A medicine for clearing heat and detoxicating, cooling blood for hemostasis, and removing stasis and dissipating macules, and its preparation method

Abstract

The present invention relates to the field of pharmaceutical technology, and specifically discloses a drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and resolving macules, and a preparation method thereof. The drug is composed of indigo naturalis, forsythia suspensa, agrimonia pilosa, cortex moutan, and licorice; the preparation method includes mixing agrimonia pilosa and cortex moutan and extracting with alcohol to obtain extract 1; soaking forsythia suspensa in water, extracting volatile oil by steam distillation method, storing the volatile oil, and collecting the medicinal residues and decoction 1 of forsythia suspensa; mixing the medicinal residues of forsythia suspensa and licorice and decocting with water to obtain a decoction, mixing with decoction 1, and concentrating to obtain extract 2; combining extract 1 and extract 2, drying, pulverizing, adding fine powder of indigo naturalis and dextrin, granulating, sizing, and then adding the volatile oil of forsythia suspensa and mixing evenly to obtain the product. The drug of the present invention can reduce the flying dust in production during preparation, is friendly to the production environment; the drug can improve the content uniformity of indirubin in indigo naturalis, meets the production standards of the pharmacopoeia, meets the production requirements of the industry, and is suitable for large-scale production.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceuticals, and particularly relates to a drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and resolving macules, and a preparation method thereof. Background Art

[0002] Indigo Naturalis is a heat-clearing drug, which is the dried powder, mass or granule prepared from the leaves or stems and leaves of Baphicacanthus cusia (Nees) Bremek. of the Acanthaceae family, Polygonum tinctorium Ait. of the Polygonaceae family, or Isatis indigotica Fort. of the Brassicaceae family, and has the effects of clearing heat and detoxifying, cooling blood and resolving macules, purging fire and calming endogenous wind.

[0003] Forsythia suspensa (Thunb.) Vahl is a heat-clearing and detoxifying drug, which is the dried fruit of Forsythia suspensa (Thunb.) Vahl of the Oleaceae family, and has the effects of clearing heat and detoxifying, detumescence and dissipating binds, dispersing wind-heat.

[0004] Agrimonia pilosa Ledeb. is a hemostatic drug, which is the dried aerial part of Agrimonia pilosa Ledeb. of the Rosaceae family, and has the effects of astringing to arrest bleeding, treating malaria, stopping dysentery, detoxifying, and tonifying deficiency.

[0005] Cortex Moutan is a heat-clearing drug, which is the dried root bark of Paeonia suffruticosa Andr. of the Ranunculaceae family, and has the effects of clearing heat and cooling blood, promoting blood circulation to remove stasis.

[0006] Licorice Root is a qi-tonifying drug, which is the dried root and rhizome of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. of the Leguminosae family, and has the functions of tonifying qi and invigorating the middle warmer, eliminating phlegm and relieving cough, detoxifying, relieving spasm and pain, and moderating the properties of other drugs.

[0007] There are relevant reports in the prior art on using the above five flavors of traditional Chinese medicine for clearing heat and detoxifying, cooling blood and stopping bleeding, and dispersing stasis and removing macules. For example, Chinese Patent CN105770057B discloses a traditional Chinese medicine composition for promoting platelet production capsules and its preparation method. This traditional Chinese medicine composition is prepared from five traditional Chinese medicines: indigo naturalis, forsythia suspensa, agrimonia pilosa, cortex moutan, and licorice root. This medicine has the effects of clearing heat and detoxifying, cooling blood and stopping bleeding, and dispersing stasis and removing macules. It is mainly used for idiopathic thrombocytopenic purpura. Symptoms include: petechiae or ecchymoses all over the body, fever and restlessness with thirst, short and red urine, constipation, or epistaxis, gingival bleeding, red tongue with yellow coating, slippery and rapid or string-taut and rapid pulse. Its process is advanced, the clinical pharmacodynamic test effect is significantly improved, the bioavailability is high, and there are no any toxic and side effects. Another example is that Chinese Patent CN1879720B discloses a quality detection method for promoting platelet production tablets. The raw materials of the medicine are composed of indigo naturalis, forsythia suspensa, agrimonia pilosa, cortex moutan, and licorice root. Grind indigo naturalis into fine powder; extract agrimonia pilosa and cortex moutan with ethanol, filter, recover ethanol and concentrate under reduced pressure to obtain a thick paste; soak forsythia suspensa and extract volatile oil by steam distillation method, store the volatile oil separately, and keep the water decoction for later use. Decoct the medicinal residues and licorice root with water, combine the water decoction with the above water decoction, filter, concentrate to obtain a thick paste, combine with the above ethanol-extracted thick paste, add indigo naturalis fine powder, mix evenly, dry, crush into fine powder, add auxiliary materials and mix evenly, make into granules, dry, size the granules, add magnesium stearate, spray in the above volatile oil, mix evenly, press into tablets, and coat with a film coating to obtain the promoting platelet production tablets. The promoting platelet production tablets studied in this invention have the effects of clearing heat and detoxifying, cooling blood and stopping bleeding, and dispersing stasis and removing macules.

[0008] However, in the preparation of the drugs in the above patents, a large amount of flying dust will be generated, which is not friendly to the production environment. Moreover, as the monarch drug, indigo naturalis has poor uniformity in the content of its main active substance indirubin, which cannot meet the production requirements of the industry.

[0009] Therefore, there is an urgent need for a drug for clearing heat and detoxifying, cooling blood and stopping bleeding, and dispersing stasis and removing macules with a simple preparation method and capable of improving the uniformity of the content of active substances in the drug. Summary of the Invention

[0010] In view of the problems existing in the prior art, the present invention provides a drug for clearing heat and detoxifying, cooling blood and stopping bleeding, and dispersing stasis and removing macules and its preparation method. This drug can clear heat and detoxify, cool blood and stop bleeding, and disperse stasis and remove macules. Moreover, the drug can reduce production dust, is friendly to the production environment, can also improve the uniformity of the indirubin content in indigo naturalis, meets the industry standards, and is suitable for large-scale production.

[0011] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0012] The present invention provides a preparation method for a drug for clearing heat and detoxifying, cooling blood and stopping bleeding, and dispersing stasis and removing macules. The raw materials of the drug include indigo naturalis, forsythia suspensa, agrimonia pilosa, cortex moutan, and licorice root;

[0013] The preparation method of the drug is as follows:

[0014] S1. Weigh indigo naturalis, cortex moutan, forsythia suspensa, agrimonia pilosa and liquorice. Grind indigo naturalis into fine powder for later use.

[0015] S2. Mix agrimonia pilosa and cortex moutan to obtain mixture 1. Add alcohol to mixture 1 for extraction 1 - 3 times. Combine the alcohol extracts, filter, recover the alcohol and concentrate under reduced pressure to obtain extract 1 for later use.

[0016] S3. Soak forsythia suspensa in water and extract the volatile oil by steam distillation method. Store the volatile oil, and collect the medicinal residues of the remaining forsythia suspensa and the first water decoction for later use.

[0017] S4. Mix the medicinal residues of forsythia suspensa and liquorice to obtain mixture 2. Decoct mixture 2 with water 1 - 2 times. Combine the water decoctions, mix them with the first water decoction, filter, and concentrate to obtain extract 2 for later use.

[0018] S5. Combine extract 1 and extract 2, dry and crush them. Add the fine powder of indigo naturalis and dextrin, mix well, granulate, size the granules, and then add the volatile oil described in step S3 and mix well to obtain the product.

[0019] Preferably, the alcohol described in step S2 is ethanol, and the volume concentration of the alcohol is 75% - 90%; the extraction time is: 1 - 3 hours each time; the material - liquid ratio of mixture 1 to alcohol is 1:4 - 6.

[0020] More preferably, the volume concentration of the alcohol described in step S2 is 75% - 80%; the extraction time is: 2 - 3 hours each time; the material - liquid ratio of mixture 1 to alcohol is 1:4 - 5.

[0021] Most preferably, the volume concentration of the alcohol described in step S2 is 80%; the extraction time is: 2 hours each time; the material - liquid ratio of mixture 1 to alcohol is 1:5.

[0022] Preferably, the relative density of extract 1 described in step S2 is 1.25 - 1.30 at 60°C.

[0023] Preferably, the soaking time described in step S3 is 3 - 5 hours, and the time for extracting the volatile oil is 5 - 7 hours.

[0024] More preferably, the soaking time described in step S3 is 3 - 4 hours, and the time for extracting the volatile oil is 5 - 6 hours.

[0025] Most preferably, the soaking time described in step S3 is 4 hours, and the time for extracting the volatile oil is 6 hours.

[0026] Preferably, the material - liquid ratio of mixture 2 to water described in step S4 is 1:4 - 6; the time for water decoction is: 1 - 2 hours each time.

[0027] Further preferably, the ratio of the mixture 2 to water in step S4 is 1:4 - 5; the time for decocting with water is: 1.5 - 2 hours each time.

[0028] Most preferably, the ratio of the mixture 2 to water in step S4 is 1:5; the time for decocting with water is: 1.5 hours each time.

[0029] Preferably, the relative density of the extract 2 in step S4 is 1.25 - 1.30 at 60°C.

[0030] Preferably, the drying temperature in step S5 is 50°C - 70°C.

[0031] Further preferably, the drying temperature in step S5 is 50°C - 60°C.

[0032] Most preferably, the drying temperature in step S5 is 60°C.

[0033] Preferably, the preparation method of the drug is as follows:

[0034] S1. Weigh indigo naturalis, moutan cortex, forsythia suspensa, agrimonia pilosa and licorice root. Grind indigo naturalis into fine powder and set aside.

[0035] S2. Mix agrimonia pilosa and moutan cortex to obtain mixture 1. Add ethanol with a volume concentration of 80% to mixture 1, with a material - liquid ratio of 1:5, extract 2 times, 2 hours each time. Combine the ethanol extracts, filter, recover the ethanol and concentrate under reduced pressure to obtain extract 1 with a relative density of 1.25 - 1.30 at 60°C, and set aside.

[0036] S3. Soak forsythia suspensa in water for 4 hours, extract volatile oil by steam distillation for 6 hours, store the volatile oil, collect the residue of forsythia suspensa and the first water decoction, and set aside.

[0037] S4. Mix the residue of forsythia suspensa with licorice root to obtain mixture 2. Add water to mixture 2, with a material - liquid ratio of 1:5, decoct 2 times, 1.5 hours each time. Combine the water decoctions, mix with the first water decoction, filter, and concentrate to obtain extract 2 with a relative density of 1.25 - 1.30 at 60°C, and set aside.

[0038] S5. Combine extract 1 and extract 2, dry at 60°C and then pulverize. Add the fine powder of indigo naturalis and dextrin, mix well, granulate, size the granules, and then add the volatile oil in step S3, and mix well to obtain the product.

[0039] The present invention also provides a drug with the functions of clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and dissipating macules, which is prepared by the above - mentioned preparation method.

[0040] Preferably, the prescription of the drug is as follows: 150-170 g of Indigo Naturalis, 400-600 g of Forsythia suspensa, 400-600 g of Agrimonia pilosa Ledeb., 700-900 g of Cortex Moutan, and 200-300 g of Glycyrrhiza uralensis Fisch.

[0041] More preferably, the prescription of the drug is as follows: 167 g of Indigo Naturalis, 500 g of Forsythia suspensa, 500 g of Agrimonia pilosa Ledeb., 833 g of Cortex Moutan, and 250 g of Glycyrrhiza uralensis Fisch.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] The drug for clearing heat and detoxifying, cooling blood for hemostasis, and dispersing stasis and removing macules in the present invention is composed of Indigo Naturalis, Forsythia suspensa, Cortex Moutan, Agrimonia pilosa Ledeb., and Glycyrrhiza uralensis Fisch. In the formula, Indigo Naturalis is salty, cold, and belongs to the liver and lung meridians, with the effects of clearing heat and detoxifying, cooling blood and removing macules, clearing liver fire, and calming endogenous wind, and is the monarch drug in the formula. Cortex Moutan is pungent, bitter, cool, slightly cold, and belongs to the heart, liver, kidney, and lung meridians, with the effects of clearing heat and promoting blood circulation to remove stasis, and can assist the monarch drug in clearing heat and detoxifying, promoting blood circulation to remove stasis, and cooling blood and removing macules, and is the ministerial drug in the formula. Forsythia suspensa is bitter, slightly cold, and belongs to the lung, heart, and gall meridians, with the effects of clearing heat and detoxifying, and dissipating swelling and dissipating nodules; Agrimonia pilosa Ledeb. is bitter, astringent, flat, and belongs to the lung, liver, and spleen meridians, with the effects of clearing heat and detoxifying, astringing to stop bleeding, and dissipating nodules and removing macules. The combination of the two drugs is the adjuvant drug in the formula, assisting the monarch and ministerial drugs in clearing heat and detoxifying, and promoting blood circulation and dissipating nodules. Glycyrrhiza uralensis Fisch. is sweet, flat, and belongs to the heart, lung, spleen, and stomach meridians, clearing heat and detoxifying, and coordinating the properties of various drugs, and is the guiding drug in the formula. The whole formula together has the effects of clearing heat and detoxifying, cooling blood and promoting blood circulation, and dissipating stasis and removing nodules. In the actual production of the present invention, it is found that because Indigo Naturalis is fine, powdery, light in weight, and easy to fly, when adding the extract, it floats on the surface and is not easy to stir evenly, and is easy to disperse, which is likely to cause cross-contamination. Therefore, in order to reduce dust, the preparation process is optimized. The optimized process can reduce the flying dust in production and is friendly to the production environment; but unexpectedly, it is found that the preparation process can also significantly improve the content uniformity of indirubin in Indigo Naturalis, which not only meets the production standards of the Chinese Pharmacopoeia but also meets the industry production requirements and is suitable for large-scale production. Description of the Drawings

[0044] Figure 1 It is a distribution diagram of the three sampling points in Example 3 of the effects of the present invention. Detailed Embodiments

[0045] The present invention will be described below through specific examples to make the technical solutions of the present invention easier to understand and master, but the present invention is not limited thereto. The described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments.

[0046] The endpoints and any values disclosed in this text are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the values between the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be regarded as specifically disclosed in this text. Unless the context clearly indicates otherwise, the singular forms "a", "an", and "the" as used in this text include singular and plural referents. Numerical ranges expressed by endpoints include all numerical values and fractions within the corresponding ranges, as well as the expressed endpoints.

[0047] Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention. The experimental methods described in the following embodiments are all conventional methods unless otherwise specified; the reagents and materials are all commercially available unless otherwise specified.

[0048] It is worth noting that during the preparation process, the amount of dextrin varies, and the amount extracted from each batch of medicinal materials is not exactly the same, with deviations within the specified range. However, the total number of granules or capsules produced in each batch is fixed, and the quality of dextrin is to make up the total amount. Taking 500,000 capsules of each batch of medicinal materials as an example, the content of dextrin = 500,000 capsules × 0.45 g / capsule - the mass of the extracted dry extract - the mass of indigo naturalis.

[0049] Example 1

[0050] A drug for clearing heat and detoxifying, cooling blood and stopping bleeding, and removing stasis and dissipating macules, with the prescription: 167 g of indigo naturalis, 500 g of forsythia suspensa, 500 g of agrimonia pilosa, 833 g of moutan cortex, and 250 g of licorice root;

[0051] The preparation method of the drug is as follows:

[0052] S1. Weigh the formulated amounts of indigo naturalis, moutan cortex, forsythia suspensa, agrimonia pilosa, and licorice root. Grind indigo naturalis into fine powder and set aside;

[0053] S2. Mix agrimonia pilosa and moutan cortex to obtain mixture 1. Add ethanol with a volume concentration of 80% to mixture 1, with a material-liquid ratio of 1:5. Extract 2 times, each time for 2 hours. Combine the ethanol extracts, filter, recover the ethanol, and concentrate under reduced pressure to an extract 1 with a relative density of 1.25 at 60 °C and set aside;

[0054] S3. Soak forsythia suspensa in water for 4 hours, and extract the volatile oil by steam distillation for 6 hours. Store the volatile oil, and collect the medicinal residues and the first water decoction of the remaining forsythia suspensa and set aside;

[0055] S4. Mix the medicinal residues of forsythia with licorice to obtain mixture 2. Add water to mixture 2 with a material-liquid ratio of 1:5, decoct twice, each time for 1.5 hours. Combine the decocted liquid, mix it with decocted liquid 1, filter, and concentrate to an extract 2 with a relative density of 1.30 at 60 °C for standby.

[0056] S5. Combine extract 1 and extract 2, dry and crush them at 60 °C, add fine indigo naturalis powder and dextrin and mix evenly. After granulating with ethanol, drying, and sizing, spray the volatile oil described in step S3 and mix evenly to obtain the product.

[0057] Example 2

[0058] A drug for clearing heat and detoxifying, cooling blood for hemostasis, and dispersing stasis and removing macules, with the prescription: 150 g of indigo naturalis, 400 g of forsythia, 400 g of agrimony, 700 g of moutan bark, and 200 g of licorice.

[0059] The preparation method of the drug is as follows:

[0060] S1. Weigh the prescribed amounts of indigo naturalis, moutan bark, forsythia, agrimony, and licorice. Grind indigo naturalis into fine powder for standby.

[0061] S2. Mix agrimony and moutan bark to obtain mixture 1. Add ethanol with a volume concentration of 75% to mixture 1 with a material-liquid ratio of 1:4, extract once for 3 hours. Combine the ethanol extract, filter, recover ethanol and concentrate it under reduced pressure to an extract 1 with a relative density of 1.30 at 60 °C for standby.

[0062] S3. Soak forsythia in water for 3 hours, extract volatile oil by steam distillation for 5 hours, store the volatile oil, collect the remaining medicinal residues of forsythia and decocted liquid 1 for standby.

[0063] S4. Mix the medicinal residues of forsythia with licorice to obtain mixture 2. Add water to mixture 2 with a material-liquid ratio of 1:4, decoct once for 2 hours. Combine the decocted liquid, mix it with decocted liquid 1, filter, and concentrate to an extract 2 with a relative density of 1.25 at 60 °C for standby.

[0064] S5. Combine extract 1 and extract 2, dry and crush them at 50 °C, add fine indigo naturalis powder and dextrin and mix evenly. After granulating with ethanol, drying, and sizing, spray the volatile oil described in step S3 and mix evenly to obtain the product.

[0065] Example 3

[0066] A drug for clearing heat and detoxifying, cooling blood for hemostasis, and dispersing stasis and removing macules, with the prescription: 170 g of indigo naturalis, 600 g of forsythia, 600 g of agrimony, 900 g of moutan bark, and 300 g of licorice.

[0067] The preparation method of the drug is as follows:

[0068] S1. Weigh the formula amounts of indigo naturalis, cortex moutan, forsythia suspensa, agrimonia pilosa, and liquorice. Grind indigo naturalis into fine powder for later use.

[0069] S2. Mix agrimonia pilosa and cortex moutan to obtain mixture 1. Add ethanol with a volume concentration of 90% to mixture 1, with a material-liquid ratio of 1:6. Extract for 3 times, 1 hour each time. Combine the ethanol extracts, filter, recover the ethanol, and concentrate under reduced pressure to obtain extract 1 with a relative density of 1.25 at 60°C for later use.

[0070] S3. Soak forsythia suspensa in water for 5 hours, and extract the volatile oil by steam distillation for 7 hours. Store the volatile oil, and collect the residue of forsythia suspensa and decoction liquid 1 for later use.

[0071] S4. Mix the residue of forsythia suspensa with liquorice to obtain mixture 2. Add water to mixture 2, with a material-liquid ratio of 1:6. Decoct for 2 times, 1 hour each time. Combine the decoction liquids, mix with decoction liquid 1, filter, and concentrate to obtain extract 2 with a relative density of 1.30 at 60°C for later use.

[0072] S5. Combine extract 1 and extract 2, dry at 70°C and then crush. Add the fine powder of indigo naturalis and dextrin, mix well, granulate with ethanol, dry, size the granules, and then spray the volatile oil obtained in step S3, and mix well to obtain the product.

[0073] Comparative Example 1

[0074] A drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and dissipating macules, with the prescription: indigo naturalis 219 g, forsythia suspensa 500 g, agrimonia pilosa 500 g, cortex moutan 833 g, liquorice 250 g;

[0075] The preparation method of the drug is as follows:

[0076] S1. Weigh the formula amounts of indigo naturalis, cortex moutan, forsythia suspensa, agrimonia pilosa, and liquorice. Grind indigo naturalis into fine powder for later use.

[0077] S2. Mix agrimonia pilosa and cortex moutan to obtain mixture 1. Add ethanol with a volume concentration of 80% to mixture 1, with a material-liquid ratio of 1:5. Extract for 2 times, 2 hours each time. Combine the ethanol extracts, filter, recover the ethanol, and concentrate under reduced pressure to obtain extract 1 with a relative density of 1.25 at 60°C for later use.

[0078] S3. Soak forsythia suspensa in water for 4 hours, and extract the volatile oil by steam distillation for 6 hours. Store the volatile oil, and collect the residue of forsythia suspensa and decoction liquid 1 for later use.

[0079] S4. Mix the residue of forsythia suspensa with liquorice to obtain mixture 2. Add water to mixture 2, with a material-liquid ratio of 1:5. Decoct for 2 times, 1.5 hours each time. Combine the decoction liquids, mix with decoction liquid 1, filter, and concentrate to obtain extract 2 with a relative density of 1.30 at 60°C for later use.

[0080] S5. After combining Extract 1 and Extract 2, add fine powder of Indigo Naturalis, mix evenly, dry at 60°C and then pulverize into fine powder, add dextrin and mix evenly. After granulating with ethanol, drying, and sizing, spray the volatile oil described in step S3, and mix evenly to obtain.

[0081] Comparative Example 2

[0082] A drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and resolving macules, with the prescription: 167 g of Indigo Naturalis, 500 g of Forsythia suspensa, 500 g of Agrimonia pilosa Ledeb., 833 g of Cortex Moutan, 250 g of Glycyrrhiza uralensis Fisch.;

[0083] The preparation method of the said drug is as follows:

[0084] S1. Weigh the formulated amounts of Indigo Naturalis, Cortex Moutan, Forsythia suspensa, Agrimonia pilosa Ledeb., and Glycyrrhiza uralensis Fisch. Grind Indigo Naturalis into fine powder and set aside;

[0085] S2. Mix Agrimonia pilosa Ledeb. and Cortex Moutan to obtain Mixture 1. Add ethanol with a volume concentration of 80% to Mixture 1, with a material-liquid ratio of 1:5, extract 2 times, each extraction for 2 hours, combine the ethanol extracts, filter, recover the ethanol and concentrate under reduced pressure to an extract 1 with a relative density of 1.25 at 60°C, and set aside;

[0086] S3. Soak Forsythia suspensa in water for 4 hours, extract the volatile oil by steam distillation for 6 hours, store the volatile oil, collect the medicinal residues of the remaining Forsythia suspensa and the first decoction liquid 1, and set aside;

[0087] S4. Mix the medicinal residues of the said Forsythia suspensa with Glycyrrhiza uralensis Fisch. to obtain Mixture 2. Add water to Mixture 2, with a material-liquid ratio of 1:5, decoct 2 times, each decoction for 1.5 hours, combine the decoction liquids, mix with the first decoction liquid 1, filter, and concentrate to an extract 2 with a relative density of 1.30 at 60°C, and set aside;

[0088] S5. After combining Extract 1 and Extract 2, add fine powder of Indigo Naturalis, mix evenly, dry at 60°C and then pulverize into fine powder, add dextrin and mix evenly. After granulating with ethanol, drying, and sizing, spray the volatile oil described in step S3, and mix evenly to obtain.

[0089] Effect Example 1

[0090] Conduct a pilot-scale process on the drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and resolving macules in Example 1 to verify the influence of the process on the quality.

[0091] The specific operation is as follows: Obtain the extract after step S5 "merging extract 1 and extract 2", that is, after mixing the extracts, dry them at 60 °C and then pulverize them. Divide them into 3 equal parts on average, and respectively add 27.8 kg of Indigo Naturalis fine powder and dextrin and mix evenly. After granulating with ethanol, drying, and sizing, spray the volatile oil described in step S3, mix evenly and fill into capsules to obtain the product. Among them, the dry extract powder is obtained by drying the mixed extract at 60 °C. The test results are shown in Table 1 below.

[0092] Table 1 Results of the pilot-scale process in Example 1

[0093]

[0094]

[0095] According to the data in the above table, each production parameter meets the predetermined index, and the finished product inspection results all meet the quality standards. It is proved that the drug for clearing heat and detoxifying, cooling blood and stopping bleeding, and removing stasis and resolving macules of the present invention is suitable for normal production, and the production process is feasible.

[0096] Effect Example 2

[0097] Taking the surface dust in the operation room as the observation index, compare the drugs for clearing heat and detoxifying, cooling blood and stopping bleeding, and removing stasis and resolving macules in Examples 1-3 and Comparative Examples 1-2. The results are shown in Table 2 below:

[0098] Table 2 Comparison results of dust in the processes of Examples and Comparative Examples

[0099]

[0100] By comparing the surface dust situation in the operation room during the preparation processes of the drugs in Examples and Comparative Examples, it is found that the examples of the present invention can avoid the flying of Indigo Naturalis during the mixing process, which is significantly better than the Comparative Examples.

[0101] Effect Example 3

[0102] Take the drugs in Examples 1-3 and Comparative Examples 1-2, and make comparisons under the condition of granule mixing (mixing frequency is 20 Hz / min, mixing time is 60 minutes). Each group is repeated 3 times, and the 3 sampling points are distributed as Figure 1 shown. Using the indirubin content as the index, make comparisons.

[0103] The detection method of indirubin content is: Determine according to the high performance liquid chromatography method (General Principles 0512, Volume IV of Chinese Pharmacopoeia 2020 Edition).

[0104] Chromatographic conditions and system suitability test: Using octadecylsilyl silica gel as the filler; using methanol-water (70:30) as the mobile phase; the detection wavelength is 293 nm. The number of theoretical plates calculated by the indirubin peak should not be less than 6000.

[0105] Preparation of reference substance solution: Weigh an appropriate amount of indirubin reference substance accurately, dissolve it in N, N-dimethylformamide to prepare a mixed solution containing 14 μg of indirubin per 1 ml, and that's it.

[0106] Preparation of test solution: Take the content of this product under the item of variation in filling quantity, grind it finely, take about 0.5 g, weigh it accurately, place it in a stoppered conical flask, accurately add 20 ml of N, N-dimethylformamide, stopper it, weigh it, ultrasonically treat it (power 140 W, frequency 42 kHz) for 30 minutes, take it out, let it cool, weigh it again, make up the lost weight with N, N-dimethylformamide, shake well, filter, and take the subsequent filtrate, and that's it.

[0107] Determination method: Accurately pipette 10 μl of the reference substance solution and the test solution respectively, inject them into the liquid chromatograph for determination, and that's it. The results are shown in Table 3 below:

[0108] Table 3: Comparison of mixing uniformity of each group

[0109]

[0110] It is stipulated in the "Guidelines for Validation of Analytical Methods" in Part IV of the Chinese Pharmacopoeia 2020 Edition that when the content of the component to be measured is 1 mg / g, the acceptance range of repeatability (RSD%) is 3%. After conversion, the indirubin content in the drug produced by the process in this example is about 0.84 mg / g, and the repeatability (RSD%) should be within 3%. According to the results in Table 3 above, it can be seen that under the same mixing process conditions, compared with the drug in the comparative example, the uniformity of indirubin content in the drug of the example is better than that of the comparative example, meeting the pharmacopoeia regulations and being suitable for large-scale production in the industry.

[0111] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than a limitation on the protection scope of the present invention. Any simple modification or equivalent replacement of the technical solution of the present invention by those of ordinary skill in the art does not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A preparation method of a drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and dissipating macules, characterized in that: The raw materials of the drug are made from indigo naturalis, forsythia suspensa, agrimonia pilosa, cortex moutan, and liquorice root; The preparation method of the drug is as follows: S1. Weigh indigo naturalis, cortex moutan, forsythia suspensa, agrimonia pilosa, and liquorice root. Grind indigo naturalis into fine powder for later use; S2. Mix agrimonia pilosa and cortex moutan to obtain mixture 1. Add alcohol to mixture 1 for extraction 1 - 3 times. Combine the alcohol extracts, filter, recover the alcohol, and concentrate under reduced pressure into extract 1 for later use; S3. Soak forsythia suspensa in water, extract the volatile oil by steam distillation method, store the volatile oil, and collect the residue of forsythia suspensa and the first decoction liquid for later use; S4. Mix the residue of forsythia suspensa with liquorice root to obtain mixture 2. Decoct mixture 2 with water 1 - 2 times. Combine the decoction liquids, mix with the first decoction liquid, filter, and concentrate into extract 2 for later use; S5. Combine extract 1 and extract 2, dry and crush them, add the fine powder of indigo naturalis and dextrin, mix well, granulate, size the granules, and then add the volatile oil described in step S3 and mix well to obtain the product; The prescription of the drug is: indigo naturalis 150 - 170 g, forsythia suspensa 400 - 600 g, agrimonia pilosa 400 - 600 g, cortex moutan 700 - 900 g, liquorice root 200 - 300 g; The alcohol described in step S2 is ethanol, and the volume concentration of the alcohol is 75% - 90%; The relative density of extract 1 described in step S2 is 1.25 - 1.30 at 60 °C; The relative density of extract 2 described in step S4 is 1.25 - 1.30 at 60 °C; The drying temperature described in step S5 is 50 °C - 70 °C.

2. The preparation method according to claim 1, characterized in that: The extraction time is: 1 - 3 hours each time; the material - liquid ratio of mixture 1 to alcohol is 1:4 - 6.

3. The preparation method according to claim 1, characterized in that: The soaking time described in step S3 is 3 - 5 hours, and the time for extracting the volatile oil is 5 - 7 hours.

4. The preparation method according to claim 1, characterized in that: The material - liquid ratio of mixture 2 to water described in step S4 is 1:4 - 6; the time for water decoction is: 1 - 2 hours each time.

5. The preparation method according to claim 1, wherein: The preparation method of the drug is as follows: S1. Weigh indigo naturalis, cortex moutan, forsythia suspensa, agrimonia pilosa, and liquorice root. Grind indigo naturalis into fine powder for later use; S2. Mix agrimonia pilosa and cortex moutan to obtain mixture 1. Add ethanol with a volume concentration of 80% to mixture 1, with a material - liquid ratio of 1:5, extract 2 times, 2 hours each time. Combine the ethanol extracts, filter, recover the ethanol, and concentrate under reduced pressure to extract 1 with a relative density of 1.25 - 1.30 at 60 °C for later use; S3. Soak forsythia suspensa in water for 4 hours, extract the volatile oil by steam distillation method for 6 hours, store the volatile oil, and collect the residue of forsythia suspensa and the first decoction liquid for later use; S4. Mix the residue of forsythia suspensa with liquorice root to obtain mixture 2. Add water to mixture 2, with a material - liquid ratio of 1:5, decoct 2 times, 1.5 hours each time. Combine the decoction liquids, mix with the first decoction liquid, filter, and concentrate to extract 2 with a relative density of 1.25 - 1.30 at 60 °C for later use; S5. Combine extract 1 and extract 2, dry and crush them at 60 °C, add the fine powder of indigo naturalis and dextrin, mix well, granulate, size the granules, and then add the volatile oil described in step S3 and mix well to obtain the product.

6. A drug for clearing heat and detoxifying, cooling blood for hemostasis, and removing stasis and dissipating macules, prepared by the preparation method according to any one of claims 1 - 5.

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