A traditional Chinese medicine composition for treating gynecological diseases and a preparation method and use thereof

Abstract

The traditional Chinese medicine composition of charred astragalus root, herba lycopi, fried atractylodes, poria, radix cyathulae, radix cyathulae, semen cuscutae, radix puerariae, fried white peony root, albizia flower, and charred licorice can be used for treating gynecological diseases or symptoms such as intrauterine adhesion, thin endometrium, oligomenorrhea, postmenstrual error, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, repeated implantation failure, and infertility, or preparing drugs for treating gynecological diseases or symptoms.

Description

Technical Field

[0001] This invention relates to a traditional Chinese medicine composition for treating gynecological diseases. This invention also relates to a method for preparing and using the traditional Chinese medicine composition for treating gynecological diseases. Background Technology

[0002] Intrauterine adhesions (IUA), also known as Asherman's syndrome, are a condition caused by repeated intrauterine procedures or infections, resulting in damage to the basal layer of the endometrium, loss of the functional layer, and adhesions within the uterine wall, leading to a loss of the normal uterine cavity shape. Its main clinical manifestations include decreased menstrual flow, amenorrhea, and dysmenorrhea, which can lead to recurrent miscarriage, infertility, and repeated embryo transfer failures, severely impacting the lives of women of reproductive age. Transcervical resection of adhesions (TCRA) is currently the preferred treatment for IUA; however, the recurrence rate after surgery is high. Therefore, effectively reducing postoperative recurrence and promoting endometrial regeneration has become a key focus and challenge in clinical treatment. Western medicine currently commonly uses sequential estrogen-progesterone therapy, intrauterine devices, balloon stents, and bioadhesive preparations to prevent re-adhesion, but these methods are less effective for patients with moderate to severe adhesions. Patients after TCRA often experience thin endometrium, scanty menstruation, and infertility. Current research has shown that traditional Chinese medicine has unique advantages in promoting endometrial recovery after intrauterine adhesion surgery and improving long-term pregnancy rates, but there are currently no related proprietary Chinese medicines available.

[0003] Therefore, there is a need to invent an effective, safe, and well-matched traditional Chinese medicine composition that can be used to prevent and / or treat conditions such as intrauterine adhesions, in order to help solve current clinical problems. Summary of the Invention

[0004] In view of the above, the inventors of this application have conducted extensive and in-depth research and found that the traditional Chinese medicine composition of Astragalus membranaceus (processed), Lycopus lucidus, Atractylodes macrocephala (fried), Poria cocos, Achyranthes bidentata, Dipsacus asper, Cuscuta chinensis, Pueraria lobata, Paeonia lactiflora (fried), Albizia julibrissin, and Glycyrrhiza uralensis (processed) has the effect of treating gynecological diseases, especially intrauterine adhesions and related conditions.

[0005] One objective of this invention is to provide a traditional Chinese medicine composition for treating gynecological diseases, particularly intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent embryo transfer failure, and infertility.

[0006] Another object of the present invention is to provide a method for preparing the traditional Chinese medicine composition of the present invention.

[0007] Another object of the present invention is to provide a medicine and / or its preparation containing the traditional Chinese medicine composition of the present invention.

[0008] Another object of the present invention is to provide a use for the traditional Chinese medicine mixture or extract of the present invention for treating gynecological diseases, especially intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent embryo transfer failure, infertility, etc., or for preparing medicines for treating the aforementioned gynecological diseases and conditions. Detailed Implementation

[0009] The amounts of each component in the traditional Chinese medicine composition described in the embodiments and examples of this invention are expressed in grams, which represent one part by weight. The amounts of each component can be scaled up several times by the same proportion.

[0010] In one embodiment, the present invention provides a traditional Chinese medicine composition, characterized by a combination of roasted Astragalus membranaceus, Lycopus lucidus, stir-fried Atractylodes macrocephala, Poria cocos, Achyranthes bidentata, Dipsacus asper, Cuscuta chinensis, Pueraria lobata, stir-fried Paeonia lactiflora, Albizia julibrissin, and roasted Glycyrrhiza uralensis.

[0011] Based on extensive clinical practice and the characteristics of diseases, the inventors determined the principal, assistant, adjuvant, and guiding herbs in the herbal combination of this invention.

[0012] Astragalus and Lycopus lucidus are the principal herbs in this herbal combination. Astragalus, sweet in taste and slightly warm in nature, enters the spleen and lung meridians. Its functions include tonifying the lungs and spleen, strengthening defensive qi, stopping sweating, promoting diuresis and reducing swelling, and promoting tissue regeneration and detoxification. It greatly tonifies vital energy, and since qi is the commander of blood, it can control, circulate, and nourish blood, thus removing blood stasis. It also promotes tissue regeneration, heals sores, and facilitates uterine cavity repair. Lycopus lucidus, bitter and pungent in taste and slightly warm in nature, enters the liver and spleen meridians. Its functions include activating blood circulation and regulating menstruation, removing blood stasis and reducing swelling, effectively relieving liver and spleen stagnation, activating blood circulation to remove blood stasis, promoting blood supply to the endometrium, and helping to restore damaged endometrium.

[0013] Atractylodes macrocephala, Poria cocos, and Achyranthes bidentata are the auxiliary herbs in this invention's herbal combination. Atractylodes macrocephala, bitter and sweet in taste, warm in nature, enters the spleen and stomach meridians. Its functions include tonifying qi and strengthening the spleen, drying dampness and promoting diuresis, and calming the fetus; it is hailed as a "holy medicine for calming the fetus." The *Essentials of Gynecology* states, "The spleen is the bridge of the body, governing all internal and external qi, and the mechanism of fetal breathing and transformation entirely depends on the spleen earth; therefore, Atractylodes macrocephala is used to assist it." Raw Atractylodes macrocephala is too pungent and drying; stir-frying reduces its drying properties and enhances its spleen-strengthening effect. Poria cocos, sweet and bland in taste, neutral in nature, enters the spleen, heart, kidney, and lung meridians. The *Shennong's Classic of Materia Medica* records, "It treats chest and rib rebellious qi… vexation, cough, dry mouth and tongue, promotes urination, and long-term use calms the soul and nourishes the spirit." Its functions include promoting diuresis and eliminating dampness, strengthening the spleen, and calming the spirit. Achyranthes bidentata, sweet, bitter, and sour in taste, neutral in nature, enters the liver and kidney meridians. It has the effects of promoting blood circulation, nourishing the liver and kidneys, strengthening muscles and bones, promoting urination, and guiding fire downwards.

[0014] The ingredients are Dipsacus asper, Cuscuta chinensis, Pueraria lobata, Paeonia lactiflora, and Albizia julibrissin. Dipsacus asper, also known as Sichuan teasel root, is bitter, pungent, and astringent in taste, warm in nature, and enters the liver and kidney meridians. It nourishes blood, strengthens tendons, and fortifies the waist and knees. The *Diannan Materia Medica* states that it "breaks up blood stasis, generates new blood, and expels stillborn fetuses." Cuscuta chinensis is pungent and sweet in taste, neutral in nature, and enters the liver, kidney, and spleen meridians. It nourishes the liver and kidneys, strengthens essence, and stabilizes the fetus, tonifying both yin and yang. It possesses estrogen-like effects and can promote endometrial proliferation. Pueraria lobata is sweet and neutral in taste, cool in nature, and enters the spleen and stomach meridians. It excels at releasing exterior pathogens, raising yang and promoting rash eruption, clearing heat and generating fluids, and unblocking meridians. When used with blood-activating herbs, it promotes blood circulation and prevents recurrence of adhesions, also possessing estrogen-like effects. Paeonia lactiflora is sour and neutral in taste, cold in nature, and enters the liver and spleen meridians. It nourishes blood, astringes yin, regulates menstruation, relieves pain, and calms liver yang. The *Rihuazi Materia Medica* states that it "treats all women's diseases, including those before and after childbirth, and regulates menstruation." It nourishes blood and promotes blood circulation. When combined with licorice, it can relieve abdominal pain. Albizia flowers are sweet in taste and neutral in nature. They enter the heart and liver meridians and have calming and mood-lifting effects, promoting blood circulation and regulating emotions.

[0015] Prepared licorice root is the guiding herb in the herbal combination of this invention. It is sweet and neutral in taste, and slightly warm in nature. Its clinical effects include tonifying the spleen and replenishing qi, moistening the lungs and relieving cough, and relieving pain. It can also harmonize the effects of other herbs. In addition, it is combined with white peony root to form Peony and Licorice Decoction, which can improve abdominal pain symptoms.

[0016] In this invention, the herbal combination of roasted Astragalus membranaceus and stir-fried Atractylodes macrocephala, along with Poria cocos, tonifies Qi and strengthens the spleen to increase the source of Qi and blood production. Since Qi flows, blood flows; tonifying Qi promotes blood circulation. Lycopus lucidus invigorates blood and regulates menstruation, removing blood stasis and promoting the recovery of damaged endometrium. Dipsacus asper, Cuscuta chinensis, and Achyranthes bidentata tonify the liver and kidneys. Stir-fried Paeonia lactiflora nourishes blood, regulates menstruation, and relieves pain. Pueraria lobata unblocks meridians and improves endometrial blood supply. Albizia julibrissin flower soothes the liver and relieves depression, enhancing the blood-activating effect. Roasted Glycyrrhiza uralensis tonifies the spleen, relieves spasms and pain, and harmonizes the effects of the other herbs. The entire formula supports the body's resistance while eliminating pathogens, balancing Qi tonification and blood activation, supplemented by soothing the liver and unblocking meridians.

[0017] In a further embodiment, the present invention provides a traditional Chinese medicine composition, characterized in that: 9-30g of roasted Astragalus membranaceus, 6-12g of Lycopus lucidus, 6-20g of stir-fried Atractylodes macrocephala, 6-20g of Poria cocos, 6-20g of Achyranthes bidentata, 6-20g of Dipsacus asper, 6-20g of Cuscuta chinensis, 6-20g of Pueraria lobata, 6-20g of stir-fried Paeonia lactiflora, 6-20g of Albizia julibrissin, and 2-10g of roasted Glycyrrhiza uralensis.

[0018] In a further embodiment, the present invention provides a traditional Chinese medicine composition, characterized by 12g of roasted Astragalus membranaceus, 12g of Lycopus lucidus, 15g of stir-fried Atractylodes macrocephala, 12g of Poria cocos, 12g of Achyranthes bidentata, 15g of Dipsacus asper, 15g of Cuscuta chinensis, 12g of Pueraria lobata, 12g of stir-fried Paeonia lactiflora, 12g of Albizia julibrissin, and 6g of roasted Glycyrrhiza uralensis.

[0019] In another embodiment, a method for preparing the traditional Chinese medicine composition of the present invention is provided, characterized by comprising the following steps:

[0020] (1) Directly mix the various Chinese herbal raw materials to obtain a Chinese herbal mixture; optionally, and

[0021] (2) Extract the mixture obtained in (1) with water and / or alcohol to obtain a traditional Chinese medicine extract.

[0022] The extraction solvent can be water or alcohol, or a mixture of water and alcohol, wherein the alcohol can be methanol or ethanol, and the mixture of water and alcohol can be prepared into different concentrations, such as 70% or 75% aqueous ethanol solutions.

[0023] The herbal extract of the present invention can also be prepared, for example, by the following method:

[0024] i) Astragalus membranaceus (processed), Poria cocos, Achyranthes bidentata, Dipsacus asper, Cuscuta chinensis, Pueraria lobata, Paeonia lactiflora (processed), Albizia julibrissin (flower), and Glycyrrhiza uralensis (processed) were extracted with ethanol, filtered, and the ethanol was recovered from the filtrate for later use.

[0025] The dregs of the medicine should be stored in a separate container;

[0026] ii) Extract the volatile oil from Lycopus lucidus and stir-fried Atractylodes macrocephala with water, collect the volatile oil, filter the liquid and set aside;

[0027] iii) Combine the dregs of Ze Lan and stir-fried Bai Zhu with the dregs of roasted Huang Qi, Fu Ling, Chuan Niu Xi, Chuan Xu Duan, Tu Si Zi, Ge Gen, stir-fried Bai Shao, He Huan Hua, and roasted Gan Cao, decoct in water, filter, combine the filtrate with the other decoctions mentioned above, concentrate, and filter.

[0028] iv) Take the volatile oils of the above-mentioned Lycopus lucidus and stir-fried Atractylodes macrocephala, dissolve them in ethanol, and mix the ethanol solution with the above-mentioned concentrated medicinal solution.

[0029] In a further embodiment, a mixture of traditional Chinese medicine or a traditional Chinese medicine extract prepared by the method of the present invention, or a mixture of traditional Chinese medicine or a traditional Chinese medicine extract containing the thereof, is provided.

[0030] In a further embodiment, a traditional Chinese medicine preparation is provided, comprising the aforementioned traditional Chinese medicine composition. Depending on actual needs, the traditional Chinese medicine preparation may also include pharmaceutically acceptable excipients. Various dosage forms, such as decoctions, granules, pills, capsules, tablets, powders, and oral liquids, are prepared according to conventional pharmaceutical processes.

[0031] In another embodiment, the present invention provides the use of the herbal mixture or herbal extract for treating gynecological diseases or conditions such as intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent implantation failure, and infertility, or for preparing drugs for treating gynecological diseases or conditions.

[0032] In a further embodiment, a drug is provided for treating gynecological diseases or conditions such as intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent embryo transfer failure, and infertility, with the traditional Chinese medicine mixture or composition of the present invention as the active ingredient.

[0033] In another embodiment, a pharmaceutical composition is provided for treating gynecological diseases or conditions such as intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent embryo transfer failure, and infertility, comprising the traditional Chinese medicine mixture or extract of the present invention as an active ingredient, optional Western medicine active ingredients, and a pharmaceutically acceptable carrier, diluent, or excipient.

[0034] In another embodiment, a pharmaceutical preparation is provided for treating gynecological diseases such as intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent embryo transfer failure, and infertility, comprising the pharmaceutical composition of the present invention.

[0035] In another embodiment, a method is provided for preparing a pharmaceutical preparation for treating gynecological diseases or conditions such as intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent embryo transfer failure, and infertility. This method includes mixing the traditional Chinese medicine mixture or extract of the present invention with a pharmaceutically acceptable matrix, optionally in combination with the Western medicine described in the present invention. The applicable Western medicines are well known to those skilled in the art.

[0036] In another embodiment, the traditional Chinese medicine mixture or extract of the present invention can also be used in combination with Western medicines such as estrogen and progesterone for treating gynecological diseases or conditions such as intrauterine adhesions, thin endometrium, oligomenorrhea, delayed menstruation, dysmenorrhea, endometritis, pelvic inflammatory disease, decreased ovarian reserve, recurrent implantation failure, and infertility, to treat intrauterine adhesions and other gynecological conditions.

[0037] The traditional Chinese medicine composition of this invention can be prepared according to conventional methods in the art. Using the traditional Chinese medicine composition of this invention, and employing conventional techniques and / or excipients in the art, those skilled in the art can prepare other drugs and preparations according to conventional techniques in the art.

[0038] Example

[0039] The following embodiments are for illustrative purposes only and are not to be construed as limiting the scope of the invention in any way.

[0040] Example 1

[0041] Weigh the following ingredients in the indicated proportions: 12g of roasted Astragalus membranaceus, 12g of Lycopus lucidus, 15g of stir-fried Atractylodes macrocephala, 12g of Poria cocos, 12g of Achyranthes bidentata, 15g of Dipsacus asper, 15g of Cuscuta chinensis, 12g of Pueraria lobata, 12g of stir-fried Paeonia lactiflora, 12g of Albizia julibrissin, and 6g of roasted Glycyrrhiza uralensis. Soak in water for 1 hour, place in a multi-functional extraction vessel, and decoct twice. For the first decoction, add 5 times the amount of water as the total ingredients and decoct for 2 hours. Filter the decoction. For the second decoction, add 3 times the amount of water as the total ingredients and decoct for 1.2 hours. Collect both decoctions, filter, and heat-seal the filtrate in a bag. Sterilize at 105℃ and package to obtain the final product.

[0042] Example 2

[0043] Weigh the following ingredients in the indicated proportions: 9g of roasted Astragalus membranaceus, 6g of Lycopus lucidus, 6g of stir-fried Atractylodes macrocephala, 6g of Poria cocos, 6g of Achyranthes bidentata, 6g of Dipsacus asper, 6g of Cuscuta chinensis, 6g of Pueraria lobata, 6g of stir-fried Paeonia lactiflora, 6g of Albizia julibrissin, and 2g of roasted Glycyrrhiza uralensis. Place them in a multi-functional extraction vessel, add water, and decoct twice. For the first decoction, add 8 times the amount of water as the total ingredients and decoct for 1 hour. Filter the decoction. For the second decoction, add 6 times the amount of water as the total ingredients and decoct for 1 hour. Filter the two decoctions, add lactose or corn starch as a carrier, add magnesium stearate as a lubricant, mix well, and then compress into tablets.

[0044] Example 3

[0045] Weigh the following ingredients in the indicated weight proportions: 9g of roasted Astragalus membranaceus, 6g of Lycopus lucidus, 6g of stir-fried Atractylodes macrocephala, 6g of Poria cocos, 6g of Achyranthes bidentata, 6g of Dipsacus asper, 6g of Cuscuta chinensis, 6g of Pueraria lobata, 6g of stir-fried Paeonia lactiflora, 6g of Albizia julibrissin, and 2g of roasted Glycyrrhiza uralensis. Soak the ingredients in water equal to 10 times their weight for 2 hours. Then decoct once for 2 hours each time. For the second decoction, add water equal to 8 times their weight and decoct once for 1.2 hours. Combine the decoctions, filter, concentrate under reduced pressure, add lactose or corn starch as a carrier to the concentrate, mix well, granulate, and then encapsulate to make capsules.

[0046] Example 4

[0047] First, take 9g of roasted Astragalus membranaceus, 6g of Lycopus lucidus, 6g of stir-fried Atractylodes macrocephala, 6g of Poria cocos, 6g of Achyranthes bidentata, 6g of Dipsacus asper, 6g of Cuscuta chinensis, 6g of Pueraria lobata, 6g of stir-fried Paeonia lactiflora, 6g of Albizia julibrissin, and 2g of roasted Glycyrrhiza uralensis. Soak the herbs in water eight times the amount of the total herbs for 2 hours. Then decoct once for 2 hours each time. For the second decoction, add water eight times the amount of the total herbs and decoct once for 1 hour. Combine the decoctions, filter, concentrate under reduced pressure, and mix the concentrate with a diluent such as lactose or corn starch. Granulate, dry, and make into granules.

[0048] Example 5

[0049] Using the raw materials described in Example 1 in the indicated weight proportions, extraction was performed according to the following method, wherein the ethanol concentration was an aqueous solution of 75% ethanol.

[0050] i) Astragalus membranaceus (processed), Poria cocos, Achyranthes bidentata, Dipsacus asper, Cuscuta chinensis, Pueraria lobata, Paeonia lactiflora (processed), Albizia julibrissin (flower), and Glycyrrhiza uralensis (processed) were extracted with ethanol at room temperature for 1 hour, filtered, and the ethanol was recovered from the filtrate for later use.

[0051] The dregs of the medicine should be stored in a separate container;

[0052] ii) Heat water with Lycopus lucidus and stir-fried Atractylodes macrocephala to extract volatile oil, collect the volatile oil, filter the liquid and set aside;

[0053] iii) Combine the dregs of Ze Lan and stir-fried Bai Zhu with the dregs of roasted Huang Qi, Fu Ling, Chuan Niu Xi, Chuan Xu Duan, Tu Si Zi, Ge Gen, stir-fried Bai Shao, He Huan Hua, and roasted Gan Cao, decoct in water, filter, combine the filtrate with the other decoctions mentioned above, concentrate, and filter.

[0054] iv) Dissolve the volatile oils of the above-mentioned Lycopus lucidus and stir-fried Atractylodes macrocephala in ethanol, and mix the ethanol solution with the above-mentioned concentrated medicinal solution to obtain the Chinese herbal extract.

[0055] Experimental Example 1

[0056] The clinical efficacy studies of the traditional Chinese medicine composition of this invention are as follows:

[0057] Sixty-four cases of intrauterine adhesions meeting the inclusion and exclusion criteria were collected and randomly divided into two groups of 32 each. All patients underwent TCRA surgery. The control group received sequential estrogen-progesterone therapy post-surgery, taking one tablet of Femoston orally daily starting from day 1 post-surgery, followed by estradiol tablets for the first 14 days and estradiol-dydrogesterone tablets for the next 14 days. The treatment group received the same treatment as the control group, plus the traditional Chinese medicine composition described in Example 1 above. The herbs were decocted by the Pharmacy Department of Guang'anmen Hospital, China Academy of Chinese Medical Sciences, and administered one dose daily, 200ml each time after breakfast and dinner. Both groups underwent treatment for three menstrual cycles.

[0058] 1. Observation indicators and methods

[0059] 1.1 Overall Clinical Effectiveness: The overall effectiveness was determined based on the "Standards for Diagnosis and Efficacy Evaluation of Diseases and Syndromes in Traditional Chinese Medicine," primarily observing the recovery of uterine cavity morphology and menstrual flow. **Significant Effect:** Menstrual flow returned to normal. A follow-up hysteroscopy at the end of the treatment course showed a normal uterine cavity morphology, with both uterine horns or fallopian tube openings clearly visible. **Effective:** Menstrual flow increased slightly compared to pre-treatment levels, but did not return to normal and remained less than before. A follow-up hysteroscopy at the end of the treatment course showed a basically normal uterine cavity morphology, with both uterine horns or fallopian tube openings visible, although some adhesions were still present. **Ineffective:** Menstrual flow showed no improvement. A follow-up hysteroscopy at the end of the treatment course showed no change in uterine cavity morphology compared to pre-treatment levels, or even worsened the condition.

[0060] Overall clinical efficacy rate = [(number of cases with significant effect + number of cases with effect) / total number of cases] × 100%.

[0061] 1.2 TCM syndrome score: Formulated with reference to the "Standards for Diagnosis and Efficacy of TCM Diseases and Syndromes", it mainly includes menstrual conditions (menstrual flow, color, quality and duration), symptoms such as lower abdominal pain, fatigue, shortness of breath and reluctance to speak, dizziness, pale or dull complexion, etc., and the changes in scores before and after treatment are statistically analyzed.

[0062] 1.3 Endometrial thickness: Both groups of patients underwent transvaginal ultrasound examinations before treatment and again during the third menstrual cycle after treatment (5-7 days after ovulation) to measure endometrial thickness. For amenorrhea patients, there was no specific menstrual cycle requirement. (The two transvaginal ultrasound examinations for the same patient were performed at the same time points and by the same hospital's ultrasound department.)

[0063] 1.4 Intrauterine adhesion scoring: Hysteroscopy was performed on both groups of patients before the operation and during the first menstrual cycle after the operation, and 3 to 7 days after menstruation ended (for those who did not have their period on time, around the 10th day of the second menstrual cycle after taking the medication). The degree of intrauterine adhesion was scored according to the "Chinese IUA Diagnostic Grading Scoring Standard".

[0064] China IUA Scoring Standards

[0065]

[0066] Note: Mild: 0-8 points; Moderate: 9-18 points; Severe: 19-28 points

[0067] The changes in scores before and after treatment were statistically analyzed, and sexual activity was prohibited during the treatment period.

[0068] 1.5 Menstrual Flow Assessment: Menstrual flow was assessed in both groups before and after treatment. The pictorial blood loss assessment chart (PBAC) was used as the standard. 1 point was awarded for blood-stained area ≤ 1 / 3 of the entire sanitary napkin area and blood clot area < 1 yuan coin area; 5 points were awarded for blood-stained area 1 / 3–3 / 5 of the entire sanitary napkin area and blood clot area ≥ 1 yuan coin area; and 20 points were awarded for blood-stained area covering the entire sanitary napkin. Lower scores indicated less menstrual flow and more severe conditions. Each 25 points represented approximately 20 ml of menstrual flow, which was used as the evaluation standard. Less than 20 ml indicated insufficient menstrual flow, and more than 80 ml indicated excessive menstrual flow. Normal menstrual flow is approximately 30–50 ml.

[0069] 1.6 Follow-up pregnancy rate and recurrence rate: Patients were followed up for 6 months after the operation. The standard for diagnosing pregnancy was intrauterine pregnancy as indicated by ultrasound examination, and the standard for diagnosing recurrence was intrauterine adhesion as indicated by hysteroscopy examination. The pregnancy rate and recurrence rate were statistically analyzed.

[0070] 1.7 Safety indicators: Liver and kidney function, blood routine, urine routine and electrocardiogram were performed on both groups of patients before and after treatment, and any serious adverse events, such as headache, gastrointestinal reaction or allergy, were recorded during the study.

[0071] 2. Experimental Results

[0072] This study included 64 patients with IUA who met the inclusion and exclusion criteria, with 32 patients in the treatment group and 32 in the control group. Four patients dropped out: 2 in the treatment group (one patient took ibuprofen for a cold and fever in the first month of treatment, and stopped taking the traditional Chinese medicine after 2 days, thus being included as an invalid case; the other patient was lost to follow-up at 6 months post-surgery, but was counted as a valid case); and 2 in the control group (one patient became pregnant in the third month of treatment and stopped taking femoston, switching to dapoxetine; the other patient was lost to follow-up after 3 months of medication, both being included as invalid cases).

[0073] 2.1 Comparison of two sets of general data

[0074] The patients' age, education level, body mass index (BMI), disease duration, degree of intrauterine adhesions, number of intrauterine procedures, and other gynecological history were collected. Table 1 shows that there were no statistically significant differences in general characteristics between the two groups (P>0.05), indicating comparability.

[0075] Table 1 Comparison of general information between the two groups of patients with intrauterine adhesions

[0076]

[0077]

[0078] 2.2 Comparison of clinical efficacy between the two groups of patients

[0079] Table 2 shows that the total effective rate in the treatment group was 90.63%, while that in the control group was 75.00%. The difference between the two groups was statistically significant (P < 0.05), and the total effective rate in the treatment group was higher than that in the control group.

[0080] Table 2 Comparison of overall clinical efficacy between the two groups [n(%)]

[0081]

[0082] 2.3 Comparison of TCM syndrome efficacy scores before and after treatment in the two groups of patients

[0083] Table 3 shows that there was no statistically significant difference in TCM syndrome scores between the two groups before treatment (P>0.05). After treatment, the TCM syndrome scores of both the treatment group and the control group decreased significantly compared with those before treatment (P<0.05), and the decrease was more significant in the treatment group than in the control group. The differences were statistically significant (P<0.05).

[0084] Table 3 Comparison of TCM syndrome scores before and after treatment in the two groups of patients (scores, )

[0085]

[0086] 2.4 Comparison of endometrial thickness before and after treatment in the two groups of patients

[0087] Table 4 shows that there was no statistically significant difference in endometrial thickness between the treatment group and the control group before treatment (P>0.05). After treatment, the endometrial thickness in both groups increased significantly (P<0.05), with a larger difference in endometrial thickness before and after treatment in the treatment group, and a more significant increase in thickness compared to the control group (P<0.05).

[0088] Table 4 Comparison of endometrial thickness before and after treatment in the two groups of patients (mm). )

[0089]

[0090] 2.5 Comparison of intrauterine adhesion scores before and after treatment in the two groups of patients

[0091] Table 5 shows that there was no statistically significant difference in intrauterine adhesion scores between the two groups before treatment (P > 0.05). After treatment, the intrauterine adhesion scores of both groups decreased significantly (P < 0.05), and the decrease in intrauterine adhesion scores was more significant in the treatment group than in the control group (P < 0.05).

[0092] Table 5 Comparison of intrauterine adhesion scores before and after treatment in the two groups (points). )

[0093]

[0094] 2.6 Comparison of menstrual flow scores before and after treatment between the two groups of patients

[0095] Table 6 shows that there was no statistically significant difference in menstrual flow scores between the treatment group and the control group before treatment (P>0.05). After treatment, the menstrual flow scores of both groups increased significantly compared with those before treatment (P<0.001); there was no statistically significant difference in menstrual flow scores between the two groups after treatment or in the difference before and after treatment (P>0.05).

[0096] Table 6 Comparison of menstrual flow scores before and after treatment in the two groups (points, )

[0097]

[0098] 2.7 Comparison of pregnancy rates between the two groups of patients

[0099] Table 7 shows that at the 6-month follow-up after surgery, the total pregnancy rate in the treatment group (37.50%) was higher than that in the control group (12.50%). The difference between the two groups was statistically significant by chi-square test (P<0.05).

[0100] Table 7 Comparison of pregnancy rates between the two groups of patients

[0101]

[0102] 2.8 Comparison of re-adhesion rates between the two groups of patients

[0103] Table 8 shows that at the 6-month follow-up, the re-adhesion rate in the treatment group was 3.13% and the re-adhesion rate in the control group was 9.38%. There was no statistically significant difference in the re-adhesion rates between the two groups (P>0.05).

[0104] Table 8 Comparison of re-adhesion rates between the two groups [n(%)]

[0105]

[0106] 2.9 Safety Observation

[0107] During the study, the liver and kidney function, blood routine, urine routine, electrocardiogram and other safety tests of patients in both the treatment group and the control group were normal, and no allergic reactions or serious adverse reactions occurred during the medication period.

[0108] 3. Discussion

[0109] In this experiment, the total effective rate in the treatment group was 90.63%, while that in the control group was 75.00%, with the treatment group showing a significantly higher rate. Furthermore, both groups showed improvement in endometrial thickness, intrauterine adhesion scores, and menstrual flow, with the treatment group demonstrating superior efficacy in the first two indicators. This suggests that the Qi-invigorating and blood-activating traditional Chinese medicine composition of this invention can promote endometrial recovery in patients with intrauterine adhesions, reduce intrauterine adhesion scores, and restore the normal uterine anatomical structure. Regarding TCM syndrome scores, the treatment group also showed better efficacy than the control group, indicating that the Qi-invigorating and blood-activating traditional Chinese medicine composition of this invention can significantly improve the clinical symptoms of patients with intrauterine adhesions. At the 6-month follow-up, the pregnancy rate in the treatment group was higher than that in the control group (P < 0.05), but there was no statistically significant difference in the re-adhesion rate between the two groups. This suggests that the Qi-invigorating and blood-activating traditional Chinese medicine composition of this invention, combined with surgical treatment, can improve the fertility and pregnancy outcomes of patients with intrauterine adhesions. In addition, no adverse reactions were observed during clinical use, indicating a certain level of safety.

[0110] 4. Conclusion

[0111] The results of this experiment demonstrate that the Qi-invigorating and blood-activating traditional Chinese medicine composition of the present invention can safely and effectively promote the restoration of the normal anatomical structure of the uterus in patients with intrauterine adhesions. After treatment, it can significantly increase the thickness of the endometrium and the amount of menstrual flow, reduce the intrauterine adhesion score, improve clinical symptoms, and increase the pregnancy rate.

[0112] Typical cases

[0113] Case 1

[0114] The patient, a 31-year-old female, presented with a chief complaint of "three miscarriages two months after surgery for intrauterine adhesions." She underwent three curettages due to miscarriages. Six months after the third curettage, intrauterine adhesions were diagnosed, and she underwent TCRA at another hospital. Intraoperative hysteroscopy revealed abnormal uterine cavity shape, with narrowing and barrel-shaped uterine cavity in the lower segment, and obvious scarring, more pronounced on the left side. Longitudinal, wide adhesions were visible in both uterine horns. She has been taking Femoston orally since the surgery. Vaginal ultrasound showed an endometrial thickness of 5mm, diagnosed as thin endometrium. Her menstrual cycle was usually regular, 22-28 days, with a 7-day menstrual period, normal flow, bright red color, blood clots, and dysmenorrhea. After the third curettage, her menstrual flow decreased by about one-third. She was given the herbal composition described in Example 1. After six months of treatment, her menstrual flow returned to the pre-operative normal level. Follow-up hysteroscopy and vaginal ultrasound showed no recurrence of adhesions, and the endometrial thickness increased to 8mm.

[0115] Case 2

[0116] The patient, a 32-year-old female, presented with a chief complaint of "chronic endometritis for 6 months and two failed embryo transfers." Hysteroscopic pathology revealed endometritis, CD138 (+), and CD38 (+). She had experienced two failed in-vitro fertilization-embryo transfers. Hysterosalpingography (HSG) showed that the left fallopian tube was partially patent and the right fallopian tube was blocked. Her menstrual cycle was regular, with a cycle of 28-30 days and a menstrual period of 7-8 days. Her menstrual flow, color, and consistency were normal, without clots or dysmenorrhea. She was prescribed the traditional Chinese medicine composition described in Example 1. After one month of treatment, a follow-up hysteroscopy showed that both CD138 and CD38 levels had become negative. After four months of treatment, she underwent in-vitro fertilization-embryo transfer, resulting in two successful implantations. Subsequent follow-up revealed that the patient had successfully given birth.

[0117] Case 3

[0118] The patient, a 36-year-old female, presented with a chief complaint of "primary infertility for 3 years." She had regular menstrual cycles of 30 days, with a menstrual period of 5 days, normal flow, color, and consistency, and no blood clots, but experienced dysmenorrhea. She was prescribed the traditional Chinese medicine composition described in Example 1. After one month of treatment, her dysmenorrhea symptoms subsided. Four months later, she discovered she was pregnant, and subsequent follow-ups confirmed a successful delivery.

[0119] Case 4

[0120] The patient, a 35-year-old female, presented with a chief complaint of "decreased ovarian reserve for 5 years." Hormone tests showed: follicle-stimulating hormone (FSH) 11.4 U / L, luteinizing hormone (LH) 4.8 U / L, estradiol 28 pmol / L, and anti-Müllerian hormone (AMH) 0.4 ng / ml. She experienced scanty menstruation, with cycles typically lasting 35 days, menstrual periods lasting 2-3 days, and no blood clots or dysmenorrhea. She was prescribed the traditional Chinese medicine composition described in Example 1. After 3 months of treatment, follow-up tests showed FSH at 9.8 U / L, LH at 4.4 U / L, and AMH at 0.8 ng / ml, with increased menstrual flow. After 6 months of treatment, follow-up tests showed FSH at 8.5 U / L, LH at 5.1 U / L, and AMH at 1.2 ng / ml.

[0121] Case 5

[0122] The patient, a 40-year-old female, presented with the chief complaint of "delayed menstruation for over a year." Since childbirth, she had experienced delayed menstruation, with cycles ranging from 30 to 60 days, mostly 45 to 50 days. Menstrual flow was slightly reduced compared to before, with no blood clots or dysmenorrhea. She had previously treated with oral dydrogesterone tablets, but the effect was unsatisfactory. Hormone tests showed: follicle-stimulating hormone (FSH) 3.32 U / L, luteinizing hormone (LH) 6.52 U / L, and anti-Müllerian hormone (AMH) 0.73 ng / ml. She was given the traditional Chinese medicine composition described in Example 1. After 3 months of treatment, her menstrual cycle shortened to approximately 40 days; after 6 months, it shortened to approximately 35 days, and menstrual flow returned to normal.

[0123] Case 6

[0124] The patient, a 20-year-old female, presented with a 7-year history of dysmenorrhea. Since menarche at age 13, she experienced lower abdominal and back pain during each menstrual period, requiring ibuprofen for severe pain. Her VAS score was 8. Pain relief was achieved after using a heat patch. Her menstrual cycle was regular, typically 28-30 days, with a period lasting 5-6 days. She experienced blood clots, lower abdominal pain, and backache during menstruation. She was prescribed the herbal composition described in Example 1. After two months of treatment, the patient reported reduced pain, with a VAS score of 6. After five months of treatment, she reported significant improvement in pain, with her VAS score decreasing to 3.

[0125] Case 7

[0126] The patient, a 29-year-old female, presented with a chief complaint of "lower abdominal pain for over a year." Following a self-induced abortion and subsequent curettage, she began experiencing intermittent lower abdominal pain, accompanied by increased vaginal discharge and a feeling of rectal pressure. She had previously consulted another hospital and was diagnosed with chronic pelvic inflammatory disease. A vaginal ultrasound revealed pelvic effusion and thickening of both fallopian tubes. She had previously received acupuncture and oral antibiotics at our hospital, but with limited effectiveness. Her menstrual cycle was usually regular, 28-29 days, with a 6-day menstrual period and normal menstrual flow. She experienced significant premenstrual abdominal pain. She was treated with the traditional Chinese medicine composition described in Example 1, combined with antibiotics. After three months of treatment, the patient reported a reduction in abdominal pain, and the lower back pain and lower abdominal pressure disappeared. After six months of treatment, the patient reported that the abdominal pain had essentially disappeared, and a follow-up vaginal ultrasound showed no significant abnormalities.

[0127] The above descriptions are merely some embodiments of the present invention. Those skilled in the art can make various modifications and improvements without departing from the inventive concept of the present invention, and these all fall within the scope of protection of the present invention.

Claims

1. A traditional Chinese medicine composition for treating gynecological diseases, characterized in that, It is composed of the following ingredients: Astragalus membranaceus (processed) 9-30g, Lycopus lucidus 6-12g, Atractylodes macrocephala (processed) 6-20g, Poria cocos 6-20g, Achyranthes bidentata 6-20g, Dipsacus asper 6-20g, Cuscuta chinensis 6-20g, Pueraria lobata 6-20g, Paeonia lactiflora (processed) 6-20g, Albizia julibrissin 6-20g, Glycyrrhiza uralensis (processed) 2-10g; Among them, the gynecological diseases mentioned are intrauterine adhesions, thin endometrium, or oligomenorrhea.

2. The traditional Chinese medicine composition according to claim 1, wherein the composition comprises: 12g of roasted Astragalus membranaceus, 12g of Lycopus lucidus, 15g of stir-fried Atractylodes macrocephala, 12g of Poria cocos, 12g of Achyranthes bidentata, 15g of Dipsacus asper, 15g of Cuscuta chinensis, 12g of Pueraria lobata, 12g of stir-fried Paeonia lactiflora, 12g of Albizia julibrissin, and 6g of roasted Glycyrrhiza uralensis.

3. The traditional Chinese medicine composition according to claim 1 or 2, wherein the gynecological disease is intrauterine adhesion.

4. The method for preparing the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that: (1) Directly mix the various Chinese herbal raw materials to obtain a Chinese herbal mixture; (2) Extract the mixture obtained in (1) with water and / or alcohol to obtain a traditional Chinese medicine extract.

5. The method for preparing the traditional Chinese medicine composition according to any one of claims 1-3, characterized in that: The traditional Chinese medicine composition is prepared by the following method: i) Astragalus membranaceus (processed), Poria cocos, Achyranthes bidentata, Dipsacus asper, Cuscuta chinensis, Pueraria lobata, Paeonia lactiflora (processed), Albizia julibrissin (flower), and Glycyrrhiza uralensis (processed) were extracted with ethanol, filtered, and the ethanol was recovered from the filtrate for later use. The dregs of the medicine should be stored in a separate container; ii) Extract the volatile oil from Lycopus lucidus and stir-fried Atractylodes macrocephala with water, collect the volatile oil, filter the liquid and set aside; iii) Combine the dregs of Lycopus lucidus and stir-fried Atractylodes macrocephala with the dregs of Astragalus membranaceus (processed), Poria cocos, Achyranthes bidentata, Dipsacus asper, Cuscuta chinensis, Pueraria lobata, stir-fried Paeonia lactiflora, Albizia julibrissin, and Glycyrrhiza uralensis (processed), decoct in water, filter, combine the filtrate with the decoctions from steps i) and ii) above, concentrate, and filter. iv) Take the volatile oils of the above-mentioned Lycopus lucidus and stir-fried Atractylodes macrocephala, dissolve them in ethanol, and mix the ethanol solution with the above-mentioned concentrated medicinal solution.

6. The traditional Chinese medicine extract prepared according to the method of claim 4 or 5.

7. The use of the traditional Chinese medicine extract according to claim 6, for preparing a drug for treating intrauterine adhesions, thin endometrium, or oligomenorrhea.

8. The use of the traditional Chinese medicine extract according to claim 7, for preparing a drug for treating intrauterine adhesions.

9. A drug for treating intrauterine adhesions, thin endometrium, and oligomenorrhea, characterized in that, The herbal extract described in claim 6 is used as the active ingredient.

10. A pharmaceutical composition for treating intrauterine adhesions, thin endometrium, or oligomenorrhea, characterized in that, This includes the Chinese herbal extracts described in claim 6 as effective components of Chinese herbal medicine and effective components of estrogen-progestin-type Western medicines.

11. A pharmaceutical composition for treating intrauterine adhesions, thin endometrium, or oligomenorrhea, characterized in that, The drug of claim 9 or the pharmaceutical composition of claim 10 is included as an active ingredient and a pharmaceutically acceptable carrier or diluent.

12. The pharmaceutical composition according to claim 11, characterized in that, The drug dosage form is decoction, granules, pills, capsules, tablets, powders, or oral liquid.

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