabar and realgar ultrafine powder, stirred at 200 rpm for 10 minutes until uniform, and refined honey equivalent to 1.25 times the mass of the raw materials was added to prepare Angong Niuhuang Pills (3 g / pill);

[0115] Particle size D of ultrafine pharmaceutical composition 50 Not more than 10μm and D 90 Not more than 50μm.

[0116] Comparative Example 3

[0117] The difference from Example 1 is that the particle size of the mixed powder A in step (1) is different, and the particle size of the mixed powder A is controlled to be D90=48 μm and D50=10 μm.

[0118] The rest are the same as in Example 1.

[0119] Comparative Example 4

[0120] The difference from Example 1 is that step (3) and step (4) are combined into one step, specifically:

[0121] Step (1)-step (2): same as in Example 1;

[0122] Step (3): natural bezoar, musk, buffalo horn concentrated powder and borneol are intermittently subjected to low-temperature ultrafine grinding, the grinding temperature is 20° C., each grinding time is 15 min, the number of grinding times is 8, and mixed powder C is obtained, and the particle size of the mixed powder C is 400 mesh;

[0123] Step (4): Mix the mixed powder B, 50% of the mixed powder A by weight, and 30% of the mixed powder C by weight, add refined honey in an amount 1.0 times the weight of the raw material drug, stir at 500 rpm and 15°C for 15 min, and make pills to obtain a honey pill core layer; then mix the remaining weight of the mixed powder A and the mixed powder C with the remaining refined honey, and coat the mixture on the surface of the honey pill core layer to obtain Angong Niuhuang Pills;

[0124] The mass of the refined honey is 1.25 times the mass of the raw material medicine.

[0125] Comparative Example 5

[0126] The difference from Example 1 is that step (3) and step (4) are different, specifically:

[0127] Step (1)-step (2): same as in Example 1;

[0128] Step (3): intermittent low-temperature ultrafine grinding of natural bezoar, musk and buffalo horn concentrated powder, the grinding temperature is 20° C., each grinding time is 15 min, the number of grinding times is 8 times, and mixed powder C is obtained, and the particle size of the mixed powder C is 400 mesh;

[0129] Step (4): intermittent low-temperature ultrafine grinding of borneol, the grinding temperature is 15°C, each grinding time is 5 minutes, the grinding number is 2 times, and borneol powder is obtained. The borneol powder is moist and has no definite particle size;

[0130] Step (5): Mix the mixed powder B, borneol powder, 50% of the formula weight of the mixed powder A, and 30% of the formula weight of the mixed powder C, add refined honey in an amount 1.0 times the weight of the raw material drug, stir at 500 rpm and 15°C for 15 minutes, and make pills to obtain a honey pill core layer; then mix the remaining formula weight of the mixed powder A and the mixed powder C with the remaining refined honey, and coat the mixture on the surface of the honey pill core layer to obtain Angong Niuhuang Pills;

[0131] The mass of the refined honey is 1.25 times the mass of the raw material medicine.

[0132] Comparative Example 6

[0133] The difference from Example 1 is that step (5) is different.

[0134] Step (1) to step (4): same as in Example 1;

[0135] Step (5): Mix the mixed powder A, mixed powder B, mixed powder C and mixed powder D evenly, and add refined honey in an amount of 1.25 times the mass of the raw material drug to prepare Angong Niuhuang Pills.

[0136] Test 1: Evaluation of the appearance of Angong Niuhuang Pills

[0137] Experimental method: 5 volunteers who received unified evaluation training evaluated the hardness, viscosity and surface roughness of the Angong Niuhuang Pills prepared in each embodiment and comparative example.

[0138] The evaluation criteria are shown in Table 1. The evaluation results gradually become worse from level A to level D.

[0139] Table 1

[0140]

[0141] The appearance of Angong Niuhuang Pills of each embodiment and comparative example was evaluated by 5 volunteers. The results are shown in Table 2.

[0142] Table 2

[0143]

[0144] In Table 2, taking hardness as an example, 5A means that all five volunteers gave an evaluation result of grade A. The numbers in brackets are the number of evaluators for each evaluation result, and the letters A, B, C, and D represent the evaluation grades in Table 1, respectively.

[0145] As can be seen from Table 2, the Angong Niuhuang Pills prepared by the preparation method of the present invention have suitable hardness, are non-sticky, have uniform and smooth appearance, and their apparent properties are all grade A. The Angong Niuhuang Pills of Comparative Examples 1 and 2 are slightly hard / soft, and the surface is rough and not fine. After the particle size of mixed powder A is changed in Comparative Example 3, the hardness is significantly affected. After the crushing steps of bezoar, musk, buffalo horn concentrated powder, and borneol are changed in Comparative Examples 4 and 5, the particle size of mixed powder C and mixed powder D is changed, and the protective effect of borneol is not provided, resulting in significant changes in the hardness, viscosity and surface roughness of the pills. Comparative Example 6 and the mixing method and pill making method of each mixed powder are changed, so that the hardness and surface roughness of the pills are significantly changed.

[0146] The preparation method of the present invention enables Angong Niuhuang Pills to have a smooth and delicate appearance and suitable hardness. In the comparative example, after the preparation method, component particle size, and the crushing and mixing methods of each component of Angong Niuhuang Pills are changed respectively, Angong Niuhuang Pills with suitable hardness and smooth and delicate surface cannot be obtained. The preparation method of the present invention has a significant effect on the appearance of Angong Niuhuang Pills.

[0147] Experiment 2: Testing the therapeutic effect on febrile convulsions

[0148] 1. Experimental Materials

[0149] 1.1 Experimental animals: SPF 4-week-old juvenile SD rats, male, weighing 100±20 g, animal certificate number: 210726240102354167, purchased from Liaoning Changsheng Biotechnology Co., Ltd., production license number: SCK (Liao) 2020-001.

[0150] Feed: SPF rat feed, purchased from Liaoning Changsheng Biotechnology Co., Ltd., batch number: 24061321, experimental animal feed license number: SCXK (Liao) 2020-0002.

[0151] Breeding environment: barrier environment animal observation room, temperature: 20℃-24℃, relative humidity: 40%-70%, rat use license: (Ji) 2022-004.

[0152] 1.2 Experimental reagents and instruments

[0153] Ultra-microplate spectrophotometer (BioTek Epoch), desktop high-speed centrifuge (Sigma, Germany). Rat IL-1β ELISA Kit (Biyuntian), American BioTek Epoch microplate reader.

[0154] 1.3 Experimental drugs: Traditional Chinese medicine compositions prepared in various examples and comparative examples.

[0155] 1.4 Experimental Animal Grouping and Dosing

[0156] Rats were randomly divided into 13 groups, 10 rats in each group. Group 1 of Example 1, Group 2 of Example 2, Group 3 of Example 4, Group 5 of Example 5, Group 1 of Comparative Example 2, Group 3 of Comparative Example 4, Group 5 of Comparative Example 6 were intragastrically administered with 2.5 g / kg of Angong Niuhuang Pills of the corresponding Examples and Comparative Examples; the model control group and the blank control group (intergastrically administered with the same dose of normal saline), rats were intragastrically administered with a volume of 20 mL / kg, once a day, for 7 consecutive days.

[0157] 2. Experimental Methods

[0158] 2.1 Model preparation

[0159] A constant temperature hot water bath was used to induce the FS (febrile convulsion) model in young male SD rats: after 3 days of adaptive feeding, the rats were placed in a 44.5-45℃ water bath, and the water depth was such that only the head of the rat was exposed when standing along the wall of the box. Those with convulsion within 5 minutes were removed and included in the experiment, and those without convulsion were eliminated. The convulsion judgment standard was based on forelimb clonus convulsion, and convulsion was induced once every other day, for a total of 10 times. Rats that met the requirements were selected for inclusion in the experiment, and those that did not meet the requirements were eliminated.

[0160] 2.2 Recording of rat seizure latency and duration

[0161] The time when the rat was placed in the hot water bath and the time when forelimb clonus was found were recorded respectively, and the difference between the two times was the rat's convulsion latency; the time from the first convulsion of the rat to the end of the convulsion was recorded respectively, and the difference between the two times was the rat's convulsion duration.

[0162] 2.3 Effect on serum IL-1β levels in rats

[0163] 24 hours after the last day of administration, the rats were anesthetized with chloral hydrate and 10 mL of blood was collected from the abdominal aorta. The blood was allowed to stand for 1.5 hours and then centrifuged in a refrigerated centrifuge at 4°C and 3000 r / min for 15 minutes. The supernatant was collected and the IL-1β content in rat serum was detected according to the instructions of the enzyme-linked immunosorbent assay kit.

[0164] 2.4 Statistical analysis

[0165] SPSS 26.0 software was used to process the data, x±s, n=10.

[0166] 3. Results

[0167] The results of rat seizure latency, seizure duration and serum IL-1β content are shown in Table 3.

[0168] Table 3

[0169]

[0170] In Table 3, the model control group was compared with the blank control group. &&& P<0.001, with extremely significant difference; each experimental group was compared with the model control group △△ P<0.01, △△△ P<0.001, indicating statistically significant difference; each comparative example group was compared with the Example 1 group. ØØØ P<0.001, with significant difference; each comparative example group was compared with Example 2 group ### P<0.001, indicating statistically significant difference; each comparative example group was compared with Example 3 group $$$ P<0.001, indicating statistically significant difference; each comparative example group was compared with Example 4 group ★★★ P<0.001, indicating statistically significant difference; each comparative example group was compared with Example 5 group ¢¢¢ P<0.001, indicating a statistically significant difference.

[0171] 4. Summary

[0172] After administration, the rats in each group of the embodiment had a significantly prolonged convulsion latency, a shortened convulsion duration, and a reduced serum IL-1β content, which was significantly different. Compared with the control group, the convulsion latency of the embodiment 1 group was prolonged, which was significantly different; the convulsion duration was shortened, and the serum IL-1β content was reduced, which was significantly different.

[0173] The experimental results show that, compared with the model control group, the conventional method can be used to prepare Angong Niuhuang Pills. Although the convulsion latency can be improved, the convulsion duration can be reduced, and the IL-1β content in serum can be reduced, compared with the Angong Niuhuang Pills of the embodiment of the present invention, there are still significant differences, indicating that the preparation method of the present invention brings significantly improved technical effects. Compared with the model control group, the particle size of the comparative example 3 is changed. Although it can improve the convulsion latency, reduce the convulsion duration, and reduce the IL-1β content in serum, it is still significantly different from the technical effect of the embodiment. The technical scheme of the present invention brings more significant technical effects than the technical scheme of conventional particle size. Comparative Examples 4 and 5 change the processing methods of bezoar, musk, buffalo horn concentrated powder and borneol, and Comparative Example 6 changes the pill making method. The anti-hyperthermic convulsion effect of Angong Niuhuang Pills is significantly lower than that of the embodiment, indicating that although the conventional processing method can resist hyperthermic convulsions and reduce IL-1β content, the technical effect is still significantly different compared with the technical scheme of the present invention.

[0174] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing Angong Niuhuang Pills, characterized in that: Includes steps: (1) Coptidis rhizome, Scutellaria baicalensis, Curcuma aromatica and Gardenia jasminoides are ground to obtain mixed powder A; the particle size of the mixed powder A is D90=26-45 μm, and D50=13-21 μm; (2) Pearl, cinnabar and realgar are subjected to water-water treatment to obtain a mixed powder B, wherein 95% of the particle size of the mixed powder B passes through a 100-150 mesh sieve; (3) intermittently grinding bezoar and musk at low temperature to obtain mixed powder C; the particle size of the mixed powder C is 325-450 mesh; the bezoar is not limited to natural bezoar, cultured bezoar or in vitro cultured bezoar; (4) Buffalo horn concentrated powder and borneol are mixed and subjected to intermittent low-temperature ultrafine grinding to obtain mixed powder D; the particle size of the mixed powder D is 80-120 mesh; (5) Mixing mixed powder B, mixed powder D, 40%-60% by weight of mixed powder A, and 20%-50% by weight of mixed powder C, adding refined honey, stirring at 400-600 rpm and 10-20° C. for 10-20 min, and making pills to obtain a honey pill core layer; coating the surface of the honey pill core layer with the remaining weight of mixed powder A and mixed powder C to obtain Angong Niuhuang Pills; The Angong Niuhuang Pills include the following raw materials in parts by weight: 50-150 parts of bezoar, 130-300 parts of buffalo horn concentrated powder, 18-32 parts of musk, 25-80 parts of pearl, 70-135 parts of cinnabar, 70-135 parts of realgar, 80-130 parts of coptis chinensis, 80-130 parts of scutellaria baicalensis, 80-130 parts of gardenia jasmine, 80-130 parts of curcuma and 15-38 parts of borneol.

2. The preparation method according to claim 1, characterized in that: In step (1), the particle size of the mixed powder A is D90=30-44 μm, D50=15-21 μm; Step (1) is specifically as follows: intermittent ultrafine grinding of coptis root, scutellaria root, curcuma and gardenia, each grinding time is 20-30 minutes, the grinding is repeated 3-5 times, and the grinding temperature is 15-25° C. to obtain mixed powder A.

3. The preparation method according to claim 2, characterized in that: In step (1), the particle size of the mixed powder A is D90=38 μm, D50=19 μm; Step (1) is specifically as follows: coptis root, scutellaria root, curcuma and gardenia are coarsely ground into 80-150 meshes, and then intermittently ultrafine ground, each time for 25 minutes, and the grinding is repeated 4 times at a grinding temperature of 20° C. to obtain mixed powder A.

4. The preparation method according to claim 1, characterized in that: In step (2), 95% of the particle size of the mixed powder B passes through a 110-140 mesh sieve; Step (2) is specifically as follows: pearl, cinnabar and realgar are subjected to water-water treatment at 10-20° C. to obtain mixed powder B.

5. The preparation method according to claim 1, characterized in that: In step (3), the particle size of the mixed powder C is 400 mesh; In step (3), the intermittent low-temperature ultrafine grinding is specifically as follows: the grinding temperature is 15-25°C, the grinding time is 10-20 minutes each time, and the number of grinding times is 6-10 times.

6. The preparation method according to claim 1, characterized in that: In step (4), the particle size of the mixed powder D is 100 mesh; In step (4), the intermittent low-temperature ultrafine grinding is specifically as follows: the grinding temperature is 10-20°C, the grinding time is 2-10 minutes each time, and the number of grinding times is 1-4 times.

7. The preparation method according to claim 1, characterized in that: Step (5) is specifically as follows: Mix the mixed powder B, the mixed powder D, 45%-55% by weight of the mixed powder A, and 25%-35% by weight of the mixed powder C, add refined honey, stir at 450-550 rpm and 10-20° C. for 10-20 min, and make pills to obtain a core layer of honey pills; then mix the remaining weight of the mixed powder A and the mixed powder C with the refined honey, and coat the mixture on the surface of the core layer of the honey pills to obtain Angong Niuhuang Pills.

8. The preparation method according to claim 7, characterized in that: Step (5) is specifically as follows: Mix mixed powder B, mixed powder D, 50% by weight of mixed powder A, and 30% by weight of mixed powder C, add refined honey, and stir at 500 rpm and 15°C for 15 min to prepare pills to obtain a core layer of honey pills; then mix the remaining weight of mixed powder A and mixed powder C with refined honey, and coat the mixture on the surface of the core layer of honey pills to obtain Angong Niuhuang Pills.

9. An Angong Niuhuang Pill, characterized in that: Prepared by the preparation method according to any one of claims 1 to 8.

10. Use of the Angong Niuhuang Pills according to claim 9 in the preparation of medicines with heat-clearing, detoxicating and anticonvulsant effects.

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