CN118845961A - A Chinese medicine composition for treating intrauterine adhesion and its application - Google Patents

Abstract

The present invention relates to a Chinese medicine composition for treating intrauterine adhesion, wherein the Chinese medicine composition is prepared from the following raw materials in parts by weight: 14-16 parts of tortoise shell, 14-16 parts of prepared rehmannia root, 1-3 parts of placenta, 14-16 parts of cuttlebone, 14-16 parts of raw madder, 11-13 parts of angelica, 11-13 parts of white peony root, 5-7 parts of peach kernel, 0.4-0.6 parts of saffron, 5-7 parts of chuanxiong, 29-31 parts of raw astragalus, 8-10 parts of antler frost, and 5-7 parts of amomum. The present invention also provides an application of the Chinese medicine composition. The present invention is combined with estrogen-progestin artificial cycle treatment and applied to intrauterine adhesion decomposition surgery under hysteroscopy, which can improve uterine artery blood flow, promote endometrial proliferation and repair, reduce the recurrence of intrauterine adhesion, and compared with the artificial cycle treatment of estrogen-progestin alone, it can reduce the intrauterine adhesion score, alleviate the TCM syndrome symptoms of kidney deficiency and blood stasis in patients, and improve the total clinical efficacy. Based on this, it is believed that Zigui Yangmo Decoction combined with estrogen-progesterone artificial cycle has certain clinical advantages in the treatment of kidney deficiency and blood stasis type intrauterine adhesions.

Description

A Chinese medicine composition for treating intrauterine adhesion and its application

Technical Field

The invention relates to the technical field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition for treating intrauterine adhesions and an application thereof.

Background Art

The causes of intrauterine adhesions (IUA) include recent history of intrauterine operation and abortion. Clinical manifestations may include scanty menstruation, and in severe cases, secondary amenorrhea; cyclical lower abdominal pain; secondary infertility, recurrent miscarriage, etc. Hysteroscopy shows that there are adhesion bands on the walls of the uterine cavity, but the normal anatomical morphology exists in the uterine cavity, the openings of the fallopian tubes on both sides are visible, and there are no adhesions on the uterine horns on both sides. Or the adhesion bands cause the uterine cavity to lose part of its normal anatomical morphology, with adhesions on one or both sides of the uterine horns, adhesions on the uterine fundus, or adhesions on the cervical canal, making it impossible for the hysteroscope to explore the uterine cavity. For cervical adhesions, the treatment principle is to remove adhesions, restore the anatomical structure, and prevent the regeneration of adhesions. The treatment methods are mainly surgery or surgery and medication.

Chinese patent document CN105381165A discloses a Chinese medicine composition for treating oligomenorrhea caused by postoperative intrauterine adhesions after cold and blood stasis blocking uterine surgery. The Chinese medicine is composed of the following Chinese medicines in parts by weight: 4-8 parts of star anise, 4-8 parts of red chuanwu, 4-8 parts of almonds, 4-8 parts of wave edge aralia, 4-8 parts of crab seven, 4-8 parts of white wood, 4-8 parts of water chestnut shell, 4-8 parts of Aliteng, and 4-8 parts of liquorice. The combination of these medicines can warm the yang and dredge the collaterals, promote blood circulation and remove blood stasis, and closely follow the etiology and pathogenesis of oligomenorrhea caused by intrauterine adhesions, and can significantly increase the patient's menstrual volume and improve the accompanying Chinese medicine symptoms.

Chinese patent document CN103446548A discloses a Chinese medicine preparation for intrauterine injection for preventing and treating intrauterine adhesion and its preparation method. The Chinese medicine preparation for intrauterine injection for preventing and treating intrauterine adhesion is composed of the following ingredients in parts by weight: 10-15 parts of salvia miltiorrhiza, 10-15 parts of angelica sinensis, 10-15 parts of chuanxiong, 8-10 parts of sophora flavescens, 8-10 parts of scutellaria baicalensis, 8-10 parts of coptis chinensis, 8-10 parts of phellodendron amurense, 8-10 parts of atractylodes lancea. The intrauterine injection Chinese medicine preparation for preventing and treating intrauterine adhesion is prepared by mixing a variety of Chinese medicinal materials and has the advantages of simple operation, low recurrence rate and no toxic side effects.

There are many traditional Chinese medicine compositions for treating intrauterine adhesions, but they all have more or less disadvantages, such as too many medicinal flavors, difficult to obtain materials, expensive prices, unclear efficacy, poor therapeutic effect, etc. Therefore, there is an urgent need for a traditional Chinese medicine composition that has obvious efficacy in treating intrauterine adhesions, few medicinal flavors, practical operability, high compliance, and is safe and effective.

Summary of the invention

The purpose of the present invention is to provide a Chinese medicine composition for treating intrauterine adhesions and its application in view of the deficiencies in the prior art.

In a first aspect, the present invention provides a traditional Chinese medicine composition for treating intrauterine adhesions, wherein the traditional Chinese medicine composition is prepared from the following raw medicines in parts by weight: 14-16 parts of tortoise shell, 14-16 parts of rehmannia root, 1-3 parts of placenta, 14-16 parts of cuttlebone, 14-16 parts of raw madder, 11-13 parts of angelica, 11-13 parts of white peony root, 5-7 parts of peach kernel, 0.4-0.6 parts of saffron, 5-7 parts of chuanxiong, 29-31 parts of raw astragalus, 8-10 parts of antler frost, and 5-7 parts of amomum.

As a preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 15 parts of tortoise shell, 15 parts of Rehmannia root, 2 parts of placenta, 15 parts of cuttlebone, 15 parts of raw madder, 12 parts of angelica, 12 parts of white peony root, 6 parts of peach kernel, 0.5 parts of saffron, 6 parts of Chuanxiong, 30 parts of raw astragalus, 9 parts of antler frost, and 6 parts of Amomum villosum.

As another preferred example, the Chinese medicine composition is in the form of tablets, capsules, granules, oral liquids or syrups.

In a second aspect, the present invention provides the use of a Chinese medicine composition in preparing a medicine for treating kidney deficiency and blood stasis type intrauterine adhesions.

In a third aspect, the present invention provides a pharmaceutical composition for treating intrauterine adhesions, wherein the pharmaceutical composition consists of a traditional Chinese medicine composition and femosterol.

In a fourth aspect, the present invention provides use of the pharmaceutical composition in preparing a drug for treating kidney deficiency and blood stasis type intrauterine adhesions.

The invention has the advantages that: the prescription is modified from the four-cuttlefish bone-luru pill and the peach red four-substance decoction. The four-cuttlefish bone-luru pill recorded in Suwen·Abdomen Theory is a prescription for treating blood deficiency and amenorrhea. The ancient prescription is used in a new way. The four-cuttlefish bone-luru pill has the functions of both tonifying and unblocking, unblocking and astringing, and embodies the magic of flexibility. The pill is applied to intrauterine adhesion to improve the menstrual condition. However, if the two medicines of cuttlefish bone and madder are used alone for the purpose of seeking offspring, the medicine is still weak. It cannot be based on one prescription or one medicine. It is necessary to form a compound prescription for treatment based on syndrome differentiation. In the prescription, tortoise shell and placenta are the main medicines. The "Compendium of Materia Medica" says: "Turtle shell is salty and flat, and is also a medicine for the kidney meridian. It has the function of tonifying water and controlling fire, so it can strengthen muscles and bones, benefit the mind... remove blood stasis and stop new bleeding." Ancient Chinese people said that placenta comes from the mother's body, and it is of the same nature as humans. It is protected by the mother and formed by the combination of the father's sperm and the mother's blood. It is favored by the true essence and cannot be compared with metal, stone, grass, and wood. It has the function of replenishing vital energy, nourishing essence and calming the mind. Placenta, tortoise shell, and antler frost are blood and flesh products that can nourish essence and blood. They can replace the functions of quail eggs and abalone juice to increase the flavor of qi and medicine. Rubia cordifolia can promote liver blood circulation and help regulate menstruation, and sea cucumber can promote lung qi and benefit the distribution of essence and blood. They are both nourishing and unblocking, and they are both clearing the middle and astringent. They are ministerial drugs. On the basis of nourishing blood and harmonizing blood, peach kernel and saffron focus on the power of promoting blood circulation and removing blood stasis. Chuanxiong promotes qi and activates blood circulation, and angelica can replenish blood and activate blood circulation. The accumulation of symptoms is formed immediately. It does not seek quick results and cannot be attacked by force. Attention should be paid to protecting blood deficiency. White peony root is added to calm pain and nourish yin, Rehmannia glutinosa can nourish blood and nourish yin, and raw astragalus and Amomum villosum can nourish qi, strengthen the spleen and regulate qi, and they are combined as adjuvant drugs. The whole formula nourishes blood and produces essence to treat the root cause, and promotes menstrual blood flow to treat the symptoms, so that Qi and blood can flow smoothly in the uterine vessels and collaterals, the uterus is replenished with essence and Qi, menstruation is smooth, and pregnancy is successful.

The present invention combines the artificial cycle treatment of estrogen and progesterone and is applied to the postoperative decomposition of intrauterine adhesions under hysteroscopy, which can improve the blood flow of the uterine artery, promote the proliferation and repair of the endometrium, and reduce the recurrence of intrauterine adhesions. Compared with the artificial cycle treatment of estrogen and progesterone alone, it can reduce the intrauterine adhesion score, alleviate the TCM syndrome symptoms of kidney deficiency and blood stasis in patients, and improve the overall clinical efficacy. Based on this, it is believed that the combination of Zigui Yangmo Decoction with artificial cycle of estrogen and progesterone has certain clinical advantages in the treatment of intrauterine adhesions of kidney deficiency and blood stasis type.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1: Boxplot comparison of endometrial thickness before and after treatment.

Figure 2: Comparison chart of PBAC scores of menstrual volume between the two groups of patients before and after treatment.

DETAILED DESCRIPTION

Below in conjunction with specific embodiment, further elaborate the present invention.Should be understood that these embodiments are only used to illustrate the present invention and are not used to limit the scope of the present invention.In addition, should be understood that after reading the content of the present invention record, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall equally within the scope limited by the appended claims of the application.

Example 1 Chinese medicine composition for treating intrauterine adhesions (I)

15 parts of Plastrum Testudinis, 15 parts of Radix Rehmanniae Preparata, 2 parts of Placenta, 15 parts of Cuttlebone, 15 parts of Raw Rubia, 12 parts of Angelica Sinensis, 12 parts of White Peony Roots, 6 parts of Semen Persicae, 0.5 parts of Crocus, 6 parts of Rhizoma Chuanxiong, 30 parts of Raw Astragalus, 9 parts of Prunus Antlers, and 6 parts of Fructus Amomi.

Example 2 Chinese medicine composition for treating intrauterine adhesions (II)

15 parts of Plastrum Testudinis, 14 parts of Radix Rehmanniae Preparata, 3 parts of Placenta, 15 parts of Cuttlebone, 14 parts of Radix Rubiae, 13 parts of Radix Angelicae Sinensis, 12 parts of Radix Paeoniae Alba, 5 parts of Semen Persicae, 0.6 parts of Saffron, 6 parts of Rhizoma Chuanxiong, 29 parts of Radix Astragali, 10 parts of Prunus Antlers, and 5 parts of Fructus Amomi.

Example 3 Chinese medicine composition for treating intrauterine adhesions (III)

14 parts of Plastrum Testudinis, 16 parts of Radix Rehmanniae Preparata, 2 parts of Placenta, 14 parts of Cuttlebone, 16 parts of Radix Rubiae, 12 parts of Radix Angelicae Sinensis, 11 parts of Radix Paeoniae Alba, 7 parts of Semen Persicae, 0.5 parts of Crocus, 5 parts of Rhizoma Chuanxiong, 31 parts of Radix Astragali, 9 parts of Prunus Antlers, 7 parts of Fructus Amomi.

Example 4 Chinese medicine composition for treating intrauterine adhesions (IV)

16 parts of Plastrum Testudinis, 15 parts of Radix Rehmanniae Preparata, 1 part of Placenta, 16 parts of Cuttlebone, 15 parts of Radix Rubiae, 11 parts of Radix Angelicae Sinensis, 13 parts of Radix Paeoniae Alba, 6 parts of Semen Persicae, 0.4 parts of Crocus, 7 parts of Rhizoma Chuanxiong, 30 parts of Radix Astragali, 8 parts of Prunus Antlers, and 6 parts of Fructus Amomi.

Example 5 Chinese medicine composition for treating intrauterine adhesions (V)

15 parts of Plastrum Testudinis, 16 parts of Radix Rehmanniae Preparata, 2 parts of Placenta, 16 parts of Cuttlebone, 16 parts of Raw Rubia, 12 parts of Angelica Sinensis, 11 parts of White Peony Roots, 7 parts of Semen Persicae, 0.5 parts of Crocus, 7 parts of Rhizoma Chuanxiong, 3 parts of Raw Radix Astragali, 10 parts of Prunus Antlers, and 7 parts of Fructus Amomi.

Example 6 Chinese medicine composition for treating intrauterine adhesions (VI)

14 parts of Plastrum Testudinis, 15 parts of Radix Rehmanniae Preparata, 1 part of Placenta, 15 parts of Cuttlebone, 15 parts of Raw Rubia, 11 parts of Angelica Sinensis, 13 parts of White Peony Root, 6 parts of Semen Persicae, 0.4 parts of Crocus, 6 parts of Rhizoma Chuanxiong, 30 parts of Raw Radix Astragali, 9 parts of Prunus Antlers, and 6 parts of Fructus Amomi.

Example 7 Chinese medicine composition for treating intrauterine adhesions (VII)

16 parts of Plastrum Testudinis, 14 parts of Radix Rehmanniae Preparata, 3 parts of Placenta, 14 parts of Cuttlebone, 14 parts of Radix Rubiae, 13 parts of Radix Angelicae Sinensis, 12 parts of Radix Paeoniae Alba, 5 parts of Semen Persicae, 0.6 parts of Crocus, 5 parts of Rhizoma Chuanxiong, 29 parts of Radix Astragali, 8 parts of Prunus Antlers, and 5 parts of Fructus Amomi.

Example 8 Clinical Trial

1 Clinical Data

1.1 Case source

The case subjects of this study were selected from patients who visited the gynecology ward of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from February 2021 to February 2022. After hysteroscopic examination and combined with TCM syndrome differentiation, they were finally diagnosed as IUA patients with kidney deficiency and blood stasis syndrome.

1.2 Diagnostic criteria

(1) Western medicine diagnostic criteria

Patients were diagnosed with IUA based on the Practical Gynecologic Endoscopy (2001 edition), Obstetrics and Gynecology (8th edition), the European Society for Gynecologic Endoscopy (ESGE) classification criteria (2000) [19], and the American Fertility Society (AFS) scoring classification criteria (1988) [20].

Causes include recent history of intrauterine operation and abortion. Clinical manifestations may include scanty menstruation, secondary amenorrhea in severe cases, cyclical lower abdominal pain, secondary infertility, recurrent miscarriage, etc. Hysteroscopy shows adhesions on the walls of the uterine cavity, but the normal anatomical morphology exists in the uterine cavity, the openings of the fallopian tubes on both sides are visible, and there are no adhesions on the uterine horns on both sides. Or the adhesions cause the uterine cavity to lose some of its normal anatomical morphology, with adhesions on one or both sides of the uterine horns, the uterine fundus, or the cervical canal, making it impossible for the hysteroscope to explore the uterine cavity.

Diagnostic criteria: Based on the diagnosis of hysteroscopy, if the cause and clinical manifestations meet one of the criteria, a diagnosis can be made.

(2) TCM diagnostic criteria

For patients who meet the Western medical diagnostic criteria, refer to the content of the “Trial Implementation of the Guidelines for Clinical Research of New Chinese Medicines (Irregular Menstruation)” [21] regarding kidney deficiency and blood stasis syndrome and make differentiation according to the following criteria:

Main symptoms: Menstrual flow is significantly reduced compared to the past, or there is only a little bleeding each time, or even amenorrhea, soreness of waist and knees, dark purple menstrual blood, occasionally mixed with blood clots;

Secondary symptoms: lower abdominal pain, which will be relieved when the blood clot is discharged from the uterus, fatigue, decreased libido, dizziness, tinnitus, insomnia, forgetfulness, lower abdominal coldness, frequent urination at night;

Tongue and pulse: The tongue is dark purple or light red with ecchymosis and petechiae, the pulse is deep, rough or stringy, and the radial pulse is weak.

Syndrome: Kidney deficiency and blood stasis syndrome.

Diagnostic criteria: Under the premise of IUA diagnosis, if the patient meets two or more of the main and secondary symptoms, a diagnosis can be made by comprehensive observation of the tongue and pulse.

1.3 Inclusion criteria

① Meet the Western medical diagnostic criteria for intrauterine adhesions and the TCM diagnostic criteria for kidney deficiency and blood stasis syndrome;

②Women aged 18 to 40;

③Sex hormone test is normal;

④ The menstrual volume is significantly less than 1/2 of the previous amount, or less than 30 ml;

⑤ No history of using any hormonal drugs or intrauterine device (IUD) contraception in the three months before treatment;

⑥ Non-pregnant state;

⑦ Patients who signed the informed consent form.

1.4 Exclusion criteria

① Patients who do not meet the inclusion criteria;

② Allergic reaction to the drugs used;

③ Congenital genital organ defects or malformations;

④ Those with genital tuberculosis;

⑤Psychiatric patients;

⑥ Combined with uterine submucosal myoma;

⑦ Those who have serious diseases and cannot tolerate this operation, are unable to participate in the entire research process, or have a history of infectious diseases, mental illness or other diseases.

1.5 Elimination criteria

① Those with poor compliance, unable to follow the prescribed treatment plan, or combined with other treatment methods, resulting in uncertainty of the final treatment effect;

② Due to various reasons, the data is incomplete and the final result will affect the judgment of efficacy and safety.

1.6 Dropout Cases

① Those who voluntarily withdraw from the clinical treatment due to personal will or cannot continue to receive treatment due to unexpected circumstances;

② Patients who stop treatment midway due to poor efficacy or adverse reactions and fail to complete the entire course of treatment;

③ Patients who were lost to follow-up for no reason during clinical treatment.

2 Research Methods

2.1 Grouping method

This study was approved by the Ethics Committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Clinical data were collected in the gynecology ward of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. A total of 90 patients with kidney deficiency and blood stasis type intrauterine adhesions were included. In order to reduce the excessive bias of the degree of intrauterine adhesions in patients, which would lead to an increase in the error of laboratory data in the later stage, a stratified random grouping method was used. The random grouping scheme was written using SPSS software. According to the intrauterine adhesion score under hysteroscopy before treatment, the patients were divided into three compatibility groups: mild, moderate, and severe. The subjects in each block group were respectively assigned to the treatment group and the control group, with 45 cases in each group. Informed consent was obtained from all participants in this project.

2.2 Treatment methods

After hysteroscopic adhesion lysis, adjuvant treatment was given for 3 menstrual cycles, and follow-up was performed until 12 months or clinical pregnancy was diagnosed.

2.3 Treatment options

Control group: After hysteroscopic intrauterine adhesion lysis surgery, fenpropanone 2/10 mg (Abbott Biologicals B.V. National Medicine Approval Number: H20150345) was taken orally, one tablet each time, once a day, for a course of 28 days, with a total treatment of 3 menstrual cycles.

Treatment group: On the basis of the control group, the patients were given the Zigui Yangmo Decoction of the present invention orally after hysteroscopic intrauterine adhesion decomposition surgery. One dose per day, the course of treatment is 3 menstrual cycles. The specific prescriptions are as follows:

Purple turtle membrane soup:

Turtle shell 15g, Rehmannia root 15g, placenta 2g, cuttlebone 15g, raw madder 15g, angelica 12g, white peony root 12g, peach kernel 6g, saffron 0.5g, Chuanxiong 6g, raw astragalus 30g, antler frost 9g, Amomum villosum 6g.

Decoction method: The Chinese medicine is decocted by the Chinese Medicine Pharmacy of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Take one dose per day, 150ml each morning and evening, orally.

Note: During the entire treatment process, subjects should abstain from sexual intercourse for 90 days.

2.4 Evaluation Method

Standards for judging the efficacy of TCM syndromes

Drafted with reference to the "Trial Implementation of the Guiding Principles for Clinical Research of New Chinese Medicines (Irregular Menstruation)":

① Cured: Clinical symptoms disappear or basically disappear after treatment, menstrual cycle, menstrual period and menstrual volume basically return to normal, and can be maintained for 3 menstrual cycles or more, and the efficacy index is ≥95%;

② Significantly effective: clinical symptoms are significantly relieved after treatment, and the menstrual cycle, menstrual period, and menstrual volume are significantly improved by 70% ≤ efficacy index < 95%;

③ Effective: Clinical symptoms are relieved after treatment, and the menstrual cycle, menstrual period, and menstrual volume are better than before treatment, with an efficacy index of 30% ≤ < 70%;

④ Ineffective: Clinical symptoms were not significantly relieved after treatment, and the menstrual cycle, menstrual period, and menstrual volume were not significantly relieved, and the efficacy index was <30%.

The nimodipine method was used to calculate the percentage of reduction in syndrome scores: N = [(score before treatment - score after treatment) ÷ score before treatment] × 100%

Clinical overall efficacy criteria

The overall clinical efficacy judgment standard is formulated with reference to the "Trial Implementation of the Guiding Principles for Clinical Research of New Chinese Medicines (Irregular Menstruation)" and the "Standards for Diagnosis and Efficacy of TCM Diseases and Syndromes":

① Cured: Menstruation returns to normal or clinical symptoms improve. Hysteroscopy 3 months after surgery shows normal uterine cavity morphology, normal bilateral fallopian tube outlets, and normal uterine horns. Compared with before surgery, uterine adhesion score is significantly reduced, and the TCM syndrome efficacy index is ≥95%;

② Significantly effective: The menstrual volume increased compared with that before the operation, but was lower than the normal menstrual volume; the uterine cavity was larger than that before the operation, but there was partial adhesion. Compared with that before the operation, the uterine adhesion score was reduced, 70%≤TCM syndrome efficacy index<95%;

③ Effective: The menstrual volume has improved compared with that before the operation, but is lower than the normal menstrual volume; there is partial adhesion in the uterine cavity. Compared with that before the operation, the uterine adhesion score is slightly reduced, 30%≤TCM syndrome efficacy index<70%;

④ Ineffective: Menstrual volume and clinical symptoms remain unchanged, and there is a large amount of adhesion tissue; the uterine cavity is barrel-shaped with adhesions, the uterine adhesion score does not decrease, and the TCM syndrome efficacy index is <30%.

The nimodipine method was used to calculate the percentage of reduction in syndrome scores: N = [(score before treatment - score after treatment)

÷Pre-treatment score] × 100%

2.5 Clinical observation indicators

① Intrauterine adhesion score: Independent scoring was performed strictly according to the classification standard of AFS score (1988). Hysteroscopic evaluation was performed before enrollment and 3-7 days after the end of menstruation in 3 menstrual cycles after treatment, see Table 1.

Table 1 American Fertility Society (AFS) intrauterine adhesion score

Note: Mild: total score (1-4 points); Moderate: total score (5-8 points); Severe: total score (9-12 points)

② TCM syndrome scoring: refer to the "Trial Implementation of the Guidelines for Clinical Research of New Chinese Medicines (Menstrual Disorders)" and "Diagnostics of Traditional Chinese Medicine" to formulate relevant diagnostic standards, and evaluate before treatment and after 3 menstrual cycles of treatment, see Table 2.

Table 2 TCM syndrome scoring table

③ Thickness of endometrium in late proliferative stage: Before treatment and after 3 menstrual cycles of treatment, patients in both groups were examined by transvaginal color Doppler ultrasound in the late proliferative stage of the menstrual period (9th _to 14th day): thickness of endometrium.

④ The menstrual volume is scored using the pictorial blood loss assessment chart (PBAC), which is graded according to the blood-stained area of the sanitary napkin. A total score > 100 is considered excessive menstrual volume, that is, menstrual volume > 80 mL.

⑤ Endometrial receptivity: 1) Endometrial type (Type A: typical three-line type, the junction of the endometrium and myometrium and the central endometrial line are both strong echoes, and the area between the outer line and the central line is low echo; Type B: weak three-line type, the strong echo center line of the uterine cavity is not obvious or is intermittent; Type C: homogeneous strong echo, without a strong echo center line of the uterine cavity).

2) Endometrial blood flow: Type I: There is no obvious blood flow signal in the endometrial area, and the number of blood flow branches is 0; Type II: Sparse blood flow signals are seen in the endometrial area, and the number of blood flow branches is 2; Type III: More blood flow signals are seen in the endometrial area, and the number of blood flow branches is 2 and 4; Type IV: Abundant blood flow signals are seen in the endometrial area, and the number of blood flow branches is 5.

3) Uterine artery resistance: PI and RI values.

⑥ Clinical pregnancy rate: The clinical pregnancy rate of patients who want to have children is counted. Patients with amenorrhea for more than 40 days, positive urine pregnancy test or blood pregnancy test, and vaginal ultrasound examination showing intrauterine gestational sac or embryo are considered intrauterine pregnancy. Record whether each group of patients is pregnant at the end of follow-up, and calculate the clinical pregnancy rate.

Early miscarriage rate: Miscarriage refers to miscarriage that occurs within 12 weeks of pregnancy.

2.6 Observation time and follow-up methods

After hysteroscopic adhesion lysis, adjuvant treatment was performed for 3 menstrual cycles, and follow-up was performed until 12 months or clinical pregnancy was diagnosed.

3 Statistical methods

All data were entered and managed using Microsoft Excel 2007, and IBM SPSS Statistics 21.0 statistical software was used for statistics and analysis. When P < 0.05, it was considered statistically significant. Measurement data that conformed to normal distribution were expressed as (x ± s), and independent sample t test was used for inter-group comparison. Measurement data that did not conform to normal distribution were expressed as [M (Q1, Q3)], and non-parametric tests were used for inter-group comparison. The number of cases and percentages [n (%)] were used to represent count data. The chi-square test was used for inter-group rate comparison, and the rank sum test was used for inter-group efficacy comparison.

4 Research results

4.1 Uterine adhesions in the two groups before and after treatment

After examination, before treatment, there was no significant statistical difference in the intrauterine adhesion between the two groups (P>0.05), indicating that the data were comparable. After treatment, the intrauterine adhesion between the two groups was as follows: in the treatment group, there were 15 cases of no adhesion after treatment, 10 cases of mild adhesion before treatment, and 23 cases after treatment, 12 cases of moderate adhesion before treatment, and 7 cases after treatment, 23 cases of severe adhesion before treatment, and no severe adhesion after treatment; in the control group, there were 2 cases of no adhesion after treatment, 12 cases of mild adhesion before treatment, and 20 cases after treatment, 10 cases of moderate adhesion before treatment, and 23 cases after treatment, and 23 cases of severe adhesion before treatment, and no severe adhesion after treatment, with significant statistical differences (P<0.05), as shown in Table 4 for details.

Table 4 Comparison of intrauterine adhesions between the two groups of patients after treatment [n (%)]

Note: Comparison of the degree of intrauterine adhesion between the two groups of patients after treatment, *P<0.05.

There was a difference in the AFS scores between the two groups after treatment (t=-2.523, p=0.014), and the specific comparison showed that the average value of the treatment group (3.04) was significantly lower than the average value of the control group (4.00). The results are shown in Table 5.

Table 5 Comparison of AFS scores between the two groups of patients before and after treatment

Note: Comparison of endometrial thickness between the two groups of patients before and after treatment, *P<0.01.

4.2 Endometrial thickness in the two groups before and after treatment

The endometrial thickness between the two groups conformed to normal distribution, and the independent sample t test was used for intergroup comparison: there was no significant statistical difference between the treatment group and the control group before treatment (t = -1.718P = 0.089), which can be considered that the endometrial thickness in the late proliferation stage before treatment was comparable. There was a significant statistical difference between the two groups after treatment (t = 3.444P < 0.01), which can be considered that the endometrial thickness of the treatment group increased more significantly after treatment compared with the control group. The results are shown in Table 6 and Figure 1.

Table 6 Comparison of endometrial thickness between the two groups of patients before and after treatment

Note: Comparison of endometrial thickness between the two groups of patients before and after treatment, *P<0.01.

4.3 Comparison of PBAC scores of menstrual volume between the two groups before and after treatment

The PBAC scores of menstrual volume between the two groups were in accordance with normal distribution, and the independent sample t test was used for intergroup comparison: there was no significant statistical difference between the treatment group and the control group before treatment (t = -0.880P = 0.382), and it can be considered that the PBAC scores of menstrual volume in the two groups before treatment were comparable. There was a significant statistical difference between the two groups after treatment (t = 7.391P < 0.01), which can be considered that the menstrual volume in the treatment group increased more significantly after treatment than that in the control group. The results are shown in Table 7 and Figure 2.

Table 7 Comparison of PBAC scores of menstrual volume between the two groups of patients before and after treatment

Note: Comparison of menstrual status and menstrual volume scores between the two groups of patients before and after treatment, *P<0.01.

4.4 Comparison of endometrial receptivity between the two groups before and after treatment

Comparison of endometrial receptivity indices of patients showed that in terms of endometrial type, the proportion of type A endometrium in the treatment group was higher than that in the control group, but the difference was not statistically significant (P>0.05). The proportion of type III+IV endometrium in the treatment group was higher than that in the control group, but the difference was not statistically significant (P>0.05). See Table 8.

Table 8 Comparison of endometrial receptivity indexes between the two groups of patients

Note: Compared with the control group, *p<0.05.

3.4.5 Comparison of PI values of bilateral uterine arteries before and after treatment in the treatment group and the control group

The PI values of the bilateral uterine arteries of the two groups before treatment were statistically analyzed. After the test, they did not conform to the normal distribution. Therefore, the Mann-Whitney U test was used to compare the two groups: there was no statistical difference between the treatment group and the control group before treatment (Z = -0.941P = 0.347). It can be considered that the PI values of the uterine arteries of the two groups before treatment were comparable. The PI values of the bilateral uterine arteries of the two groups after treatment were statistically analyzed. After the test, they did not conform to the normal distribution. Therefore, the Mann-Whitney U test was used to compare the two groups: there was no statistically significant difference between the groups after treatment (Z = -3.933P < 0.001). Combined with the average rank, it can be considered that there is a difference in the PI values of the bilateral uterine arteries after treatment, and the PI value of the treatment group after treatment decreased more significantly than that of the control group, as shown in Table 9.

Table 9 Comparison of PI values of bilateral uterine arteries between the two groups of patients after treatment [M(Q1,Q3)]

**p<0.01

Comparison of RI values of bilateral uterine arteries between the two groups before and after treatment

The RI values of the bilateral uterine arteries of the two groups before treatment were statistically analyzed. After the test, they did not conform to the normal distribution. Therefore, the Mann-Whitney U test was used to compare the two groups: there was no statistical difference between the treatment group and the control group before treatment (Z = -1.649P = 0.099). It can be considered that the RI values of the uterine arteries of the two groups before treatment were comparable. The RI values of the bilateral uterine arteries of the two groups after treatment were statistically analyzed. After the test, they did not conform to the normal distribution. Therefore, the Mann-Whitney U test was used to compare the two groups: there was no statistically significant difference between the two groups after treatment (Z = -5.574P < 0.001). Combined with the average rank, it can be considered that there is a difference in the RI values of the bilateral uterine arteries after treatment. The RI value of the treatment group after treatment decreased more significantly than that of the control group, as shown in Table 10.

Table 10 Comparison of RI values of bilateral uterine arteries between the two groups of patients after treatment [M(Q1,Q3)]

**p<0.01

4.7 TCM syndrome scores of the two groups before and after treatment

In terms of TCM syndrome score, nine major and minor symptoms of kidney deficiency and blood stasis syndrome were selected, including abdominal pain during menstruation, delayed menstruation, dark menstrual blood, menstrual blood mixed with clots, frequent urination, dark complexion, or petechiae and ecchymosis, lower abdominal distension, sore waist and knees, dizziness and tinnitus, loss of libido, insomnia and forgetfulness, thirst and unwillingness to drink, and cold limbs. The total TCM syndrome score of kidney deficiency and blood stasis syndrome before treatment between the two groups was statistically analyzed. After the test, it did not conform to the normal distribution, so the Mann-Whitney U test was used for comparison between the two groups: there was no statistical difference between the treatment group and the control group before treatment (Z=-0.206P=0.837), which can be considered that the TCM syndrome scores of the two groups before treatment were comparable, and the difference between the groups after treatment was statistically significant (Z=-4.643P<0.001). Combined with the average rank, it can be considered that the treatment of the treatment group has a greater effect on reducing the TCM syndrome score than the control group. See Table 11.

Table 11 Comparison of TCM syndrome scores between the two groups of patients before and after treatment [M(Q1,Q3)]

**p<0.01

5 Overall efficacy

5.1 Evaluation of TCM Syndrome Efficacy

The results of the evaluation of the efficacy of TCM syndromes in the treatment group of 45 patients after treatment are as follows: 6 cases were cured, 27 cases were markedly effective, 12 cases were effective, and 0 cases were ineffective; the results of the evaluation of the efficacy of TCM syndromes in the control group of 45 patients after treatment are as follows: 3 cases were cured, 5 cases were markedly effective, 28 cases were effective, and 9 cases were ineffective. The comparison of the efficacy of TCM syndromes in the two groups of patients showed a statistically significant difference (P<0.05), as shown in Table 12.

Table 12 Comparison of TCM syndrome efficacy between two groups of patients [n(%)]

Note: Comparison of TCM syndrome efficacy between the two groups of patients, *P<0.001.

5.2 Evaluation of overall clinical efficacy

After treatment, among the 45 patients in the treatment group, 10 were cured, 13 were significantly effective, 20 were effective, and 2 were ineffective. Among the 45 patients in the control group, 4 were cured, 7 were significantly effective, 26 were effective, and 7 were ineffective. After comparison of the two groups, the difference in comprehensive therapeutic effects was statistically significant (P<0.05), indicating that the treatment group was superior to the control group in improving the comprehensive therapeutic effect, see Table 13.

Table 13 Comparison of overall clinical efficacy between the two groups of patients [n (%)]

Note: Comparison of the overall clinical efficacy between the two groups of patients, *P<0.05.

5 Pregnancy

After the follow-up, the final pregnancy status was statistically analyzed and found that 45 patients in the treatment group had fertility requirements, of which 22 were pregnant and 23 were not pregnant, with a pregnancy rate of 48.9%; 45 patients in the control group had fertility requirements, of which 9 were pregnant and 36 were not pregnant, with a pregnancy rate of 20%. The Fisher exact probability test was used to compare the clinical pregnancy rate between the two groups, and the results showed that the difference was statistically significant (P<0.05), and the early abortion rate was lower than that of the control group, and the difference was also not statistically significant.

The results are shown in Table 14.

Table 14 Comparison of pregnancy status between the two groups of patients [n (%)]

Note: Comparison of pregnancy status between the two groups of patients, *P<0.05.

6 Safety evaluation

No allergic reactions, abnormal bleeding in the oral mucosa or subcutaneous tissue occurred during the medication period. Follow-up of liver, kidney and coagulation functions in the outpatient clinic were all within normal range.

The above is only a preferred embodiment of the present invention. It should be pointed out that ordinary technicians in this technical field can make several improvements and supplements without departing from the method of the present invention. These improvements and supplements should also be regarded as the scope of protection of the present invention.

Claims (6)

1. A Chinese medicine composition for treating intrauterine adhesion, characterized in that the Chinese medicine composition is made of the following raw materials in parts by weight: 14-16 parts of tortoise shell, 14-16 parts of rehmannia root, 1-3 parts of placenta, 14-16 parts of cuttlebone, 14-16 parts of raw madder, 11-13 parts of angelica, 11-13 parts of white peony root, 5-7 parts of peach kernel, 0.4-0.6 parts of saffron, 5-7 parts of chuanxiong, 29-31 parts of raw astragalus, 8-10 parts of antler frost, and 5-7 parts of amomum. 2. The Chinese medicine composition according to claim 1 is characterized in that the Chinese medicine composition is made of the following raw medicines in parts by weight: 15 parts of tortoise shell, 15 parts of rehmannia root, 2 parts of placenta, 15 parts of cuttlebone, 15 parts of raw madder, 12 parts of angelica, 12 parts of white peony root, 6 parts of peach kernel, 0.5 parts of saffron, 6 parts of chuanxiong, 30 parts of raw astragalus, 9 parts of antler frost, and 6 parts of amomum. 3. The Chinese medicine composition according to claim 1 or 2, characterized in that the medicine composition is in the form of tablets, capsules, granules, oral liquid or syrup. 4. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a medicament for treating kidney deficiency and blood stasis type intrauterine adhesions. 5. A pharmaceutical composition for treating intrauterine adhesions, characterized in that the pharmaceutical composition consists of the traditional Chinese medicine composition according to any one of claims 1 to 3 and femosterol. 6. Use of the pharmaceutical composition according to claim 5 in preparing a drug for treating kidney deficiency and blood stasis type intrauterine adhesions.