A traditional Chinese medicine composition for treating dysmenorrhea and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for treating dysmenorrhea and application thereof, and belongs to the technical field of biological medicine. The traditional Chinese medicine composition comprises the following components in parts by weight: 10-20 parts of Astragalus membranaceus, 10-20 parts of Foeniculum vulgare, 7-15 parts of Angelica sinensis, 7-15 parts of Cistanche deserticola, 7-15 parts of Lonicerae japonicae, 3-10 parts of Ligusticum chuanxiong, 3-10 parts of Cinnamomum cassia, 3-10 parts of Zingiber officinale, 3-10 parts of Radix glycyrrhizae, 3-10 parts of Cyperus rotundus, and 3-10 parts of Corydalis bungeana. The components in the traditional Chinese medicine composition can soothe channels and relieve pain, relieve pain caused by uterine contraction or uterine spasm, and the raw materials are free of side effects compared with western medicines.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to a traditional Chinese medicine composition for treating dysmenorrhea and application thereof. Background Art

[0002] Dysmenorrhea, also known as period pain, is one of the most common complaints among gynecological patients. Many women experience mild discomfort during their periods, but dysmenorrhea refers to period pain that interferes with normal activities and requires medication. Cyclic menstrual pain is common and occurs during most menstrual cycles. The pain is often cramping and accompanied by lower back pain, nausea, vomiting, headache, or diarrhea. Dysmenorrhea can be divided into primary and secondary dysmenorrhea. Primary dysmenorrhea is cyclical menstrual pain without a physical cause, while secondary pain is often associated with endometriosis, fibroids, pelvic inflammatory disease, adenomyosis, endometrial polyps, and menstrual outflow obstruction. Therefore, secondary pain is often accompanied by other gynecological symptoms such as dyspareunia, dysuria, abnormal bleeding, uterine fibroids, or infertility. Primary dysmenorrhea is more likely to begin after menstruation than secondary dysmenorrhea. While the characteristics of the pain are similar, the diagnosis of primary dysmenorrhea can only be made after a physical cause has been excluded.

[0003] Existing dysmenorrhea medications have side effects, including gastrointestinal adverse reactions. There are also concerns about drug addiction. Although antipyretic and analgesic drugs (such as ibuprofen) are not addictive, users may harbor concerns due to misunderstandings. Therefore, providing a traditional Chinese medicine composition for treating dysmenorrhea is of great significance. Summary of the Invention

[0004] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating dysmenorrhea and its application, so as to solve the problems existing in the above-mentioned prior art.

[0005] In order to solve the above problems, the present invention provides the following solutions:

[0006] A traditional Chinese medicine composition for treating dysmenorrhea comprises the following components, measured by weight: 10-20 parts of astragalus, 10-20 parts of fennel, 7-15 parts of angelica, 7-15 parts of cistanche, 7-15 parts of lindera, 7-15 parts of wolfberry, 3-10 parts of chuanxiong, 3-10 parts of cinnamon, 3-10 parts of dried ginger, 3-10 parts of pre-roasted liquorice, 3-10 parts of cyperus, and 3-10 parts of corydalis.

[0007] Furthermore, the following components are included by weight: 15 parts of astragalus, 15 parts of fennel, 10 parts of angelica, 10 parts of cistanche, 10 parts of lindera, 10 parts of wolfberry, 6 parts of chuanxiong, 6 parts of cinnamon, 6 parts of dried ginger, 6 parts of roasted licorice, 6 parts of cyperus and 6 parts of corydalis.

[0008] Technical Solution 2: Use of the traditional Chinese medicine composition in the preparation of products for treating dysmenorrhea.

[0009] Furthermore, the product includes a medicine.

[0010] Furthermore, the medicine also includes pharmaceutically used excipients.

[0011] Technical Solution 2: Use of the traditional Chinese medicine composition in the preparation of products for treating dysmenorrhea.

[0012] The present invention discloses the following technical effects:

[0013] The traditional Chinese medicine composition provided by the present invention is explained according to its monarch, minister, assistant, and guiding ingredients: the monarch ingredients (Danggui, Linderae Root, and Fennel) warm the meridians, dispel cold, dredge the collaterals, relieve pain, and activate blood circulation. The minister ingredients (Chuanxiong, Cyperus rotundus, and Corydalis Root) warm the meridians, dispel cold, and promote qi circulation to promote blood circulation and relieve pain. The adjuvant ingredients (Astragalus Root, dried ginger, warm the middle and dispel cold, reinforcing the effects of Fennel and Linderae Root) dispel cold and relieve pain. The guiding ingredient (Cinnamon Bark) directs fire back to the origin. Cistanche Deserticola and Lycium Barbarum prevent excessive warming of yang and nourish kidney yin. Roasted Licorice Root harmonizes the various ingredients, moderates their properties, and relieves pain while providing warming and tonic effects.

[0014] During a woman's menstrual period, herbal remedies can reduce her immunity. Cistanche deserticola contains a variety of bioactive substances with antioxidant and anti-inflammatory properties, helping to boost immunity. It can regulate menstruation, relieve dysmenorrhea symptoms, and improve the health of the female reproductive system. Other components of traditional Chinese medicine have the effects of warming the meridians and dispelling cold, promoting blood circulation and removing blood stasis, and relieving pain. The components in the Chinese medicine composition of this invention can soothe menstruation and relieve pain, alleviating pain caused by uterine contractions or uterine spasms. By regulating the function of the endocrine system, it can improve problems such as irregular menstrual cycles and help restore normal menstruation. It also increases blood circulation, accelerates endometrial shedding, helps alleviate menstrual abdominal pain, and expel blood that accumulates in the body. Compared to Western medicine, the raw materials used have no side effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0016] Figure 1 This is a comparative study of the effects of each treatment group on uterine morphology during dysmenorrhea;

[0017] Figure 2 This is a comparative study of the effects of each treatment group on uterine histology during dysmenorrhea. The scale bar for each group is 50 μm. DETAILED DESCRIPTION

[0018] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0019] It should be understood that the terms described herein are intended only to describe particular embodiments and are not intended to limit the present invention. In addition, for numerical ranges herein, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. The intermediate value within any stated value or stated range, and each smaller range between any other stated value or intermediate value within the stated range, is also encompassed within the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded within the scope.

[0020] Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as commonly understood by those skilled in the art. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of any conflict with any incorporated document, the contents of this specification shall prevail.

[0021] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments described herein without departing from the scope or spirit of the invention. Other embodiments will be apparent to those skilled in the art from the description of the invention. The description and examples are intended to be illustrative only.

[0022] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0023] Example

[0024] 1. Preparation of Chinese medicine composition

[0025] 15 g of Astragalus, 15 g of fennel, 10 g of Angelica, 10 g of Cistanche, 10 g of Linderae, 10 g of Lycium barbarum, 6 g of Ligusticum chuanxiong, 6 parts of cinnamon, 6 g of dried ginger, 6 g of pre-roasted liquorice, 6 g of Cyperus rotundus, and 6 g of Corydalis were ground separately, mixed, and passed through a 60-mesh sieve using a vibrating screen. The coarse particles sieved out were fed into a new type of grading continuous grinder (KF-55 model, Ruian Kangyuan Pharmaceutical Machinery Co., Ltd.) for grinding, and then put into a three-dimensional mixer. The mixer was started, the frequency was adjusted to 40 Hz, and mixing was carried out for 30 minutes to obtain a traditional Chinese medicine composition.

[0026] 2. Experimental Methods

[0027] 2.1 Animal model establishment

[0028] A mouse model of dysmenorrhea was established using estradiol benzoate combined with oxytocin. After three days of adaptive feeding, all mice except the blank group were subcutaneously injected with estradiol benzoate and oxytocin to establish a dysmenorrhea mouse model. The subcutaneous administration site was the groin area, and the typical dose of estradiol benzoate per mouse was 2 mg / kg for 10 consecutive days. Twenty-four hours after the last estradiol injection, the typical intraperitoneal dose of oxytocin was 10 units / kg per mouse. During this period, the blank group received an equal volume of distilled water. Immediately after the last administration, mice were observed for writhing within 30 minutes. Increased writhing patterns were observed in mice other than the blank group. The main manifestations of the writhing patterns were abdominal constriction, twisting movements, extended hind limbs, and raised hips. Successful modeling was confirmed by the presence of these behaviors.

[0029] 2.2 Grouping and drug intervention

[0030] Mice were divided into six groups (8 mice each): Group A (normal group), Group B (model group), Group C (low-dose Chinese herbal medicine combination-L), Group D (medium-dose Chinese herbal medicine combination-M), Group E (high-dose Chinese herbal medicine combination-H), and Group F (positive drug combination (Yuanhuzhitong Tablets). The mice were divided into a normal control group (distilled water / subcutaneous injection), a model group (estradiol benzoate + oxytocin 0.28U / mouse / subcutaneous injection); a positive control (Yuanhuzhitong Tablets solution 0.057g / kg / mouse gavage for 10 days); a model group (no other intervention); and a Chinese herbal medicine combination group (syrup preparation gavage for 10 days).

[0031] Before the experiment, the mice were subjected to abdominal villi removal to completely expose the abdomen of the mice. During the experiment, the growth of abdominal villi of each group of mice was observed and weighed. Mice with villi regeneration could be shaved a second time. Except for the above operations, the blank group did not undergo any intervention; the model group was injected with oxytocin, and no other intervention was performed during the modeling of the model group; the Chinese medicine composition drug group was gavaged with drugs from the fourth day of modeling. According to the dosage of animal experiments, the equivalent dose of each mouse was converted to 4g / kg. The control group and the model group were gavaged with distilled water every day. The drug concentration was calculated based on the equivalent measurement of human and mouse body surface areas. The equivalent dose was used as the medium dose concentration, twice the dosage was used as the high dose concentration, and half the dose was used as the low dose concentration. The high, medium, and low dose groups of the Chinese medicine composition were given 19.8, 9.9, and 5.0 g·kg per day, respectively. -1The dose was administered orally once for 10 consecutive days; the mice in the Yuanhu analgesic tablet group were also given orally, and the drug was ground and crushed into a solution, and then orally administered with equal doses for 10 consecutive days. In the dysmenorrhea mouse model, the dosage of Yuanhu analgesic tablets is usually given according to a certain dosage. According to the relevant studies in the search results, the dosage of Yuanhu analgesic tablets in the mouse dysmenorrhea model is administered at a dose of grams per kilogram (g / kg). This dose was derived based on the experimental design and efficacy evaluation, and was used to investigate the effects of Yuanhu analgesic tablets on the dysmenorrhea mouse model and its possible mechanism of action.

[0032] 2.3 Specimen preparation and collection

[0033] After the end of drug administration and a 24-hour fast, samples were collected. Following intraperitoneal anesthesia with 10 mL kg⁻¹ of 0.3% sodium pentobarbital, the abdominal cavity was immediately opened and the extent of adhesions and lesions carefully examined. The uterus was removed from the control group, while all endometrial tissue in the remaining groups was excised, rinsed with saline, and weighed (dry weight). A portion of the tissue was fixed in 10% paraformaldehyde solution, and a portion was placed in cryovials and stored at -80°C for marker analysis.

[0034] 2.4 Observation indicators

[0035] 2.4.1 Observation of the number of twists

[0036] Observation of the number of writhing reactions After the last oxytocin injection, each group of mice was placed in an observation cage individually, and the number of writhing reactions and the latency time of each mouse within 30 minutes were recorded.

[0037] 2.4.2 Mouse uterus weighing record

[0038] After the writhing observation, mice were anesthetized by intraperitoneal injection for uterine dissection. Fresh uterine tissue was quickly removed on an ice tray. Blood was flushed from the uterus with homemade pre-chilled PBS buffer. Fat and connective tissue were removed, and the mass was measured using an electronic balance. After weighing, the uterine tissue was sealed in an EP tube, quickly frozen with liquid nitrogen, and stored in a -80°C freezer.

[0039] 2.4.3 Histopathological evaluation

[0040] On the morning of the 16th day after drug intervention, samples were collected and the degree of abdominal adhesions was assessed on the same day. After removal of the ectopic lesions, their volume and total weight were measured. The uterus and ectopic lesions were fixed with 4% paraformaldehyde and embedded in paraffin. Sections were then stained with hematoxylin and eosin (HE). HE staining was used to observe the cellular morphology of the ectopic lesions, and immunohistochemical staining was used to detect NF-κB expression. Images were analyzed using ImageJ software.

[0041] 2.4.4 ELISA test

[0042] After anesthesia with sodium pentobarbital, 1 mL of peripheral blood was collected from the mice by the eyeball bleeding method. The supernatant was collected by centrifugation and the PGF2α and PGE2 levels in the peripheral blood of the mice were detected according to the steps in the kit instructions.

[0043] 2.5 Statistical analysis

[0044] Statistical analysis was performed using GraphPad Prism 9.0. Measurement data were expressed as x ± s and tested using the One-Way ANOVA method.

[0045] 3 Results

[0046] 3.1 Number of writhing episodes and latency time of mice in each group

[0047] As shown in the table above, compared with the blank control group, the latency of mice in the model group was significantly reduced (P<0.01), while the number of writhing times was significantly increased (P<0.01). Compared with the model group, the latency of mice in the Yuanhu group and the Chinese herbal combination group was significantly prolonged (P<0.05), and the number of writhing times was significantly reduced (P<0.05).

[0048] Table 1 Number of writhing times and latency time of mice in each group after drug administration (x±s, n=12)

[0049] Group Incubation period (min) Number of twists within 30 minutes Inhibition rate (%) Blank control group 30.00±0.00 0.00±0.00 100%±0.00 Model Group 3.29±1.02## 18.78±5.56## 0 Low-dose group of Chinese medicine composition 7.01±2.22 10.89±2.56 46.75% Medium dose group of Chinese medicine composition 10.43±2.35 8.96±1.46 52% High-dose group of Chinese medicine composition 11.86±2.77** 8.41±2.38** 55% Corydalis group 14.29±3.32 5.61±1.43 70%

[0050] Note: Inhibition rate (%) = (mean number of writhing reactions in the model group - mean number of writhing reactions in the treatment group) / number of writhing reactions in the model group, *100%; ##P<0.01 vs A; *P<0.05, **P<0.01 vs B.

[0051] 3.2 The Chinese herbal composition can reduce the uterine weight of mice with dysmenorrhea

[0052] As shown in the table above, compared with the blank control group, the uterine weight of the mice in the model group increased significantly (P<0.05). Compared with the model group, the uterine weight of the mice in the Yuanhu group and the Chinese medicine combination group decreased significantly, and there was a significant difference in the small size between the high-dose groups (P<0.05). The comparison of the uterine weight of each group is shown in Table 2, and the comparative study of the effects of each treatment group on the uterine morphology during dysmenorrhea is shown in Figure 1 .

[0053] Table 2 Comparison of uterine weight among groups (x±s, n=12)

[0054] Group Uterine weight (mg) Blank control group 22.67±9.81 Model Group 38.33±7.07 Low-dose group of Chinese medicine composition 29±6.1 Medium dose group of Chinese medicine composition 27.67 ± 5.8 * ]] High-dose group of Chinese medicine composition <![CDATA[26.60±7.1 * ]]> Corydalis group <![CDATA[24.06±5.51 * ]]>

[0055] *Indicates significant difference after treatment compared with the control group (P<0.05).

[0056] 3.3 Chinese herbal medicine compositions can reduce uterine pathophysiology of dysmenorrhea

[0057] By observing the histopathological changes through hematoxylin and eosin (H&E) staining, it was found that the area of ​​the uterine myometrium in the dysmenorrhea mouse model decreased significantly with increasing thickness. In addition, uterine tissue pathology showed moderate to severe edema in the endometrial lamina propria. The uterine tissue of the model group mice had fewer blood vessels, dense interstitial tissue, and inflammatory cell proliferation and infiltration. In addition, proliferation and infiltration of inflammatory cells were observed, which may be related to the inflammatory response associated with dysmenorrhea. Compared with the model group, the uterine tissue of the treatment group mice was richer in blood vessels, loose interstitial tissue, and reduced inflammatory cell infiltration. In some treatment groups, reduced fibroblast proliferation was observed, which may be related to the improvement of dysmenorrhea symptoms by therapeutic drugs. These changes in tissue structure reflect the effects of dysmenorrhea on the uterine tissue of mice, including changes in the thickness of the uterine myometrium, the density of blood vessels and interstitial tissue, and the infiltration of inflammatory cells. These changes may be related to the pathophysiological mechanism of dysmenorrhea, and provide an important histological basis for studying the pathogenesis of dysmenorrhea and evaluating the therapeutic effect. A comparative study on the effects of Chinese herbal compositions on uterine histology during dysmenorrhea can be found in Figure 2 .

[0058] 3.4 Chinese herbal medicine composition can reduce the levels of PGF2α and PGE2 in the uterus of patients with dysmenorrhea

[0059] During dysmenorrhea, PGF2α and PGE2 levels are elevated. The pathological mechanism of primary dysmenorrhea is closely related to prostaglandins (PGs) in the endometrium, particularly PGE2 and PGF2α. Studies have shown that PGF2α and PGE2 levels in the endometrium and menstrual blood of women with dysmenorrhea are significantly elevated compared to normal. During menstruation, endometrial cells synthesize and release prostaglandins. High levels of prostaglandins, especially PGF2α, are closely associated with dysmenorrhea because they can induce uterine smooth muscle contractions, potentially leading to uterine hypercontraction and ischemia, thus triggering dysmenorrhea symptoms. The more severe the dysmenorrhea, the higher the PGF2α levels in a woman's menstrual blood. PGF2α levels also peak during the first two days of menstruation, when symptoms are most severe. Most modern medical theories believe that primary dysmenorrhea is primarily related to elevated prostaglandin levels in the endometrium during menstruation, and that elevated PGF2α levels are the primary cause of dysmenorrhea. Primary dysmenorrhea is primarily related to elevated prostaglandin levels in the endometrium during menstruation. Elevated PGF2α levels are the primary cause of dysmenorrhea. After treatment, serum PGF2α and PGE2 levels in the treatment group were significantly improved compared to pre-treatment levels, with statistical significance (P < 0.05). In summary, PGF2α and PGE2 levels are elevated during dysmenorrhea, playing a significant role in the development of dysmenorrhea. The Chinese herbal composition can significantly improve serum PGF2α and PGE2 levels in patients with primary dysmenorrhea, resulting in a positive clinical therapeutic effect. See Table 3 for details.

[0060] Table 3 Comparison of serum PGF2α and PGE2 levels in each group (x±s, n=12)

[0061] Group PGF2α PGE2 Blank control group 22.08±0.21 25.11±0.54 Model Group 37.35±5.02 38.54±4.67 Low-dose group of Chinese medicine composition 29.87±5.91 29.55±5.88 Medium dose group of Chinese medicine composition 28.69±5.76 29.06±5.32 High-dose group of Chinese medicine composition <![CDATA[26.54±8.61 * ]]> <![CDATA[27.79±8.67 * ]]> Corydalis group <![CDATA[25.66±8.51 * ]]> 26.43 ± 3.56 * ]]

[0062] *Indicates significant difference after treatment compared with the control group (P<0.05).

[0063] The embodiments described above are merely descriptions of preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Without departing from the spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by persons skilled in the art should fall within the scope of protection defined by the claims of the present invention.

Claims

1. A Chinese medicine composition for treating dysmenorrhea, characterized in that: The invention is composed of the following components by weight: 10-20 parts of astragalus, 10-20 parts of fennel, 7-15 parts of angelica, 7-15 parts of cistanche, 7-15 parts of lindera, 7-15 parts of wolfberry, 3-10 parts of chuanxiong, 3-10 parts of cinnamon, 3-10 parts of dried ginger, 3-10 parts of roasted licorice, 3-10 parts of cyperus and 3-10 parts of corydalis.

2. The Chinese medicine composition according to claim 1, characterized in that The invention is composed of the following components by weight: 15 parts of astragalus, 15 parts of fennel, 10 parts of angelica, 10 parts of cistanche, 10 parts of lindera, 10 parts of wolfberry, 6 parts of chuanxiong, 6 parts of cinnamon, 6 parts of dried ginger, 6 parts of roasted licorice, 6 parts of cyperus and 6 parts of corydalis.

3. Use of the Chinese medicine composition according to claim 1 or 2 in preparing a medicine for treating dysmenorrhea.

4. The use according to claim 3, characterized in that The medicine also includes pharmaceutically used excipients.

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