Pharmaceutical composition for treating pelvic inflammatory disease sequelae and method for preparing the same

Abstract

This application discloses a pharmaceutical composition for treating sequelae of pelvic inflammatory disease and its preparation method. One pharmaceutical composition, by weight, comprises: 150-220 parts of stir-fried white peony root, 100-150 parts of bupleurum root, 150-220 parts of angelica root, 150-220 parts of poria cocos, 150-220 parts of chuanxiong rhizome, 100-150 parts of peony bark, 150-220 parts of turmeric root, 150-450 parts of astragalus root, 150-220 parts of vaccaria seed, 100-150 parts of stir-fried yam root, 40-80 parts of licorice root, 150-220 parts of patrinia root, 100-150 parts of corydalis rhizome, and 60-120 parts of turmeric root. This application targets the core pathogenesis of "lingering pathogenic factors" in the sequelae of pelvic inflammatory disease, significantly enhancing its effects of clearing heat and detoxifying, promoting blood circulation and relieving pain, and eliminating masses and nodules. It is more suitable for severe patients with severe pain, significant blood stasis and damp-heat, and accompanied by masses or thickening of the adnexa. This application optimizes the process, resulting in better overall efficacy and drug properties.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical technology, and in particular to pharmaceutical compositions for treating sequelae of pelvic inflammatory disease and methods for their preparation. Background Technology

[0002] Chronic pelvic pain (CPP) in women is a sequela of untreated pelvic inflammatory disease (PID). Currently, there is no internationally accepted definition, especially regarding the location, duration, and cyclical nature of the pain. The internationally accepted standard is non-cyclical pain located in the pelvic region, including the abdominal wall, pelvic organs, perineum, lumbosacral region, and buttocks, lasting for more than 6 months. Cyclic pain that significantly impacts daily life and mental well-being is also classified as CPP. For example, dysmenorrhea and ovulation pain are cyclical pelvic pain and, in principle, not CPP. However, if accompanied by significant adverse outcomes in cognition, behavior, sexual life, and emotions, it is considered a form of CPP. It is important to emphasize that pain is a subjective sensation; even if examinations reveal no abnormalities, a diagnosis of CPP cannot be ruled out. According to the above definition, the incidence of CPP in women ranges from 5.7% to 26.6%, affecting a wide range of people and significantly impacting patients' quality of life. A high-quality systematic review study in 2006 found that the prevalence of non-cyclic pain in women was 2.1%–24%, and the prevalence of dyspareunia was 8%–21.1%.

[0003] CPP is prone to long-term recurrence, significantly impacting patients' physical, psychological, and daily lives, and placing pressure on healthcare systems. In high-income countries like the United States, the estimated annual healthcare cost is as high as $2.8 billion. The decreased productivity and increased medical expenses caused by CPP create a huge socioeconomic burden and are a pressing clinical problem. CPP in women can be categorized into three types based on etiology: organ-related diseases, neuromuscular pain, and pain caused by psychosocial factors. SPID-CPP, resulting from untreated or inadequate PID treatment, clinically manifests as lower abdominal distension, pain, and lumbosacral aches, often exacerbated by exertion, sexual intercourse, and before and after menstruation. PID is a clearly defined cause of chronic pelvic pain; one study showed that women with a history of PID have a more than four times higher risk of developing chronic pelvic pain than women of normal reproductive age.

[0004] To date, comprehensive epidemiological data on SPID-CPP is lacking globally. A survey by the UK Health Security Agency showed that in 2023 in the UK, the diagnosis rates of PID in hospitals, sexual health services, and general practitioners were approximately 1 in 420, 1 in 1500, and 1 in 930, respectively. Literature indicates that approximately 20% of PID cases result in chronic pelvic pain.

[0005] CPP affects a wide range of women, and women with a history of PID have a risk of developing CPP more than four times higher than women of normal reproductive age. Therefore, SPID-CPP is indicated for a large patient population. Currently, there is no effective treatment for SPID-CPP, and Western medicine treatment has limitations: for example, analgesics have many adverse reactions, and antibiotics are not very effective for local aseptic inflammation and long-term chronic pain. Therefore, there is an unmet clinical need for treatment of this disease, and traditional Chinese medicine is often the main approach in clinical practice.

[0006] The existing drug for treating sequelae of pelvic inflammatory disease, Baijin Fu'an Granules (CN1698862A), has the following shortcomings.

[0007] (1) The formula of Baijin Fu'an Granules contains a large amount of Astragalus membranaceus. The principle of treatment is to replenish and promote blood circulation by replenishing the original Qi. It is suitable for patients with severe Qi deficiency (such as extreme fatigue, shortness of breath, spontaneous sweating) and no prominent blood stasis and heat symptoms, but it cannot clear the residual damp heat and blood stasis in the pelvic cavity.

[0008] (2) The blood-activating group of Baijin Fu'an Granules has a relatively mild effect, mainly nourishing blood and activating blood (Angelica sinensis, Ligusticum chuanxiong) and unblocking collaterals (Vaccaria segetalis). It is more suitable for patients with mild pain and distending pain, and is suitable for treating patients with relatively mild blood stasis syndrome. However, it is less effective for patients with severe pain. Summary of the Invention

[0009] To address the shortcomings of existing technologies and meet real clinical needs, this application provides a pharmaceutical composition for treating sequelae of pelvic inflammatory disease. This pharmaceutical composition is particularly suitable for treating patients with qi deficiency and blood stasis, accompanied by significant damp-heat and toxicity, characterized by stabbing, fixed, or burning pain, or pelvic tenderness, possibly accompanied by yellow vaginal discharge, dark red menstrual blood with clots, and dry mouth. The prescription in this application offers a more classic and comprehensive approach to treating sequelae of chronic pelvic inflammatory disease, directly targeting the key pathological factor of "residual pathogenic factors not cleared, blood stasis forming masses," which leads to chronic pain, and it has proven effective in clinical practice.

[0010] A pharmaceutical composition, comprising, by weight: 150-220 parts of stir-fried white peony root, 100-150 parts of bupleurum root, 150-220 parts of angelica root, 150-220 parts of poria cocos, 150-220 parts of chuanxiong rhizome, 100-150 parts of peony bark, 150-220 parts of turmeric root, 150-450 parts of astragalus root, 150-220 parts of vaccaria seed, 100-150 parts of stir-fried yam root, 40-80 parts of licorice root, 150-220 parts of patrinia root, 100-150 parts of corydalis rhizome, and 60-120 parts of turmeric root.

[0011] In some embodiments, the pharmaceutical composition comprises, by weight, 180-190 parts of stir-fried white peony root, 120-130 parts of bupleurum root, 180-190 parts of angelica root, 180-190 parts of poria cocos, 180-190 parts of chuanxiong rhizome, 120-130 parts of peony bark, 180-190 parts of turmeric root, 220-280 parts of astragalus root, 180-190 parts of vaccaria seed, 120-130 parts of stir-fried yam root, 40-80 parts of licorice root, 180-190 parts of patrinia root, 120-130 parts of corydalis rhizome, and 90-100 parts of turmeric root.

[0012] This application also provides the use of the pharmaceutical composition in the preparation of a medicament for treating sequelae of gynecological pelvic inflammatory disease.

[0013] This application provides a method for preparing the pharmaceutical composition, comprising: 1) Angelica sinensis, Ligusticum chuanxiong, Curcuma longa and Curcuma zedoaria are treated by distillation to obtain volatile oil, medicinal liquid and medicinal residue. The volatile oil is encapsulated to obtain an inclusion complex. The medicinal liquid and medicinal residue are used for future reference. 2) The peony bark is treated by distillation to obtain paeonol, a medicinal liquid and a residue. Paeonol is then encapsulated to obtain an inclusion complex. The medicinal liquid and residue are kept for later use. 3) Mix Poria cocos, Astragalus membranaceus, Vaccaria segetalis, stir-fried Dioscorea opposita, Glycyrrhiza uralensis, Patrinia scabiosaefolia, Corydalis yanhusuo with the dregs from 1) and 2), and process with water extraction to obtain the extract. Discard the dregs. 4) Combine the medicinal solutions from 1) and 2) and the extract from 3), and concentrate them into a clear paste for later use; 5) Mix and pulverize the stir-fried white peony root and bupleurum root, process them with alcohol extraction to obtain an extract, and concentrate it into a clear paste for later use; 6) Using a top-spray granulation process, the inclusion complexes described in 1) and 2) and the extracts described in 4) and 5) are granulated.

[0014] In some embodiments, during inclusion in 1), the volatile oil is mixed with hydroxypropyl β-cyclodextrin and ethanol for inclusion, wherein the weight of hydroxypropyl β-cyclodextrin is 2-10 times the weight of the volatile oil and the weight of ethanol is 1-5 times the weight of hydroxypropyl β-cyclodextrin.

[0015] In some implementations, when processing peony bark, 6-18 times its weight of water is added for extraction.

[0016] In some implementations, when processing peony bark, 5-15 times the amount of distillate is received to obtain paeonol.

[0017] In some embodiments, when encapsulating paeonol, paeonol is dissolved and encapsulated with hydroxypropyl β-cyclodextrin and ethanol, wherein the weight of hydroxypropyl β-cyclodextrin is 1-8 times the weight of paeonol and the weight of ethanol is 1-8 times the weight of hydroxypropyl β-cyclodextrin.

[0018] In some implementations, colloidal silica is also added during the inclusion process.

[0019] In some embodiments, the amount of colloidal silica added is 1-12% of the weight of hydroxypropyl β-cyclodextrin.

[0020] The pharmaceutical composition of this application has the following advantages compared with the prior art drug Baijin Fu'an Granules (CN1698862A) for treating sequelae of pelvic inflammatory disease.

[0021] (1) The fundamental treatment principles are different.

[0022] The pharmaceutical composition of this application reduces the dosage of Astragalus membranaceus and increases the dosage of Patrinia scabiosaefolia. The combination of the two emphasizes both tonifying the body's resistance (replenishing Qi) and eliminating pathogenic factors (clearing heat and detoxifying). While replenishing Qi, it directly clears away residual damp-heat and stagnant toxins in the pelvic cavity. This is a classic approach to treating the pathogenesis of "residual pathogenic factors not yet cleared" in chronic pelvic inflammatory disease.

[0023] (2) The pain relief and blood stasis removal effects are different.

[0024] The blood-activating group of Baijin Fu'an granules has a relatively mild effect, mainly nourishing and activating blood (Angelica sinensis, Ligusticum chuanxiong) and unblocking collaterals (Vaccaria segetalis). It is more suitable for patients with dull pain and distending pain. It is more effective for patients with relatively mild blood stasis syndrome, but less effective for patients with severe pain.

[0025] The pharmaceutical composition of this application includes Corydalis Rhizome and Curcuma Rhizome, whose ability to promote blood circulation, relieve pain, and dissipate masses is far stronger than that of Baijin Fu'an Granules. For cases of severe pain (especially stabbing or fixed pain) or where masses may be palpable (such as thickening or cysts in the adnexal region), the pharmaceutical composition of this application is more suitable.

[0026] (3) The indications are different.

[0027] Based on the above analysis, the optimal indications for the two are clearly distinguishable: The core pathogenesis of Baijin Fu'an Granules is qi deficiency and blood stasis, with no obvious signs of damp-heat. The pain is characterized by dull, aching pain that worsens after exertion, accompanied by fatigue, shortness of breath, prominent spontaneous sweating, thin and clear vaginal discharge, a pale and dark tongue, a swollen tongue body or teeth marks, and a white tongue coating. The core pathogenesis of the prescription in this application is qi deficiency and blood stasis, with significant damp-heat and blood stasis. The pain is characterized by stabbing, fixed, or burning pain, or accompanied by pelvic tenderness, possibly accompanied by yellow vaginal discharge, dark red menstrual blood with clots, and dry mouth. The drug composition in this application has a more classic and comprehensive approach to treating the sequelae of chronic pelvic inflammatory disease, directly targeting the key pathological factor leading to chronic pain: "residual pathogenic factors not cleared, blood stasis forming masses."

[0028] On the other hand, this application also optimizes the preparation method of the pharmaceutical composition. The main active ingredient in peony bark is paeonol, a white or slightly yellow crystalline powder with a melting point of 48-51℃. It is readily soluble in ethanol and methanol, soluble in hot water, but insoluble in cold water, and can volatilize with steam. During the preparation of the medicine, a large amount of distillate needs to be collected and cooled to allow crystals to precipitate. The volatile oils of angelica and turmeric are oily liquids, extracted by distillation. These volatile oils are insoluble in water, and during extraction, they agglomerate, allowing for direct oil-water separation. Since paeonol is insoluble in other volatile oils, if all the medicinal materials are distilled together, the drug cannot be completely extracted, and paeonol precipitation cannot be achieved. Therefore, peony bark needs to be distilled separately to extract paeonol. Paeonol and its volatile oils are easily volatile and require inclusion to maintain temperature. Compared with conventional β-cyclodextrin inclusion, hydroxypropyl-β-cyclodextrin inclusion can increase the water solubility of the inclusion compound, making it more suitable for granule formulation. To maximize product stability, this application adopts a two-step method of "inclusion first, adsorption later". Hydroxypropyl-β-cyclodextrin is used to encapsulate the volatile oil to protect it. The resulting inclusion compound solution or wet block is then adsorbed with colloidal silica, which can more completely encapsulate the volatile oil. The inclusion compound is also easy to dry. The preparation method of inclusion first can improve the flowability and moisture resistance of the powder, as well as the stability of the granule dissolution solution. Detailed Implementation

[0029] Specific embodiments of this application will now be described in more detail. While the following description illustrates specific embodiments of this application, it should be understood that this application can be implemented in various forms and should not be limited to the specific embodiments or implementations set forth herein. Rather, these specific embodiments or implementations are provided to enable a more thorough understanding of this application and to fully convey the scope of this application to those skilled in the art.

[0030] In this application, the term "sequelae of pelvic inflammatory disease" refers to sequelae of pelvic inflammatory disease (PSPID), formerly known as chronic pelvic inflammatory disease. It is a long-term, chronic pathological change caused by the failure to treat pelvic inflammatory disease (PID) in a timely and standardized manner, or by repeated and prolonged illness. The core of the disease is adhesion, hyperplasia, and scar formation of pelvic tissues, involving the uterus, fallopian tubes, ovaries, and pelvic peritoneum. It is a common gynecological disease in women of reproductive age and an important cause of infertility, ectopic pregnancy, and chronic pelvic pain.

[0031] In this application, the term "v / v" refers to a volume ratio, for example, "50% (v / v) aqueous ethanol solution" means that in an aqueous ethanol solution, the volume of ethanol accounts for 50% of the total volume of the aqueous solution.

[0032] In this application, the terms "relative density" or "specific gravity" refer to the specific gravity in traditional Chinese medicine extraction. The core meaning is the ratio of the weight of the extract (extract, concentrate, medicinal liquid) to the weight of the same volume of pure water at a specific temperature. In this application, a hydrometer is used for measurement.

[0033] The terms "pharmaceutically acceptable carrier" or "pharmaceutically acceptable excipient" refer to pharmaceutically acceptable materials, compositions, or carriers, such as liquid or solid fillers, diluents, solvents, or encapsulating materials. In some embodiments, each component is "pharmaceutically acceptable" in the sense that it is compatible with other components of the pharmaceutical preparation and suitable for contact with the tissues or organs of a subject (e.g., a human) without excessive toxicity, irritation, allergic reactions, immunogenicity, or other problems or complications, and has a reasonable benefit / risk ratio.

[0034] This application provides a pharmaceutical composition comprising stir-fried white peony root, bupleurum root, angelica root, poria cocos, chuanxiong rhizome, peony bark, turmeric root, astragalus root, vaccaria seed, stir-fried yam, licorice root, patrinia root, corydalis rhizome, and turmeric rhizome.

[0035] In some embodiments, the pharmaceutical composition comprises, by weight, 150-220 parts of stir-fried white peony root, 100-150 parts of bupleurum root, 150-220 parts of angelica root, 150-220 parts of poria cocos, 150-220 parts of chuanxiong rhizome, 100-150 parts of peony bark, 150-220 parts of turmeric root, 150-450 parts of astragalus root, 150-220 parts of vaccaria seed, 100-150 parts of stir-fried yam root, 40-80 parts of licorice root, 150-220 parts of patrinia root, 100-150 parts of corydalis rhizome, and 60-120 parts of turmeric root.

[0036] In some embodiments, the pharmaceutical composition comprises, by weight, 180-190 parts of stir-fried white peony root, 120-130 parts of bupleurum root, 180-190 parts of angelica root, 180-190 parts of poria cocos, 180-190 parts of chuanxiong rhizome, 120-130 parts of peony bark, 180-190 parts of turmeric root, 220-280 parts of astragalus root, 180-190 parts of vaccaria seed, 120-130 parts of stir-fried yam root, 40-80 parts of licorice root, 180-190 parts of patrinia root, 120-130 parts of corydalis rhizome, and 90-100 parts of turmeric root.

[0037] In some embodiments, the pharmaceutical composition comprises, by weight, 187 parts of stir-fried white peony root, 125 parts of bupleurum root, 187 parts of angelica root, 187 parts of poria cocos, 187 parts of chuanxiong rhizome, 125 parts of peony bark, 187 parts of turmeric root, 250 parts of astragalus root, 187 parts of vaccaria seed, 125 parts of stir-fried yam root, 62 parts of licorice root, 187 parts of patrinia root, 125 parts of corydalis rhizome, and 93 parts of turmeric root.

[0038] In one embodiment, the pharmaceutical composition, by weight, comprises: 187 parts of stir-fried white peony root, 125 parts of bupleurum root, 187 parts of angelica root, 187 parts of poria cocos, 187 parts of chuanxiong rhizome, 125 parts of peony bark, 187 parts of turmeric root, 250 parts of astragalus root, 187 parts of vaccaria seed, 125 parts of stir-fried yam root, 62 parts of licorice root, 187 parts of patrinia root, 125 parts of corydalis rhizome, and 93 parts of turmeric root.

[0039] In some embodiments, the pharmaceutical composition further includes at least one pharmaceutically acceptable carrier.

[0040] In some embodiments, the pharmaceutical composition, by weight, comprises 187 parts of stir-fried white peony root, 125 parts of bupleurum root, 187 parts of angelica root, 187 parts of poria cocos, 187 parts of chuanxiong rhizome, 125 parts of peony bark, 187 parts of turmeric root, 250 parts of astragalus root, 187 parts of vaccaria seed, 125 parts of stir-fried yam root, 62 parts of licorice root, 187 parts of patrinia root, 125 parts of corydalis rhizome, 93 parts of turmeric root, and at least one pharmaceutically acceptable carrier.

[0041] This application provides the use of the pharmaceutical composition described herein in the preparation of a medicament for treating sequelae of pelvic inflammatory disease.

[0042] In some implementations, the sequelae of the gynecological pelvic inflammatory disease are chronic pelvic pain.

[0043] This application provides a method for preparing the pharmaceutical composition, specifically including steps 1) to 6).

[0044] Step 1) The herbs Angelica sinensis, Ligusticum chuanxiong, Curcuma longa, and Curcuma zedoaria are processed by distillation. Specifically, the herbs are mixed, water is added to the mixture and the mixture is soaked, followed by steam distillation to extract the volatile oil. The remaining liquid and residue after extracting the volatile oil are reserved. Hydroxypropyl β-cyclodextrin and ethanol are added to the volatile oil, and the mixture is ground and dried under reduced pressure to obtain the volatile oil inclusion complex.

[0045] In some implementations, step 1) involves adding water to the mixture of medicinal materials in a ratio of 5 to 12 times the total weight of the medicinal materials. Specifically, this can be water in a ratio of 5, 6, 7, 8, 10, or 12 times the total weight of the medicinal materials.

[0046] In some implementations, step 1) involves adding water to the mixture of medicinal materials in a ratio of 10 times the total weight of the medicinal materials.

[0047] In some implementations, the steam distillation time in step 1) is 2-8 hours, specifically, the distillation time can be 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, or 8 hours.

[0048] In some implementations, step 1) steam distillation takes 5 hours.

[0049] In some implementations, step 1) involves adding 2-10 times the weight of the volatile oil to the volatile oil. Specifically, 2, 3, 4, 5, 6, 7, 8, 9, or 10 times the weight of the volatile oil can be added.

[0050] In some implementations, step 1) involves adding hydroxypropyl β-cyclodextrin to the volatile oil at a weight of 5 times that of the volatile oil.

[0051] In some embodiments, step 1) involves adding ethanol at 1-5 times the weight of hydroxypropyl β-cyclodextrin to the volatile oil. Specifically, ethanol at 1, 2, 3, 4, or 5 times the weight of hydroxypropyl β-cyclodextrin can be added.

[0052] In some implementations, step 1) involves adding ethanol at a weight of twice the weight of hydroxypropyl β-cyclodextrin to the volatile oil.

[0053] In some implementations, during the inclusion process in step 1), an aqueous ethanol solution with a concentration of 20% (v / v) is added.

[0054] In some embodiments, in step 1), after mixing and grinding hydroxypropyl β-cyclodextrin and ethanol, the volatile oil is added and ground again, followed by the addition of colloidal silica and further grinding, and then drying to obtain a volatile oil inclusion complex. The amount of colloidal silica added is 1-12% of the weight of hydroxypropyl β-cyclodextrin. Specifically, the amount of colloidal silica added can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, or 12% of the weight of hydroxypropyl β-cyclodextrin.

[0055] In some embodiments, the amount of colloidal silica added in step 1) is 10% of the weight of hydroxypropyl β-cyclodextrin. Step 2) The peony bark is processed by distillation. Specifically, water is added to the peony bark, steam distillation is performed, and the distillate is collected. The distillate is then refrigerated and filtered to obtain paeonol. The remaining liquid and residue after extraction are reserved. The extracted paeonol is dissolved in a small amount of ethanol, and then hydroxypropyl β-cyclodextrin and ethanol are added. After grinding and drying, paeonol inclusion complexes are obtained.

[0056] In some implementations, step 2) involves adding water to the peony bark in quantities of 6-18 times its total weight. Specifically, water can be added in quantities of 6, 8, 10, 12, 14, or 16 times the total weight of the peony bark.

[0057] In some implementations, step 2) involves adding water to the peony bark in an amount equal to 12 times its total weight.

[0058] In some implementations, the steam distillation time in step 2) is 2-8 hours, specifically, the distillation time can be 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, or 8 hours.

[0059] In some implementations, the steam distillation time in step 2) is 4 hours.

[0060] In some implementations, during step 2) of distillation, a distillate of 6-12 times the weight of the medicinal material is received. Specifically, a distillate of 6, 7, 8, 9, 10, 11, or 12 times the weight of the medicinal material can be received.

[0061] In some implementations, during step 2) of distillation, a distillate equal to nine times the weight of the medicinal material is received.

[0062] In some implementations, step 2) involves dissolving the extracted paeonol in a 50% (v / v) aqueous ethanol solution.

[0063] In some embodiments, step 2) involves adding 1-8 times the weight of paeonol to the dissolved paeonol. Specifically, 1, 2, 3, 4, 5, 6, 7, or 8 times the weight of paeonol can be added.

[0064] In some implementations, step 2) involves adding 5 times the weight of hydroxypropyl β-cyclodextrin to the dissolved paeonol.

[0065] In some implementations, step 2) involves adding ethanol at 1-5 times the weight of hydroxypropyl β-cyclodextrin to the dissolved paeonol. Specifically, ethanol at 1, 2, 3, 4, or 5 times the weight of hydroxypropyl β-cyclodextrin can be added.

[0066] In some implementations, step 2) involves adding ethanol at a weight of twice the weight of hydroxypropyl β-cyclodextrin to the dissolved paeonol.

[0067] In some implementations, during the inclusion process in step 2), an aqueous ethanol solution with a concentration of 50% (v / v) is added.

[0068] In some embodiments, during step 2) inclusion, hydroxypropyl β-cyclodextrin and ethanol are added to the dissolved paeonol, and after grinding, colloidal silica is added and grinding is continued. After drying, the paeonol inclusion complex is obtained. The amount of colloidal silica added can be 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, or 12% of the weight of hydroxypropyl β-cyclodextrin.

[0069] In some implementations, the amount of colloidal silica added in step 2) is 10% of the weight of hydroxypropyl β-cyclodextrin.

[0070] Step 3) Water extraction method for processing medicinal materials: Specifically, Poria cocos, Astragalus membranaceus, Vaccaria segetalis, stir-fried Dioscorea opposita, Glycyrrhiza uralensis, Patrinia scabiosaefolia, Corydalis yanhusuo are mixed with the dregs from Step 1) and Step 2), and water is added in 12 times the total weight of the above mixed medicinal materials. The mixture is heated for 2 hours to obtain an extract. The remaining dregs are then added to water in 8 times the total weight of the medicinal materials and heated for 2 hours to obtain an extract. The two extracts are combined for later use, and the dregs are discarded.

[0071] Step 4) Combine the medicinal liquids from Step 1) and Step 2) with the extract from Step 3), heat and concentrate to form a clear paste for later use.

[0072] In some implementations, after heating and concentration in step 4), the relative density of the extract is 1.1-1.2.

[0073] Step 5) Alcohol extraction method for processing medicinal materials. Specifically, stir-fried white peony root and bupleurum root are mixed, and 70% (v / v) ethanol with a concentration of 8 times the total weight of the medicinal materials is added. The mixture is heated for 2 hours to obtain an extract. The remaining residue is then added to 70% (v / v) ethanol with a concentration of 6 times the total weight of the medicinal materials and heated for 2 hours to obtain an extract. The two extracts are combined and concentrated into a clear paste for later use. The residue is discarded.

[0074] In some implementations, step 5) involves heating and concentrating the extract to a clear paste with a relative density of 1.1-1.2.

[0075] Step 6), granulation, specifically, using a top-spray granulation process, the inclusion complexes from steps 1) and 2) are mixed with hydroxypropyl β-cyclodextrin as the base material, and the clear paste from steps 4) and 5) is top-sprayed and granulated through a fluidized bed.

[0076] In some implementations, flavoring agents are added during granulation in step 6) to mask bitterness and improve taste. Specifically, these include, but are not limited to, maltodextrin, L-arabinose, sucrose, lactose, mannitol, steviol glycosides, sucralose, flavorings, menthol, etc.

[0077] Compared with the existing technology of Baijin Fu'an granules, the pharmaceutical composition of this application has significant advantages in terms of formulation principles, efficacy, and indications: it emphasizes both strengthening the body's resistance and eliminating pathogenic factors, targeting the core pathogenesis of "residual pathogenic factors" in the sequelae of pelvic inflammatory disease. By adding Patrinia scabiosaefolia, Corydalis yanhusuo, and Curcuma zedoaria, it significantly enhances the effects of clearing heat and detoxifying, promoting blood circulation and relieving pain, and eliminating masses and nodules, making it more suitable for severe patients with severe pain, obvious blood stasis and damp heat, and accompanied by masses or thickening of the adnexa. At the same time, this application optimizes the extraction and preparation process, separately distilling paeonol from Paeonia suffruticosa, and using a two-step method of "encapsulation followed by adsorption" with hydroxypropyl-β-cyclodextrin to treat the volatile oil, and optimizing the inclusion process to effectively improve the extraction rate of active ingredients, inclusion effect, formulation stability, water solubility, and oral stability, resulting in better overall efficacy and drug properties.

[0078] The pharmaceutical composition described in this application can improve symptoms such as fallopian tube inflammation, blockage, adhesion, and tissue hyperplasia, and can also protect the mucosal epithelium and muscle layer connective tissue of the fallopian tube tissue. It can also relieve symptoms such as endometrial epithelial necrosis, muscle layer connective tissue hyperplasia, and interstitial pathological changes.

[0079] Example Example 1 The pharmaceutical composition in this embodiment includes, by weight, 187 parts of stir-fried white peony root, 125 parts of bupleurum root, 187 parts of angelica root, 187 parts of poria cocos, 187 parts of chuanxiong rhizome, 125 parts of peony bark, 187 parts of turmeric root, 250 parts of astragalus root, 187 parts of vaccaria seed, 125 parts of stir-fried yam root, 62 parts of licorice root, 187 parts of patrinia root, 125 parts of corydalis rhizome, and 93 parts of turmeric root.

[0080] The specific steps for preparing granules from the above-mentioned medicinal materials are as follows.

[0081] Step 1) Mix Angelica sinensis, Ligusticum chuanxiong, Curcuma longa and Curcuma zedoaria. Add water five times the total weight of the herbs to the mixture and steam distill for 5 hours to extract the volatile oil. The remaining liquid and residue after extracting the volatile oil are reserved for later use.

[0082] Five times the weight of the volatile oil, 20% (v / v) ethanol (twice the weight of the volatile oil), were ground into a paste. The volatile oil was then added, and the mixture was ground for 2 hours with a grinding gap of 5 micrometers. Then, 10% of the weight of the hydroxypropyl β-cyclodextrin, colloidal silica was added, and the mixture was ground for another hour. The mixture was then dried under reduced pressure at 40°C to obtain the volatile oil inclusion complex.

[0083] Step 2) Add water to the peony bark in a volume 12 times its total weight, steam distill for 4 hours, collect the distillate in a volume 9 times the weight of the medicinal material, refrigerate and filter the distillate to obtain paeonol, and keep the remaining liquid and residue after paeonol extraction for later use.

[0084] The extracted paeonol was dissolved in a small amount of 50% (v / v) ethanol aqueous solution. Then, 5 times the weight of hydroxypropyl β-cyclodextrin and 2 times the weight of hydroxypropyl β-cyclodextrin in 50% (v / v) ethanol solution were added. After grinding for 1 hour, 10% of the weight of hydroxypropyl β-cyclodextrin in colloidal silica was added, and grinding was continued for 40 minutes. The mixture was then dried at 40°C to obtain the paeonol inclusion complex.

[0085] Step 3) Mix Poria cocos, Astragalus membranaceus, Vaccaria segetalis, stir-fried Dioscorea opposita, Glycyrrhiza uralensis, Patrinia scabiosaefolia, Corydalis yanhusuo with the dregs from Step 1) and Step 2), add water at 12 times the total weight of the above medicinal materials, heat for 2 hours to obtain an extract. Add water at 8 times the total weight of the medicinal materials to the remaining dregs again, and continue heating for 2 hours to obtain an extract. Combine the two extracts for later use and discard the dregs.

[0086] Step 4) Combine the medicinal solutions from Step 1) and Step 2) with the extract from Step 3), heat and concentrate to a clear paste with a specific gravity of 1.1-1.2 for later use.

[0087] Step 5) Mix and grind the stir-fried white peony root and bupleurum root together, add 8 times the weight of the total weight of the above medicinal materials to a 70% (v / v) ethanol aqueous solution, heat for 2 hours to obtain an extract. Add 6 times the weight of the total weight of the medicinal materials to a 70% (v / v) ethanol aqueous solution again, and continue heating for 2 hours to obtain an extract. Combine the two extracts and concentrate them to a clear paste with a specific gravity of 1.1-1.2 for later use.

[0088] Step 6) Using a top-spray granulation process, the inclusion complexes from Steps 1) and 2) are mixed with hydroxypropyl β-cyclodextrin as the base material, and the clear paste from Steps 4) and 5) is top-sprayed and granulated in a fluidized bed.

[0089] The prepared granule formulation was tested for paeonol extraction yield, encapsulation efficiency, and flowability, as detailed below.

[0090] Paeonol extraction yield = Paeonol weight / Moutan bark weight * 100.

[0091] Encapsulation rate of volatile oil = (total extracted volatile oil volume - unencapsulated volatile oil volume) / total extracted volatile oil volume * 100%.

[0092] Paeonol encapsulation rate = (total paeonol weight - unencapsulated paeonol weight) / total paeonol weight.

[0093] The fluidity was determined using the angle of repose method as described in the Chinese Pharmacopoeia (2025 edition).

[0094] Table 1. Liquidity and Corresponding Angle of Repose The paeonol extraction yield of the granule formulation in Example 1 was tested, and the test results are shown in Table 2.

[0095] Example 2-3 The difference between Examples 2-3 and Example 1 is that the distillate received during distillation is different when processing peony bark. The extraction rate of paeonol in the granule preparations of Examples 2-3 was tested, and the results are shown in Table 2.

[0096] Table 2 Extraction rate of paeonol

[0097] Example 4 Example 4 is an orthogonal optimization experiment based on Example 1. The difference from Example 1 is that when including the volatile oil in step 1), the amount of hydroxypropyl β-cyclodextrin (β-CD) added, the amount of colloidal silica added, and the concentration of ethanol are changed, and an orthogonal optimization experiment is carried out on the above three factors.

[0098] Table 3. Levels of orthogonal factors for the inclusion of volatile oils such as Angelica sinensis

[0099] Table 4 Encapsulation of volatile oils from Angelica sinensis, etc., into L9 (3) 4 Orthogonal experimental table

[0100] Table 5. Analysis of Variance of Encapsulation Rate of Volatile Oils from Angelica Sinensis, etc.

[0101] Table 6. Analysis of Variance of Flowability of Inclusion Complexes of Angelica sinensis and Other Volatile Oils

[0102] Based on the experimental results in Table 3-6, A2B3C2 is preferred, which consists of 5 times the amount of hydroxypropyl β-cyclodextrin, 10% colloidal silica, and 20% (v / v) ethanol.

[0103] Example 5 Example 5 is based on Example 1 and an orthogonal optimization experiment is conducted. The difference from Example 1 is that when encapsulating paeonol, the amount of hydroxypropyl β-cyclodextrin added, the amount of colloidal silica added, and the concentration of ethanol are changed, and an orthogonal optimization experiment is conducted on the above three factors.

[0104] Table 7. Levels of orthogonal factors for paeonol inclusion.

[0105] Table 8 Paeonol inclusion complex L9 (3 4 Orthogonal experimental table

[0106] Table 9. Analysis of Variance of Paeonol Encapsulation Efficiency

[0107] Table 10. Analysis of Variance of the Flowability of Paeonol Inclusion Complex

[0108] Based on the experimental results in Table 7-10, A2B3C2 is preferred, which consists of 5 times the amount of hydroxypropyl β-cyclodextrin, 10% colloidal silica, and 50% ethanol.

[0109] Example 6: Combined Extraction and Individual Extraction Following the volatile oil extraction method in step 1) of Example 1, volatile oil was extracted from peony bark together with angelica, chuanxiong, turmeric, and zedoaria. The volatile oil was collected, and the content of paeonol in the extract was detected to calculate the paeonol yield. Paeonol was detected in the extracts from Examples 1 and 6, and the paeonol extraction yield was calculated.

[0110] The specific detection method involved dissolving the volatile oil in methanol and detecting the paeonol content according to the method described in the Chinese Pharmacopoeia (2025 edition) under the section on Paeonia suffruticosa. The paeonol extraction yield was then calculated. The detection results in Examples 1 and 6 are shown in Table 11.

[0111] Table 11 Comparison of Paeonol Extract Yield

[0112] Pharmacological trials 1. Experimental Materials 1.1 Laboratory Animals Wistar rat.

[0113] 1.2 Experimental reagents Test drug: The pharmaceutical composition in Example 1 of this application.

[0114] Control drug: Baijin Fu'an Granules (the drug in Example 3 of CN1698862A).

[0115] 1.3 Statistical Methods The result is The results were analyzed using SPSS 11.5 statistical software, and the differences between groups were compared using t-tests.

[0116] 2. Experimental Methods and Results 2.1 Effects of the pharmaceutical composition of this application on rats with fallopian tube inflammation Drugs: 1% sodium pentobarbital, 10% formaldehyde solution, ether, phenol.

[0117] Equipment: rat restraint, surgical instruments, syringe.

[0118] Modeling: Forty female rats weighing 200-220g were anesthetized with ether, and the skin of the lower abdomen was disinfected with alcohol. An incision of about 2cm was made in the middle of the lower abdomen to expose the bilateral oviducts. 0.1ml of phenol paste was injected into each side and then sutured.

[0119] Forty rats were randomly divided into five groups of eight after surgery. The five groups were administered the following drugs: the high-dose group received the drug composition of this invention at a dose of 9.6 g crude drug / kg rat body weight (equivalent to 10 times the human clinical dose); the medium-dose group received the drug composition of this invention at a dose of 4.8 g crude drug / kg rat body weight (equivalent to 5 times the human clinical dose); the low-dose group received the drug composition of this invention at a dose of 2.4 g crude drug / kg rat body weight (equivalent to 2.5 times the human clinical dose); the control group received Baijin Fu'an granules at a dose of 4 g crude drug / kg rat body weight (equivalent to 5 times the human clinical dose); and the model group received an equal volume of water. In this application, crude drug weight refers to the total weight of the medicinal materials.

[0120] On the second day after modeling, each group began receiving oral administration of the drug. After 20 consecutive days of oral administration, 40 female rats were anesthetized by intraperitoneal injection of 1% sodium pentobarbital (45 mg / kg). The abdominal cavity was opened, and blood was collected from the inferior vena cava for hemorheological analysis. Subsequently, both fallopian tubes were removed, fixed in 10% formalin, and used for histological examination.

[0121] The condition of the fallopian tubes removed from each group of rats was observed visually, mainly to observe the patency of the fallopian tubes. Specifically, a needle was inserted at the uterine-fallopian tube junction, and about 3 ml of diluted methylene blue solution was injected into the fallopian tube-ovary direction. At the same time, the uterine side was pinched tightly. Based on the observed patency of the fallopian tubes, they were divided into those with patent lumens and those without.

[0122] Results: A total of 16 fallopian tubes were collected from 8 rats in each group. In the high-dose group, 13 of the 16 fallopian tubes were completely patent; in the medium-dose group, 12 of the 16 fallopian tubes were patent; in the low-dose group, 9 of the 16 fallopian tubes were patent; in the control group, 8 of the 16 fallopian tubes were patent; and in the model group, 1 of the 16 fallopian tubes was patent.

[0123] Microscopic observation of the fallopian tube tissue revealed chronic inflammation, which was classified into four grades according to the degree of histological changes, as shown in Table 12.

[0124] Table 12 Histological Changes and Scoring Table

[0125] The rats in each group were scored, and the results are shown in Tables 13-15 and the pathological report.

[0126] Table 13 Effects on different layers of the rat oviduct

[0127] Table 14 Effects on different layers of the rat oviduct (pathological results scored) )

[0128] Note: Compared with the model group, *P<0.05, **P<0.01.

[0129] The results showed that the drug composition of this application had a significant repair effect on all layers of the rat fallopian tube, with the high dose being the most sensitive to mucosal epithelial necrosis, followed by muscle layer connective tissue hyperplasia. The medium and low dose groups also showed significant repair effects on mucosal epithelial necrosis, pathological changes in folds, and muscle layer connective tissue hyperplasia. The experimental results indicated that, compared with the control group, the drug composition of this application improved symptoms such as fallopian tube inflammation, blockage, adhesions, and tissue hyperplasia in the sequelae of pelvic inflammatory disease.

[0130] Whole blood viscosity represents the viscosity of a liquid. Higher viscosity results in slower flow, which can increase blood flow resistance, slow blood flow velocity, cause blood stagnation, and affect blood supply to organs, thus leading to disease. Reduced viscosity is the ratio of whole blood viscosity to hematocrit, and inflammation can alter blood viscosity. Inflammation-induced endothelial damage may increase vascular wall adhesion, promoting erythrocyte and platelet aggregation, leading to microcirculatory disturbances, and consequently, increased blood viscosity and slowed blood flow. Whole blood viscosity and reduced whole blood viscosity were measured in each group of rats using a blood viscometer, and the results are shown in Table 15.

[0131] Table 15 Effects on hemorheology in rats with fallopian tube inflammation and obstruction model ( (n=8)

[0132] Note: Compared with the model group, *P<0.05, **P<0.01.

[0133] The experimental results show that, compared with the model group, the pharmaceutical composition of this application can significantly reduce the whole blood viscosity and whole blood reduced viscosity in model rats, exhibiting significant blood-activating and stasis-removing functions, and its effect is superior to that of the control group. Data in Table 15 indicate that the pharmaceutical composition of this invention can improve blood circulation in the fallopian tubes while inhibiting inflammation.

[0134] In summary, the pharmaceutical composition of this application can significantly inhibit phenol paste-induced oviduct inflammation and obstruction in rats, has a good protective effect on the mucosal epithelium and muscle connective tissue of the oviduct, and can significantly reduce the whole blood viscosity and whole blood reduced viscosity in rats with oviduct inflammation.

[0135] 2.2 Effects of the pharmaceutical composition of this application on rats with a uterine inflammation model Drugs: Ether, sodium penicillin.

[0136] Equipment: Surgical instruments, 1mm diameter plastic tubing.

[0137] Forty female rats weighing 200-220g were selected. Under light anesthesia with ether, the hair on the lower abdomen of each rat was clipped, and the skin was disinfected with alcohol. A 2cm incision was made in the midline of the lower abdomen to expose the uterus. A transverse incision was made 1cm above the left uterine horn, and a plastic tube (1mm diameter, 4mg weight, disinfected with alcohol) was placed inside the uterus and sutured to the uterine incision to prevent dislodgement. 0.1mg of penicillin (dissolved in 0.2ml of water for injection) was instilled into the wound to prevent infection. The 40 rats were then randomly divided into 5 groups of 8 rats each, with the same grouping and gavage dosage as described in section 2.1. The rats were gavaged once daily for 7 consecutive days. After this, the 40 rats were sacrificed in their respective groups. The lower abdomen was opened, and both uteri were removed and weighed. The degree of inflammation and swelling was determined by subtracting the weight of the right uterus from the weight of the left uterus. The results are shown in Table 16.

[0138] Table 16 Effects on rats with uterine inflammation ( )

[0139] Note: Compared with the model group, *P<0.05, **P<0.01.

[0140] The experimental results show that the pharmaceutical composition of the present invention can significantly inhibit the degree of uterine swelling in rats with a uterine inflammation model. Among them, the high-dose group and the medium-dose group are superior to the control group.

[0141] 2.3 Effects of the pharmaceutical composition of this application on chronic pelvic inflammatory disease in rats Drugs: Beef extract, peptone, sodium chloride, sodium hydroxide, agar, barium chloride, sulfuric acid, sodium pentobarbital.

[0142] Equipment: Electric steam sterilizer, incubator, surgical instruments.

[0143] Female rats weighing 200-220g were anesthetized intraperitoneally with 1% sodium pentobarbital (45mg / kg). After disinfecting the skin with alcohol, a 2cm incision was made in the midline of the lower abdomen to expose the uterus. A mixed bacterial suspension (Escherichia coli and Staphylococcus aureus dissolved in sterile saline at a 2:1 ratio to prepare a bacterial suspension of 3 billion CFU / ml) was injected into both uteri of the rats, approximately 0.08-0.1ml each, followed by suturing. If redness and swelling of the uterus were observed visually during the operation, or if there was resistance to injection, the rat was removed. Sixty rats were used to establish the model using the above method, of which 50 were successful and 10 were discarded. The 50 successful rats were randomly divided into 5 groups of 10 each, with the same grouping and gavage dosage as the blank control 2.1. The rats were given the drug starting on day 30 after modeling, once a day by gavage for 15 consecutive days. After 15 days, the rats in each group were decapitated and the bilateral fallopian tubes and uterus were removed from the abdominal cavity and fixed with 1% formaldehyde solution for histological examination. The fallopian tubes showed chronic inflammation under endoscopic observation. They were divided into four grades according to the degree of histological changes. The grading criteria are the same as in Table 12. The experimental results are shown in Tables 17-21 and the pathological report.

[0144] Table 17 Effects on different layers of the rat oviduct

[0145] Table 18 Effects on different layers of the rat oviduct (pathological results scored) )

[0146] Note: Compared with the model group, *P<0.05, **P<0.01.

[0147] The results in Tables 17-18 show that the pharmaceutical composition of this application has a significant repair effect on all layers of the rat oviduct, with the most sensitive effects on mucosal epithelial necrosis and muscle layer connective tissue hyperplasia. Even small doses of the pharmaceutical composition of this application have a significant repair effect on mucosal epithelial necrosis and muscle layer connective tissue hyperplasia. Among them, the high-dose and medium-dose groups are superior to the control group.

[0148] Microscopic observation revealed chronic inflammation in the uterine tissues of all rat groups. The degree of histological changes was categorized into four grades: normal (0), mild (I), moderate (II), and severe (III). The uterus was divided into five parts: endometrial epithelium, stroma, myometrium, serosa, and uterine cavity. Each sample was observed and graded under a microscope according to the following criteria.

[0149] (1) The endometrial epithelial cells are arranged in a single columnar layer, which is normal (-); the disappearance of the low columnar part of the cells is mild (+); the disappearance of most of the low columnar part of the cells is moderate (++); the complete disappearance of the epithelium is severe (+++).

[0150] (2) Normal (-) Interstitial cells with no congestion or edema; mild (+) interstitial congestion and edema; moderate (++) interstitial congestion and edema with a small amount of inflammatory cell infiltration; severe (+++) interstitial congestion and edema with a large amount of inflammatory cell infiltration.

[0151] (3) Normal (-) if there is no fibrous tissue extension, no inflammatory cell infiltration, and no thinning of the muscle layer; mild (+) if slightly thinned; moderate (++) if slightly thinned, with a small amount of inflammatory cell infiltration or a small amount of fibrous tissue extension; severe (+++) if significantly thinned, with a large amount of inflammatory cell infiltration or a large amount of fibrous tissue extension.

[0152] (4) No vasodilation, congestion, inflammatory cell infiltration, or fibroblast proliferation in the inflammatory cell layer is normal (-); only vasodilation and congestion are mild (+); vasodilation and congestion with a small amount of inflammatory cell infiltration or fibroblast proliferation are moderate (++); vasodilation and congestion with a large amount of inflammatory cell infiltration or fibroblast proliferation are severe (+++).

[0153] Table 19 Effects on different layers of the rat uterus

[0154] Note: - is 0 points, + is 1 point, ++ is 2 points, and +++ is 3 points.

[0155] Table 20 Effects on different layers of the rat uterus (pathological results scored) )

[0156] Note: Compared with the model group, *P<0.05, **P<0.01.

[0157] Tables 19-20 show that the drug composition of this application has a significant repair effect on all layers of the rat uterus, with the most sensitive effect on endometrial epithelial necrosis, followed by myometrial connective tissue hyperplasia, etc. The high-dose and medium-dose groups are superior to the control group.

[0158] In summary, the pharmaceutical composition of this application can significantly inhibit oviduct and uterine inflammation induced by mixed bacterial suspension in rats. The high-dose group showed significant repair of all layers of the oviduct, particularly sensitive to mucosal epithelial necrosis and lamina propria connective tissue hyperplasia, followed by myometrial connective tissue hyperplasia. The medium-dose group also showed significant repair of mucosal epithelial necrosis, lamina propria connective tissue hyperplasia, and myometrial connective tissue hyperplasia. Similarly, the high-dose group showed significant repair of all layers of the uterus, with endometrial epithelial necrosis being the most sensitive, followed by myometrial connective tissue hyperplasia. The medium-dose group also showed significant repair of endometrial epithelial necrosis, stroma, and myometrial pathological changes.

[0159] The technical features of the above embodiments can be combined in any way. For the sake of brevity, not all possible combinations of the technical features in the above embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0160] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are specific and detailed, they should not be construed as limiting the scope of this application. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. A pharmaceutical composition, characterized in that, The ingredients, by weight, are 180-190 parts of stir-fried white peony root, 120-130 parts of bupleurum root, 180-190 parts of angelica root, 180-190 parts of poria cocos, 180-190 parts of chuanxiong rhizome, 120-130 parts of peony bark, 180-190 parts of turmeric, 220-280 parts of astragalus root, 180-190 parts of vaccaria seed, 120-130 parts of stir-fried yam, 180-190 parts of patrinia root, 120-130 parts of corydalis rhizome, 90-100 parts of turmeric root, 40-80 parts of licorice root, and at least one pharmaceutically acceptable carrier.

2. Use of the pharmaceutical composition of claim 1 in the preparation of a medicament for treating sequelae of gynecological pelvic inflammatory disease.

3. The method for preparing the pharmaceutical composition according to claim 1, characterized in that, The method includes: 1) Angelica sinensis, Ligusticum chuanxiong, Curcuma longa, and Curcuma zedoaria were treated by distillation to obtain volatile oil, medicinal liquid, and medicinal residue. The volatile oil was mixed with hydroxypropyl β-cyclodextrin and ethanol, and colloidal silica was added for inclusion to obtain an inclusion complex. The medicinal liquid and medicinal residue were reserved for later use. 2) The peony bark was treated by distillation to obtain paeonol, a medicinal solution and residue. Paeonol was dissolved and hydroxypropyl β-cyclodextrin, ethanol and colloidal silica were added for inclusion to obtain an inclusion complex. The medicinal solution and residue were reserved for later use. 3) Mix Poria cocos, Astragalus membranaceus, Vaccaria segetalis, stir-fried Dioscorea opposita, Glycyrrhiza uralensis, Patrinia scabiosaefolia, Corydalis yanhusuo with the dregs from 1) and 2), and process with water extraction to obtain the extract. Discard the dregs. 4) Combine the medicinal solutions from 1) and 2) and the extract from 3), and concentrate them into a clear paste for later use; 5) Mix and pulverize the stir-fried white peony root and bupleurum root, process them with alcohol extraction to obtain an extract, and concentrate it into a clear paste for later use; 6) Using a top-spray granulation process, the inclusion complexes described in 1) and 2) and the extracts described in 4) and 5) are granulated.

4. The preparation method according to claim 3, characterized in that, When inclusion is performed in 1), the weight of hydroxypropyl β-cyclodextrin is 2-10 times the weight of the volatile oil, and the weight of ethanol is 1-5 times the weight of hydroxypropyl β-cyclodextrin.

5. The preparation method according to claim 3, characterized in that, When processing peony bark, add 6-18 times its weight of water for extraction.

6. The preparation method according to claim 3, characterized in that, When processing peony bark, collect 5-15 times the amount of distillate to obtain paeonol.

7. The preparation method according to claim 3, characterized in that, When paeonol is included, the weight of hydroxypropyl β-cyclodextrin is 1-8 times the weight of paeonol, and the weight of ethanol is 1-8 times the weight of hydroxypropyl β-cyclodextrin.

8. The preparation method according to claim 3, characterized in that, The amount of colloidal silica added is 1-12% of the weight of hydroxypropyl β-cyclodextrin.

Images