Traditional Chinese medicine composition for improving hypomenorrhea and application thereof

Abstract

The invention relates to a traditional Chinese medicine composition for improving hypomenorrhea and application thereof, and belongs to the technical field of biological medicine. The herba leonuri, the anisodamine and the Dingkundan are combined to form the composition, efficacy complementation can be achieved, it is guaranteed that the medicine takes effect quickly, the long-acting treatment effect is maintained, meanwhile, the side effect caused by long-term single medication is avoided, the treatment safety and tolerance are improved, the menstrual volume can be remarkably increased, endometrial blood circulation can be improved, and the curative effect is improved. The hypomenorrhea is effectively improved. The medicines in the composition are all approved compliant medicines, the source is clear, the quality is controllable, the administration scheme is simple and easy to implement, the composition is suitable for clinical popularization and application, and a novel safe, efficient and reproducible treatment method is provided for hypomenorrhea.

Description

Technical Field

[0001] This invention belongs to the field of biomedical technology, and in particular relates to a traditional Chinese medicine composition for improving scanty menstruation and its application. Background Technology

[0002] Scanty menstruation is a common symptom of gynecological endocrine disorders, belonging to the category of menstrual irregularities, with a prevalence rate of up to 12% among women of reproductive age in China. It manifests as a normal menstrual cycle, but a significant reduction in menstrual flow compared to previous periods, exceeding one-third of the original flow, or menstruation lasting less than two days, with a flow of less than 30 mL, or even just spotting. The causes of scanty menstruation are complex, mainly involving uterine factors (endometrial damage / insufficient local microcirculation blood perfusion in the endometrium), ovarian factors (insufficient ovarian sex hormone secretion / anovulation), central factors (high stress, excessive exercise, etc. leading to central nervous system depression), and genetic factors. If left untreated, it can develop into amenorrhea, and in severe cases, premature ovarian failure. It can also affect the implantation and development of fertilized eggs in the endometrium, leading to recurrent miscarriages, infertility, and other adverse effects on women's fertility and physical and mental health. Therefore, early treatment of this condition is of positive significance for maintaining normal physiological function, delaying aging, and preserving fertility.

[0003] Western medicine often treats this condition with artificial cycle therapy. For those with intrauterine adhesions, hysteroscopic surgery can be chosen. However, some patients may have contraindications to hormone therapy, which can cause adverse reactions such as dizziness and nausea. Furthermore, the condition is prone to relapse after discontinuation of hormone therapy, and the treatment effect is not yet satisfactory. Traditional Chinese medicine believes that the pathogenesis of oligomenorrhea is divided into two types: deficiency and excess, with deficiency being the most common clinically (especially kidney deficiency). However, single-herb treatments are often unstable in efficacy and slow in onset, failing to meet patients' needs for safe and effective treatment options. Therefore, finding safer, more effective treatment options with fewer side effects is particularly important. Summary of the Invention

[0004] In view of this, the purpose of the present invention is to provide a traditional Chinese medicine composition for improving scanty menstruation and its application. By combining Leonurus japonicus, Dingkun Dan and scopolamine into a composition, it can improve scanty menstruation, increase menstrual flow and improve blood circulation in the endometrium.

[0005] This invention provides a composition for improving oligomenorrhea, comprising the following drugs: Motherwort injection, Dingkun Dan, and scopolamine.

[0006] Preferably, the ratio of the motherwort injection, Dingkundan and scopolamine is 2mL:14g:10mg.

[0007] Preferably, the Dingkun Dan and scopolamine are oral medications.

[0008] The present invention also provides the use of the composition in the preparation of a medicament for improving oligomenorrhea.

[0009] Preferably, the composition can increase menstrual flow.

[0010] Preferably, the composition can improve blood circulation in the endometrium.

[0011] Preferably, the motherwort injection is used alone, while the anisodamine and Dingkundan are used simultaneously.

[0012] Preferably, the motherwort injection is taken 10 days before each menstrual cycle, and the scopolamine and Dingkun Dan are taken simultaneously from day 11 to day 30 of each menstrual cycle.

[0013] Preferably, the dosage of the motherwort injection is 2 mL / time, once daily.

[0014] Preferably, the dosage of scopolamine and Dingkun Dan used simultaneously is scopolamine 10mg / time, once a day; Dingkun Dan 7g / time, twice a day.

[0015] The beneficial effects of this invention are: This invention combines Leonurus japonicus, scopolamine, and Dingkun Dan into a single composition, achieving complementary effects: Leonurus japonicus invigorates blood circulation and regulates menstruation to resolve blood stasis; scopolamine improves microcirculation and relieves smooth muscle spasms; and Dingkun Dan nourishes qi and blood to consolidate the therapeutic effect. The combined use of these three drugs effectively increases menstrual flow and improves endometrial blood circulation. Compared to single-drug treatment, this significantly improves the treatment effect for oligomenorrhea, solving the problems of unstable efficacy and slow onset of action in traditional treatments. This invention combines intramuscular injection and oral medications, allowing for precise administration in stages according to the menstrual cycle. This ensures both rapid onset of action and long-term therapeutic effect, while avoiding the side effects of long-term single-drug use, thus improving treatment safety and tolerability. The composition of this invention can directly improve core symptoms such as oligomenorrhea and short menstrual periods, improve uterine microcirculation, and enhance patients' quality of life. All drugs in the composition of this invention are approved and compliant pharmaceutical products with clear sources and controllable quality. The administration regimen is simple and easy to implement, suitable for clinical application, and provides a safe, efficient, and replicable new treatment method for oligomenorrhea. Detailed Implementation

[0016] This invention provides a composition for improving oligomenorrhea, comprising the following drugs: Leonurus japonicus injection, Dingkun Dan, and scopolamine. In this invention, the preferred ratio of Leonurus japonicus injection, Dingkun Dan, and scopolamine is 2 mL:14 g:10 mg. Dingkun Dan and scopolamine are preferably oral medications. The composition for improving oligomenorrhea described in this invention is preferably a composition used in sequential therapy to improve oligomenorrhea.

[0017] This invention does not specifically limit the sources of Leonurus japonicus injection, Dingkun Dan, and scopolamine; conventional commercially available products in the field are acceptable. In some embodiments, the Leonurus japonicus injection may be sourced from Chengdu First Pharmaceutical Co., Ltd., with approval number Z51021448; the scopolamine may be sourced from Chengdu First Pharmaceutical Co., Ltd., with approval number H51023899; and the Dingkun Dan may be sourced from Shanxi Guangyuyuan Pharmaceutical Co., Ltd., with approval number Z20059003.

[0018] This invention also provides the use of the composition in the preparation of a medicament for improving oligomenorrhea. The oligomenorrhea is preferably oligomenorrhea that meets the diagnostic criteria of both traditional Chinese medicine and Western medicine. The Western medicine diagnostic criteria are preferably menstrual flow of less than 30 mL or menstrual period of less than 2 days; the traditional Chinese medicine diagnostic criteria are preferably those conforming to the diagnostic criteria of qi and blood deficiency and kidney essence deficiency. The medicament is preferably a medicament for improving oligomenorrhea using sequential therapy, and the preferred application includes the use of the composition as the sole active ingredient in the preparation of a medicament for improving oligomenorrhea using sequential therapy.

[0019] This invention combines motherwort, anisodamine, and Dingkun Dan to improve oligomenorrhea, achieving complementary effects: motherwort invigorates blood circulation, regulates menstruation, removes blood stasis, and promotes tissue regeneration, laying the foundation for subsequent treatment; anisodamine relaxes uterine smooth muscle and improves microcirculation; Dingkun Dan nourishes qi and blood, regulates menstruation, and relieves stagnation, with the addition of anisodamine providing a synergistic effect. The combination of these three ingredients preferably increases menstrual flow and improves blood circulation in the endometrium. Compared to single-drug treatment or the synergistic treatment of motherwort and Dingkun Dan, the addition of anisodamine significantly enhances the treatment effect of oligomenorrhea, solving the problems of unstable efficacy and slow onset of action in traditional treatments.

[0020] In this invention, when the composition is used, the motherwort injection is preferably used alone, and the scopolamine and Dingkun Dan are preferably used simultaneously. The motherwort injection is preferably used 10 days before each menstrual cycle, and the scopolamine and Dingkun Dan are preferably used simultaneously from day 11 to day 30 of each menstrual cycle. The preferred dosage of the motherwort injection is 2 mL / time, once daily. The preferred dosage of the simultaneous use of scopolamine and Dingkun Dan is 10 mg / time, once daily; and 7 g / time, twice daily. The preferred route of administration for the motherwort injection is intramuscular injection, and the preferred route of administration for the scopolamine and Dingkun Dan is oral administration. The composition of this invention is preferably used for one course of treatment every three menstrual cycles.

[0021] This invention combines intramuscularly injected and oral medications to treat oligomenorrhea. The precise, phased administration according to the menstrual cycle ensures both rapid onset of action and long-term therapeutic effect, while avoiding the side effects of long-term monotherapy, thus improving treatment safety and tolerability. All medications in the composition are approved and compliant drugs with clear sources and controllable quality. The administration regimen is simple and easy to implement, suitable for clinical application, and provides a safe, efficient, and reproducible new treatment method for oligomenorrhea.

[0022] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0023] Unless otherwise specified, the following embodiments are all conventional methods.

[0024] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0025] Example 1 A composition comprising the following raw materials: 2 mL of Leonurus japonicus injection, 14 g of Dingkun Dan and 10 mg of scopolamine.

[0026] The Leonurus japonicus injection is sourced from Chengdu First Pharmaceutical Co., Ltd., with approval number Z51021448; the scopolamine hydrobromide tablets are from Chengdu First Pharmaceutical Co., Ltd., with approval number H51023899; and the Dingkun Dan is sourced from Shanxi Guangyuyuan Pharmaceutical Co., Ltd., with approval number Z20059003.

[0027] Experimental Example 1 Effect verification of the composition in Example 1 of this invention 1. Materials and Methods 1.1 Research Subjects This is a prospective, multicenter, randomized controlled trial. The trial complies with the ethical standards of the Declaration of Helsinki and the guidelines harmonized by international conferences, and was approved by the Ethics Committee of Peking Union Medical College Hospital (Project No.: K7344; Acceptance No.: K25C0531 and registered in the National Health Security Information Platform Medical Research Registration and Filing Information System, Filing No.: MR-11-25-009854). The other two hospitals also completed the corresponding ethical filings. Informed consent was obtained from all patients. One hundred patients with menstrual disorders who visited Peking Union Medical College Hospital, Hangzhou Maternal and Child Health Hospital, and Shenyang Maternal and Child Health Hospital between March and June 2025 were selected. One hundred patients were randomly divided into three groups at a ratio of 1:1 using a random number table: a three-in-one group (using the composition of Example 1 of this invention, the method of administration is: 2mL of Leonurus japonicus intramuscular injection QD for the first 10 days of each menstrual cycle, followed by 10mg of hyoscyamine benzoate orally QD for the next 20 days (days 11-30) + 1 bottle of Dingkun Dan taken with warm water BID, for a total of 3 menstrual cycles); and a control group (1 bottle of Dingkun Dan taken with warm water BID starting from day 11 of each menstrual cycle (days 20)).

[0028] 1.2 Observation Indicators Enrollment data included age, disease duration, parity, obstetrics, and history of chronic diseases. Menstrual blood loss assessment chart (PBAC) scores, TCM syndrome scores, 36-item short form health survey (SF-36) scores, sex hormone levels (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2)), endometrial thickness, uterine artery Doppler indices (peak systolic velocity (PSV), pulsatility index (PI), resistance index (RI)), and safety indicators (alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL), direct bilirubin (DBiL), serum creatinine, blood urea nitrogen (BUN), and uric acid) were measured before medication, and at 1 month and 3 months after medication.

[0029] 1.3 Diagnostic criteria Western medicine diagnostic criteria: Scanty menstruation is defined as menstrual flow of less than 30mL or menstrual period of less than 2 days.

[0030] Traditional Chinese Medicine (TCM) syndrome diagnosis criteria: Qi and blood deficiency, kidney essence deficiency syndrome: Main symptoms: (1) Scanty menstruation (normal menstrual cycle, significantly reduced menstrual flow, or menstruation lasting less than 2 days, or even just spotting). (2) Pale and thin menstrual blood. Secondary symptoms: (1) Soreness and weakness of the lower back and knees, (2) Dizziness and tinnitus, (3) Frequent urination at night, (4) Fatigue and weakness, (5) Pale or sallow complexion, (6) Palpitation and insomnia. Tongue and pulse: Pale tongue, thin white coating, deep and thready or deep and weak pulse. The above main symptoms are essential, and any one of the secondary symptoms (1) to (3) and any one of the secondary symptoms (4) to (6) must be present at the same time. Combined with the tongue and pulse, the syndrome can be diagnosed as this syndrome.

[0031] 1.4 Inclusion Criteria (1) Age between 18 and 45 years old. (2) Patients who meet the diagnostic criteria of both traditional Chinese medicine and Western medicine. (3) Patients who are willing to participate in the entire research process according to the research requirements for three consecutive menstrual cycles and sign an informed consent form.

[0032] 1.5 Exclusion Criteria (1) Women aged <18 years or >45 years who are pregnant or lactating. (2) Women with ovarian dysfunction due to local ovarian surgery, radiotherapy or chemotherapy for malignant tumors, etc. (3) Women with uterine cavity and cervical adhesions due to multiple intrauterine and / or cervical procedures. (4) Women with endometrial tuberculosis. (5) Women who have used estrogen or other drugs that affect endometrial thickness within the past three months. (6) Women with serious or unstable physical illnesses that may affect the efficacy of the drug or the trial. (7) Women who have a history of allergy or severe adverse reactions to the drug used in the trial. (8) Women who have participated in another clinical trial of a drug within the three months prior to inclusion in this study. Any of the above criteria will result in exclusion.

[0033] 1.6 Exit Criteria (1) Failure to meet the inclusion criteria during the trial. (2) Occurrence of a serious adverse event related to treatment, or intolerance to the study drug. (3) Worsening of the original condition, making it impossible to continue medication. (4) Voluntary withdrawal from the study. (5) Other circumstances deemed necessary by the physician in charge of the clinical study to discontinue medication.

[0034] 1.7 Rejection Criteria (1) Those who were randomly assigned to groups but did not take the medication or complete the treatment course according to the dosage and time requirements of this study protocol. (2) Those who met the inclusion criteria but received other related treatments during the observation period. (3) Those whose incomplete clinical data affected the determination of efficacy and safety.

[0035] 1.8 Research Drugs (1) Motherwort Injection: National Drug Approval Number Z51021448, Chengdu First Pharmaceutical Co., Ltd., Specification: 2mL per vial. (2) Dingkun Dan: National Drug Approval Number Z20059003, Shanxi Guangyuyuan Pharmaceutical Co., Ltd., Specification: 7g per bottle. (3) Scopolamine (Scolophonamine Hydrobromide Tablets): National Drug Approval Number H51023899, Chengdu First Pharmaceutical Co., Ltd., Specification: 5mg per tablet.

[0036] 1.9 Statistical Methods This study used SPSS 27.0 for statistical analysis. Normally distributed continuous data were expressed as mean ± standard deviation, and independent samples t-tests were used for between-group comparisons, while paired t-tests were used for within-group comparisons. Non-normally distributed continuous data were described statistically using median and interquartile ranges, and nonparametric tests were used for between-group comparisons, while Wilcoxon signed-rank tests were used for within-group comparisons. Categorical data were expressed as percentages (%), and chi-square tests were used for between-group comparisons. 2 Test. P<0.05 indicates a statistically significant difference, and P<0.01 indicates a statistically significant difference.

[0037] 2. Results 2.1 Comparison of Basic Data There were no statistically significant differences in baseline data between the groups (P>0.05), indicating that the baseline data were comparable. See Table 1.

[0038] Table 1 Comparison of baseline data between the two groups 2.2 Menstrual blood loss score The PBAC scores and their changes after 3 months of treatment were compared between the two groups, and the results are shown in Table 2. The PBAC scores of both groups were significantly higher after 3 months of treatment than before treatment [Triple-combination group: (16.32±8.61) points vs. (33.40±22.79) points, P<0.01; Dingkun Dan group: (19.31±11.92) points vs. (31.00±18.04) points], and the improvement in PBAC scores in the triple-combination group was more significant than that in the Dingkun Dan group (P<0.01).

[0039] Menstrual blood loss mapping is a precise semi-quantitative visual scoring system for assessing menstrual blood loss and is the most commonly used evaluation tool in research on menstrual disorders. The results of this trial showed that both groups experienced significant increases in menstrual blood loss after 3 months of treatment compared to before treatment, and the improvement was significantly greater in the three-drug combination group than in the Dingkun Dan group, indicating that the combined use of the three drugs can better improve oligomenorrhea and increase menstrual flow.

[0040] 2.3 Traditional Chinese Medicine Syndrome Scoring No significant differences were found in the TCM syndrome scores between groups or within groups. See Table 2.

[0041] 2.4 General health status (SF-36) score No significant differences were found in the patients' overall health scores between or within groups. See Table 2.

[0042] Table 2 Comparison of the two sets of scoring indicators 2.5 Changes in sex hormone levels After 3 months of treatment, no significant differences were found in FSH, LH, and E2 levels between or within the two groups. See Table 3.

[0043] Table 3 Comparison of sex hormone levels between the two groups 2.6 Changes in endometrial markers After 3 months of treatment, the peak systolic velocity (PSV) of the three-in-one group increased, while the pulsatility index (PI) and resistance index (RI) decreased, and the differences before and after treatment were significantly different from those in the Dingkun Dan group [PSV: P=0.037; PI: P<0.01; RI: P=0.021]. See Table 4.

[0044] Uterine artery perfusion and hormone levels can influence each other: increased uterine artery blood flow resistance can lead to insufficient blood supply to the endometrium, directly affecting endometrial growth, and can also affect ovarian hormone secretion, thus indirectly affecting endometrial growth. Conversely, estrogen plays an important role in regulating uterine artery blood flow, and its mechanism of action includes dilating the uterine artery to reduce vascular resistance, thereby improving endometrial growth and ovarian blood supply. Clinically, ultrasound examination can detect the dynamic parameters of uterine artery blood flow, including RI, PI, and PSV. Low RI and PI values ​​in the uterine artery indicate low vascular resistance and good ovarian and uterine blood perfusion. In this trial, compared with the Dingkun Dan group, the three-in-one group showed a more significant increase in PSV and a lower decrease in RI and PI after treatment, suggesting that the three-in-one therapy improved endometrial blood supply (blood circulation) in patients with oligomenorrhea.

[0045] Table 4 Comparison of endometrial parameters between the two groups 2.7 Safety Index Results and Adverse Reactions Specific safety indicators were collected from the two groups of patients before and after treatment. The results showed that there were no significant differences in blood test results before and after treatment in either group, and there were also no differences between the groups at any follow-up time points. See Table 5.

[0046] Table 5 Comparison of the two groups of safety indicators No serious adverse events occurred in any of the subjects participating in this trial after medication.

[0047] In summary, the combination of the present invention, namely "Leonurus japonicus + Scopolamine + Dingkun Dan", when used in combination for patients with oligomenorrhea, can significantly increase menstrual flow and endometrial blood supply, with considerable long-term efficacy and safety, and has further promotion value.

[0048] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A composition for improving oligomenorrhea, characterized in that, Including the following medications: Motherwort injection, Dingkun Dan, and scopolamine.

2. The composition according to claim 1, characterized in that, The ratio of Leonurus japonicus injection, Dingkun Dan, and scopolamine is 2 mL: 14 g: 10 mg.

3. The composition according to claim 1, characterized in that, The aforementioned Dingkun Dan and scopolamine are oral medications.

4. Use of the composition according to any one of claims 1 to 3 in the preparation of a medicament for improving oligomenorrhea.

5. The application according to claim 4, characterized in that, The composition can increase menstrual flow.

6. The application according to claim 4, characterized in that, The composition can improve blood circulation in the endometrium.

7. The application according to any one of claims 4 to 6, characterized in that, The Leonurus japonicus injection is used alone, while the scopolamine and Dingkun Dan are used simultaneously.

8. The application according to claim 7, characterized in that, The Leonurus japonicus injection is administered 10 days before each menstrual cycle, and the scopolamine and Dingkun Dan are administered simultaneously from day 11 to day 30 of each menstrual cycle.

9. The application according to claim 8, characterized in that, The dosage of the Leonurus japonicus injection is 2 mL / time, once daily.

10. The application according to claim 8, characterized in that, The dosage of anisodamine and Dingkun Dan used simultaneously is 10 mg anisodamine once daily; and 7 g Dingkun Dan twice daily.

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