A qingkailing composition, qingkailing tablets, and a preparation method and application thereof
By improving the extraction process and preparation method, Qingkailing tablets with better anti-inflammatory effects and higher uniformity were prepared, solving the problems of poor anti-inflammatory effects and insufficient uniformity in the existing technology.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- ZHEJIANG YUANLIJIAN PHARMA
- Filing Date
- 2024-07-22
- Publication Date
- 2026-05-19
AI Technical Summary
Current technology has failed to provide Qingkailing tablets with better anti-inflammatory effects and better uniformity.
An improved extraction process was used to prepare Qingkailing composition, including the preparation method of Scutellaria baicalensis-Gardenia jasminoides extract, mother-of-pearl extract, buffalo horn extract, etc., and reflux extraction and drying were carried out under specific solvent and temperature conditions to prepare Qingkailing tablets.
This study achieved efficient extraction of Scutellaria baicalensis and Gardenia jasminoides from the Qingkailing composition, improving the anti-inflammatory properties and product quality uniformity of Qingkailing tablets.
Smart Images
Figure SMS_1 
Figure SMS_2 
Figure SMS_3
Abstract
Description
Technical Field
[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, and relates to a Qingkailing composition, Qingkailing tablets, their preparation method and application. Background Technology
[0002] Qingkailing is a traditional Chinese medicine preparation based on the ancient formula "Angong Niuhuang Wan" with modifications. Angong Niuhuang Wan originated from *Wenbing Tiaobian* (Treatise on Warm Diseases) written by Wu Jutong in the Qing Dynasty, and has the effects of clearing heat and detoxifying, resolving phlegm and opening the orifices. According to *Wenbing Tiaobian*, Angong Niuhuang Wan consists of bezoar, turmeric, buffalo horn, coptis, cinnabar, borneol, musk, pearl (mother-of-pearl), gardenia, realgar, and scutellaria. To enhance the effects of clearing heat and detoxifying, resolving phlegm and unblocking the meridians, Qingkailing retains five herbs: bezoar, buffalo horn, mother-of-pearl, gardenia, and scutellaria, while removing turmeric, cinnabar, borneol, musk, and realgar. Coptis is replaced with isatis root. Furthermore, honeysuckle, cholic acid, and deoxycholic acid are added. Qingkailing has the effects of clearing heat and detoxifying, calming the mind and relieving anxiety, and is suitable for symptoms such as high fever and restlessness caused by febrile diseases. Currently, Qingkailing pharmaceutical preparations come in various dosage forms, such as Qingkailing capsules, Qingkailing effervescent tablets, Qingkailing soft capsules, Qingkailing oral liquid, Qingkailing drop pills, and Qingkailing tablets.
[0003] Chinese patent application 201310669594.0 discloses a Qingkailing freeze-dried tablet and its preparation method. The Qingkailing tablet contains cholic acid, deoxycholic acid, pearl powder, buffalo horn powder, refined honeysuckle, refined gardenia, refined isatis root, baicalin, and other excipients (fillers, matrix agents, binders, flavoring agents, and solubilizers). The pre-freeze-dried solution of this Qingkailing freeze-dried tablet is simple to prepare, the freeze-drying process is feasible, the product quality is uniform and stable, it is convenient to use, transport, and carry, and its onset of action is faster than ordinary tablets.
[0004] Chinese patent application 202110694597.4 discloses a method for preparing Qingkailing tablets. This method improves upon traditional industrial methods by adding an alcohol precipitation purification step after the decoction extraction of plant components (honeysuckle, gardenia, and isatis root). A lower concentration (65%) of ethanol and a lower temperature (0-5℃) are used for alcohol precipitation of the concentrated decoction extract, significantly reducing energy consumption and reagent usage, preventing damage to active ingredients, effectively removing excessive impurities from the extract, and fully extracting components such as geniposide and chlorogenic acid. An improved method is used for granulation and tableting, thereby improving the disintegration performance and strength of Qingkailing tablets. This method allows for a series of operations, including mixing, granulation, and drying, to be performed in a single piece of equipment, simplifying the process, saving costs, and adapting to existing industrial production lines for large-scale material processing, effectively saving costs while ensuring production efficiency.
[0005] Chinese patent application 202211388323.3 discloses a method for preparing Qingkailing preparation. The method involves extracting Isatis root twice using a 64-69 wt% ethanol aqueous solution under reflux. The resulting extracts are combined, refrigerated, and directly filtered. The ethanol in the filtrate is directly recovered until no alcohol odor remains. The filtrate is then concentrated, and the pH is adjusted to neutral to obtain the Isatis root extract. The Qingkailing preparation is prepared using this Isatis root extract. This application effectively extracts (R,S)-gaoyichun and other active ingredients by using a specific concentration of ethanol aqueous solution as a solvent for reflux extraction. Since these active ingredients are highly soluble in this concentration of ethanol aqueous solution, they are not filtered out with the residue during subsequent filtration, thus improving the quality of the Qingkailing preparation.
[0006] However, none of the above-mentioned existing technologies can provide a Qingkailing tablet with better anti-inflammatory effects and better uniformity. Summary of the Invention
[0007] In view of this, and considering that the existing technology cannot provide a Qingkailing tablet with better anti-inflammatory effect and better uniformity, the purpose of this invention is to provide a Qingkailing composition, Qingkailing tablets, its preparation method and application.
[0008] To achieve the above-mentioned objectives, in one aspect, the present invention provides a Qingkailing composition comprising the following components:
[0009] Cholic acid, deoxycholic acid, Scutellaria baicalensis-gardenia extract, mother-of-pearl extract, buffalo horn extract, Isatis indigotica, honeysuckle, dextrin, magnesium stearate and corn starch;
[0010] The preparation method of the Scutellaria baicalensis-Gardenia jasminoides extract includes the following steps:
[0011] S101. Mix Scutellaria baicalensis and Gardenia jasminoides with water, reflux to extract, filter, and obtain dregs 1 and filtrate 1.
[0012] S102. Mix the residue 1 obtained in step S101 with an aqueous solution of acetic acid with a mass fraction of 0.1%-1%, reflux for extraction, filter, and obtain residue 2 and filtrate 2.
[0013] S103. Mix the residue 2 obtained in step S102 with solvent A, reflux for extraction, filter, and obtain filtrate 3.
[0014] In step S103, solvent A is a mixture of methyl ethyl ketone, methanol and tetrahydrofuran;
[0015] S104. Mix the filtrate 1 obtained in step S101, the filtrate 2 obtained in step S102 and the filtrate 3 obtained in step S103, and dry them to obtain Scutellaria baicalensis-gardenia extract.
[0016] The preparation method of the mother-of-pearl extract includes the following steps:
[0017] S201. Mix mother-of-pearl with 8-12 times the mass of pyruvic acid aqueous solution, heat to react, evaporate to dryness under reduced pressure, redissolve in water, filter to obtain supernatant, and dry to obtain mother-of-pearl extract.
[0018] The preparation method of the buffalo horn extract includes the following steps:
[0019] S301. Mix buffalo horn with 2-4 times its mass of an ethanol-acetic acid-water solution, steam, distill under reduced pressure until there is no ethanol or acetic acid odor, and dry to obtain buffalo horn extract.
[0020] Preferably, in step S101, the mass ratio of Scutellaria baicalensis, Gardenia jasminoides and water is 4-8:1-5:50, more preferably 6:3:50; preferably, the reflux extraction time is 4-6 hours, more preferably 5 hours.
[0021] Preferably, in step S102, the mass of the acetic acid aqueous solution is 6-8 times the mass of the residue 1, more preferably 7 times; preferably, the reflux extraction time is 4-6 hours, more preferably 5 hours.
[0022] Preferably, in step S102, the mass fraction of the acetic acid aqueous solution is 0.5%.
[0023] Preferably, in step S103, the mass of solvent A is 6-8 times the mass of the residue 2, more preferably 7 times; preferably, solvent A is a mixture of methyl ethyl ketone, methanol, and tetrahydrofuran in a volume ratio of 0.4-0.6:1:0.6-0.8, more preferably, solvent A is a mixture of methyl ethyl ketone, methanol, and tetrahydrofuran in a volume ratio of 0.5:1:0.7; preferably, the reflux extraction time is 4-6 hours, more preferably 5 hours.
[0024] Preferably, in step S104, the drying is specifically vacuum drying.
[0025] Preferably, in step S201, the mass concentration of the pyruvic acid aqueous solution is 4%-8%, more preferably 6%; preferably, the temperature of the heating reaction is 60-70℃, more preferably 65℃; preferably, the heating reaction time is 4-6h, more preferably 5h; preferably, the drying is freeze drying.
[0026] Preferably, in step S301, the ethanol-acetic acid-water solution has a mass concentration of 10%-20%, more preferably 15%, and a mass concentration of acetic acid of 3%-5%, more preferably 4%; preferably, the steaming time is 8-10 hours, more preferably 9 hours; preferably, the drying is freeze-drying; preferably, after freeze-drying, the buffalo horn is crushed.
[0027] Preferably, the Qingkailing composition comprises the following components by weight:
[0028] 10-50 parts of cholic acid, 10-50 parts of porcine deoxycholic acid, 10-20 parts of Scutellaria baicalensis-Gardenia jasminoides extract, 6-10 parts of mother-of-pearl extract, 6-10 parts of buffalo horn extract, 12-16 parts of Isatis indigotica root, 12-16 parts of honeysuckle, 7-11 parts of dextrin, 2-4 parts of magnesium stearate, and 2-4 parts of corn starch.
[0029] More preferably, the Qingkailing composition comprises the following components by weight:
[0030] 30 parts of cholic acid, 30 parts of deoxycholic acid from pigs, 15 parts of Scutellaria baicalensis-gardenia extract, 8 parts of mother-of-pearl extract, 8 parts of buffalo horn extract, 14 parts of Isatis indigotica root, 14 parts of honeysuckle, 9 parts of dextrin, 3 parts of magnesium stearate, and 3 parts of corn starch.
[0031] On the other hand, the present invention provides a Qingkailing tablet, the main components of which include the above-mentioned Qingkailing composition.
[0032] Preferably, the Qingkailing tablets also include excipients.
[0033] The excipients include, but are not limited to, coatings, pigments, flavoring agents, antioxidants, fragrances, penetration enhancers, etc.
[0034] Furthermore, the present invention provides a method for preparing the above-mentioned Qingkailing tablets, comprising the following steps:
[0035] T1. Mix the prescribed amount of Isatis root and honeysuckle with 8-12 times the weight of water, decoct, repeat 2-3 times, combine the filtrates, dry, and obtain the extract powder.
[0036] T2. Mix the extract powder obtained in step T1 with the prescribed amounts of cholic acid, deoxycholic acid, scutellaria-gardenia extract, mother-of-pearl extract, buffalo horn extract, dextrin, and corn starch, granulate, sizing, add the prescribed amount of magnesium stearate, and compress into tablets to obtain Qingkailing tablets.
[0037] Preferably, the pressure of the tablet is 8-12 kN.
[0038] As an example of the present invention, the pressure of the tablet is 10kN.
[0039] In another aspect, the present invention provides the application of the above-mentioned Qingkailing composition, the above-mentioned Qingkailing tablets, or the above-mentioned preparation method in the production of Qingkailing products.
[0040] Compared with the prior art, the present invention has the following beneficial effects:
[0041] (1) By improving the extraction process, the efficient extraction of Scutellaria baicalensis and Gardenia jasminoides from the Qingkailing composition was achieved. The obtained Scutellaria baicalensis-Gardenia jasminoides extract was confirmed by cell experiments to have good anti-inflammatory properties.
[0042] (2) The present invention provides a method for preparing the above-mentioned Qingkailing tablets. By combining process parameters with extract extraction methods, the process stability and product quality of Qingkailing production process are effectively improved. Detailed Implementation
[0043] The following non-limiting embodiments are intended to enable those skilled in the art to gain a more comprehensive understanding of the present invention, but do not limit the invention in any way. The following content is merely an exemplary description of the scope of protection claimed by the present invention, and those skilled in the art can make various changes and modifications to the present invention based on the disclosed content, and such changes should also fall within the scope of protection claimed by the present invention.
[0044] The present invention will be further described below by way of specific embodiments. Unless otherwise specified, all chemical reagents used in the embodiments of the present invention were obtained through conventional commercial means. Unless otherwise specified, all contents mentioned below are mass contents. Unless otherwise specified, it is understood that the process was carried out at room temperature.
[0045] Example 1.1
[0046] A method for preparing a Scutellaria baicalensis-Gardenia jasminoides extract.
[0047] Scutellaria baicalensis and Gardenia jasminoides in a mass ratio of 6:3:50 were mixed with water and refluxed for 5 hours. The mixture was then filtered, and the filtrate was collected. The resulting residue was mixed with 7 times its mass of a 0.5% (w / w) aqueous acetic acid solution and refluxed for 5 hours. The mixture was then filtered, and the filtrate was collected. The resulting residue was then mixed with 7 times its mass of a solvent (a mixture of methyl ethyl ketone, methanol, and tetrahydrofuran in a volume ratio of 0.5:1:0.7) and refluxed for 5 hours. The mixture was then filtered, and the filtrate was collected. The three filtrates were combined and dried under reduced pressure using a rotary evaporator to obtain the Scutellaria baicalensis-Gardenia jasminoides extract, denoted as HZ-A01.
[0048] Example 1.2
[0049] Compared to Example 1.1, the mass ratio of Scutellaria baicalensis, Gardenia jasminoides, and water was changed to 8:1:50, while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-A02.
[0050] Example 1.3
[0051] Compared to Example 1.1, the mass ratio of Scutellaria baicalensis, Gardenia jasminoides, and water was changed to 4:5:50, while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-A03.
[0052] Example 1.4
[0053] Compared to Example 1.1, the concentration of the acetic acid aqueous solution was changed to 1% (w / w), while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-A04.
[0054] Example 1.5
[0055] Compared to Example 1.1, the concentration of the acetic acid aqueous solution was changed to 0.1% (w / w), while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-A05.
[0056] Example 1.6
[0057] Compared to Example 1.1, the volume ratio of methyl ethyl ketone, methanol, and tetrahydrofuran was changed to 0.6:1:0.6, while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-A06.
[0058] Example 1.7
[0059] Compared to Example 1.1, the volume ratio of methyl ethyl ketone, methanol, and tetrahydrofuran was changed to 0.4:1:0.8, while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-A07.
[0060] Comparative Example 1.1
[0061] Compared to Example 1.1, the mass ratio of Scutellaria baicalensis, Gardenia jasminoides, and water was changed to 3:6:50, while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-B01.
[0062] Comparative Example 1.2
[0063] Compared to Example 1.1, the mass ratio of Scutellaria baicalensis, Gardenia jasminoides, and water was changed to 8.5:0.5:50, while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-B02.
[0064] Comparative Example 1.3
[0065] Compared to Example 1.1, the volume ratio of methyl ethyl ketone, methanol, and tetrahydrofuran was changed to 1:0.5:0.7, while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-B03.
[0066] Comparative Example 1.4
[0067] Compared to Example 1.1, gardenia was omitted, the mass ratio of scutellaria to water was 9:50, and all other parameters remained the same. The resulting extract was designated HZ-B04.
[0068] Comparative Example 1.5
[0069] Compared to Example 1.1, Scutellaria baicalensis was omitted, the mass ratio of Gardenia jasminoides to water was 9:50, and all other parameters remained the same. The resulting extract was designated HZ-B05.
[0070] Comparative Example 1.6
[0071] Compared to Example 1.1, the concentration of the acetic acid aqueous solution was changed to 2.5% (w / w), while all other parameters remained the same. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-B06.
[0072] Comparative Example 1.7
[0073] Scutellaria baicalensis and Gardenia jasminoides in a mass ratio of 6:3:50 were mixed with water and refluxed for 5 hours. The mixture was filtered, and the filtrate was collected. The residue was mixed with the same amount of water used in the first extraction and refluxed for 5 hours. The mixture was filtered, and the filtrate was collected. The residue was mixed with the same amount of water used in the first extraction and refluxed again for 5 hours. The mixture was filtered, and the filtrate was collected. All filtrates were combined and dried under reduced pressure using a rotary evaporator. The resulting Scutellaria baicalensis-Gardenia jasminoides extract was designated HZ-B07.
[0074] Example 1
[0075] Evaluation of the anti-inflammatory effects of Scutellaria baicalensis-Gardenia jasminoides extract at the cellular level.
[0076] The anti-inflammatory effects of the Scutellaria baicalensis-Gardenia jasminoides extracts obtained in Examples 1.1-1.7 and Comparative Examples 1.1-1.6 were evaluated. The specific evaluation methods are as follows:
[0077] 1. Cell Culture
[0078] Mouse monocyte / macrophage RAW264.7 cells were cultured in high-glucose DMEM medium containing 10% fetal bovine serum, with the addition of 100 mg / L penicillin and 100 mL / L streptomycin. The cells were incubated at 37°C with 5% carbon dioxide. The cells were passaged every other day.
[0079] 2. Determination of drug dosage in cell experiments
[0080] Take RAW264.7 cells in good growth condition and divide them into groups of 5 × 10⁶ cells per well. 3Cells were seeded in 96-well plates and incubated for 24 h. Afterward, the cells were treated with gradient concentrations of HZ-A01, with six replicates for each concentration. After co-culturing for 24 h and 48 h, the culture medium was discarded, and 20 μL of MTT (0.5 g / L) solution was added to each well. The plates were then incubated at 37°C for another 4 h. The MTT solution was carefully discarded, and 150 μL of DMSO was added. The plates were shaken for 5 min, and the absorbance was measured at 490 nm using a microplate reader.
[0081] The experimental results are shown in the table below (unit: %, mean ± standard deviation, n=6, # indicates p < 0.05 compared to the control group, ## indicates p < 0.01 compared to the control group):
[0082]
[0083] Based on the experimental results in the table above, the concentrations of Scutellaria baicalensis-Gardenia jasminoides extract were selected as 160 ppm, 320 ppm, and 640 ppm for the experiment.
[0084] 3. Effect of Scutellaria baicalensis-Gardenia jasminoides extract on NO release from lipopolysaccharide-induced RAW264.7 macrophages.
[0085] Nitric oxide (NO) is an important signaling molecule regulating macrophage inflammatory processes and has the effect of promoting the development of inflammatory responses. Measuring the amount of NO released by macrophages after stimulation with lipopolysaccharide (LPS) can reflect the degree of inflammation to some extent; furthermore, the addition of anti-inflammatory substances reduces NO release, demonstrating that the degree of inflammation is reduced to a certain extent.
[0086] Count the RAW264.7 cells and adjust the cell concentration to 2 × 10⁻⁶. 5 Cells were seeded at a density of 2 mL / well in 6-well plates. After cell attachment, LPS (Sigma, catalog number L2880, 0.5 μg / L per well) was administered, followed by different concentrations of Scutellaria baicalensis-Gardenia jasminoides extract (0, 160 ppm, 320 ppm, 640 ppm) or dexamethasone (positive control, 1 μmol / L). After incubation at 37°C and 5% CO2 for 24 h, 50 μL of cell supernatant was collected from each group and added to 50 μL per well in 96-well plates.
[0087] The grouping is as follows:
[0088] Blank control group: No LPS, Scutellaria baicalensis-Gardenia jasminoides extract, or dexamethasone were added.
[0089] Negative control group: with added LPS, without added Scutellaria baicalensis-Gardenia jasminoides extract and dexamethasone.
[0090] Positive control group: with added LPS and dexamethasone, without added Scutellaria baicalensis-gardenia extract.
[0091] Low-dose extract (HZ): with added LPS and 160 ppm of Scutellaria baicalensis-Gardenia jasminoides extract, without added dexamethasone.
[0092] Scutellaria baicalensis-Gardenia jasminoides extract (HZ) medium dose group: with added LPS and 320 ppm of Scutellaria baicalensis-Gardenia jasminoides extract, without added dexamethasone.
[0093] Scutellaria baicalensis-Gardenia jasminoides extract (HZ) high-dose group: with added LPS and 640 ppm of Scutellaria baicalensis-Gardenia jasminoides extract, without added dexamethasone.
[0094] NO concentration was detected using a NO detection kit (Beyotime, S0021S) (detection process omitted).
[0095] The test results are shown in the table below (n=6, mean ± standard deviation, unit μmol / L, "-" indicates no data, # indicates a significant difference compared with the negative control group and p<0.05, ## indicates a significant difference compared with the negative control group and p<0.01):
[0096]
[0097] It is evident that the average NO concentration of the Scutellaria baicalensis-Gardenia jasminoides extracts provided in Examples 1.1-1.7 was generally lower than that of the corresponding extracts provided in Comparative Examples 1.1-1.7, indicating that the technical effects provided in Examples 1.1-1.7 were better.
[0098] Example 2.1
[0099] Preparation method of mother-of-pearl extract.
[0100] Mother-of-pearl was mixed with 10 times its weight of a 6% (w / w) aqueous solution of pyruvic acid, heated to 65°C, and heated for 5 hours. The mixture was evaporated to dryness under reduced pressure, reconstituted with sufficient water, filtered, and the supernatant was freeze-dried to obtain the mother-of-pearl extract, designated ZM-A01.
[0101] Example 2.2
[0102] Preparation method of mother-of-pearl extract.
[0103] Mother-of-pearl was mixed with 12 times its weight of a 4% (w / w) aqueous solution of pyruvic acid, heated to 70°C, and heated for 6 hours. The mixture was evaporated to dryness under reduced pressure, reconstituted with sufficient water, filtered, and the supernatant was freeze-dried to obtain the mother-of-pearl extract, denoted as ZM-A02.
[0104] Example 2.3
[0105] Preparation method of mother-of-pearl extract.
[0106] Mother-of-pearl was mixed with 8 times its mass of 8% (w / w) pyruvic acid aqueous solution, heated to 60°C, and heated for 4 hours. The mixture was evaporated to dryness under reduced pressure, reconstituted with sufficient water, filtered, and the supernatant was freeze-dried to obtain the mother-of-pearl extract, designated ZM-A03.
[0107] Comparative Example 2
[0108] Preparation method of mother-of-pearl extract.
[0109] Mother-of-pearl was mixed with 8 times its weight of a 6% acetic acid aqueous solution and heated to 65°C for 5 hours. The mixture was then evaporated to dryness under reduced pressure, reconstituted with sufficient water, filtered, and the supernatant was freeze-dried to obtain the mother-of-pearl extract, denoted as ZM-B01.
[0110] Example 2
[0111] Determination of protein content in mother-of-pearl extract.
[0112] Studies show that mother-of-pearl contains not only abundant calcium carbonate, but also amino acids, polypeptides, and proteins, which are among the active ingredients of mother-of-pearl. The protein content in mother-of-pearl extract can, to some extent, reflect the quality of the extract.
[0113] The protein content in ZM-A01, ZM-A02, ZM-A03, and ZM-B01 was detected using the BCA protein concentration kit (Beyotime, P0012). The results are shown in the table below:
[0114]
[0115] It can be seen that, compared with Comparative Example 2, the mother-of-pearl extract obtained by the extraction method of Examples 2.1-2.3 has a higher protein content.
[0116] Example 3
[0117] A method for preparing buffalo horn extract
[0118] Buffalo horn was mixed with three times its mass of an ethanol-acetic acid-water solution and steamed for 9 hours. The ethanol concentration in the ethanol-acetic acid-water solution was 15% (w / w), and the acetic acid concentration was 4% (w / w). The mixture was then distilled under reduced pressure until no ethanol or acetic acid odor remained. The extract was freeze-dried and pulverized to obtain the buffalo horn extract, designated NJ-A01.
[0119] As an alternative method, buffalo horn was mixed with three times its mass of an ethanol-acetic acid-water solution and steamed for 10 hours. The ethanol-acetic acid-water solution contained 20% (w / w) ethanol and 3% (w / w) acetic acid. The mixture was then distilled under reduced pressure until no ethanol or acetic acid odor remained, freeze-dried, and pulverized to obtain the buffalo horn extract, designated NJ-A02.
[0120] As an alternative method, buffalo horn was mixed with three times its mass of an ethanol-acetic acid-water solution and steamed for 8 hours. The ethanol-acetic acid-water solution contained 10% (w / w) ethanol and 5% (w / w) acetic acid. The mixture was then distilled under reduced pressure until no ethanol or acetic acid odor remained, freeze-dried, and pulverized to obtain the buffalo horn extract. This extract was designated NJ-A03.
[0121] Steaming with an ethanol-acetic acid aqueous solution fully opens the internal structure of the buffalo horn keratin. Vacuum distillation effectively removes ethanol and acetic acid, maximizing the extraction of flavonoids, polypeptides, and other components from the buffalo horn. Freeze-drying further preserves the active ingredients to the maximum extent. The resulting buffalo horn extract achieves a powder yield (mass of powder passed through a 20-mesh sieve ÷ total mass of material before sieving) of 95%-97%, resulting in a finer extract. Furthermore, there is no significant difference in effectiveness among the three preparation methods described above.
[0122] Comparative Example 3
[0123] A method for preparing buffalo horn extract
[0124] Buffalo horn was mixed with three times its mass of an ethanol-acetic acid-water solution and steamed for 9 hours. The ethanol concentration in the ethanol-acetic acid-water solution was 4% (w / w), and the acetic acid concentration was 15% (w / w). The mixture was then distilled under reduced pressure until no ethanol or acetic acid odor remained. The extract was freeze-dried and pulverized to obtain the buffalo horn extract, designated NJ-B01.
[0125] The buffalo horn extract obtained in Comparative Example 3 had a powder yield of only 86% after passing through a 20-mesh sieve. The extract contained large particles that were difficult to crush, and its utilization rate was lower than that of Example 3.
[0126] Example 4.1
[0127] A Qingkailing composition, formulated in the following proportions by weight:
[0128] 30 parts of cholic acid, 30 parts of deoxycholic acid from pigs, 15 parts of Scutellaria baicalensis-gardenia extract, 8 parts of mother-of-pearl extract, 8 parts of buffalo horn extract, 14 parts of Isatis indigotica root, 14 parts of honeysuckle, 9 parts of dextrin, 3 parts of magnesium stearate, and 3 parts of corn starch.
[0129] Among them, the Scutellaria baicalensis-Gardenia jasminoides extract is HZ-A01 provided in Example 1.1; the mother-of-pearl extract is ZM-A01 provided in Example 2.1; and the buffalo horn extract is NJ-A01 provided in Example 3.
[0130] Example 4.2
[0131] A Qingkailing composition, formulated in the following proportions by weight:
[0132] 10 parts of cholic acid, 50 parts of porcine deoxycholic acid, 10 parts of Scutellaria baicalensis-Gardenia jasminoides extract, 10 parts of pearl extract, 10 parts of buffalo horn extract, 12 parts of Isatis indigotica root, 16 parts of honeysuckle, 11 parts of dextrin, 2 parts of magnesium stearate, and 2 parts of corn starch.
[0133] Among them, the Scutellaria baicalensis-Gardenia jasminoides extract is HZ-A01 provided in Example 1.1; the mother-of-pearl extract is ZM-A01 provided in Example 2.1; and the buffalo horn extract is NJ-A01 provided in Example 3.
[0134] Example 4.3
[0135] A Qingkailing composition, formulated in the following proportions by weight:
[0136] 50 parts of cholic acid, 10 parts of porcine deoxycholic acid, 20 parts of Scutellaria baicalensis-Gardenia jasminoides extract, 6 parts of pearl extract, 6 parts of buffalo horn extract, 16 parts of Isatis indigotica root, 12 parts of honeysuckle, 7 parts of dextrin, 4 parts of magnesium stearate, and 4 parts of corn starch.
[0137] Among them, the Scutellaria baicalensis-Gardenia jasminoides extract is HZ-A01 provided in Example 1.1; the mother-of-pearl extract is ZM-A01 provided in Example 2.1; and the buffalo horn extract is NJ-A01 provided in Example 3.
[0138] Example 4.4
[0139] Compared with Example 4.1, the Scutellaria baicalensis-Gardenia jasminoides extract was replaced with HZ-A02 provided in Example 1.2; the mother-of-pearl extract was replaced with ZM-A03 provided in Example 2.3; and the buffalo horn extract was replaced with NJ-A02 provided in Example 3. All other parts were the same.
[0140] Example 4.5
[0141] Compared with Example 4.1, the Scutellaria baicalensis-Gardenia jasminoides extract was replaced with HZ-A05 provided in Example 1.2; the mother-of-pearl extract was replaced with ZM-A02 provided in Example 2.3; and the buffalo horn extract was replaced with NJ-A03 provided in Example 3. All other parts were the same.
[0142] Comparative Example 4.1
[0143] Compared with Example 4.1, the buffalo horn extract was replaced with NJ-B01 provided in Comparative Example 3, and all other aspects were the same.
[0144] Comparative Example 4.2
[0145] Compared with Example 4.1, the dextrin was changed to 5 parts, the magnesium stearate was changed to 5 parts, and the starch was changed to 5 parts, while the rest remained the same.
[0146] Comparative Example 4.3
[0147] Compared with Example 4.1, the use of dextrin is omitted, magnesium stearate is replaced with 5 parts, and starch is replaced with 10 parts, while the rest are the same.
[0148] Comparative Example 4.4
[0149] Compared to Example 4.1, the starch was replaced with an equal amount of povidone K30, and everything else remained the same.
[0150] Example 5
[0151] Preparation of Qingkailing tablets.
[0152] Qingkailing tablets were prepared using the Qingkailing compositions of Examples 4.1-4.5 and Comparative Examples 4.1-4.4, and the specific methods are as follows:
[0153] T1. Mix the prescribed amount of Isatis root and honeysuckle with 10 times the weight of water, decoct, repeat 3 times, combine the filtrates, dry, and obtain the extract powder.
[0154] T2. Mix the extract powder obtained in step T1 with the prescribed amounts of cholic acid, deoxycholic acid, Scutellaria baicalensis-gardenia extract, mother-of-pearl extract, buffalo horn extract, dextrin, and corn starch, granulate, sizing, add the prescribed amount of magnesium stearate, and compress into tablets (compression pressure 10.0 kN) to obtain Qingkailing tablets.
[0155] The tablet weight of Qingkailing tablets obtained by this method can be 0.1g, 0.2g, 0.3g, 0.4g, 0.5g, 0.6g, 0.7g, 0.8g, 0.9g, or 1.0g, which can be selected as needed. Specifically, 0.4g was selected as the tablet weight, and Qingkailing tablets were prepared using the Qingkailing compositions of Examples 4.1-4.5 and Comparative Examples 4.1-4.4. Random samples were taken to test the tablet weight uniformity of the Qingkailing tablets.
[0156] The method for detecting baicalin content in Qingkailing tablets was based on the article "Preparation of Baicalin Standard and Study on its Solid Phase Extraction-HPLC Determination" (Yunnan Chemical Industry, January 19, 2006). The baicalin content in 20 tablets of Qingkailing tablets from different examples and comparative examples was determined, and the relative standard deviation (%) was calculated.
[0157] Method for testing tablet weight uniformity:
[0158] 1. Take an empty weighing bottle and weigh it accurately; then take 20 tablets of the test sample, place them in the weighing bottle, and weigh them accurately. The difference between the two weighing values is the total weight of the 20 tablets of the test sample. Divide the weight by 20 to get the average tablet weight.
[0159] 2. From the 20 test samples whose total weight has been determined, take out one sample at a time with tweezers and weigh each sample precisely to obtain the weight of each sample.
[0160] 3. Recording and Calculation
[0161] (1) Record the weighing data for each weighing.
[0162] (2) Calculate the average slice weight and retain three significant figures. Round to two significant figures and select the weight variation limit.
[0163] (3) The weight difference limit is ±7.5% for average weight below 0.30g and ±5% for average weight ≥0.30g.
[0164] 4. Results and Judgments
[0165] (1) The weight of each tablet does not exceed the allowable weight difference limit; or the weight of each tablet does not exceed the weight difference limit in the table above when compared with the average tablet weight; or the number of tablets exceeding the weight difference limit is no more than 2, and none of them exceed the limit by 1 time; all are deemed to be in compliance with the regulations.
[0166] (2) If more than 2 tablets exceed the weight difference limit compared to the average tablet weight, or if no more than 2 tablets exceed the weight difference limit but one of them exceeds the limit by 100%, they are deemed to be non-compliant.
[0167] The results of the determination of baicalin content uniformity and tablet weight uniformity are shown in the table below.
[0168]
[0169] As can be seen, the Qingkailing tablets provided in Examples 4.1-4.5 have a significantly lower standard deviation of baicalin and the tablet weight uniformity is qualified.
[0170] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.
Claims
1. A Qingkailing composition, characterized in that, It consists of the following components by weight: Cholic acid 10-50 parts, porcine deoxycholic acid 10-50 parts, Scutellaria baicalensis-gardenia extract 10-20 parts, mother-of-pearl extract 6-10 parts, buffalo horn extract 6-10 parts, Isatis indigotica root 12-16 parts, honeysuckle 12-16 parts, dextrin 7-11 parts, magnesium stearate 2-4 parts, and corn starch 2-4 parts; The preparation method of the Scutellaria baicalensis-Gardenia jasminoides extract includes the following steps: S101. Mix Scutellaria baicalensis and Gardenia jasminoides in a mass ratio of 4-8:1-5:50 with water, reflux to extract, filter, and obtain residue 1 and filtrate 1. S102. Mix the residue 1 obtained in step S101 with an aqueous solution of acetic acid with a mass fraction of 0.1%-1%, reflux for extraction, filter, and obtain residue 2 and filtrate 2. S103. Mix the residue 2 obtained in step S102 with solvent A, reflux for extraction, filter, and obtain filtrate 3. In step S103, solvent A is a mixture obtained by mixing methyl ethyl ketone, methanol, and tetrahydrofuran in a volume ratio of 0.4-0.6:1:0.6-0.
8. S104. Mix the filtrate 1 obtained in step S101, the filtrate 2 obtained in step S102 and the filtrate 3 obtained in step S103, and dry them to obtain Scutellaria baicalensis-gardenia extract. The preparation method of the mother-of-pearl extract includes the following steps: S201. Mix mother-of-pearl with 8-12 times the mass of pyruvic acid aqueous solution, heat to react, filter and discard the filter residue, adjust the pH to 6-7 with calcium carbonate, centrifuge to collect the supernatant, dry to obtain mother-of-pearl extract. The preparation method of the buffalo horn extract includes the following steps: S301. Mix buffalo horn with 2-4 times its mass of an ethanol-acetic acid-water solution, steam, distill under reduced pressure until there is no ethanol or acetic acid odor, and dry to obtain buffalo horn extract. In the ethanol-acetic acid-water solution, the mass concentration of ethanol is 10%-20% and the mass concentration of acetic acid is 3%-5%.
2. The Qingkailing composition according to claim 1, characterized in that, In step S101, the reflux extraction time is 4-6 hours; In step S102, the mass of the acetic acid aqueous solution is 6-8 times the mass of the residue 1, and the reflux extraction time is 4-6 hours. In step S103, the mass of solvent A is 6-8 times the mass of the residue 2; the reflux extraction time is 4-6 hours. In step S104, the drying process specifically involves reduced pressure drying.
3. The Qingkailing composition according to claim 1, characterized in that, S201. Mix mother-of-pearl with 8-12 times its weight of pyruvic acid aqueous solution, heat to react, evaporate to dryness under reduced pressure, redissolve in water, filter to obtain supernatant, and dry to obtain mother-of-pearl extract.
4. The Qingkailing composition according to claim 1, characterized in that, In step S301, the steaming time is 8-10 hours, and the drying is freeze drying.
5. The Qingkailing composition according to claim 1, characterized in that, The Qingkailing composition comprises the following components in parts by weight: 30 parts of cholic acid, 30 parts of deoxycholic acid from pigs, 15 parts of Scutellaria baicalensis-gardenia extract, 8 parts of mother-of-pearl extract, 8 parts of buffalo horn extract, 14 parts of Isatis indigotica root, 14 parts of honeysuckle, 9 parts of dextrin, 3 parts of magnesium stearate, and 3 parts of corn starch.
6. A Qingkailing tablet, characterized in that, It is made from the Qingkailing composition and excipients as described in any one of claims 1-5.
7. The method for preparing Qingkailing tablets according to claim 6, characterized in that, Includes the following steps: T1. Mix the prescribed amount of Isatis root and honeysuckle with 8-12 times the weight of water, decoct, repeat 2-3 times, combine the filtrates, dry, and obtain the extract powder. T2. Mix the extract powder obtained in step T1 with the prescribed amounts of cholic acid, deoxycholic acid, scutellaria-gardenia extract, mother-of-pearl extract, buffalo horn extract, dextrin, and corn starch, granulate, sizing, add the prescribed amount of magnesium stearate, and compress into tablets to obtain Qingkailing tablets.
8. The use of the Qingkailing composition according to any one of claims 1-5, the Qingkailing tablet according to claim 6, or the preparation method according to claim 7 in the preparation of Qingkailing medicine.