Refined honeysuckle and fructus forsythiae detoxification tablet and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and particularly relates to a refined honeysuckle and fructus forsythiae detoxification tablet and a preparation method thereof. The preparation method comprises the following steps: taking a mixture of fructus forsythiae, fermented soybean, liquorice, lophatherum gracile, honeysuckle and fructus arctii, adding 4-8 times amount of water, decocting for 2-4 times to obtain filtrate, and concentrating to obtain extract with the relative density of 1.28-1.33 at 60-70 DEG C; and mixing the extract with an adhesive, mixing the obtained extract adhesive, platycodon grandiflorum powder, paracetamol, a volatile oil solution and the like, drying, granulating, tabletting, and coating with a film, thereby obtaining the platycodon grandiflorum paracetamol tablet. Wherein the volatile oil solution is an ethanol water solution of menthol and schizonepeta spike volatile oil; the adhesive comprises corn starch, low-substituted hydroxypropyl cellulose and carboxymethyl starch sodium in a mass ratio of 1: (1.5-1.8): (3.2-3.5). The method can effectively control the extract yield, realizes high-efficiency granulation without caking, expands audiences by adopting film coating, and is suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of traditional Chinese medicine preparation, and particularly relates to a refined Yinqie Jiedu tablet and a preparation method thereof. BACKGROUND

[0002] The refined Yinqie Jiedu tablet is a commonly used traditional Chinese medicine, and has the functions and indications of clearing heat and removing wind, relieving exterior and reducing fever, and is used for treating influenza, cold and fever, four limbs being lazy and sore, headache and cough, sore throat, warm toxin and facial swelling. The refined Yinqie Jiedu tablet is recorded in the Department of Prescription Traditional Chinese Medicine Formulas (the third volume), and is prepared from paracetamol (72 g), platycodon grandiflorum (120 g), forsythia suspensa (200 g), soybean milk (100 g), licorice (100 g), lophatherum gracile (80 g), honeysuckle (200 g), burdock fruit (120 g), schizonepeta tenuifolia (80 g) and menthol (0.6 g) as raw materials by the following method: the above ten kinds of materials are crushed into fine powder, the schizonepeta tenuifolia is extracted to obtain volatile oil, the schizonepeta tenuifolia oil and menthol are dissolved in ethanol, and the rest forsythia and other six kinds of materials are decocted twice with water, filtered, combined, concentrated into a paste, and then mixed with platycodon grandiflorum powder, paracetamol powder and a proper amount of excipients, granulated, dried, cooled, and then mixed with the schizonepeta tenuifolia oil and menthol ethanol solution, and finally, the granules are pressed into tablets and coated with sugar to obtain the refined Yinqie Jiedu tablet.

[0003] Patents CN101491650A and CN103845635A disclose the preparation method of the refined Yinqie Jiedu tablet, which is basically the same as the method in the Department of Prescription Traditional Chinese Medicine Formulas (the third volume). The extraction method of volatile oil is improved, which is to soak the schizonepeta tenuifolia in water, discard the water, directly heat with steam, collect the aromatic water, extract until the flavor is exhausted, and then obtain the schizonepeta oil after refining the aromatic water.

[0004] However, the above standards or patents only give a brief preparation process without specific method parameters, which may cause the following problems and is not conducive to industrial production: firstly, the extraction of the extract is overyielded or the yield is too low. The overyielded extract will result in high content of impurities and low content of effective components, which will affect the content of effective components in the unit preparation and ultimately affect the curative effect of the product. These impurities often contain excessive sticky substances, which are easy to stick together during the granulation process. From the industrial cost point of view, it will increase the production energy consumption and is not conducive to the control of production cost. The low yield will also reduce the content of effective components and the insufficient stickiness may cause the granules to be loose, affecting the subsequent granulation and whole granulation process. Secondly, the excipients used in the granulation process are not suitable, and the granules prepared are easy to cake during storage, affecting the quality stability of the product and the drug efficacy. Thirdly, the current sugar coating process is complex and difficult to operate, has low production efficiency, small production capacity, high cost, high energy consumption, and the patient audience of sugar-coated tablets is small, which cannot meet the needs of diabetic patients.

[0005] Therefore, how to optimize the extraction steps and parameters of refined Yin Qiu Jie Du tablets, adjust the proportion of adjuvants, and change the sugar coating into film coating, so as to provide a preparation method of refined Yin Qiu Jie Du tablets which can improve product quality and stability and thus improve efficacy, while also reducing production energy consumption and production cost, and is suitable for industrial production, has important significance. SUMMARY

[0006] The following is a summary of the subject matter described in detail herein.

[0007] The present application aims to provide a refined Yin Qiu Jie Du tablet and a preparation method thereof. In line with the principles of adapting to industrial mass production, controlling production cost, and improving product quality and effectiveness, the present application provides a preparation method of refined Yin Qiu Jie Du film-coated tablets which can efficiently extract volatile oil, effectively control the yield content of extract, optimize the proportion of adjuvants to achieve efficient granulation without caking, and is more widely applicable to a wider audience, and is suitable for industrial production.

[0008] To achieve the above-mentioned purpose, the present application adopts the following technical solutions: In one aspect, the present application provides a preparation method of refined Yin Qiu Jie Du tablets, comprising the following steps: S1, taking a mixture of forsythia, sophorae, glycyrrhiza, lophatheri, honeysuckle and arctii, adding 4-8 times the amount of water, and decocting 2-4 times to obtain a filtrate, and concentrating to an extract with a relative density of 1.28-1.33 at 60-70℃ (65℃) ; S2, mixing the extract with a binder to obtain an extract binder; S3, mixing the extract binder, platycodon powder, paracetamol and the first adjuvant, drying, granulating, mixing the obtained dry granules with a volatile oil solution and the second adjuvant, tabletting, and coating with a film, to obtain the refined Yin Qiu Jie Du tablets; The volatile oil solution is an ethanol aqueous solution of menthol and volatile oil extracted from the bracts of schizonepeta. The binder comprises corn starch, low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch in a mass ratio of 1:1.5-1.8:3.2-3.5.

[0009] The present application emphasizes controlling the relative density of the extract within a certain range, because below or above this range will affect the extract yield, subsequent granulation process and the quality stability of the obtained granules.

[0010] The adhesive plays an important role in the shaping and stabilization of the tablet, and the optimization of the type or amount of adhesive can improve the physical properties of the tablet to a certain extent. Corn starch has good adhesive effect, and the formed granules have certain plasticity and hardness, which ensures the basic shaping and integrity of the granules after drying; low-substituted hydroxypropyl cellulose has a large surface area and porosity, and in the granulation process, low-substituted hydroxypropyl cellulose is intertwined with each other in the soft material to form a "micro network" structure, which significantly improves the adhesive strength of the wet granules, so that the wet granules are not easy to deform, stick or break during granulation (such as sieving), and more complete and uniform granules can be obtained. Sodium carboxymethyl starch has water absorption and swelling effect, which can adjust the dryness and humidity of the soft material; the three of them play a synergistic role in the preparation, and together enhance the adhesive strength, flowability and compressibility of the granules, so that the finally prepared granules are not easy to break and have appropriate bulk density.

[0011] According to some embodiments of the present application, the particle size of the platycodon grandiflorum powder is over 100 mesh.

[0012] According to some embodiments of the present application, the volatile oil solution is prepared by the following steps: taking a catmint spike and 1-4 (for example, 1-3, 1-2) times the amount of water, steam distilling for 1-2 hours to extract volatile oil; mixing the volatile oil, menthol and 90%-99% (v / v) ethanol aqueous solution, and obtaining the volatile oil solution.

[0013] Preferably, the concentration of the ethanol aqueous solution is about 95% (v / v).

[0014] According to some embodiments of the present application, in step S1, the concentration is carried out in a double-effect concentrator, the primary vacuum degree of the double-effect concentrator is controlled to be -0.04 to -0.06 Mpa, and the evaporation temperature is 78-85℃; the secondary vacuum degree of the double-effect concentrator is controlled to be -0.06 to -0.08 Mpa, and the evaporation temperature is 58-65℃.

[0015] According to some embodiments of the present application, the relative density of the extract at 60-70℃ is 1.3-1.33.

[0016] According to some embodiments of the present application, the extract has a extract rate of 25.0%-37.3%, for example, 28.0%-37.3%, 30.0%-37.3%, 32.0%-37.3%, 35.0%-37.0%.

[0017] According to some embodiments of the present application, in step S1, the mixture of forsythia suspensa, radix sophorae tonkinensis, radix glycyrrhizae, lophatheri herba, honeysuckle and radix arctii is subjected to first decocting with 6-8 times the amount of water to obtain a first filtrate and a residue; and the residue is subjected to second decocting with 4-6 times the amount of water to obtain a second filtrate; and the first filtrate and the second filtrate are combined and concentrated to a relative density of 1.28-1.33 at 60-70℃.

[0018] Preferably, the first decocting time is 0.5-2 h, for example, 0.5-1 h, 1-2 h; and / or, the second decocting time is 0.5-2 h, for example, 0.5-1 h, 1-2 h.

[0019] According to some embodiments of the present application, the mass ratio of the corn starch, low-substitution hydroxypropyl cellulose and sodium carboxymethyl starch is 1:1.5-1.8:3.2-3.5, for example, 1:1.5-1.8:3.2-3.4, 1:1.6:3.3.

[0020] According to some embodiments of the present application, the mass ratio of the extract and the binder is 40-55:1.

[0021] According to some embodiments of the present application, step S2 comprises: mixing the extract with a binder and water, heating, dissolving the extract and the binder, and passing the mixture (temperature maintained at 50-60℃) through a 60-mesh sieve to obtain the extract binder.

[0022] According to some embodiments of the present application, the first auxiliary material comprises dextrin; and / or, the second auxiliary material comprises at least one of magnesium stearate and silicon dioxide.

[0023] Dextrin is used as a diluent. In addition, when the amount of extract is large, it is easy to absorb moisture and cause caking. Magnesium stearate is used as a lubricant, and silicon dioxide is used as a flow enhancer in tablets, which can improve the flowability of the granules, increase the bulk density, increase the hardness of the prepared tablets, shorten the disintegration time, thereby improving the drug dissolution rate, and at the same time, improving the moisture absorption characteristics of the extract of traditional Chinese medicine.

[0024] The drying method in step S3 is not particularly limited in the present application, for example, spray drying can be used, and the temperature of the spray drying is 40-70℃.

[0025] According to some embodiments of the present application, in step S3, after drying, the granules are passed through an 18-mesh sieve before the granulating step.

[0026] According to some embodiments of the present application, in step S3, the coating material is a gastric-soluble film coating premix.

[0027] According to some embodiments of the present application, the refined Yinqiao Jiedu tablet comprises the following raw materials by mass: paracetamol 50-70 parts, Platycodon grandiflorum 200-300 parts, Forsythia suspensa 250-400 parts, Radix Sophorae Tonkinensis 100-200 parts, Radix Glycyrrhizae 100-200 parts, Lophatheri Herba 100-150 parts, Lonicera japonica 250-400 parts, Fructus Arctii 165-240 parts, Schizonepeta 100-150 parts, and menthol 0.4-0.7 parts.

[0028] According to some preferred embodiments of the present application, the refined Yinqiao Jiedu tablet comprises the following raw materials by mass: paracetamol 50-70 parts, Platycodon grandiflorum 200-250 parts, Forsythia suspensa 250-350 parts, Radix Sophorae Tonkinensis 100-200 parts, Radix Glycyrrhizae 100-200 parts, Lophatheri Herba 100-150 parts, Lonicera japonica 250-350 parts, Fructus Arctii 165-215 parts, Schizonepeta 100-150 parts, and menthol 0.4-0.7 parts.

[0029] According to some more preferred embodiments of the present application, the refined Yinqiao Jiedu tablet comprises the following raw materials by mass: paracetamol 55 parts, Platycodon grandiflorum 217 parts, Forsythia suspensa 305.6 parts, Radix Sophorae Tonkinensis 152.8 parts, Radix Glycyrrhizae 152.8 parts, Lophatheri Herba 122.2 parts, Lonicera japonica 305.6 parts, Fructus Arctii 183.4 parts, Schizonepeta 122.2 parts, and menthol 0.4585 parts.

[0030] According to some preferred embodiments of the present application, the refined Yinqiao Jiedu tablet further comprises 40-100 parts (e.g. 40-60 parts, 45-55 parts, about 55 parts) of the first auxiliary material.

[0031] According to some preferred embodiments of the present application, the refined Yinqiao Jiedu tablet further comprises 8-20 parts (e.g. 10-20 parts, 10-15 parts, about 13 parts) of the second auxiliary material; more preferably, the second auxiliary material comprises magnesium stearate and silicon dioxide in a mass ratio of 1-3 : 1 (e.g. 1-2.5 : 1, 1-2 : 1, 1.5-2 : 1).

[0032] If the amount of magnesium stearate is too large, the tablet will disintegrate or dissolve slowly. If the amount of silicon dioxide is too low, it cannot effectively improve the flowability; if the amount of silicon dioxide is too high, it will damage the adhesion strength of the granules, reduce the compressibility of the fine powder, and cause the compressed tablet to be fragile and easy to crack.

[0033] In another aspect of the present application, there is provided a refined Yinqiao Jiedu tablet prepared by the above method.

[0034] Compared with the prior art, some embodiments of the present application have at least the following beneficial effects: This invention effectively controls the extract yield by adjusting the amount of water added and the density of the extract in the water extraction process; it achieves one-step granulation by screening the proportion of binder; and it obtains refined Yinqiao Jiedu tablets with volatile oil extraction rate and particle yield that meet the quality standard requirements, thus achieving energy saving and cost reduction and meeting the requirements of large-scale industrial production.

[0035] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Detailed Implementation

[0036] The following will describe the concept and technical effects of the present invention clearly and completely with reference to embodiments, so as to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are all within the scope of protection of the present invention.

[0037] Unless otherwise specified, in this invention, "about" means that the allowable error is within ±5%, and further, within ±2%.

[0038] The raw materials of traditional Chinese medicine used to prepare refined Yinqiao Jiedu tablets in the following embodiments and comparative examples of the present invention include: 110 parts of acetaminophen, 434 parts of Platycodon grandiflorus, 611.2 parts of Forsythia suspensa, 305.6 parts of fermented soybean, 305.6 parts of licorice, 244.4 parts of Lophatherum gracile, 611.2 parts of Lonicera japonica, 366.8 parts of Arctium lappa, 244.4 parts of Schizonepeta tenuifolia, and 0.917 parts of menthol.

[0039] Unless otherwise specified in the examples, the procedures should be performed under standard conditions or conditions recommended by the manufacturer. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0040] In the following embodiments and comparative examples of this invention, the calculation formulas for oil yield, extract yield, and yield are as follows: Oil yield (%) = Weight of volatile oil (kg) / Total weight of medicinal slices (kg) × 100%. Extract yield (%) = Total weight of extract (kg) / Total weight of medicinal slices (kg) × 100%. Yield (%) = Actual particle weight (kg) / Theoretical particle weight (kg) × 100%. The internal control standard for oil yield is 0.6%~0.8%; the internal control standard for extract yield is 25.0%~37.3%; and the internal control standard for particle yield is 90%~110%.

[0041] The above three internal control standards are all formulated by the applicant based on the pharmacopoeia, ministry-issued standards and combined with the results of process validation. The applicant found in the production process (taking the following examples and comparative examples as examples) that exceeding or failing to meet the oil collection rate and paste collection rate standards will have an adverse impact on the subsequent granulation and tabletting processes, and lead to poor quality stability of the granules.

[0042] Example 1 It takes about 4 hours to extract the volatile oil from Schizonepeta tenuifolia herbs until the taste is exhausted after soaking. According to the experience of extracting volatile oil from refined Yinqiao Jiedu Tablets, the oil output of Schizonepeta tenuifolia volatile oil mainly concentrates in the first 2 hours, and there is basically no more volatile oil produced after 2 hours. What is extracted is mainly aromatic water, and too much aromatic water will affect the subsequent granule yield. Secondly, discarding the water after soaking the herbs with 10 times the amount of water will also cause the loss of volatile oil components in the herbs. In this example, the influence of shortening the volatile oil extraction time was investigated by first conducting small-scale tests and then performing process validation. Using the same batch of cut herbs, adding 2 times the amount of water, the collected amount of volatile oil in different extraction time periods was statistically analyzed, and combined with the process requirements, the optimal volatile oil extraction time was determined. The investigation results of the volatile oil extraction time are shown in Table 1.

[0043] In addition, the volatile oil obtained by extracting the above batch of herbs was used for the chromatographic identification of Schizonepeta tenuifolia. The thin-layer chromatography method for Schizonepeta tenuifolia is as follows: Take 0.1 g of this product, add 10 mL of methanol, tightly stopper, ultrasonically treat for 15 minutes, filter, and the filtrate is used as the test solution. Take the pulegone reference substance, and make a solution containing 4 mg per 1 mL with petroleum ether (60 - 90 °C) as the reference solution. According to the thin-layer chromatography method (General Principles 0502) test, absorb 4 μL of the test solution and 1 μL of the reference solution, respectively spot them on the same silica gel G thin-layer plate, use petroleum ether (60 - 90 °C) - ethyl acetate (37:3) as the developing agent, develop, take out, dry, spray with 1% vanillin sulfuric acid solution, and heat until the spots are clearly colored. In the test solution chromatogram, at the position corresponding to the reference solution chromatogram, there are spots of the same color. The test results are shown in Table 1.

[0044] Table 1 Investigation results of the oil extraction time of refined Yinqiao Jiedu Tablets

[0045] Based on the results in Table 1, the optimal volatile oil extraction time was determined to be 2 h.

[0046] Example 2 This example provides a preparation method for refined Yinqiao Jiedu Tablets, including the following steps: Herb pulverization: Platycodon grandiflorum is dried at 80 - 90 °C on a belt dryer for about 8 hours, then pulverized by a pulverizer with a 20-mesh sieve, coarsely pulverized and then passed through a 100-mesh sieve, and sterilized for standby.

[0047] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0048] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 8 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 6 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.30 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 36.38%.

[0049] Preparation of extract binder: According to the mass ratio of extract to excipients = 55:1, add the extract to the excipients (corn starch, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch (excipient ratio of 1:1.6:3.3)), boil with an appropriate amount of purified water, stir to dissolve and pass through a 60-mesh sieve (keeping the temperature at 50~60℃) to prepare the extract binder for later use.

[0050] Drying and granulation: The extract binder, fine powder of Platycodon grandiflorus, paracetamol, and 50 parts of dextrin were added to a fluidized bed granulator for premixing and spray drying (40℃~70℃). After drying, the granules were sieved through an 18-mesh sieve, with a granule yield of 99.5%. After cooling, an ethanol solution of menthol and catnip oil was sprayed into the granules. 8 parts of magnesium stearate and 5 parts of silica were added and placed in a cone mixer for total mixing and tableting to obtain unprocessed tablets.

[0051] Coating: Take the uncoated tablets and spray a layer of brown film coating premix (gastric-soluble type) directly.

[0052] Example 3 This embodiment provides a method for preparing refined Yinqiao Jiedu tablets, including the following steps: Herbal powdering: Platycodon grandiflorus is dried in a belt dryer at 80-90℃ for about 8 hours, then pulverized in a pulverizer with a 20-mesh sieve. After coarse pulverization, it is passed through a 100-mesh sieve and sterilized for later use.

[0053] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0054] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 6 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 4 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.28 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 35.78%.

[0055] Preparation of extract binder: According to the mass ratio of extract to excipients = 40:1, add the extract to the excipients (corn starch, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch (excipient ratio of 1:1.5:3.4)), boil with an appropriate amount of purified water, stir to dissolve and pass through a 60-mesh sieve (keeping the temperature at 50~60℃) to prepare the extract binder for later use.

[0056] Drying and granulation: The extract binder, platycodon powder, acetaminophen, and 50 parts dextrin were added to a fluidized bed granulator for premixing and spray drying (40℃~70℃). After drying, the granules were sieved through an 18-mesh sieve, with a granule yield of 94.5%. After cooling, an ethanol solution of menthol and catnip oil was sprayed into the granules. 8 parts magnesium stearate and 5 parts silica were added and placed in a cone mixer for total mixing and tableting to obtain unprocessed tablets.

[0057] Coating: Take the uncoated tablets and spray a layer of brown film coating premix (gastric-soluble type) directly.

[0058] Example 4 This embodiment provides a method for preparing refined Yinqiao Jiedu tablets, including the following steps: Herbal powdering: Platycodon grandiflorus is dried in a belt dryer at 80-90℃ for about 8 hours, then pulverized in a pulverizer with a 20-mesh sieve. After coarse pulverization, it is passed through a 100-mesh sieve and sterilized for later use.

[0059] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0060] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 8 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 6 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.33 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 35.14%.

[0061] Preparation of extract binder: According to the mass ratio of extract to excipients = 55:1, add the extract to the excipients (corn starch, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch (excipient ratio of 1:1.6:3.3)), boil with an appropriate amount of purified water, stir to dissolve and pass through a 60-mesh sieve (keeping the temperature at 50~60℃) to prepare the extract binder for later use.

[0062] Drying and granulation: The extract binder, platycodon powder, acetaminophen, and 50 parts dextrin were premixed in a fluidized bed granulator and spray-dried (40℃~70℃). After drying, the granules were sieved through an 18-mesh sieve, with a granule yield of 98.8%. After cooling, an ethanol solution of menthol and catnip oil was sprayed into the granules. 8 parts magnesium stearate and 5 parts silica were added and placed in a cone mixer. The mixture was then mixed, compressed, and tableted to obtain unprocessed tablets.

[0063] Coating: Take the uncoated tablets and spray a layer of brown film coating premix (gastric-soluble type) directly.

[0064] Comparative Example 1 This comparative example provides a method for preparing refined Yinqiao Jiedu tablets, including the following steps: Herbal powdering: Platycodon grandiflorus is dried in a belt dryer at 80-90℃ for about 8 hours, then pulverized in a pulverizer with a 20-mesh sieve. After coarse pulverization, it is passed through a 100-mesh sieve and sterilized for later use.

[0065] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0066] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 8 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 6 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.35 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 23.03%.

[0067] Preparation of extract binder: According to the mass ratio of extract to excipients = 40:1, add the extract to the excipients (corn starch, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch (excipient ratio of 1:1.5:3.4)), boil with an appropriate amount of purified water, stir to dissolve and pass through a 60-mesh sieve (keeping the temperature at 50~60℃) to prepare the extract binder for later use.

[0068] Drying and granulation: The extract binder, platycodon powder, acetaminophen, and 50 parts dextrin were premixed in a fluidized bed granulator and spray-dried (40℃~70℃). After drying, the granules were sieved through an 18-mesh sieve, with a granule yield of 89.1%. After cooling, an ethanol solution of menthol and catnip oil was sprayed into the granules. 8 parts magnesium stearate and 5 parts silica were added and placed in a cone mixer. The mixture was then mixed, compressed, and tableted to obtain unprocessed tablets.

[0069] Coating: Take the uncoated tablets and spray a layer of brown film coating premix (gastric-soluble type) directly.

[0070] In Comparative Example 1, the high relative density of the concentrated extract resulted in a low yield, failing to meet the internal control standard. The granule yield after granulation also failed to meet the internal control standard.

[0071] Comparative Example 2 This comparative example provides a method for preparing refined Yinqiao Jiedu tablets, including the following steps: Herbal powdering: Platycodon grandiflorus is dried in a belt dryer at 80-90℃ for about 8 hours, then pulverized in a pulverizer with a 20-mesh sieve. After coarse pulverization, it is passed through a 100-mesh sieve and sterilized for later use.

[0072] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0073] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 8 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 6 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.30 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 34.03%.

[0074] Preparation of extract binder: According to the mass ratio of extract to excipients = 55:1, add the extract to the excipients (corn starch, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch (excipient ratio of 1:2:3)), boil with an appropriate amount of purified water, stir to dissolve and pass through a 60-mesh sieve (temperature maintained at 50~60℃) to prepare the extract binder for later use.

[0075] Drying and granulation: The extract binder, fine powder of Platycodon grandiflorus, paracetamol, and 100 parts of dextrin were added to a fluidized bed granulator for premixing and spray drying (40℃~70℃). After drying, the granules were sieved through an 18-mesh sieve, with a granule yield of 78.2%. After cooling, an ethanol solution of menthol and catnip oil was sprayed into the granules. 6 parts of magnesium stearate and 3 parts of silica were added and placed in a cone mixer for total mixing and tableting to obtain unprocessed tablets.

[0076] Coating: Take the uncoated tablets and spray a layer of brown film coating premix (gastric-soluble type) directly.

[0077] In Comparative Example 2, the unsuitable ratio of excipients resulted in a low granule yield and a large amount of fine powder, which did not meet the internal control standards and affected the subsequent tableting and formulation stability.

[0078] Comparative Example 3 This comparative example provides a method for preparing refined Yinqiao Jiedu tablets, including the following steps: Herbal powdering: Platycodon grandiflorus is dried in a belt dryer at 80-90℃ for about 8 hours, then pulverized in a pulverizer with a 20-mesh sieve. After coarse pulverization, it is passed through a 100-mesh sieve and sterilized for later use.

[0079] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0080] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 8 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 6 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.25 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 42.81%.

[0081] In Comparative Example 3, the excessively high yield of extract resulted in excessively high moisture content in the extract, requiring the addition of excessive excipients for granulation, which led to unsuccessful granulation and thus prevented subsequent steps from being carried out.

[0082] Comparative Example 4 This comparative example provides a method for preparing refined Yinqiao Jiedu tablets, including the following steps: Herbal powdering: Platycodon grandiflorus is dried in a belt dryer at 80-90℃ for about 8 hours, then pulverized in a pulverizer with a 20-mesh sieve. After coarse pulverization, it is passed through a 100-mesh sieve and sterilized for later use.

[0083] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0084] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 5 times the amount of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 3 times the amount of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.30 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 20.20%. Insufficient water added during extraction resulted in a yield that did not meet the internal control standard.

[0085] Preparation of extract binder: According to the mass ratio of extract to excipients = 40:1, add the extract to the excipients (corn starch, low-substituted hydroxypropyl cellulose, sodium carboxymethyl starch (excipient ratio of 1:1.6:3.3)), boil with an appropriate amount of purified water, stir to dissolve and pass through a 60-mesh sieve (keeping the temperature at 50~60℃) to prepare the extract binder for later use.

[0086] Drying and granulation: The extract binder, platycodon powder, acetaminophen, and 45 parts dextrin were added to a fluidized bed granulator for premixing and spray drying (40℃~70℃). After drying, the granules were sieved through an 18-mesh screen, with a granule yield of 88.6%. After cooling, an ethanol solution of menthol and catnip oil was sprayed into the granules. 7 parts magnesium stearate and 4 parts silica were added to a cone mixer, and the mixture was mixed and compressed into tablets.

[0087] Coating: Simply spray a layer of brown film coating premix (gastric-soluble type) directly onto the uncoated tablets to obtain the coating.

[0088] In Comparative Example 4, the yield was low and did not meet the internal control standards. Even with an appropriate reduction in the amount of excipients used in the granulation process, the stability of the subsequent formulation was still affected.

[0089] Comparative Example 5 This comparative example provides a method for preparing refined Yinqiao Jiedu tablets, including the following steps: Herbal powdering: Platycodon grandiflorus is dried in a belt dryer at 80-90℃ for about 8 hours, then pulverized in a pulverizer with a 20-mesh sieve. After coarse pulverization, it is passed through a 100-mesh sieve and sterilized for later use.

[0090] Volatile oil extraction: Take catnip spikes, add twice the amount of water, steam distill for 2 hours to extract volatile oil, and collect the volatile oil; dissolve the catnip spike volatile oil and menthol in an appropriate amount of 95% ethanol for later use.

[0091] Water extraction and concentration: Forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds were extracted twice with water. For the first extraction, 8 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. For the second extraction, 6 times the volume of water was added, and the mixture was boiled and extracted for 1 hour. The extracts were collected separately, filtered, and combined. The extracts were then drawn into a double-effect concentrator and concentrated to a relative density of 1.30 (65℃) (double-effect concentrator parameters: first-effect vacuum: -0.04~-0.06 MPa, evaporation temperature: 78~85℃; second-effect vacuum: -0.06~-0.08 MPa, evaporation temperature: 58~65℃), with a yield of 36.22%.

[0092] Preparation of extract adhesive: According to the mass ratio of extract to excipients = 55:1, add the extract to the excipients (corn starch), boil with an appropriate amount of purified water, stir to dissolve and pass through a 60-mesh sieve (keeping the temperature at 50~60℃) to prepare the extract adhesive for later use.

[0093] Drying and granulation: The extract binder, platycodon powder, acetaminophen, and 50 parts dextrin were premixed in a fluidized bed granulator and spray-dried (40℃~70℃). After drying, the granules were sieved through an 18-mesh sieve, with a granulation yield of 52.3%. After cooling, an ethanol solution of menthol and catnip oil was sprayed into the granules. 8 parts magnesium stearate and 5 parts silica were added and placed in a cone mixer for total mixing and tableting to obtain uncoated tablets. The resulting uncoated tablets were prone to cracking and could not be coated.

[0094] Cost and quality analysis in industrial production processes The refined Yinqiao Jiedu tablets prepared in each example and comparative example were subjected to a high temperature (50℃±2℃) and high humidity (90%±5%) accelerated test. The results showed that, except for the unsuccessful granulation of comparative example 3, although the granulation and tableting of comparative examples 1, 2 and 4 were successful, the refined Yinqiao Jiedu tablets obtained showed cracking after 30 days. Although comparative example 5 could be granulated, the tableting was unsuccessful. The refined Yinqiao Jiedu tablets prepared in the other examples 2 to 4 did not show obvious cracking after 30 days.

[0095] The present invention uses sugar-coated sheets, which have higher industrial economic efficiency than film-coated sheets. The comparison results of the two coatings are shown in Table 2.

[0096] Table 2

[0097] The coating process for refined Yinqiao Jiedu sugar-coated tablets is complex, requiring highly skilled operators and precise techniques. Furthermore, uneven coating is prone to occur in the finished product, affecting quality. Sugar-coating materials are more expensive than film-coated tablets, and a large amount of talc powder is wasted during production due to exhaust from the equipment's ventilation system, which also shortens the lifespan of the dust collection system. The material consumption for sugar-coated tablets far exceeds that of film-coated tablets, resulting in lower production volumes. The sugar content of the coating is 20%, making it unsuitable for some patients. Switching to film-coated tablets offers several advantages. The thinner coating layer and better water solubility of the coating material facilitate drug disintegration. Film-coated tablets also produce a more uniform appearance, further improving product quality.

[0098] The above description provides a detailed account of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention. Furthermore, unless otherwise specified, the embodiments of the present invention and the features thereof can be combined with each other.

Claims

1. A method for preparing refined Yinqiao Jiedu tablets, characterized in that, Includes the following steps: S1. Take a mixture of forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle and burdock seeds, add 4 to 8 times the amount of water and decoct 2 to 4 times to obtain the filtrate, and concentrate it to an extract with a relative density of 1.28 to 1.33 at 60 to 70°C. S2. Mix the extract with the adhesive to obtain the extract-adhesive; S3. Mix the extract binder, platycodon powder, acetaminophen and the first excipient, dry, granulate, mix the resulting dry granules with the volatile oil solution and the second excipient, compress into tablets, and coat with a film to obtain the final product. The volatile oil solution is an ethanol-water solution of menthol and volatile oil extracted from catnip spikes; The adhesive comprises corn starch, low-substituted hydroxypropyl cellulose, and sodium carboxymethyl starch in a mass ratio of 1:1.5~1.8:3.2~3.

5.

2. The preparation method according to claim 1, characterized in that, The particle size of the Platycodon grandiflorus powder is such that it passes through a 100-mesh sieve 3. The preparation method according to claim 1, characterized in that, The volatile oil solution is prepared by the following steps: Take catnip spikes, add 1 to 4 times the amount of water, and steam distill for 1 to 2 hours to extract the volatile oil; mix the volatile oil, menthol, and an aqueous solution of ethanol with a volume fraction of 90% to 99% to obtain the final product.

4. The preparation method according to claim 1, characterized in that, In step S1, a mixture of forsythia, fermented soybean, licorice, bamboo leaves, honeysuckle, and burdock seeds is boiled with 6-8 times the amount of water to obtain a first filtrate and a residue; the residue is then boiled with 4-6 times the amount of water to obtain a second filtrate; the first and second filtrates are combined and concentrated to an extract with a relative density of 1.28-1.33 at 60-70°C. Preferably, the first decoction time is 0.5 to 2 hours; and / or, the second decoction time is 0.5 to 2 hours.

5. The preparation method according to claim 1, characterized in that, In step S2, the mass ratio of the extract to the adhesive is 40~55:

1.

6. The preparation method according to claim 1, characterized in that, The first excipient includes dextrin; and / or the second excipient includes at least one of magnesium stearate and silicon dioxide.

7. The preparation method according to claim 1, characterized in that, The coating material is a gastrosoluble film coating premix.

8. The preparation method according to any one of claims 1 to 7, characterized in that, The refined Yinqiao Detoxification Tablets comprise the following raw materials in parts by weight: Paracetamol 50-70 parts, Platycodon grandiflorus 200-300 parts, Forsythia suspensa 250-400 parts, fermented soybean 100-200 parts, licorice root 100-200 parts, Lophatherum gracile 100-150 parts, honeysuckle 250-400 parts, burdock fruit 165-240 parts, Schizonepeta tenuifolia 100-150 parts, menthol 0.4-0.7 parts.

9. The preparation method according to claim 8, characterized in that, The refined Yinqiao Jiedu tablets further include 40-100 parts of the first excipient; and / or, the refined Yinqiao Jiedu tablets further include 8-20 parts of the second excipient; Preferably, the second excipient comprises magnesium stearate and silicon dioxide in a mass ratio of 1 to 3:

1.

10. The refined Yinqiao Jiedu tablets prepared by any one of claims 1 to 9.

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