A method for preparing an oral solid dosage form of gynecological inflammation relief

Abstract

The present invention provides a preparation method of a Fuyanxiao oral solid preparation, belonging to the field of pharmaceutical technology. The Fuyanxiao oral solid preparation is made from seven medicinal materials including Oxalis corniculata, Patrinia scabiosaefolia, Trichosanthes kirilowii Maximowicz, Rheum officinale, Paeonia suffruticosa, Atractylodes lancea, and Lindera aggregata. The preparation method is to coarsely crush 1 / 2 weight portion of the Rheum officinale medicinal material with a 4-cm diameter sieve plate into coarse granules with a particle size of 4 cm, conduct moist heat sterilization and drying, and then superfine pulverize it into nanoscale fine powder for standby. Then, take the remaining Rheum officinale medicinal material and the other medicinal materials to extract and prepare dry extract powder for standby. Finally, select appropriate excipients according to the oral solid preparation to be prepared and mix them to make the corresponding dosage form. Compared with the prior art, the present invention solves the problem of unstable emodin content by changing the addition method of raw Rheum officinale powder, and at the same time provides preparation methods for various oral solid preparations, providing more medication options for patients.

Description

Technical Field

[0001] The present invention relates to a preparation method of Fuyixiao oral solid preparation, belonging to the field of pharmaceutical technology. Background Art

[0002] Gynecological diseases refer to various diseases related to the female reproductive system, including vulvar diseases, vaginal diseases, cervical diseases, fallopian tube diseases, ovarian diseases, etc., which are common and frequently-occurring diseases among adult women. Due to the complex pathogenesis of gynecological diseases and accompanied by various serious complications, the clinical symptoms are diverse. Common ones include vaginitis, pelvic inflammatory disease, adnexitis, cervicitis, endometritis, cervical erosion, vaginal pruritus, excessive leucorrhea, abnormal leucorrhea odor, irregular menstruation, lower abdominal distending pain, etc. Due to the special physiological structure of women and various factors such as the increasing competition pressure in modern society and the accelerating pace of work and life, it seriously harms women's health and leads to a high incidence of gynecological diseases.

[0003] Currently, the drugs for treating gynecological diseases on the market are mainly drugs for treating gynecological inflammation and gynecological menstrual regulation drugs. Fuyixiao Capsule is a representative drug for treating gynecological inflammation. Through long-term clinical verification, Fuyixiao Capsule has three functions: antibacterial and anti-inflammatory, repairing the endometrium, and assisting in the success of abortion surgery. It can also regulate the balance of flora, treat various vaginal inflammations, and prevent cervical canceration, and has always been well received by doctors and patients.

[0004] According to statistics, among the 212 batches of Fuyixiao Capsule powder produced in recent years, the highest content of emodin reached 1.70 mg / g, the lowest was 0.82 mg / g, and the average was 1.21 mg / g. There was a large difference in content between batches. Although all could meet the requirements of the product quality standard, the difference between the maximum value and the average value was 40.49%, and the difference between the minimum value and the average value was 32.23%, which was greater than the confidence requirement of 5%. This indicates that the production process of Fuyixiao powder is not stable enough, which will also affect the product efficacy and process research is needed. At the same time, this product has only one dosage form, the capsule dosage form, for a long time. Therefore, it is urgent to conduct in-depth research on the preparation process and dosage forms of Fuyixiao to solve the existing technical problems. Summary of the Invention

[0005] In view of the above problems, the purpose of the present invention is to provide a preparation method of Fuyixiao oral solid preparation, which not only solves the problem of unstable emodin content in Fuyixiao preparation, but also provides preparation methods for various oral solid preparations such as Fuyixiao tablets, pills, granules, and powders.

[0006] The present invention is realized by the following technical solutions:

[0007] A preparation method of a Fuyanxiao oral solid preparation, wherein the Fuyanxiao oral solid preparation is made from raw medicinal materials in the following weight ratios: Oxalis corniculata 300 parts, Patrinia scabiosaefolia 300 parts, Trichosanthes kirilowii Maxim. 250 parts, Rheum officinale 300 parts, Moutan cortex 150 parts, Atractylodes lancea (Thunb.) DC. 250 parts, Lindera aggregata (Sims) Kosterm. 300 parts, and specifically includes the following steps:

[0008] Sort all the raw medicinal materials, remove sand and impurities, cut the Oxalis corniculata into small segments with a length of 20 cm for standby;

[0009] Take the Rheum officinale medicinal material for dry cleaning;

[0010] Coarsely crush, sterilize, and dry 1 / 2 weight portion of the dry-cleaned Rheum officinale medicinal material, and then superfine pulverize it into nano-level fine powder to obtain large medicine raw powder for standby;

[0011] Take the remaining Rheum officinale medicinal material and all the other raw medicinal materials, add 120% of the water by the weight of the raw materials and soak for 2 hours, then add 10 times the amount of water and decoct for 3 times, each time for 1 hour. Combine the extraction solutions, filter, and concentrate the filtrate under reduced pressure to an extract with a relative density of 1.20 - 1.30, dry, and pulverize it into fine powder to obtain dry extract powder for standby;

[0012] Mix the large medicine raw powder in step with the dry extract powder in step , and add pharmaceutically acceptable medicinal excipients to make various oral solid preparations.

[0013] The dry cleaning in the above step is to add the Rheum officinale medicinal material to a drum-type screening machine for screening to remove sand and impurities; the coarse crushing in the above step is to coarsely crush the Rheum officinale with a 4 cm diameter sieve plate, and the sterilization is moist heat sterilization, with a sterilization temperature of 115 °C and a time of 30 minutes; the reduced pressure concentration in the above step is specifically carried out under the conditions of 75 °C and a vacuum degree of -0.085 MPa; the drying is vacuum drying at 80 °C.

[0014] Preferably, the oral solid preparation is tablets, capsules, powders, pills, granules.

[0015] Furthermore, the tablets are prepared by mixing the large medicine raw powder in step [[ID=4)] with the dry extract powder in step , adding a filler, a disintegrant, mixing evenly, using an ethanol solution as a wetting agent, preparing soft materials, granulating, drying, sizing, and tabletting;

[0016] Preferably, the filler is a mixture of microcrystalline cellulose and soluble starch in a weight ratio of 1:1, and the disintegrant is low-substituted hydroxypropyl cellulose.

[0017] Preferably, the amount of filler added is 10%-15% of the total amount of rhubarb powder and dry extract powder, the amount of disintegrant added is 2.5%-3.5% of the total amount of rhubarb powder and dry extract powder, and the wetting agent is 90% ethanol;

[0018] Preferably, the amount of filler added is 12% of the total amount of rhubarb powder and dry extract powder, and the amount of disintegrant added is 3.0% of the total amount of rhubarb powder and dry extract powder.

[0019] The capsule is prepared by the steps described above. rhubarb starch and steps The dry extract powder is mixed evenly and then filled into capsules to obtain the final product.

[0020] To prevent the capsules from absorbing moisture, soluble starch can be added to the capsules at a ratio of 1:1 to the total amount of mixed powder, mixed well, and then filled into capsules.

[0021] The powder is prepared by the steps... rhubarb starch and steps Mix the dry extract powder evenly, add soluble starch to a total of 1000g, mix well, and pack into bags to obtain the final product.

[0022] The pills are prepared by the steps described above. rhubarb starch and steps Mix the dry extract powder evenly, add corn starch and low-substituted hydroxypropyl cellulose, mix evenly, use water as a wetting agent to prepare soft material, make into pellet strips, pass through a pelleting machine to make pellets, and dry at 80℃ to obtain the final product.

[0023] Preferably, the amount of corn starch added is 30% of the total amount of rhubarb raw powder and dry extract powder, and the amount of low-substituted hydroxypropyl cellulose added is 1% of the total amount of rhubarb raw powder and dry extract powder.

[0024] The granules are prepared by the steps... rhubarb starch and steps Mix the dry extract powder evenly, add an appropriate amount of sugar-free sweetener, and then add corn starch to a total of 1000g. Mix well, use 88% ethanol as a wetting agent to prepare a soft material, granulate, dry, granulate, and package.

[0025] Preferably, the sugar-free sweetener is sucralose, and the amount of sucralose added to 1000g of Fuyanxiao granules is 0.2-1g, preferably 0.5g.

[0026] The relative humidity of the environment during the preparation of various oral solid dosage forms is controlled below 65%, preferably below 60%.

[0027] Compared with the prior art, the beneficial effects of the present invention are: it provides a new preparation method for oral solid dosage forms of Fuyanxiao, which not only solves the problem of unstable emodin content in Fuyanxiao preparations and effectively increases the emodin content, but also provides preparation methods for various oral solid dosage forms of Fuyanxiao such as tablets, pills, granules, and powders.

[0028] The preparation method described in this invention is an improvement on existing methods. In existing technologies, rhubarb is pulverized, mixed with the extracted extract, and then dried together. This drying process is lengthy and results in significant loss of emodin. Therefore, the pulverized rhubarb is mixed with the extracted dry extract powder, and various excipients are added to prepare the corresponding dosage form. Because there is no sterilization step after mixing, all materials must meet the standard microbial requirements during mixing; otherwise, microbial levels will exceed the standard. Therefore, the rhubarb needs to be sterilized first. Research has found that even sterilization after pulverizing rhubarb into fine powder can lead to emodin loss due to high temperatures. Therefore, it is necessary to first coarsely crush the rhubarb into coarse powder, sterilize it, and then pulverize it into fine powder for feeding. Specifically, the preparation method is as follows: First, the rhubarb is dry-washed. Half of the rhubarb is coarsely crushed, then subjected to moist heat sterilization and drying, and then ultra-finely pulverized into nano-sized fine powder for later use. The remaining rhubarb is then extracted with water along with other medicinal materials to prepare a dry extract powder for later use. Finally, appropriate excipients are added according to the requirements of the desired oral solid dosage form to prepare the corresponding dosage form.

[0029] In order to illustrate the content and beneficial effects of the present invention, the following experiments were also conducted to demonstrate the present invention, but in no way are they intended to limit the scope of the present invention.

[0030] Experimental Example 1: Study on the mixing and drying of rhubarb raw powder and extract:

[0031] The production data of 30 batches of Fuyanxiao capsules were analyzed and summarized, as detailed in Table 1:

[0032] Table 1. Summary of emodin content in samples of Fuyanxiao capsules produced in large quantities.

[0033]

[0034] As can be seen from Table 1, the content of rhein decreased significantly after mixing and drying. There was no loss during the process of pulverizing and making the powder before filling. Therefore, through analysis, the raw rhubarb powder was sterilized and pulverized first, and then added and mixed evenly after the extract was extracted, dried and pulverized.

[0035] Experimental Example 2: Study on the sterilization of rhubarb powder

[0036] Three batches of rhubarb medicinal materials were taken, ultra-finely pulverized into nano-sized powder, sterilized by moist heat at 115℃ for 30 minutes, and vacuum dried three times at 100℃ for 15 minutes each time. The experimental results are shown in Table 2.

[0037] Table 2. Comparison of rhubarb pulverization and sterilization content.

[0038]

[0039] As can be seen from Table 2, the rhubarb used in Fuyanxiao was subjected to significant loss of emodin during the sterilization process after being pulverized into nano-sized fine powder, with a loss rate of 29.2%.

[0040] Experimental Example 3: Study on the sterilization of rhubarb powder

[0041] Three batches of rhubarb were taken, crushed into coarse powder (2 cm), sterilized by moist heat at 115℃ for 30 minutes, and vacuum dried three times at 100℃ for 15 minutes each time, then ultra-finely pulverized into nano-sized powder. Significant loss of emodin was observed; the experimental results are shown in Table 3.

[0042] Table 3. Comparison of emodin content before and after sterilization of rhubarb powdered into 2cm particles.

[0043]

[0044] As can be seen from Table 3, there is still a loss of rhubarb in the sterilization process after the rhubarb used in Fuyanxiao is crushed into 2cm coarse particles, with a loss rate of 24.72%, but the loss is reduced compared to crushing it directly into nano-fine powder.

[0045] Experimental Example 4: Study on Sterilization of Rhubarb Particle Size

[0046] Three batches of rhubarb were taken, crushed using a 4cm diameter sieve (samples were taken to measure moisture content), weighed, and placed into trays. The samples were then sterilized by moist heat at 115℃ for 30 minutes, followed by vacuum drying at 100℃ three times, 15 minutes each time. Samples were taken from the top, middle, and bottom of the trays, ultra-finely pulverized into nano-sized powder, mixed thoroughly, and samples were taken to measure moisture content. The experiment was repeated twice. The results are shown in Table 4.

[0047] Table 4. Comparison of emodin content before and after sterilization of rhubarb powdered into 4cm particles.

[0048]

[0049] Table 4 shows that by crushing rhubarb using a 4cm diameter sieve before sterilization and drying, the loss of its active ingredient, emodin, was minimal after sterilization. Therefore, using a 4cm diameter sieve for coarse crushing of rhubarb can reduce the impact of the sterilization process on emodin.

[0050] Experimental Example 5: Comparative Study of Different Methods of Adding Rhubarb Starch

[0051] Take the same batch of Rheum officinale药材, and prepare Fuyankang medicinal powder using two different preparation processes. Example 1 is the original standard process, that is, adding raw Rheum officinale powder to the water extract paste, mixing, and drying; Example 2 is to roughly crush Rheum officinale with a sieve plate with a diameter of 4 cm into coarse particles with a particle size of 4 cm, sterilize at 115 °C under moist heat for 30 minutes, dry at 70 °C under low temperature and vacuum until the moisture content is less than 4%, and then pulverize into nano-scale fine powder, which is mixed with the dry extract powder extracted with water. Compare the differences in the content of emodin in Fuyankang produced by the two preparation methods. The results are shown in Table 5:

[0052] Table 5 Comparative study on two methods of adding raw Rheum officinale powder

[0053]

[0054] As can be seen from Table 5, the loss of emodin in the original process is very large. In Example 2 of the present invention, by changing the method of adding raw Rheum officinale powder, the content of the active ingredient emodin has increased by 33.0%.

[0055] Experimental Example 6: Study on the extraction process of medicinal materials

[0056] 6.1 Investigation of liquid absorption rate

[0057] Weigh 1 / 40 of the medicinal materials in the Fuyankang prescription, place them in a beaker, add water to submerge the medicinal materials (about 4 times the amount), close it, observe once every half hour until the soaking is thorough, filter out the unabsorbed liquid, and calculate the liquid absorption rate at the last thorough soaking time to determine the soaking time. The results are shown in Table 6:

[0058] Table 6 Results of the investigation of the liquid absorption rate of the prescription medicinal materials

[0059]

[0060] Experimental results: As can be seen from Table 6, all the medicinal materials can be soaked thoroughly after 2 hours of soaking, so the soaking time is set at 2 hours. Secondly, it is the liquid absorption rate. 1 / 40 of the medicinal materials in the prescription is 42.5 g, and the weight of the medicinal materials after absorbing moisture is 93.66 g, and the liquid absorption rate is 120.38%.

[0061] 6.2 Orthogonal experiment for extraction

[0062] 6.2.1 Weigh 1 / 20 of the medicinal materials in the prescription, about 85 g, add water at 120% for soaking for 2 h, and then take the amount of added water, decoction time, and decoction times as the investigation factors. Conduct an orthogonal experiment for extraction twice, and conduct an L9(3 4 ) orthogonal experiment, and take the content of the anti-inflammatory components in this product (gallic acid, protocatechuic acid, epicatechin, swertisin, isovitexin, emodin, chrysophanol, physcion, aloe-emodin, rhein) and the extract yield as the evaluation indexes, among which the content weight accounts for 70%, and the extract yield weight accounts for 30%, and screen out the best process.

[0063] Relevant literature indicates that the screened components all possess anti-inflammatory effects, which are closely related to the efficacy of this product. Using these components as evaluation indicators can indirectly reflect the drug's efficacy. Simultaneously, the indicator components contain elements with varying solubility; gallic acid, protocatechuic acid, epicatechin, quercetin, and isochaetin exhibit good water solubility. Using multiple indicator components can simultaneously characterize the dissolution of different medicinal materials. Since traditional Chinese medicine treats diseases through the interaction of multiple components and multiple targets, using the content of multiple effective components as indicators is superior to evaluating a single component when evaluating the extraction process.

[0064] 6.2.2 Content determination method:

[0065] 1) Chromatographic conditions

[0066] The chromatographic column used was a GL Sciences Inertsil ODS-35um (250mm × 4.6mm), with acetonitrile as mobile phase A and 0.2% phosphoric acid solution as mobile phase B. Elution was performed according to the gradient in Table 7. The column temperature was 35℃; the flow rate was 1ml / min; the injection volume was 10µL; and the detection wavelength was 230nm. Based on the maximum wavelength and resolution of each reference standard, 230nm was used for 0-10min and 30-40min, and 280nm was used for 10-30min and 40-90min.

[0067] Table 7 Elution gradient

[0068]

[0069] 2) Preparation of reference solution

[0070] Take appropriate amounts of gallic acid, protocatechuic acid, epicatechin, zeaxanthin, isochaetin, rhein, chrysophanol, rhein methyl ether, aloe-emodin, and rhein reference standards, accurately weigh them, and add methanol to prepare a mixed solution containing 0.1 mg of each per ml.

[0071] 3) Preparation of test sample

[0072] Take 0.15g of extract powder, accurately weigh it, place it in a stoppered conical flask, accurately add 20ml of 50% methanol, weigh it, sonicate for 10 minutes, cool it, weigh it again, make up the reduced weight with 50% methanol, shake well, centrifuge (13000r, 20min), and take the supernatant to obtain the test solution.

[0073] 4) Determination: Accurately inject 10 μl of the reference solution and the test solution into the liquid chromatograph, record the chromatogram, and calculate the content of each component and the total content by the external standard method.

[0074] 6.2.3 Determination of Extract Yield (Total Solids Yield): Accurately pipette 25 mL of the extract into an evaporating dish that has been dried to constant weight, evaporate to dryness, dry at 105℃ for 5 hours, transfer to a desiccator, cool for 30 minutes, and then dry at 105℃ for another hour. Transfer to a desiccator, cool, and quickly and accurately weigh the extract. Calculate the yield. Extract Yield (%) =

[0075] 2.4 Results of the orthogonal experiment: See Table 8-10

[0076]

[0077]

[0078]

[0079] Intuitive analysis shows that the order of influence of each factor is B>A>C, i.e., water volume > number of decoctions > decoction time, indicating that the optimal process is A3B3C1. Analysis of variance shows that factor B has a significant impact on the results and is the main factor affecting the extraction effect, while factors A and C have no significant impact and are secondary factors. Based on the above analysis, the optimal extraction process can be determined as follows: soak the medicinal materials in water equal to 120% of their volume for 2 hours, then add 10 times the amount of water and decoct 3 times, 1 hour each time.

[0080] 6.3 Research on Concentration Process

[0081] The extract was concentrated using a vacuum concentration process to isolate air, shorten the concentration time, lower the concentration temperature, and reduce component loss. The main focus was on the effect of concentration temperature on the content of the components. The study used a large-scale production extract as the subject, comparing the content of multiple components before and after concentration. Concentration temperatures of 75℃, 85℃, and 95℃ were set, with a vacuum degree of -0.085 MPa, concentrating to a thick paste with a relative density of 1.12–1.20 (60–70℃). The transfer rate of effective components at the three concentration temperatures was investigated. For content measurement, 5 mL of the extract before concentration was accurately measured and added to 5 mL of methanol for quantitative determination; 0.25 g of the concentrated extract was accurately measured and added to 20 mL of 50% methanol for quantitative determination. The results are shown in Table 11.

[0082] Table 11 Content results before and after concentration process (n=2)

[0083]

[0084] As shown in Table 11, under a fixed vacuum of -0.085 MPa, the higher the concentration temperature, the lower the transfer rate of the effective components. The transfer rate after concentration is the highest at 75℃. Therefore, the optimal conditions for the concentration process are vacuum of -0.085 MPa and concentration at 75℃ under reduced pressure.

[0085] 6.4 Validation of Extraction Process

[0086] Take 10 times the prescribed amount of medicinal materials, soak them in water equal to 120% of the material volume for 2 hours, then add 10 times the amount of water and decoct 3 times, extracting for 1 hour each time. A total of 6 batches were produced. The experimental results are shown in Table 12.

[0087] Table 12 Extraction yield of 6 batches of medicinal materials

[0088]

[0089] As can be seen from Table 12, the extraction method is stable and has good repeatability, with an average yield of 17.32% for 6 batches.

[0090] Experimental Example 7: Study on the Forming Process of Fuyanxiao Capsules and Powders

[0091] 7.1 Investigation of hygroscopicity, flowability and bulk density:

[0092] Take the mixed powder and add soluble starch, corn starch, dextrin and lactose in a 1:1 weight ratio, mix well and then test the hygroscopicity.

[0093] Determination method: Place a glass desiccator containing a supersaturated sodium chloride solution at the bottom into a constant temperature incubator at 25°C for 24 hours. During this time, the relative humidity inside the desiccator will be 75%. Take a certain amount of sample according to the formula ratio in Table 13, dry it in a phosphorus pentoxide desiccator for 48 hours until constant weight, place it at the bottom of a weighing bottle (about 2 mm thick), weigh it accurately, and then place it in a glass desiccator containing a supersaturated sodium chloride solution (with the weighing bottle cap open). Store it in a constant temperature incubator at 25°C, weigh it periodically, and calculate the moisture absorption percentage using the following formula.

[0094]

[0095] Table 13 Hygroscopicity results of different mixtures

[0096]

[0097] Experimental results show that the powder has strong hygroscopicity. Through the investigation of the hygroscopicity of different excipients, the powder and soluble starch are mixed in a 1:1 ratio, which has the best hygroscopic resistance and can solve the problem of the powder's hygroscopicity. Therefore, soluble starch is used as an excipient.

[0098] The flowability and bulk density of mixtures made from medicinal powder and soluble starch at ratios of 1:0.5, 1:1, and 1:2 were investigated. The results are shown in Table 14.

[0099] Table 14 Results of the investigation on the flowability and bulk density of different excipient ratios

[0100]

[0101] Table 14 shows that as the amount of excipients added increases, the flowability, bulk density, and hygroscopicity all decrease. When the drug-to-excipient ratio is 1:1, both the flowability and bulk density meet the requirements. Therefore, soluble starch is used as the excipient, and the drug-to-excipient ratio is 1:1 to prepare the powder and capsule contents.

[0102] 7.2 Determination of Critical Relative Humidity

[0103] Accurately weigh 31.58, 28.16, 24.66, 20.80, 16.10, and 9.83 g of solid sodium hydroxide, respectively, and place them in 100 mL volumetric flasks. Dissolve them in water and place them in a desiccator for one day to equilibrate, obtaining constant temperature and humidity conditions of 40%, 50%, 60%, 70%, 80%, and 90%, respectively. Accurately weigh the contents (approximately 1.5 g per portion) of a 1:1 mixture of pharmaceutical powder and soluble starch into constant-weight weighing bottles, and place the weighing bottles in the desiccator under the above constant temperature and humidity conditions for 24 hours. Remove them, accurately weigh them, and calculate the moisture absorption percentage. The results are shown in Table 15. Plot the moisture absorption rate on the ordinate and the relative humidity on the abscissa to obtain the moisture absorption rate curve. Plot the tangents of the curve at low and high humidity. The intersection of the two tangents corresponds to the CRH on the abscissa. The results are shown in Table 15. Figure 1 .from Figure 1 It can be seen that the critical relative humidity (CRH) of the sample is approximately 69%. Therefore, it can be determined that the relative humidity of the production process and storage environment for the Fuyanxiao oral solid dosage form should be below 69%.

[0104] Table 15 Sample Moisture Absorption Rate Table

[0105]

[0106] 7.3 Formulation of Fuyanxiao Capsules

[0107] 300g wood sorrel, 300g patrinia, 250g trichosanthes root, 300g rhubarb

[0108] 150g of Moutan bark, 250g of Atractylodes lancea, 300g of Lindera strychnifolia, and approximately 445g of soluble starch.

[0109] Make 1000 pills

[0110] According to the "Extraction Process Verification" in Experiment 6, the average yield of the dry extract after water extraction of the prescription medicine for Fuyanxiao was 17.32%. Based on the original prescription of Fuyanxiao capsules, 1700g of dry extract powder can be obtained by 1700×17.32%=294.44g. After mixing with 150g of rhubarb powder, about 445g of soluble starch is added at a weight ratio of 1:1 between the medicine powder and excipients. After mixing well, it is filled into 1000 capsules of size 00.

[0111] The capsules produced by this invention are less prone to moisture absorption and have better stability. The dosage and administration method are the same as those for commercially available capsules: 3 capsules each time, 3 times a day.

[0112] 7.4 Formulation of Gynecological Inflammation Relief Agent

[0113] 300g wood sorrel, 300g patrinia, 250g trichosanthes root, 300g rhubarb

[0114] 150g of Moutan bark, 250g of Atractylodes lancea, 300g of Lindera strychnifolia, and approximately 556g of soluble starch.

[0115] Made into 333 bags

[0116] According to the "Extraction Process Verification" in Experiment 6, the average yield of the dry extract after water extraction of the prescription medicine for Fuyanxiao was 17.32%. Based on the original prescription of Fuyanxiao capsules, 1700g of dry extract powder can be obtained by 1700×17.32%=294.44g. After mixing with 150g of rhubarb powder, about 556g of soluble starch is added to make the total amount of medicine powder reach 1000g. Mix well and package into 333 bags, each bag containing 3g.

[0117] The powder prepared by this invention satisfies the needs of some patients who are not used to taking capsules or tablets. Only one packet needs to be taken each time, three times a day, which is convenient. On the other hand, the powder is absorbed quickly and has higher bioavailability.

[0118] Experimental Example 8: Study on the molding process of Fuyanxiao granules

[0119] 8.1 Research on Granulation Process

[0120] The prescribed amount of Fuyanxiao medicinal materials were extracted according to the extraction process determined in Experiment 6 to prepare a dry extract powder. It was then mixed with rhubarb fine powder in a certain proportion, and excipients were added. An appropriate amount of 80% ethanol was used as a wetting agent to prepare a soft material and granulate it. After drying, the granule forming rate, moisture absorption rate, angle of repose and solubility were measured, and a comprehensive score was made.

[0121] Each indicator has a weighting coefficient of 0.25. The comprehensive score (%) = (forming rate / maximum forming rate × 0.25 + minimum moisture absorption rate × 0.25 + minimum angle of repose / angle of repose × 0.25 + minimum solubility / solubility × 0.25) × 100%

[0122] 8.2 Single-factor analysis

[0123] The types of excipients, the ratio of excipient dosage, the volume of ethanol, and the amount of ethanol used were selected to investigate the effects of each factor on pellet formation.

[0124] 8.2.1 Examination of the types of excipients

[0125] Different types of excipients, including lactose, soluble starch, corn starch, and dextrin, were selected to prepare granules. The granule formation rate, moisture absorption rate, angle of repose, and solubility were measured, and a comprehensive score was calculated to screen out the optimal excipients. The results are shown in Table 16.

[0126] Table 16 Evaluation Results of Screening Different Excipients

[0127]

[0128] Table 16 shows that lactose, soluble starch, corn starch, dextrin and other excipients can all be used in the preparation of Fuyanxiao granules. To obtain the optimal molding process of Fuyanxiao granules, corn starch was used as an excipient for single-factor and response surface methodology studies.

[0129] 8.2.2 Auxiliary material usage ratio

[0130] Preliminary experiments were conducted using extract-to-excipient ratios of 1:1, 1:3, and 1:5 for granulation. The results showed that at a ratio of 1:5, the granules were too viscous, and the soft material stuck to the sieve. The results are shown in Table 17.

[0131] Table 17 Results of excipient screening with different excipient ratios

[0132]

[0133] 8.2.3 Ethanol volume fraction

[0134] Granulation was performed using 60%, 70%, 80%, and 90% ethanol as wetting agents, and the results are shown in Table 18. According to the screening results, the soft material prepared with 60% ethanol was more sticky to the sieve and not easy to granulate, while 80% ethanol as a wetting agent had a better granulation effect.

[0135] Table 18 Screening results of different volume fractions of ethanol as a wetting agent

[0136]

[0137] 8.2.4 Ethanol dosage

[0138] Using 80% ethanol as a wetting agent, the dosages were 5%, 10%, and 20% of the mixed powder, respectively, for evaluation. The soft material prepared with 20% ethanol was relatively wet and the particles were not formed. The soft material prepared with 5% ethanol was better and the particle formation rate was high. The results are shown in Table 19.

[0139] Table 19 Screening results for different dosages of wetting agent

[0140]

[0141] 8.2.5 Box-Behnken Response Surface Optimization Experiment

[0142] When the single-factor experiments were conducted at ratios of 1:3 and 1:5, drawbacks such as screen sticking, low granulation rate, and difficulty in granulation occurred. Therefore, a ratio of 1:1 to 1:2 was used in the response surface methodology. A factor level table was designed based on the single-factor experiments, as shown in Table 20. According to the Box-Behnken central composite design principle, the excipient ratio, wetting agent concentration, and wetting agent dosage were used as independent variables, and the normalized value of the overall evaluation of granulation rate, angle of repose, moisture absorption rate, and solubility was used as the response value. (For factors where smaller values ​​are better, the normalized value d...) min =(y max -y i ) / (y max -y min Factors where a larger value is better, the normalized value dmax = (y i -y min ) / (y max -y min The total score normalized value OD = (d1×d2×d3×d4). A three-factor, three-level Box-Behnken central composite experimental design was conducted using Design-Expert 8.0.6 software. The experimental results are shown in Table 21.

[0143] Table 20 Response Surface Experiment Factor Levels

[0144]

[0145]

[0146] 8.2.6 Analysis of Box-Behnken Response Surface Data Results

[0147] A regression model was established for the above data, and significance tests and analysis of variance were performed on the regression model. The results are shown in Table 22.

[0148] Table 22. Coefficients of the regression model equations and their significance variance analysis

[0149]

[0150] As shown in the table, the linear terms A, B, and C are all less than 0.01, indicating that their influence on the response value is extremely significant. The interaction terms A and C, and B and C, have significant effects on the response value, while A and B have no significant effect. The quadratic terms A² and B² have extremely significant effects on the response value, while C² has no significant effect. Analysis of variance shows that the model's p-value is <0.0001, indicating that the model used in this experiment is extremely significant. The F-value for the lack-of-fit term is 5.56, and the p-value is 0.0654 (not significant), indicating that the fitted regression equation conforms to the actual situation and is reasonable for optimizing the molding process.

[0151] The correlation coefficient R² represents the correlation between the dependent variables. This model's correlation coefficient is 0.9810, indicating a high correlation between the measured and predicted values, and that the model can predict the results well. The corrected coefficient of determination (AdjR) is 0.9565, indicating that the model can explain 95.6% of the response value variation. The AdeqR value measures the noise ratio; a value greater than 4 is acceptable. Here, the ratio is 18.256, indicating sufficient signal-to-noise ratio and a reasonable model design. The residual term is due to random error. The coefficient of variation (CV%) is 10.34%, indicating that the model is reproducible. In summary, this model can effectively demonstrate the relationship between various factors and the response values, and the model fits well.

[0152] 8.2.7 Response Surface Optimization and Analysis

[0153] The response surface and contour plots of the interactions between various factors were obtained using Design-Expert version 8.0.6 software. (See...) Figure 2-7 Based on different levels of excipient-to-pharmaceutical ratio, ethanol volume fraction, and ethanol dosage, the optimal molding process was determined using Design-Expert 8.0.6 software: excipient ratio 1:1, ethanol volume fraction 88%, ethanol dosage 5%, and theoretical OD value 0.8560.

[0154] 8.2.8 Taste Study

[0155] To meet the diverse taste preferences of patients, the inventors conducted research on the mouthfeel based on the original flavor. Stevia, aspartame, cyclamate, and sucralose were added to the granule excipients to create the granules. Sucralose was selected as the sweetener based on comprehensive evaluation.

[0156] Taste evaluation was conducted by adding 0.2%, 0.5%, 1%, and 2% sucralose. Adding 0.5% sucralose could appropriately adjust the taste of Lifuyanxiao granules, so the final addition amount was determined to be 0.5% sucralose in the total amount of the powder.

[0157] 8.2.9 Process Validation

[0158] Three batches of verification tests were conducted based on the optimal molding process conditions obtained through screening. The test results are shown in Table 23. The deviation between the actual measured OD value and the theoretical predicted value is within 5%.

[0159] Table 23 Verification Experiment Results

[0160]

[0161] 8.3 Research on the Formulation of Fuyanxiao Granules

[0162] 300g wood sorrel, 300g patrinia, 250g trichosanthes root, 300g rhubarb

[0163] 150g of peony bark, 250g of atractylodes rhizome, 300g of lindera root, and approximately 556g of corn starch.

[0164] Made into 333 bags

[0165] According to the "Extraction Process Verification" in Experiment 6, the average yield of the dry extract after water extraction of the Fuyanxiao prescription herbs was 17.32%. Based on the original prescription of Fuyanxiao capsules, 1700g of dry extract powder could yield 1700 × 17.32% = 294.44g. This was mixed with 150g of rhubarb powder, and then approximately 556g of corn starch was added to bring the total powder weight to 1000g. After mixing thoroughly, approximately 45ml of 88% ethanol was added as a wetting agent to prepare a soft mass. The mass was then sieved, granulated, dried at 70℃, and sized to obtain granules. These were then packaged into 333 bags, each containing 3g.

[0166] The granules produced by this invention meet the needs of some patients who are not used to taking capsules or tablets. They only need to take one sachet each time, three times a day, which is convenient. In addition, the granules have a good taste, are absorbed quickly, and have higher bioavailability.

[0167] Experimental Example 9: Study on the molding process of Fuyanxiao tablets

[0168] 9.1 Research on the molding process of Fuyanxiao tablets

[0169] The prescribed amount of gynecological anti-inflammatory herbs were extracted using the extraction process determined in Experiment 6 to prepare a dry extract powder. This powder was then mixed with rhubarb powder in a specific ratio, excipients were added, and a suitable amount of 80% ethanol was used as a wetting agent to form a soft mass. The granules were then dried and sized, and finally, a disintegrant was added for tableting. The tablets were then evaluated based on their hardness, friability, and disintegration time, with a comprehensive score calculated according to Table 24.

[0170] Table 24 Evaluation Indicators and Scoring Standards for Tablet Formation

[0171]

[0172] 9.2 Single-factor analysis

[0173] The effects of various factors on tablet formation were investigated by selecting the type of filler, the ratio of filler to active ingredient, the type of binder, and the type and amount of disintegrant.

[0174] 9.2.1 Examination of Pressure

[0175] The effects of different pressures on the molding process of Fuyanxiao tablets were investigated, and the results are shown in Table 25.

[0176] Table 25 Screening results under different pressures

[0177]

[0178] 9.2.2 Investigation of Filler Types

[0179] In the preliminary experiment, the tablets compressed without any filler were too soft. We then attempted to increase the tablet hardness by using different types of fillers. We mixed rhubarb powder and dry extract powder, added 10% of different types of fillers, granulated with 80% ethanol, dried, sized, and compressed into tablets. The tablets were scored according to the scoring criteria in Table 24. Experimental data are shown in Table 26, and the scoring results are shown in Table 27.

[0180] Table 26 Effects of different fillers on tablets

[0181]

[0182] As shown in the table, single excipients, extract powder, and rhubarb powder can all be used to prepare tablets. Based on the overall score, the highest score was achieved when microcrystalline cellulose and soluble starch were mixed as fillers. In subsequent considerations of other factors, microcrystalline cellulose and corn starch were used as fillers.

[0183] 9.2.3 Ratio of filler to active ingredient

[0184] The extract powder was mixed with raw rhubarb, and different proportions of filler were added. Granulation was carried out with 80% ethanol, followed by drying, granulation, and tableting. The tablets were scored according to the scoring criteria in Table 24. The experimental data are shown in Table 28, and the scoring results are shown in Table 29.

[0185] Table 28 Effect of different filler ratios on tablets

[0186]

[0187] 9.2.4 Types of Adhesives

[0188] In the preliminary experiment, the soft material prepared using water and PVP as binders had high viscosity and was prone to clumping, requiring granulation. Therefore, the effect of different concentrations of ethanol on moldability was investigated, and the results are shown in Table 30.

[0189] Table 30 Screening results for different volume fractions of ethanol

[0190]

[0191] 9.2.5 Types and dosages of disintegrants

[0192] Different proportions of low-substituted hydroxypropyl cellulose and sodium carboxymethyl starch were added to extract powder and rhubarb powder, respectively, and compared with those without any disintegrant. The disintegration time was used as the indicator for evaluation. The results are shown in Table 31.

[0193] Table 31 Screening results of different types and dosages of disintegrants

[0194]

[0195] 9.3 Box-Behnken Response Surface Optimization Experiment

[0196] Based on the single-factor investigation, a factor level table was designed, as shown in Table 32. According to the Box-Behnken central composite experimental design principle, the ratio of filler to active ingredient, the type of binder, and the amount of disintegrant were used as independent variables, and the normalized values ​​of friability, disintegration time, and molding rate were used as response values. (For factors where smaller values ​​are better, the normalized value d...) min =(y max -y i ) / (y max -y min Factors where a larger value is better, the normalized value dmax = (y i -y min ) / (y max -y min The total score normalization value OD = (d1 × d2 × d3) 1 / 3 A three-factor, three-level Box-Behnken central composite design was conducted using Design-Expert version 8.0.6 software. The experimental results are shown in Table 33.

[0197] Table 32 Response Surface Experiment Factor Levels

[0198]

[0199]

[0200] 9.4 Analysis of Box-Behnken Response Surface Data Results

[0201] A regression model was established for the above data, and significance tests and analysis of variance were performed on the regression model. The results are shown in Table 34.

[0202] Table 34. Coefficients of the regression model equation and their significance variance analysis

[0203]

[0204] As shown in the table, the linear terms A and C are both less than 0.01, indicating that their influence on the response value is extremely significant. B is less than 0.05, indicating that its influence on the response value is significant. The interaction terms A and B have a significant influence on the response value; the quadratic term A2 has a significant influence on the response value; the interaction terms A and C, B and C, and the quadratic term C2 have no significant influence on the response value. Analysis of variance shows that the p-value of the model is <0.0001, indicating that the model selected in this experiment is extremely significant. The F-value for the lack-of-fit term is 4.78, and the p-value is 0.0825 (not significant), indicating that the fitted regression equation conforms to the actual situation and is reasonable for optimizing the molding process.

[0205] The correlation coefficient R² represents the correlation between the dependent variables. This model's correlation coefficient is 0.9216, indicating a high correlation between the measured and predicted values, and that the model can predict the results well. The corrected coefficient of determination (AdjR) is 0.8207, indicating that the model can explain 82.07% of the response value variation. The AdeqR value measures the noise ratio; a value greater than 4 is acceptable, and here the ratio is 12.95, indicating that the model signal-noise ratio is sufficient and the model design is reasonable. The residual term is due to random error. The coefficient of variation (CV%) is 17.88%, indicating that the model is reproducible. In summary, this model can effectively demonstrate the relationship between various factors and the response values, and the model fit is good.

[0206] 9.5 Response Surface Optimization and Analysis

[0207] The response surface and contour plots of the interactions between various factors were obtained using Design-Expert version 8.0.6 software. (See...) Figure 8-13 The optimal molding process was determined through software analysis and calculation: 11.96% filler, 89.79% binder, and 2.97% disintegrant. Based on the actual situation, the final selected amounts were 12% filler, 90% binder, and 3% disintegrant.

[0208] 9.6 Process Validation

[0209] Three batches of verification tests were conducted based on the optimal molding process conditions obtained through screening. The test results are shown in Table 35. The deviation between the actual measured OD value and the theoretical predicted value is within 5%.

[0210]

[0211] 9.7 Research on the Formulation of Fuyanxiao Tablets

[0212] 300g wood sorrel, 300g patrinia, 250g trichosanthes root, 300g rhubarb

[0213] 150g of Moutan Cortex, 250g of Atractylodes Rhizome, 300g of Lindera Root

[0214] Filler (a 1:1 mixture of microcrystalline cellulose and soluble starch) approximately 53g

[0215] Approximately 14g of low-substituted hydroxypropyl cellulose

[0216] Make 1000 pieces

[0217] According to the "Extraction Process Verification" in Experiment 6, the average yield of the dry extract after water extraction of the prescription medicine for Fuyanxiao was 17.32%. Based on the original prescription of Fuyanxiao capsules, 1700g of dry extract powder can be obtained by 1700×17.32%=294.44g. After mixing with 150g of rhubarb powder, about 53g of filler (a 1:1 mixture of microcrystalline cellulose and soluble starch) of 12% of the total amount of medicine powder is added. About 14g of disintegrant low-substituted hydroxypropyl cellulose of 3.0% of the total amount of medicine powder is added. After mixing, 90% ethanol is added as a wetting agent to prepare soft material. The material is sieved and granulated, dried at 70℃, granulated, and compressed into 1000 tablets.

[0218] The tablets produced by this invention meet the requirements for hardness, disintegration time, and friability. They are also convenient to carry and take, meeting the needs of patients who are not accustomed to taking capsules. The dosage and administration are the same as commercially available capsules: 3 tablets each time, 3 times daily.

[0219] Experimental Example 10: Study on the molding process of Fuyanxiao pills

[0220] 10.1 Selection of auxiliary materials

[0221] Following the method for preparing soft material for Fuyanxiao tablets, dry extract powder and rhubarb powder were mixed in a certain proportion, with 30% excipients added. Water was used as a wetting agent to prepare a soft material of suitable hardness. The material was then made into pills and passed through a pill-making machine to obtain pills. The types and amounts of excipients and disintegrants were investigated, and the results are shown in Tables 36 and 37.

[0222]

[0223]

[0224] The table shows that the pelleting process is better when corn starch, lactose excipients, and 1% low-substituted cellulose disintegrant are added.

[0225] 10.2 Research on the Formulation of Fuyanxiao Pills

[0226] 300g wood sorrel, 300g patrinia, 250g trichosanthes root, 300g rhubarb

[0227] 150g of Moutan Cortex, 250g of Atractylodes Rhizome, 300g of Lindera Root

[0228] Approximately 133g of corn starch

[0229] Approximately 44g of low-substituted hydroxypropyl cellulose

[0230] Make 1000 pills

[0231] According to the "Extraction Process Verification" in Experiment 6, the average yield of the dry extract after water extraction of the prescription medicine for Fuyanxiao was 17.32%. Based on the original prescription of Fuyanxiao capsules, 1700g of dry extract powder can be obtained by 1700×17.32%=294.44g. After mixing with 150g of rhubarb powder, about 133g of corn starch (30% of the total medicine powder) and 44g of low-substituted hydroxypropyl cellulose (1.0% of the total medicine powder) disintegrant are added. The mixture is mixed well, water is added as a wetting agent to prepare a soft material, which is then made into pill strips, passed through a pill-making machine, and made into 1000 pills. The pills are then dried at 80℃.

[0232] The pills produced by this invention meet the required disintegration time and are convenient to carry and take, satisfying the needs of patients who are not accustomed to taking capsules. The dosage and administration are the same as commercially available capsules: 3 tablets each time, 3 times daily.

[0233] Experiment Example 11: Stability Test

[0234] Samples from Examples 1-7 were subjected to accelerated stability testing for 3 months according to the relevant provisions of the Guidelines for Stability Testing of Raw Materials and Preparations in the 2020 Edition of the Chinese Pharmacopoeia (Volume IV). The results are shown in Table 38.

[0235] Table 38 Results of Accelerated Stability Test for Fuyanxiao Oral Solid Dosage Form

[0236]

[0237]

[0238] Results: As can be seen from the table, on the one hand, the emodin content of the Fuyanxiao preparation of the present invention is 27% higher than that of commercially available Fuyanxiao capsules; on the other hand, the results of the accelerated testing of the oral solid dosage form of Fuyanxiao of the present invention meet the requirements.

[0239] To enable those skilled in the art to better understand this invention, the applicant has conducted a series of animal experiments to demonstrate the effectiveness of this invention:

[0240] Experiment Example 12: Anti-inflammatory effect test:

[0241] Investigating the effects of the gynecological anti-inflammatory preparation of the present invention on experimental uterine inflammation in rats.

[0242] Eighty female Wistar rats weighing 200-300g were randomly divided into 8 groups. Under ether anesthesia, the abdominal hair was clipped, and after disinfection, a 2cm incision was made in the midline of the abdomen to expose the uterus. A small incision was made 1cm above the left uterine horn, and a plastic tube (2mm diameter, 0.5mm length, 2mg weight, disinfected before use) was placed inside the uterus and sutured in place to prevent dislodgement. The uterine incision and abdominal cavity were then sutured in layers. Two hours post-surgery, each group was administered the drug via gavage for 7 consecutive days. Afterward, the animals were sacrificed, and both uteri were removed and weighed using a microbalance. The weight of the left uterus was reduced by 2mg (the weight of the plastic tube) before calculation. The swelling rate and inhibition rate were calculated. The mean and standard deviation of each group were calculated, and a t-test was performed to compare the significance of differences between groups. The calculation formula is as follows:

[0243] Swelling rate E (%) = (vt - vn) / vn × 100% (Note: Vn and Vt represent the weights of the non-inflammatory and inflammatory uteruses, respectively)

[0244] Inhibition rate (%) = (Ec - En) / Ec × 100% (Note: En and Ec represent the swelling rates of the treatment group and the control group, respectively)

[0245] The experimental results are shown in Table 39:

[0246] Table 39 Effects of the present invention on inflammatory swelling caused by uterine foreign bodies

[0247]

[0248] The results show that the formulations of the present invention have good anti-inflammatory effects, and their effects are superior to those of commercially available Fuyanxiao capsules.

[0249] Experimental Example 13: Analgesic Effect Test

[0250] Investigating the effect of the gynecological anti-inflammatory preparation of the present invention on the acetic acid-induced writhing response in mice.

[0251] Eighty female Kunming mice weighing 18–22 g with a pain threshold between 10 and 60 seconds were randomly divided into eight groups. Each group received the drug for 10 consecutive days. Forty minutes after the last administration, each mouse was injected intraperitoneally with 0.2 ml of 0.6% acetic acid solution. The number of writhing movements was used as a pain index. The number of writhing movements in each mouse within 15 minutes after injection was recorded. The inhibition rate of the writhing response was calculated using the following formula to evaluate the analgesic effect of the drug:

[0252] Inhibition rate % = (Mean number of writhing movements in the saline group - Mean number of writhing movements in the drug-treated group) / Mean number of writhing movements in the saline group × 100%

[0253] The experimental results are shown in Table 40:

[0254] Table 40 Effects of the present invention on acetic acid-induced writhing response in mice

[0255]

[0256] The results show that the formulations of the present invention have good analgesic effects, and their effects are superior to those of commercially available Fuyanxiao capsules.

[0257] Experiment Example 14: Antibacterial Activity Test

[0258] Take the powder of the gynecological anti-inflammatory preparation, add distilled water and decoct twice, 30 minutes each time. Combine the two decoctions and filter the liquid to make a decoction with a drug concentration of 0.5g / ml. Sterilize and disinfect before use.

[0259] Take several sterile test tubes and dilute the drug solution with the corresponding liquid culture medium, 1 ml per tube, to achieve final concentrations of 100, 50, 25, 12.5, 6.25, and 3.125 mg / ml, respectively; drug controls and bacterial controls should also be included. Add 0.1 ml of 10... -3 Diluted fresh bacterial suspensions were incubated at 37°C for 18 hours. Observe for bacterial growth. If the drug is dark in color or opaque, making it impossible to determine cell growth, the suspected tubes can be transferred to petri dishes and incubated for another 18 hours. Observe for bacterial growth at the highest drug dilution where no bacterial growth occurs. The lowest inhibitory concentration (MIC) of the drug is defined as the highest drug dilution. Experimental results are shown in Table 41.

[0260] Table 41 Results of the antibacterial effect of the oral solid dosage form of Fuyanxiao of the present invention

[0261]

[0262]

[0263]

[0264]

[0265] The results show that the formulation of the present invention has a good antibacterial effect, and the antibacterial effect is better than that of commercially available Fuyanxiao capsules. Attached Figure Description

[0266] Figure 1 For the sample moisture absorption curve

[0267] Figure 2 Response surface plot of the effect of the interaction between excipient ratio and ethanol volume fraction on OD value

[0268] Figure 3 Contour plot showing the effect of the interaction between excipient ratio and ethanol volume fraction on OD value.

[0269] Figure 4Response surface plot of the effect of the interaction between excipient ratio and ethanol dosage on OD value

[0270] Figure 5 Contour plot showing the effect of the interaction between the ratio of excipients and the amount of ethanol on the OD value.

[0271] Figure 6 Response surface plot of the effect of the interaction between ethanol volume fraction and ethanol dosage on OD value

[0272] Figure 7 Contour plot showing the effect of the interaction between ethanol volume fraction and ethanol dosage on OD value.

[0273] Figure 8 Response surface plot of the effect of filler ratio and binder interaction on OD value

[0274] Figure 9 Contour plot showing the effect of filler ratio and binder interaction on OD value

[0275] Figure 10 Response surface plot of the interaction between filler ratio and disintegrant dosage on OD value

[0276] Figure 11 Contour plot showing the effect of the interaction between filler ratio and disintegrant dosage on OD value.

[0277] Figure 12 Response surface plot of the effect of the interaction between the amount of adhesive and disintegrant on the OD value

[0278] Figure 13 Contour plot showing the effect of the interaction between adhesive and disintegrant dosages on OD value Detailed Implementation

[0279] Example 1

[0280] Prescription: 300g of Oxalis corniculata, 300g of Patrinia scabiosaefolia, 250g of Trichosanthes kirilowii, 300g of Rheum palmatum, 150g of Paeonia suffruticosa, 250g of Atractylodes lancea, and 300g of Lindera strychnifolia;

[0281] Preparation process:

[0282] Weigh out 150g of rhubarb and grind it into a fine powder for later use;

[0283] Take the remaining rhubarb and the other 6 herbs including wood sorrel, decoct twice with water, 2 hours each time, combine the decoctions, filter, and concentrate the filtrate to a clear extract with a relative density of 1.15 (60-70℃), then add to the steps in... The finely powdered rhubarb is mixed, dried, and pulverized to obtain 425g of medicinal powder, which is then made into 1000 capsules.

[0284] Example 2:

[0285] Prescription: 300g of Oxalis corniculata, 300g of Patrinia scabiosaefolia, 250g of Trichosanthes kirilowii, 300g of Rheum palmatum, 150g of Paeonia suffruticosa, 250g of Atractylodes lancea, and 300g of Lindera strychnifolia;

[0286] Preparation process:

[0287] All raw medicinal materials are selected, and mud, sand and impurities are removed. The wood sorrel is cut into small sections 20cm long for later use.

[0288] The rhubarb medicinal material is dry-cleaned using a drum-type screening machine;

[0289] Half a weight of dry-washed rhubarb is coarsely crushed using a sieve plate with a diameter of 4cm, sterilized at 115℃ for 30 minutes, vacuum dried at 70℃ until the moisture content is less than 4%, and then pulverized into nano-sized powder to obtain rhubarb raw powder for later use.

[0290] Take the remaining rhubarb and all other raw materials, add 2.04L of water and soak for 2 hours. Then add 17L of water and decoct 3 times, 1 hour each time. Combine the extracts, filter, concentrate the filtrate under reduced pressure at 75℃ to an extract with a relative density of 1.30, dry under vacuum at 80℃, and pulverize into fine powder to obtain 301g of dry extract powder for later use.

[0291] Under conditions of 60% relative humidity, the steps are as follows: rhubarb starch and steps The dry extract powder is mixed evenly and made into 1000 capsules.

[0292] Example 3:

[0293] Prescription: 300g of Oxalis corniculata, 300g of Patrinia scabiosaefolia, 250g of Trichosanthes kirilowii, 300g of Rheum palmatum, 150g of Paeonia suffruticosa, 250g of Atractylodes lancea, and 300g of Lindera strychnifolia;

[0294] Preparation process:

[0295] All raw medicinal materials are selected, and mud, sand and impurities are removed. The wood sorrel is cut into small sections 20cm long for later use.

[0296] The rhubarb medicinal material is dry-cleaned using a drum-type screening machine;

[0297] Half a weight of dry-washed rhubarb is coarsely crushed using a sieve plate with a diameter of 4cm, sterilized at 115℃ for 30 minutes, vacuum dried at 70℃ until the moisture content is less than 4%, and then pulverized into nano-sized powder to obtain rhubarb raw powder for later use.

[0298] Soak the remaining rhubarb and all other raw materials in 2.04L of water for 2 hours, then add 17L of water to each of the three decoctions, each for 1 hour. Combine the extracts, filter, and concentrate the filtrate under reduced pressure at 80℃ to an extract with a relative density of 1.28. Dry under vacuum at 85℃ and pulverize into a fine powder to obtain 292g of dry extract powder for later use.

[0299] Under conditions of 60% relative humidity, the steps are as follows: rhubarb starch and steps Mix the dry extract powder evenly, add 558g of soluble starch to make the total weight 1000g, mix well, and package into bags of 3g each to obtain the gynecological inflammation dispersant.

[0300] Example 4:

[0301] Prescription: 300g of Oxalis corniculata, 300g of Patrinia scabiosaefolia, 250g of Trichosanthes kirilowii, 300g of Rheum palmatum, 150g of Paeonia suffruticosa, 250g of Atractylodes lancea, and 300g of Lindera strychnifolia;

[0302] Preparation process:

[0303] All raw medicinal materials are selected, and mud, sand and impurities are removed. The wood sorrel is cut into small sections 20cm long for later use.

[0304] The rhubarb medicinal material is dry-cleaned using a drum-type screening machine;

[0305] Half a weight of dry-washed rhubarb is coarsely crushed using a sieve plate with a diameter of 4cm, sterilized at 115℃ for 30 minutes, dried at 70℃ until the moisture content is less than 4%, and then pulverized into nano-sized powder to obtain rhubarb raw powder for later use.

[0306] Take the remaining rhubarb and all other raw materials, add 2.04L of water and soak for 2 hours. Then add 17L of water and decoct 3 times, 1 hour each time. Combine the extracts, filter, concentrate the filtrate under reduced pressure at 80℃ to an extract with a relative density of 1.26, dry under vacuum at 85℃, and pulverize into fine powder to obtain 295g of dry extract powder for later use.

[0307] Under conditions of 60% relative humidity, the steps are as follows: rhubarb starch and steps Mix the dry extract powder evenly, add 555g of corn starch to make the total weight 1000g, mix evenly, use 88% ethanol solution as a wetting agent to prepare soft material, granulate, dry, granulate, and package in 3g bags to obtain Fuyanxiao granules.

[0308] Example 5:

[0309] Prescription: 300g of Oxalis corniculata, 300g of Patrinia scabiosaefolia, 250g of Trichosanthes kirilowii, 300g of Rheum palmatum, 150g of Paeonia suffruticosa, 250g of Atractylodes lancea, and 300g of Lindera strychnifolia;

[0310] Preparation process:

[0311] All raw medicinal materials are selected, and mud, sand and impurities are removed. The wood sorrel is cut into small sections 20cm long for later use.

[0312] The rhubarb medicinal material is dry-cleaned using a drum-type screening machine;

[0313] Half a weight of dry-washed rhubarb is coarsely crushed using a sieve plate with a diameter of 4cm, sterilized at 115℃ for 30 minutes, vacuum dried at 70℃ until the moisture content is less than 4%, and then pulverized into nano-sized powder to obtain rhubarb raw powder for later use.

[0314] Soak the remaining rhubarb and all other raw materials in 2.04L of water for 2 hours, then add 17L of water to each of the three decoctions, each for 1 hour. Combine the extracts, filter, and concentrate the filtrate under reduced pressure at 75°C to an extract with a relative density of 1.28. Dry under vacuum at 80°C, pulverize into a fine powder, and obtain 297g of dry extract powder for later use.

[0315] Under conditions of 60% relative humidity, the steps are as follows: rhubarb starch and steps Mix the dry extract powder evenly, add 0.5g of sucralose and 552.5g of corn starch to make a total weight of 1000g, mix well, use 88% ethanol solution as a wetting agent to prepare soft material, granulate, dry, granulate, and package in 3g bags to obtain Fuyanxiao granules.

[0316] Example 6:

[0317] Prescription: 300g of Oxalis corniculata, 300g of Patrinia scabiosaefolia, 250g of Trichosanthes kirilowii, 300g of Rheum palmatum, 150g of Paeonia suffruticosa, 250g of Atractylodes lancea, and 300g of Lindera strychnifolia;

[0318] Preparation process:

[0319] All raw medicinal materials are selected, and mud, sand and impurities are removed. The wood sorrel is cut into small sections 20cm long for later use.

[0320] The rhubarb medicinal material is dry-cleaned using a drum-type screening machine;

[0321] Half a weight of dry-washed rhubarb is coarsely crushed using a sieve plate with a diameter of 4cm, sterilized at 115℃ for 30 minutes, vacuum dried at 70℃ until the moisture content is less than 4%, and then pulverized into nano-sized powder to obtain rhubarb raw powder for later use.

[0322] Take the remaining rhubarb and all other raw materials, add 2.04L of water and soak for 2 hours. Then add 17L of water and decoct 3 times, 1 hour each time. Combine the extracts, filter, concentrate the filtrate under reduced pressure at 75℃ to an extract with a relative density of 1.27, dry under vacuum at 80℃, and pulverize into fine powder to obtain 302g of dry extract powder for later use.

[0323] Under conditions of 60% relative humidity, the steps are as follows: rhubarb starch and steps Mix the dry extract powder evenly, add 54g of a mixture of microcrystalline cellulose and soluble starch in a weight ratio of 1:1, add 13.5g of low-substituted hydroxypropyl cellulose, use 90% ethanol solution as a wetting agent to prepare soft material, granulate, dry, granulate and compress into 1000 tablets to obtain Fuyanxiao tablets.

[0324] Example 7:

[0325] Prescription: 300g of Oxalis corniculata, 300g of Patrinia scabiosaefolia, 250g of Trichosanthes kirilowii, 300g of Rheum palmatum, 150g of Paeonia suffruticosa, 250g of Atractylodes lancea, and 300g of Lindera strychnifolia;

[0326] Preparation process:

[0327] All raw medicinal materials are selected, and mud, sand and impurities are removed. The wood sorrel is cut into small sections 20cm long for later use.

[0328] The rhubarb medicinal material is dry-cleaned using a drum-type screening machine;

[0329] Half a weight of dry-washed rhubarb is coarsely crushed using a sieve plate with a diameter of 4cm, sterilized at 115℃ for 30 minutes, dried at 70℃ until the moisture content is less than 4%, and then pulverized into nano-sized powder to obtain rhubarb raw powder for later use.

[0330] Soak the remaining rhubarb and all other raw materials in 2.04L of water for 2 hours, then add 17L of water to each of the three decoctions, each for 1 hour. Combine the extracts, filter, and concentrate the filtrate under reduced pressure at 80℃ to an extract with a relative density of 1.25. Dry under vacuum at 85℃, pulverize into fine powder, and obtain 295g of dry extract powder for later use.

[0331] Under conditions of 60% relative humidity, the steps are as follows: rhubarb starch and steps Mix the dry extract powder evenly, add 133g of corn starch and 44g of low-substituted cellulose, add water as a wetting agent, prepare soft material, make into pill strips, pass through a pill-making machine to make 1000 pills, dry at 80℃ to obtain Fuyanxiao pills.

Claims

1. A method for preparing a solid oral dosage form of Fuyanxiao, characterized in that, The oral solid preparation of Fuyanxiao is prepared from the following raw materials in the following proportions: Oxalis corniculata L. 300 parts, Patrinia scabiosaefolia Fisch. 300 parts, Trichosanthes kirilowii Maxim. 250 parts, Rheum palmatum L. 300 parts, Paeonia suffruticosa Andr. 150 parts, Atractylodes lancea DC. 250 parts, and Liriodendron chinense Oliv. 300 parts, and comprises the following steps: ①All raw medicinal materials are selected and cleaned to remove dirt and sundries, and O. corniculata is cut into small pieces with a length of 20 cm for later use; ②R. palmatum medicinal materials are dry washed by adding them into a drum-type screening machine; ③Half of the dry washed R. palmatum medicinal materials are coarsely crushed with a 4 cm diameter sieve plate, subjected to moist heat sterilization at 115°C for 30 minutes, vacuum dried at 100°C for 3 times, each for 15 minutes, and then ultra-micro pulverized into nanoscale fine powder to obtain R. palmatum raw powder for later use; ④The remaining R. palmatum medicinal materials and all other raw medicinal materials are added into water in an amount of 120% of the weight of the raw materials, soaked for 2 hours, and then boiled in water in an amount of 10 times for 3 times, each for 1 hour. The extraction liquid is combined, filtered, and concentrated under reduced pressure at 75°C and a vacuum degree of -0.085 MPa to a relative density of 1.20-1.

30. The concentrated extraction liquid is vacuum dried at 80°C until the water content is less than 4%, and then pulverized into fine powder to obtain dry extraction powder for later use; ⑤The R. palmatum raw powder of step ③ and the dry extraction powder of step ④ are uniformly mixed, and pharmaceutically acceptable pharmaceutical adjuvants are added to prepare various oral solid preparations; The solid preparation is tablets, capsules, powders, pills, and granules. The environment for preparing the various oral solid preparations is controlled to have a relative humidity of less than 60%.

2. The production method according to claim 1, characterized by, The tablets are prepared by uniformly mixing the R. palmatum raw powder of step ③ and the dry extraction powder of step ④, adding a filler and a disintegrant, uniformly mixing, using an ethanol solution as a wetting agent, preparing soft material, granulating, drying, and whole-granulating, and then tabletting to obtain the tablets. The filler is a mixture of microcrystalline cellulose and soluble starch in a weight ratio of 1:1, and the disintegrant is low-substituted hydroxypropyl cellulose.

3. The preparation method according to claim 2, characterized in that, The filler is added in an amount of 10%-15% of the total amount of the R. palmatum raw powder and the dry extraction powder, and the disintegrant is added in an amount of 2.5%-3.5% of the total amount of the R. palmatum raw powder and the dry extraction powder. The wetting agent is 90% ethanol.

4. The production method according to claim 3, characterized by, The filler is added in an amount of 12% of the total amount of the R. palmatum raw powder and the dry extraction powder, and the disintegrant is added in an amount of 3.0% of the total amount of the R. palmatum raw powder and the dry extraction powder.

5. The preparation method according to claim 1, characterized in that, The capsules are prepared by uniformly mixing the R. palmatum raw powder of step ③ and the dry extraction powder of step ④, and then loading the mixture into capsules.

6. The method of claim 1, wherein, The capsules are prepared by uniformly mixing the R. palmatum raw powder of step ③ and the dry extraction powder of step ④, adding soluble starch in an amount of 1:1 of the total amount of the mixed powder, uniformly mixing, and then loading the mixture into capsules.

7. The preparation method according to claim 1, characterized in that, The powders are prepared by uniformly mixing the R. palmatum raw powder of step ③ and the dry extraction powder of step ④, adding soluble starch, uniformly mixing, and then loading the mixture into bags.

8. The method of claim 1, wherein, The pills are prepared by uniformly mixing the R. palmatum raw powder of step ③ and the dry extraction powder of step ④, adding corn starch and low-substituted hydroxypropyl cellulose, uniformly mixing, using water as a wetting agent, preparing soft material, preparing pill strips, passing the pill strips through a pill machine to form pills, and then drying the pills at 80°C to obtain the pills.

9. The preparation method according to claim 7, characterized in that, The added amount of the corn starch is 30% of the total amount of the rhubarb powder and the dry extract powder, and the added amount of the low-substituted hydroxypropyl cellulose is 1% of the total amount of the rhubarb powder and the dry extract powder.

10. The method of claim 1, wherein, The granules are prepared by mixing the rhubarb powder of step ③ with the dry extract powder of step ④, adding sucralose, adding corn starch, mixing, preparing soft material with 88% ethanol as a wetting agent, granulating, drying, sizing, and packaging.

Images