A palace clearing pill for clearing palace and removing blood stasis and a preparation method thereof

Abstract

The application provides a kind of palace pill for clearing palace and removing blood stasis and a preparation method thereof, which is prepared from the following raw materials in parts by weight: 25-30 parts of wine red peony root, 15-20 parts of vinegar-fried aconite, 15-20 parts of bran-fried broad wood, 15-20 parts of fried five spirit resins, 15-20 parts of vinegar-fried corydalis, 10-15 parts of hirudin, 5-10 parts of earthworm protein peptide powder and 5-10 parts of oyster peptide powder. The preparation steps of the oyster peptide powder are as follows: fresh oysters are selected, washed with running water, cleaned of internal organs and mucus, soaked in a citric acid solution, ultrasonically broken, enzymatically hydrolyzed, deodorized, purified, filtered, concentrated and dried to obtain oyster peptide powder. The palace pill has a scientific formula, a synergistic effect of various components, the efficacy of clearing palace and removing blood stasis, heat-clearing and detoxifying, carbuncle-dissolving and pus-discharging, blood stasis-removing and pain-stopping, is convenient to carry and take, and has clinical drug value.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a Qinggong Pill for clearing uterine stasis and its preparation method. Background Technology

[0002] After a miscarriage or childbirth, restoring the health of the uterus is crucial for women. The presence of retained placental or fetal membranes can lead to lower abdominal pain, persistent lochia, and acute or chronic inflammation, potentially causing pelvic inflammatory disease and fallopian tube blockage, thus posing a risk of infertility and ectopic pregnancy, endangering women's health. Currently, the main preventative and treatment medications for this condition have the following problems: 1. The widespread use of Western medicine, such as ergonovine injections and antibiotics to prevent infection, only treats the symptoms, not the root cause, resulting in inconsistent treatment effectiveness. While effective in controlling acute infections, Western medicine often fails to significantly improve local circulatory disorders and tissue adhesions in chronic diseases and their sequelae. Furthermore, repeated and long-term antibiotic use may lead to drug resistance and significant side effects. 2. Commercially available traditional Chinese medicine for uterine cleansing has received mixed reviews and cannot fully achieve the therapeutic effects of clearing the uterus, removing blood stasis, clearing heat and detoxifying, eliminating carbuncles and draining pus, and relieving pain. The ingredients in commercially available uterine cleansing pills are relatively simple, potentially interfering with the growth of normal vaginal flora, leading to flora imbalance. This weakens the vagina's self-cleaning ability, increases the risk of infection, and can lead to gynecological inflammations such as vaginitis and cervicitis. Hirudin is a natural anticoagulant polypeptide, mainly found in the salivary glands of medicinal leeches (such as *Hirudo medicinalis*). Its complete molecule consists of 65 amino acids. Earthworm protein peptides can accelerate metabolism, promote drug absorption, and have a diuretic effect, which can be used to help improve urinary tract infections. Oyster peptides can clear blood vessels, remove blood waste, eliminate active oxygen in the body, and promote metabolism. Research combining traditional Chinese medicine with short peptides has application value. Summary of the Invention

[0003] In view of this, the present invention provides a Qinggong Pill for clearing uterine stasis and its preparation method, in order to meet the medication needs of patients.

[0004] The technical solution of this invention is implemented as follows:

[0005] A type of uterine-clearing pill for clearing uterine stasis is made from the following ingredients in parts by weight: 25-30 parts of wine-processed red peony root, 15-20 parts of vinegar-fried Cyperus rotundus, 15-20 parts of wheat bran-fried Aucklandia lappa, 15-20 parts of fried Trogopterus xanthipes, 15-20 parts of vinegar-fried Corydalis yanhusuo, 10-15 parts of hirudin, 5-10 parts of earthworm protein peptide powder, and 5-10 parts of oyster peptide powder.

[0006] The preparation of oyster peptide powder includes the following steps:

[0007] S1: Select fresh oysters, rinse them under running water to remove the viscera and mucus, soak them in citric acid solution, and then ultrasonically crush them to obtain oyster pulp.

[0008] S2: Targeted enzymatic hydrolysis of oyster slurry to obtain enzymatic hydrolysate;

[0009] S3: Deodorize the enzymatic hydrolysate, and then purify the deodorized enzymatic hydrolysate by ultrafiltration fractionation. Filter the solution to obtain the chromatography solvent.

[0010] S4: Concentrate the chromatography solution at low temperature, add maltodextrin carrier and dry to obtain oyster peptide powder.

[0011] Furthermore, in step S1, the citric acid solution has a mass fraction of 0.1%-0.2%; the ultrasonic breaking frequency is 20-40kHz, and the time is 10-15min.

[0012] Further, in step S2, the targeted enzymatic hydrolysis is performed in two steps. In the first step, Bacillus subtilis alkaline protease is added to the oyster slurry. The hydrolysis pH is 7.0-7.3, the amount of enzyme added is 1%-1.5% of the mass of the oyster slurry, the hydrolysis temperature is 35-45℃, and the hydrolysis time is 1-1.5h to obtain the initial hydrolysate. In the second step, Aspergillus oryzae and trypsin are added to the initial hydrolysate in a mass ratio of 1:1-2. The hydrolysis pH is 7.0-7.5, the amount of enzyme added is 4%-6% of the mass of the initial hydrolysate, the hydrolysis temperature is 35-40℃, and the hydrolysis time is 3-5h.

[0013] Furthermore, in step S3, the enzymatic hydrolysate is deodorized by adding 0.5%-1% food-grade activated carbon by mass fraction to the enzymatic hydrolysate and stirring at 45-50°C for 30-40 minutes.

[0014] Furthermore, in step S3, the ultrafiltration fractionation purification involves adding a 10kDa ultrafiltration membrane to the deodorized enzymatic hydrolysate for filtration, followed by filtration using a 3kDa ultrafiltration membrane.

[0015] Furthermore, in step S4, the low-temperature concentration involves concentrating the chromatographic solution under reduced pressure at a temperature below 45°C until the solid content is 30%-40%.

[0016] Furthermore, in step S4, the drying is spray drying, drying under nitrogen atmosphere, with an inlet air temperature of 150-160℃ and an outlet air temperature of 80-85℃, and the amount of maltodextrin as carrier added is 2%-4% of the mass of the chromatography solution.

[0017] The preparation steps of a Qinggong Pill for clearing the uterus and removing blood stasis are as follows: 1. Grind the following ingredients into powder: wine-processed red peony root, vinegar-fried Cyperus rhizome, wheat bran-fried costus root, fried five-spice powder, and vinegar-fried Corydalis rhizome. 2. Add hirudin, earthworm protein peptide powder, and oyster peptide powder, mix and stir, pass through a 100-mesh sieve, soak in water to form pills, and seal for storage.

[0018] Compared with the prior art, the beneficial effects of the present invention are:

[0019] 1. The Qinggong Pill of this invention can promote the circulation of Qi and blood, reduce inflammation, promote blood circulation, gradually reduce abdominal pain, and effectively improve the excretion of the lower body. The leech extract, earthworm protein peptide powder and oyster peptide powder in the formula, combined with other Chinese medicine ingredients, have a good effect on the treatment of urinary tract infections.

[0020] 2. The Qinggong Pill of this invention has the effects of clearing heat and detoxifying, and eliminating carbuncles and draining pus. The ingredients include oyster peptide powder prepared by enzymatic hydrolysis, which promotes metabolism in the body. It is chemically stable, easy to carry, and has application value in treating gynecological abdominal pain. Detailed Implementation

[0021] To better understand the technical content of this invention, specific embodiments are provided below to further illustrate the invention. Unless otherwise specified, the experimental methods used in the embodiments of this invention are conventional methods.

[0022] Unless otherwise specified, all materials and reagents used in the embodiments of this invention are commercially available.

[0023] The following is a basic introduction to the main active pharmaceutical ingredients based on the Chinese Pharmacopoeia.

[0024] Red peony root (processed with wine): It is cool in nature and bitter in taste, and has the effect of promoting blood circulation and removing blood stasis;

[0025] Stir-fried Cyperus rotundus with vinegar: It has a pungent, slightly bitter, and sweet taste, and is neutral in nature. It has the effects of soothing the liver and regulating qi, regulating menstruation and relieving pain.

[0026] Stir-fried costus root: It is warm in nature and pungent in taste, and enters the spleen and stomach meridians. It has the effects of promoting qi circulation and relieving pain, strengthening the spleen and stomach, and relaxing muscles and tendons.

[0027] Stir-fried Five-Tortoise Powder: It is warm in nature and salty and sweet in taste. It has the effects of dispelling wind and relieving pain, promoting blood circulation and regulating qi.

[0028] Stir-fried Corydalis Rhizome with Vinegar: It has a pungent and bitter taste, is warm in nature, and enters the liver, spleen, and heart meridians. It has the effects of promoting qi circulation and relieving pain.

[0029] The microbial limits of the drug were determined according to the Microbial Limit Test Method of Part IV (General Chapters 1105-1107) of the 2020 edition of the Chinese Pharmacopoeia, and the test results were in compliance with the microbial limit test.

[0030] Preparation Example 1

[0031] The preparation of oyster peptide powder includes the following steps:

[0032] Step (1): Select fresh oysters, rinse them under running water to remove the oyster viscera and mucus, soak them in a 0.1% citric acid solution, and then sonicate them at a frequency of 20 kHz for 10 minutes to obtain oyster slurry.

[0033] Step (II): Targeted enzymatic hydrolysis of oyster slurry is performed in two steps. In the first step, Bacillus subtilis alkaline protease is added to the oyster slurry. The hydrolysis pH is 7.0, the enzyme dosage is 1% of the oyster slurry, the temperature is 35℃, and the hydrolysis time is 1 hour, yielding the initial hydrolysate. In the second step, Aspergillus oryzae and trypsin are added to the initial hydrolysate in a 1:1 mass ratio. The hydrolysis pH is 7.0, the enzyme dosage is 4% of the initial hydrolysate mass, the temperature is 35℃, and the hydrolysis time is 3 hours, yielding the final hydrolysate.

[0034] Step (3): Deodorize the enzymatic hydrolysate, add 0.5% food-grade activated carbon to the enzymatic hydrolysate, stir at 45°C for 30 min, and then perform ultrafiltration fractionation purification. After adding a 10kDa ultrafiltration membrane to the deodorized enzymatic hydrolysate for filtration, continue filtration with a 3kDa ultrafiltration membrane to obtain the chromatographic solution.

[0035] Step (4): Concentrate the chromatography solution at low temperature. Concentrate the chromatography solution at 43°C under reduced pressure to a solid content of 30%. Add 2% by weight of maltodextrin carrier to the chromatography solution. Spray dry under nitrogen atmosphere with an inlet air temperature of 150°C and an outlet air temperature of 80°C to obtain oyster peptide powder.

[0036] Preparation Example 2

[0037] The preparation of oyster peptide powder includes the following steps:

[0038] Step (1): Select fresh oysters, rinse them under running water to remove the oyster viscera and mucus, soak them in a 0.2% citric acid solution, and then sonicate them at a frequency of 40kHz for 15 minutes to obtain oyster slurry.

[0039] Step (II): Targeted enzymatic hydrolysis of oyster pulp is performed in two steps. In the first step, Bacillus subtilis alkaline protease is added to the oyster pulp. The hydrolysis pH is 7.3, the enzyme dosage is 1.5% of the oyster pulp mass, the temperature is 45℃, and the hydrolysis time is 1.5 hours, yielding the initial hydrolysate. In the second step, Aspergillus oryzae and trypsin are added to the initial hydrolysate in a 1:2 mass ratio. The hydrolysis pH is 7.5, the enzyme dosage is 6% of the initial hydrolysate mass, the temperature is 40℃, and the hydrolysis time is 5 hours, yielding the final hydrolysate.

[0040] Step (3): Deodorize the enzymatic hydrolysate, add 1% food-grade activated carbon to the enzymatic hydrolysate, stir at 50°C for 40 min, and then perform ultrafiltration fractionation purification. After adding a 10 kDa ultrafiltration membrane to the deodorized enzymatic hydrolysate for filtration, continue filtration with a 3 kDa ultrafiltration membrane to obtain the chromatographic solution.

[0041] Step (4): Concentrate the chromatography solution at low temperature. Concentrate the chromatography solution at 40°C under reduced pressure to a solid content of 40%. Add 4% by weight of maltodextrin carrier to the chromatography solution. Spray dry under nitrogen atmosphere with an inlet air temperature of 160°C and an outlet air temperature of 85°C to obtain oyster peptide powder.

[0042] Preparation Example 3

[0043] The preparation of oyster peptide powder includes the following steps:

[0044] Step (1): Select fresh oysters, rinse them under running water to remove the oyster viscera and mucus, soak them in a 0.2% citric acid solution, and then sonicate them at a frequency of 40kHz for 15 minutes to obtain oyster slurry.

[0045] Select fresh oysters, rinse them under running water to remove the internal organs and mucus, soak them in a 0.15% citric acid solution, and then sonicate them at a frequency of 30 kHz for 15 minutes to obtain oyster pulp.

[0046] Step (II): Targeted enzymatic hydrolysis of oyster pulp is performed in two steps. In the first step, Bacillus subtilis alkaline protease is added to the oyster pulp. The hydrolysis pH is 7.2, the enzyme dosage is 1% of the oyster pulp mass, the temperature is 40℃, and the hydrolysis time is 1.2 hours, yielding the initial hydrolysate. In the second step, Aspergillus oryzae and trypsin are added to the initial hydrolysate in a mass ratio of 1:1.5. The hydrolysis pH is 7.2, the enzyme dosage is 5% of the initial hydrolysate mass, the temperature is 36℃, and the hydrolysis time is 4 hours, yielding the final hydrolysate.

[0047] Step (3): Deodorize the enzymatic hydrolysate, add 1% food-grade activated carbon to the enzymatic hydrolysate, stir at 46℃ for 35 min, and then perform ultrafiltration fractionation purification. After adding a 10kDa ultrafiltration membrane to the deodorized enzymatic hydrolysate for filtration, continue to filter with a 3kDa ultrafiltration membrane to obtain the chromatographic solution.

[0048] Step (4): Concentrate the chromatography solution at low temperature. Concentrate the chromatography solution under reduced pressure at a temperature below 45°C until the solid content is 35%. Add 3% by weight of maltodextrin carrier to the chromatography solution. Spray dry under nitrogen atmosphere with an inlet air temperature of 155°C and an outlet air temperature of 82°C to obtain oyster peptide powder.

[0049] Example 1

[0050] The preparation steps of Example 1 of the Qinggong Pill for Clearing Uterine Blood Stasis of the present invention are as follows: the wine-processed red peony root, vinegar-fried cyperus rhizome, wheat bran-fried costus root, fried five-spice powder, and vinegar-fried corydalis rhizome are ground into powders respectively. Hirudin and earthworm protein peptide powder are added to prepare the oyster peptide powder prepared in Example 1. The mixture is stirred, passed through a 100-mesh sieve, and made into pills with water. The pills are then sealed and stored.

[0051] Among them, there are 25 parts of wine-processed red peony root, 15 parts of vinegar-fried cyperus rhizome, 15 parts of wheat bran-fried costus root, 15 parts of stir-fried five-spice powder, 15 parts of vinegar-fried corydalis rhizome, 10 parts of hirudin, 5 parts of earthworm protein peptide powder, and 5 parts of oyster peptide powder.

[0052] Example 2

[0053] The preparation steps of Example 2 of the Qinggong Pill for clearing uterine stasis of the present invention are as follows: the wine-processed red peony root, vinegar-fried cyperus rhizome, wheat bran-fried costus root, fried five-spice powder, and vinegar-fried corydalis rhizome are ground into powders respectively. Hirudin and earthworm protein peptide powder are added to prepare the oyster peptide powder prepared in Example 2. The mixture is stirred, passed through a 100-mesh sieve, and made into pills with water. The pills are then sealed and stored.

[0054] Among them, there are 30 parts of wine-processed red peony root, 20 parts of vinegar-fried cyperus rhizome, 20 parts of wheat bran-fried costus root, 20 parts of stir-fried five-spice powder, 20 parts of vinegar-fried corydalis rhizome, 15 parts of hirudin, 10 parts of earthworm protein peptide powder, and 10 parts of oyster peptide powder.

[0055] Example 3

[0056] The preparation steps of Example 3 of the Qinggong Pill for Clearing Uterine Blood Stasis of the present invention are as follows: the wine-processed red peony root, vinegar-fried cyperus rhizome, wheat bran-fried costus root, fried five-spice powder, and vinegar-fried corydalis rhizome are ground into powders respectively. Hirudin and earthworm protein peptide powder are added to prepare the oyster peptide powder prepared in Example 3. The mixture is stirred, passed through a 100-mesh sieve, and made into pills with water. The pills are then sealed and stored.

[0057] Among them, there were 26 parts of wine-processed red peony root, 17 parts of vinegar-fried cyperus rhizome, 16 parts of wheat bran-fried costus root, 16 parts of fried five-spice powder, 18 parts of vinegar-fried corydalis rhizome, 12 parts of hirudin, 8 parts of earthworm protein peptide powder, and 8 parts of oyster peptide powder.

[0058] Commercially available comparison

[0059] Motherwort granules, manufactured by Luoshangshan Pharmaceutical Factory in Quanzhou, Fujian Province, contain motherwort as an ingredient.

[0060] test

[0061] Sixty patients who visited the gynecology outpatient clinic of an affiliated hospital of a university of traditional Chinese medicine and met the inclusion criteria were selected and randomly divided into two groups: a treatment group of 30 patients treated with Qinggong Wan prepared according to the method in Example 3, and a control group of 30 patients treated with commercially available motherwort. Case selection criteria included women who had experienced miscarriage or childbirth, with poor recovery of the uterus, fallopian tubes, and pelvic cavity, abdominal pain, and pelvic adhesions. Patients meeting the above diagnostic criteria were identified by two attending physicians or above and signed informed consent forms. Patients with congenital physiological defects or malformations, endocrine or immune factors, serious primary diseases of the cardiovascular, liver, kidney, and hematopoietic systems, or mental illness were excluded; patients with allergies or allergies to the medications were excluded. Patients who could not adhere to treatment or developed other organ diseases during the clinical trial were also excluded.

[0062] Treatment duration: Continue medication for 6 courses, each course lasting 7 days, for a total of 42 days. Take 6g twice daily, morning and evening, with warm water. Cure refers to the absence of inflammatory markers and no adverse reactions such as abdominal pain; Significant effect refers to mild inflammatory markers and occasional adverse reactions such as abdominal pain; Improvement refers to a decrease in inflammatory markers and a reduction in adverse reactions such as abdominal pain; Ineffective refers to no decrease in inflammatory markers and abdominal pain remaining the same as before treatment.

[0063] Effectiveness rate % = (Number of cured cases + Number of cases with significant improvement + Number of cases with improvement) / Total number of cases × 100%.

[0064] Cure rate % = Number of cured cases / Total number of cases × 100%.

[0065] Table 1 Comparison of the distribution of TCM syndrome types

[0066]

[0067] The distribution of TCM syndrome types (Table 1) shows that among the 30 cases in the treatment group, there were 18 primary cases and 12 secondary cases. Among them, there were 14 cases of Qi stagnation and blood stasis, 9 cases of cold-dampness stagnation, and 7 cases of damp-heat stagnation.

[0068] Table 2 Comparison of clinical symptoms and treatment efficacy between the two groups of patients

[0069]

[0070]

[0071] Table 3 Comparison of observations after 42 days

[0072]

[0073] After 35 days of continuous treatment, in the treatment group, 16 cases were cured, 8 cases showed significant improvement, 5 cases improved, and 1 case was ineffective, with a cure rate of 53.3% and an effective rate of 96.7%. After taking the medicine, the amount of vaginal discharge increased, abdominal pain symptoms gradually decreased, and the color of the uterus improved to a light red. The leech extract, earthworm protein peptide powder, and oyster peptide powder in the formula, combined with other Chinese herbal ingredients, have a good effect on the treatment of urinary tract infections.

[0074] Conclusion: The Qinggong Pill of this invention has achieved good clinical efficacy. In the example group of 30 patients, after 42 days of continuous medication, there were no adverse reactions, 16 patients were cured (cured rate 53.3%), 8 patients showed significant improvement, and 5 patients showed improvement (effective rate 96.7%). The therapeutic effect of oral Qinggong Pill for 42 days was higher than that of oral Yimucao granules. The Qinggong Pill of this invention has significant efficacy in treating gynecological inflammation, and no obvious toxic side effects were found. It has application value in clearing the uterus, removing blood stasis, and relieving pain.

[0075] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A uterine-clearing pill for clearing uterine stasis, characterized in that: It is made from the following raw materials in parts by weight: 25-30 parts of wine-processed red peony root, 15-20 parts of vinegar-fried Cyperus rotundus, 15-20 parts of wheat bran-fried Aucklandia lappa, 15-20 parts of fried Trogopterus xanthipes, 15-20 parts of vinegar-fried Corydalis yanhusuo, 10-15 parts of hirudin, 5-10 parts of earthworm protein peptide powder, and 5-10 parts of oyster peptide powder. The preparation of the oyster peptide powder includes the following steps: S1: Select fresh oysters, rinse them under running water to remove the viscera and mucus, soak them in citric acid solution, and then ultrasonically crush them to obtain oyster pulp. The citric acid solution has a mass fraction of 0.1%-0.2%; the ultrasonic disruption frequency is 20-40 kHz, and the time is 10-15 min. S2: Targeted enzymatic hydrolysis of oyster slurry to obtain enzymatic hydrolysate; The targeted enzymatic hydrolysis consists of two steps. The first step involves adding Bacillus subtilis alkaline protease to oyster slurry, maintaining a pH of 7.0-7.3, adding 1%-1.5% of the oyster slurry mass, hydrolyzing at 35-45℃ for 1-1.5 hours to obtain the initial hydrolysate. The second step involves adding Aspergillus oryzae and trypsin at a mass ratio of 1:1-2 to the initial hydrolysate, maintaining a pH of 7.0-7.5, adding 4%-6% of the initial hydrolysate mass, hydrolyzing at 35-40℃ for 3-5 hours. S3: Deodorize the enzymatic hydrolysate, and then purify the deodorized enzymatic hydrolysate by ultrafiltration fractionation. Filter the solution to obtain the chromatography solvent. The ultrafiltration fractionation purification involves adding a 10 kDa ultrafiltration membrane to the deodorized enzymatic hydrolysate for filtration, followed by filtration using a 3 kDa ultrafiltration membrane. S4: Concentrate the chromatography solution at low temperature, add maltodextrin carrier and dry to obtain oyster peptide powder; The drying process is spray drying, performed under a nitrogen atmosphere, with an inlet air temperature of 150-160℃ and an outlet air temperature of 80-85℃.

2. The uterine-clearing pill for clearing uterine stasis according to claim 1, characterized in that: In step S3 of the preparation of oyster peptide powder, the enzymatic hydrolysate is deodorized by adding 0.5%-1% food-grade activated carbon by mass to the enzymatic hydrolysate and stirring at 45-50℃ for 30-40 minutes.

3. The uterine-clearing pill for clearing uterine stasis according to claim 1, characterized in that: In step S4 of the preparation of oyster peptide powder, the low-temperature concentration involves concentrating the chromatographic solution under reduced pressure at a temperature below 45°C until the solid content is 30%-40%.

4. The uterine-clearing pill for clearing uterine stasis according to claim 1, characterized in that: In step S4 of the preparation of oyster peptide powder, the amount of maltodextrin added as a carrier is 2%-4% of the mass of the chromatography solvent.

5. A uterine-clearing pill for clearing uterine stasis according to claim 1, characterized in that: The preparation steps are as follows: grind the wine-processed red peony root, vinegar-fried cyperus rhizome, wheat bran-fried costus root, fried five-spice powder, and vinegar-fried corydalis rhizome into powder respectively, add hirudin, earthworm protein peptide powder, and oyster peptide powder, mix and stir, pass through a 100-mesh sieve, soak in water to form pills, and seal and store.

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