A traditional Chinese medicine composition for treating irregular menstruation and its preparation method and application

Abstract

This invention discloses a traditional Chinese medicine composition for treating menstrual disorders, its preparation method, and its application. The formula and weight proportions of the traditional Chinese medicine composition are as follows: 8-15 parts of stir-fried Bupleurum chinense, 8-15 parts of dried Leonurus japonicus, 6-10 parts of Ligusticum chuanxiong, 6-10 parts of Angelica sinensis, 2-6 parts of wine-processed Ligustrum lucidum, 2-6 parts of Rubus idaeus, 2-6 parts of salt-processed Cuscuta chinensis, 2-6 parts of stir-fried Citrus aurantium, 2-6 parts of Cinnamomum cassia, 6-10 parts of Paeonia lactiflora, 6-10 parts of Carthamus tinctorius, 2-6 parts of Spatholobus suberectus, 2-6 parts of Euonymus alatus, 2-6 parts of Prunella vulgaris, 2-6 parts of Lycopus lucidus, and 2-6 parts of Poria cocos. This traditional Chinese medicine composition has a unique and reasonable formulation, a simple preparation method, no toxic side effects, significant therapeutic effect, low recurrence rate, and low adverse reactions.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, specifically to a traditional Chinese medicine composition for treating menstrual disorders, its preparation method, and its application. Background Technology

[0002] Menstrual disorders refer to abnormalities in the timing, amount, color, and quality of menstruation, as well as significant discomfort during menstruation. These include early menstruation, late menstruation, irregular menstruation, excessive menstrual bleeding, and scanty menstruation. The main manifestations are shortened or delayed menstrual cycles, significantly increased or decreased menstrual flow, or even amenorrhea. These may be accompanied by abdominal pain, dizziness, fatigue, anemia, lower back and knee weakness, breast pain, and premenstrual irritability. The main causes are: ① psychological factors, such as prolonged periods of depression, anxiety, tension, or panic, or experiencing significant emotional setbacks or trauma; ② medication factors, such as long-term use of various contraceptives; ③ medical conditions, such as uterine fibroids, endometriosis, and adenomyosis; ④ other factors, such as excessive dieting, excessive exercise, smoking, alcohol abuse, and staying up late. In recent years, with changes in lifestyle, menstrual disorders have become a common and frequently occurring gynecological condition. The menstrual cycle comprises four phases: menstruation, post-menstruation, intermenstrual, and premenstrual. Physicians throughout history have explained this from various perspectives, including Qi and blood, the internal organs, Yin and Yang, Tian Gui (menstrual blood), and the Chong and Ren meridians. They have also analyzed it from the unique perspectives of different treatment methods. For example, the *Jingyue Quanshu* (Complete Works of Jingyue) states in its Yin-Yang chapter: "The original Yin...is what grows and establishes Tian Gui, its strength and weakness are related to it." The liver and kidneys both belong to the lower Jiao (lower burner). The kidneys store essence, and the liver stores blood. Menstrual blood and essence share the same origin, mutually generating and transforming each other. Both essence and blood are material components of menstruation. The liver governs free flow, and the kidneys govern storage. The liver and kidneys work together to regulate menstruation, stabilizing the menstrual cycle, fixing the timing of menstruation, and ensuring the orderly storage and release of menstrual blood. The *Sisheng Xinyuan* (Four Sacred Sources of the Heart) states: "When the three Yang rises to the left, it becomes liver wood. Liver wood is the warming and rising of kidney water. Therefore, liver blood is warm and its nature is ascending. Kidney water warms and transforms into wood, due to the leftward rotation of the Earth element... Heart fire descends and transforms into metal, due to the rightward rotation of the Earth element."

[0003] Currently, Western medicine primarily treats menstrual disorders using estrogen and progesterone to regulate the menstrual cycle and induce ovulation, a relatively simple approach. Its function is to regulate the feedback function of the hypothalamus-pituitary-ovarian axis, causing the corpus luteum to atrophy promptly and the endometrium to shed more completely. However, hormone therapy is prone to relapse after discontinuation and has poor safety profile. Progesterone, as a hormonal drug, has certain side effects, potentially causing weight gain, sodium and water retention, and in severe cases, edema. Frequent use of progesterone can cause endometrial atrophy, reduced menstrual flow, and increased susceptibility to vaginal yeast infections. The high relapse rate and poor safety profile after discontinuation of hormone therapy are drawbacks of purely Western medical treatment. The greatest advantage of Traditional Chinese Medicine (TCM) in treating menstrual disorders lies in its individualized approach, emphasizing individual differences. It combines TCM's diagnostic and treatment principles with a holistic view, paying attention to the cyclical changes of the ovaries and integrating them with clinical medication. Treatment is tailored to the patient's Qi, blood, deficiency, excess, cold, and heat patterns, employing a combination of disease differentiation and syndrome differentiation. The treatment is adjusted according to the patient's clinical manifestations during the menstrual cycle and any accompanying symptoms. Currently, various TCM treatment methods are used in menstrual disorders, such as acupuncture, moxibustion, medicated fumigation, and rectal administration of Chinese medicine, making TCM treatment of menstrual disorders more systematic and its efficacy more stable, thus achieving the goal of treating both the symptoms and the root cause.

[0004] Many traditional Chinese medicine compositions for treating menstrual disorders are disclosed in the prior art. For example, patent number "CN108904697A" discloses "A Menstrual Disorder Regulating Ointment for Women and Its Preparation Method," which is prepared from the following traditional Chinese medicine raw materials: 1-5 parts of Polygonatum sibiricum, 1-5 parts of Carthamus tinctorius, 0.5-3 parts of Angelica sinensis, 1-5 parts of donkey-hide gelatin, 1-5 parts of Citrus medica, 1-5 parts of double-petaled rose, 1-10 parts of brown sugar, 1-5 parts of dried tangerine peel, 0.5-2 parts of sunflower pollen, and 0.1-0.55 parts of complex multivitamins. Although the patent application discloses several ingredients similar to those in the formula of this application, it lacks animal experimental data, the compatibility needs improvement, and the adverse reactions and recurrence rate are unknown. Summary of the Invention

[0005] To address the shortcomings of existing technologies, the purpose of this invention is to develop a traditional Chinese medicine composition for treating menstrual disorders and its preparation method. The traditional Chinese medicine composition has a unique and reasonable formulation, no toxic side effects, significant therapeutic effects, low adverse reactions and low recurrence rate, and a simple and reasonable preparation method.

[0006] The technical solution of this invention is:

[0007] A traditional Chinese medicine composition for treating menstrual disorders, wherein the formula and proportions of the traditional Chinese medicine composition are as follows: 8-15 parts of stir-fried Bupleurum chinense, 8-15 parts of dried Leonurus japonicus, 6-10 parts of Ligusticum chuanxiong, 6-10 parts of Angelica sinensis, 2-6 parts of wine-processed Ligustrum lucidum, 2-6 parts of Rubus idaeus, 2-6 parts of salt-processed Cuscuta chinensis, 2-6 parts of stir-fried Citrus aurantium, 2-6 parts of Cinnamomum cassia, 6-10 parts of Paeonia lactiflora, 6-10 parts of Carthamus tinctorius, 2-6 parts of Spatholobus suberectus, 2-6 parts of Euonymus alatus, 2-6 parts of Prunella vulgaris, 2-6 parts of Lycopus lucidus, and 2-6 parts of Poria cocos.

[0008] Preferred Option 1: The formula and proportions of the traditional Chinese medicine composition are as follows: 10 parts of stir-fried Bupleurum chinense, 10 parts of dried Leonurus japonicus, 8 parts of Ligusticum chuanxiong, 8 parts of Angelica sinensis, 4 parts of wine-processed Ligustrum lucidum, 4 parts of Rubus idaeus, 4 parts of salt-processed Cuscuta chinensis, 4 parts of stir-fried Citrus aurantium, 4 parts of Cinnamomum cassia, 8 parts of Paeonia lactiflora, 8 parts of Carthamus tinctorius, 4 parts of Spatholobus suberectus, 4 parts of Euonymus alatus, 4 parts of Prunella vulgaris, 4 parts of Lycopus lucidus, and 4 parts of Poria cocos.

[0009] Preferred Option 2: The formula and proportions of the traditional Chinese medicine composition are as follows: 12 parts of stir-fried Bupleurum chinense, 12 parts of dried Leonurus japonicus, 9 parts of Ligusticum chuanxiong, 9 parts of Angelica sinensis, 5 parts of wine-processed Ligustrum lucidum, 5 parts of Rubus idaeus, 5 parts of salt-processed Cuscuta chinensis, 5 parts of stir-fried Citrus aurantium, 5 parts of Cinnamomum cassia, 10 parts of Paeonia lactiflora, 10 parts of Carthamus tinctorius, 5 parts of Spatholobus suberectus, 5 parts of Euonymus alatus, 5 parts of Prunella vulgaris, 5 parts of Lycopus lucidus, and 5 parts of Poria cocos.

[0010] The preferred preparation method is as follows: The preparation method includes selecting the following ingredients according to the above proportions: stir-fried Bupleurum chinense, dried Leonurus japonicus, Ligusticum chuanxiong, Angelica sinensis, wine-processed Ligustrum lucidum, Rubus idaeus, salt-processed Cuscuta chinensis, stir-fried Citrus aurantium, Cinnamomum cassia, Paeonia lactiflora, Carthamus tinctorius, Spatholobus suberectus, Euonymus alatus, Prunella vulgaris, Lycopus lucidus, and Poria cocos. Add water and decoct 2-3 times, adding 8-10 times the amount of water each time and decoct for 1-2 hours. Combine the decoctions, filter, and concentrate the filtrate to a thick paste with a relative density of 1.20-1.25 (60℃).

[0011] Furthermore, honey and water are added to the paste and heated and stirred to dissolve. One part of sorbic acid is added, and the paste is concentrated to a final product with a relative density greater than or equal to 1.35 (20°C).

[0012] Furthermore, the thick paste can be further formulated into one of tablets, granules, pills, capsules, and oral liquids using conventional techniques in the art.

[0013] The present invention also provides the application of the traditional Chinese medicine composition in the preparation of a medicine for treating menstrual disorders.

[0014] The prescription of this invention is explained as follows:

[0015] Stir-fried Bupleurum chinense: pungent, slightly bitter, and slightly cold. It enters the liver and gallbladder meridians. Its functions include soothing the liver and relieving stagnation, and raising yang to lift prolapse. It is used for liver qi stagnation, irregular menstruation, chest and rib pain, and fever due to colds.

[0016] Dried motherwort: Bitter, pungent, slightly cold. It enters the liver, pericardium, and bladder meridians. Its functions include promoting blood circulation and regulating menstruation, and promoting diuresis and reducing swelling. It is used for women's irregular menstruation, dysmenorrhea, postpartum abdominal pain due to blood stasis, edema, and difficulty urinating.

[0017] Chuanxiong (Ligusticum striatum): pungent, warm. It enters the liver, gallbladder, and pericardium meridians. Its functions include promoting blood circulation, regulating qi, dispelling wind, and relieving pain. It is used for headaches, rheumatic pain, irregular menstruation, and dysmenorrhea.

[0018] Angelica sinensis: sweet, pungent, and warm. It enters the liver, heart, and spleen meridians. Its functions include nourishing and invigorating blood, regulating menstruation, and relieving pain. It is used for blood deficiency, pale complexion, irregular menstruation, dysmenorrhea, and injuries from falls and blows.

[0019] Ligustrum lucidum (purple privet fruit): Sweet, slightly bitter, and cool in nature. It enters the liver and kidney meridians. Its functions include nourishing yin and tonifying the liver and kidneys, improving eyesight and darkening hair. It is used for liver and kidney deficiency, dizziness, tinnitus, lower back and knee weakness, and blurred vision.

[0020] Raspberry: Sweet, sour, and neutral in nature. It enters the liver and kidney meridians. Its functions include strengthening essence and reducing urination, nourishing the liver and improving eyesight. It is used for seminal emission, frequent urination, and blurred vision caused by liver and kidney deficiency.

[0021] Salt-processed Cuscuta: Sweet, pungent, and neutral in nature. It enters the liver and kidney meridians. Its functions include tonifying the kidneys and replenishing essence, strengthening the kidneys and calming the fetus. It is used for kidney deficiency causing lower back pain, seminal emission, urinary incontinence, and threatened miscarriage.

[0022] Fried Bran-Fried Aurantium: Bitter, pungent, slightly cold. Enters the spleen, stomach, and large intestine meridians. Functions: Regulates qi, relieves abdominal distension, promotes digestion, and eliminates food stagnation. Used for abdominal distension, belching, acid reflux, and indigestion.

[0023] Cinnamon twig: pungent, sweet, and warm. It enters the heart, lung, and bladder meridians. Its functions include inducing sweating and relieving muscle tension, warming the meridians and promoting blood circulation. It is used for colds due to wind-cold, shoulder and back pain, and cold extremities.

[0024] Red peony root: Bitter, slightly cold. Enters the liver meridian. Functions: Clears heat and cools the blood, disperses blood stasis and relieves pain. Used for hematemesis and epistaxis due to blood heat, irregular menstruation, dysmenorrhea, and traumatic injuries.

[0025] Safflower: Pungent, warm. Enters the heart and liver meridians. Functions include promoting blood circulation, regulating menstruation, dispersing blood stasis, and relieving pain. Used for amenorrhea, dysmenorrhea, postpartum abdominal pain due to blood stasis, and traumatic injuries.

[0026] Chicken blood vine: bitter, sweet, and warm in nature. It enters the liver and kidney meridians. Its functions include nourishing and invigorating blood circulation, and relaxing muscles and tendons. It is used for blood deficiency and chlorosis, numbness of limbs, and rheumatic pain.

[0027] Euonymus alatus: Bitter, pungent, neutral. Enters the liver and spleen meridians. Functions include breaking up blood stasis, killing parasites, and relieving itching. Used for blood stasis, itchy skin, sores, and boils.

[0028] Prunella vulgaris: Bitter, pungent, and cold in nature. It enters the liver and gallbladder meridians. Its functions include clearing liver heat and improving eyesight, dispersing nodules and reducing swelling. It is used for red, swollen, and painful eyes, scrofula, and phlegm nodules caused by liver fire rising upwards.

[0029] Eupatorium japonicum Thunb.: Bitter, pungent, slightly warm. It acts on the liver and spleen meridians. Its effects are activating blood circulation to regulate menstruation and promoting diuresis to alleviate edema. It is applied to irregular menstruation, postpartum blood stasis abdominal pain, edema, etc.

[0030] Poria cocos (Schw.) Wolf: Sweet, bland, neutral. It acts on the heart, spleen and kidney meridians. Its effects are promoting diuresis to eliminate dampness, strengthening the spleen and calming the heart. It is applied to oliguria, edema, anorexia due to spleen deficiency, palpitation and insomnia, etc.

[0031] The basic pathogenesis of irregular menstruation is stagnation of liver qi, qi stagnation and blood stasis, and the blood stasis staying in the face causes irregular menstruation. Therefore, the basic treatment principle in clinical treatment should be soothing the liver and regulating qi, activating blood circulation to regulate menstruation.

[0032] Bupleurum chinense DC.: Bitter, slightly cold. It acts on the liver and gallbladder meridians. It soothes the liver and reduces fever. "Explanation of Materia Medica": "For Bupleurum chinense DC., the reason it can mainly treat the stagnant qi in the heart, abdomen, stomach and intestines is that the heart, abdomen, stomach and intestines are the five zang-organs and six fu-organs, and there are a total of twelve meridians in the zang-fu organs. All eleven zang-organs depend on the gallbladder. Bupleurum chinense DC. is light and clear, ascending and dispersing the qi of the gallbladder. When the qi of the gallbladder is smooth, the eleven zang-organs will follow and be diffused and transformed. Therefore, all stagnant qi in the heart, abdomen, stomach and intestines can be dispersed by it." Bupleurum chinense DC. is a commonly used herb for soothing the liver and has the effect of reducing fever, preventing the blood stasis from turning into heat over time, which is preventing the progression of the disease; Leonurus japonicus Houtt.: Bitter, pungent, slightly cold. It acts on the liver and pericardium meridians. It activates blood circulation to regulate menstruation. "Comprehensive Collection of Materia Medica": "Leonurus japonicus Houtt. promotes blood circulation and nourishes blood, promotes blood circulation without damaging the new blood, and nourishes blood without stagnating the stasis blood. It is truly a holy herb for blood diseases." Leonurus japonicus Houtt. activates blood circulation to regulate menstruation, can promote blood circulation without damaging the new blood, nourish blood without leaving stasis, and has a significant effect on regulating menstrual abnormalities. The two herbs together serve as the monarch drugs.

[0033] Ligusticum chuanxiong Hort.: Pungent, warm. It acts on the liver, gallbladder and pericardium meridians. It soothes the liver and promotes qi movement, activates blood circulation to relieve pain. "Comprehensive Collection of Materia Medica": "Ligusticum chuanxiong Hort. ascends to the head, regulates menstruation downward, and relieves the internal stasis in the middle. It is a qi drug in blood. It is often used in combination with Angelica sinensis (Oliv.) Diels. It not only has great effects on treating blood diseases, but also is very effective in treating qi diseases. It can dispel cold dampness, expel wind, improve eyesight, relieve headache, relieve pain in the hypochondrium, nourish during pregnancy, benefit after childbirth, and can also treat mass accumulation, blood stasis obstruction, pain and itching of sores and ulcers, carbuncle and swelling with fever and chills, weakness of the feet and flaccidity of the muscles, swelling and pain preventing walking, etc. Its taste is pungent and its nature is yang, and its qi is good at running around without the state of yin coagulation and stagnation. Although it enters the blood aspect, it can also expel all wind and regulate all qi." Ligusticum chuanxiong Hort. is a qi drug in blood, ascending to the head and guiding the medicinal power to the head and face; Angelica sinensis (Oliv.) Diels, as recorded in "Materia Medica of Japan": "It can treat all wind, all blood, tonify all deficiencies, break up evil blood, nourish new blood and mainly treat mass accumulation." "Correct Meaning of Materia Medica" states that "its taste is sweet and heavy, so it can specifically nourish blood. Its qi is light and pungent, so it can also promote blood circulation. There is movement in nourishing and supplementation in promoting blood circulation. It is truly a qi drug in blood and also a holy drug in blood." Angelica sinensis (Oliv.) Diels nourishes blood and promotes blood circulation, regulates menstruation and relieves pain, nourishes blood and promotes blood circulation at the same time, and has a significant effect on irregular menstruation; Paeonia lactiflora Pall. dissipates stasis and relieves pain. When combined with Angelica sinensis (Oliv.) Diels, it enhances the power of nourishing blood, regulating menstruation and relieving pain; Carthamus tinctorius L. activates blood circulation to dredge the meridians, dissipates stasis and relieves pain, enhancing the power of activating blood circulation in the formula. The four herbs together serve as the ministerial drugs to supplement the deficiencies of the monarch drugs, and jointly achieve the effects of activating blood circulation to regulate menstruation and soothing the liver and promoting qi movement.

[0034] Wine-processed privet fruit, raspberry, and salt-processed dodder seed nourish the liver and kidneys. Fried bitter orange peel promotes qi circulation and relieves pain. Cinnamon twig invigorates yang and transforms qi, aiding the other herbs in their efficacy. Chicken blood vine and Euonymus alatus both promote blood circulation and regulate menstruation. Prunella vulgaris can both soothe the liver and reduce fever, similar to Bupleurum chinense. Lycopus lucidus and Poria cocos promote diuresis and eliminate dampness; Lycopus lucidus also invigorates blood circulation and regulates menstruation. All the above herbs are adjuvants, working together to invigorate blood circulation, regulate menstruation, soothe the liver, and promote qi circulation.

[0035] This invention utilizes the principles of soothing the liver and regulating qi, promoting blood circulation and removing blood stasis, making it suitable for treating menstrual disorders caused by liver qi stagnation and blood stasis. The entire formula is meticulously formulated, with appropriate combinations, and it can prevent disease progression, demonstrating its effectiveness in clinical practice.

[0036] Compared with the prior art, the advantages of the present invention are:

[0037] 1. The traditional Chinese medicine composition of the present invention uses stir-fried Bupleurum chinense and dried Leonurus japonicus as principal herbs, and Ligusticum chuanxiong, Angelica sinensis, Paeonia lactiflora and Carthamus tinctorius as assistant herbs. The four herbs work together to assist the principal herbs, and other adjuvant herbs are added to make the combination more reasonable and the efficacy better.

[0038] 2. The preparation method of the traditional Chinese medicine composition of the present invention is simple and has a high efficacy rate in clinical trials.

[0039] 3. Compared with the comparative formulation, the drug synergistic effect between the drugs in the traditional Chinese medicine composition of the present invention is stronger and the therapeutic effect is better.

[0040] 4. Repeated-dose toxicity tests and single-dose toxicity tests conducted by oral administration of the traditional Chinese medicine composition of the present invention to rats over a period of 6 months showed that the traditional Chinese medicine composition of the present invention has high safety and no toxic side effects.

[0041] 5. Pharmacokinetic studies have shown that the herbal composition of this invention has a significant analgesic effect on dysmenorrhea model mice; the herbal composition of this invention has a good therapeutic effect on qi stagnation and blood stasis model rats, significantly reducing whole blood viscosity (low shear, medium shear, high shear) and plasma viscosity, as well as activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT), and has a significant improvement effect on blood rheological parameters and coagulation parameters of qi stagnation and blood stasis model rats.

[0042] 6. Clinical efficacy has demonstrated that patients treated with the herbal composition of this invention showed significantly increased levels of estradiol and progesterone, while significantly decreased levels of FSH and LH. This suggests that the herbal composition of this invention can effectively regulate hormone levels and improve hormonal imbalances in patients with menstrual disorders. Furthermore, patients using the herbal composition of this invention have a low incidence of adverse reactions, a low recurrence rate, and stable therapeutic effects.

[0043] The detailed structure of the present invention will be further described below with reference to the accompanying drawings and specific embodiments. Attached Figure Description

[0044] Figure 1 This is a flowchart of the preparation process of the traditional Chinese medicine composition of the present invention. Detailed Implementation

[0045] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. The following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0046] The weight parts mentioned in the embodiments of the present invention refer to mass, and the units are generally g or kg.

[0047] Example 1

[0048] A traditional Chinese medicine composition for treating menstrual disorders, the formula and proportions by weight are as follows: 10 parts of stir-fried Bupleurum chinense, 10 parts of dried Leonurus japonicus, 8 parts of Ligusticum chuanxiong, 8 parts of Angelica sinensis, 4 parts of wine-processed Ligustrum lucidum, 4 parts of Rubus idaeus, 4 parts of salt-processed Cuscuta chinensis, 4 parts of stir-fried Citrus aurantium, 4 parts of Cinnamomum cassia, 8 parts of Paeonia lactiflora, 8 parts of Carthamus tinctorius, 4 parts of Spatholobus suberectus, 4 parts of Euonymus alatus, 4 parts of Prunella vulgaris, 4 parts of Lycopus lucidus, and 4 parts of Poria cocos.

[0049] Preparation method: The above sixteen herbs are decocted twice with water. The first decoction is decocted with 10 times the amount of water for 2 hours, and the second decoction is decocted with 8 times the amount of water for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.20-1.25 (60℃). Take an appropriate amount of honey, add an appropriate amount of water, heat and stir to dissolve, mix with the above thick paste, add 1 part of sorbic acid, and concentrate to a finished thick paste with a relative density of not less than 1.35 (20℃).

[0050] Table 1. Detailed preparation process and control parameters for Example 1

[0051]

[0052] Dosage and administration: Oral administration, one sachet each time, three times a day, or as directed by a physician.

[0053] Comparative Example 1

[0054] A traditional Chinese medicine composition, wherein the formula and proportions of the traditional Chinese medicine composition are as follows: 10 parts of stir-fried Bupleurum chinense, 8 parts of Ligusticum chuanxiong, 8 parts of Angelica sinensis, 4 parts of wine-processed Ligustrum lucidum, 4 parts of Rubus idaeus, 4 parts of salt-processed Cuscuta chinensis, and 4 parts of stir-fried Citrus aurantium.

[0055] The preparation method is the same as in Example 1: the above seven herbs are decocted twice with water. The first decoction is decocted with 10 times the amount of water for 2 hours, and the second decoction is decocted with 8 times the amount of water for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.20-1.25 (60℃). Take an appropriate amount of honey, add an appropriate amount of water, heat and stir to dissolve, mix with the above thick paste, add 1g of sorbic acid, and concentrate to a finished thick paste with a relative density of not less than 1.35 (20℃).

[0056] Comparative Example 2

[0057] A traditional Chinese medicine composition, wherein the formula and proportions of the traditional Chinese medicine composition are as follows: 10 parts of stir-fried Bupleurum chinense, 10 parts of dried Leonurus japonicus, 8 parts of Ligusticum chuanxiong, 8 parts of Angelica sinensis, 4 parts of wine-processed Ligustrum lucidum, 4 parts of Rubus idaeus, 4 parts of salt-processed Cuscuta chinensis, 4 parts of stir-fried Citrus aurantium, 4 parts of Cinnamomum cassia, 4 parts of Spatholobus suberectus, 4 parts of Euonymus alatus, and 4 parts of Prunella vulgaris.

[0058] The preparation method is the same as in Example 1: the above twelve herbs are decocted twice with water. The first decoction is decocted with 10 times the amount of water for 2 hours, and the second decoction is decocted with 8 times the amount of water for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.20-1.25 (60℃). Take an appropriate amount of honey, add an appropriate amount of water, heat and stir to dissolve, mix with the above thick paste, add 1g of sorbic acid, and concentrate to a finished thick paste with a relative density of not less than 1.35 (20℃).

[0059] Example 2: Single-dose toxicity test of the traditional Chinese medicine composition of Example 1 administered orally to rats.

[0060] Objective: This study was conducted in accordance with national GLP standards to observe the acute toxic reactions and mortality of SD rats after two oral administrations of the traditional Chinese medicine composition of Example 1 within 24 hours, providing reference data for its repeated-dose toxicity test.

[0061] Experimental materials: Forty SPF-grade SD rats, female, weighing 180.3–214.2 g, were selected for the experiment and housed in cages measuring 475 mm × 350 mm × 200 mm, with 5 rats per cage. They were housed according to the international (GB14925-2010) requirements for SPF-grade laboratory animal environmental conditions, and underwent quarantine and environmental acclimatization for 5 days.

[0062] This experiment observed the acute toxicity response of the traditional Chinese medicine composition of Example 1 administered orally to SD rats. Forty female SD rats were randomly divided into two groups according to body weight: a blank control group and a group receiving the traditional Chinese medicine composition of Example 1 (156.4 g crude drug / kg), with 20 rats in each group. Before the experiment, the rats were fasted but allowed free access to water for at least 12 hours. Then, they were administered pure water or the traditional Chinese medicine composition of Example 1 orally at a dose of 20 mL / kg, respectively. The administration was performed twice on the same day (6 hours apart). Within 4 hours after each administration, the animals in each group were closely observed and recorded for 4 days, noting the characteristics of poisoning, the onset and recovery time of toxic reactions, and mortality. Observations were then performed twice daily, once in the morning and once in the afternoon, for 14 consecutive days. The animals were weighed before administration on the day of administration and on days 4, 7, 10, and 14 after administration, and changes in body weight and mortality were recorded.

[0063] Experimental Results: Effects on general activity, animal poisoning symptoms, and mortality: Within 4 hours after each oral gavage administration, no significant abnormalities were observed in the spontaneous activity, mental state, and diet of rats in both the blank control group and the group containing the traditional Chinese medicine composition of Example 1. No related toxic reactions or animal deaths were observed. After 14 consecutive days of observation following administration, no significant abnormalities were observed in the spontaneous activity, mental state, and diet of rats in both the blank control group and the group containing the traditional Chinese medicine composition of Example 1. No related toxic reactions or animal deaths were observed.

[0064] Effect on body weight: Animals were weighed before administration on the day of administration and on the 4th, 7th, 10th and 14th days after administration. The weight of the animals in the traditional Chinese medicine composition group of Example 1 was compared with that of the blank control group at the same time. There was no statistically significant difference in weight between the animals and the blank control group at the same time, and the weight gain was within the normal range. This indicates that oral administration of the traditional Chinese medicine composition of Example 1 to SD rats had no significant effect on the weight gain of the rats.

[0065] At the end of the experiment, gross anatomical observation of SD rats showed no obvious abnormalities on the surface and cut surfaces of any organs.

[0066] Conclusion: Under the conditions of this experiment, rats were orally administered the traditional Chinese medicine composition of Example 1 at a volume of 20 mL / kg, twice a day (6 hours apart), with a cumulative dose of 156.4 g crude drug / kg, which is equivalent to 133 times the clinical dose per kilogram of body weight for adults. No related toxic reactions or deaths were observed in the animals.

[0067] Table 2. Effects of the traditional Chinese medicine composition in Example 1 on the body weight of female SD rats ( n=20)

[0068]

[0069] Note: There was no statistically significant difference between the traditional Chinese medicine composition group in Example 1 and the blank control group.

[0070] Example 3: Toxicity test of rats after 6 months of repeated oral administration of the traditional Chinese medicine composition of Example 1

[0071] Objective: This study was conducted in accordance with national GLP standards to observe the toxicity of repeated administration of different doses of the traditional Chinese medicine composition of Example 1 to female SD rats via oral gavage, and to evaluate the toxic effects of the traditional Chinese medicine composition of Example 1 on female SD rats after multiple administrations, so as to provide reference data for the clinical use of the traditional Chinese medicine composition of Example 1.

[0072] Experimental method: 120 qualified female SD rats, weighing 185.7-219.8g and measuring 475×350×200mm, were selected. 3 Five rats were housed in cages. They were raised according to the international (GB14925-2010) SPF-grade laboratory animal environmental conditions requirements, and underwent quarantine and environmental acclimatization for 7 days. They were randomly divided into four groups of 30 animals each, based on body weight. The experiment included a blank control group and low, medium, and high dose groups of the traditional Chinese medicine composition from Example 1 (14.67, 29.33, and 58.65 g crude drug / kg, respectively). The drugs were administered by gavage at a volume of 15 mL / kg for 6 consecutive months. At the end of the mid-treatment period (weekend of week 13), the end of the treatment period (weekend of week 26), and the end of the recovery period (weekend of week 30), 10 female rats from each group were dissected as planned. Examinations included: general clinical observation; body weight and food intake measurements; hematological, blood biochemistry, coagulation, and organ coefficient measurements; and histopathological examination.

[0073] Results: All experimental animals were euthanized as planned during the experiment, and no abnormal deaths occurred during the experiment.

[0074] General clinical observation: During the administration and recovery periods, compared with the blank control group, no abnormalities related to drug toxicity were observed in the appearance, behavior, and general condition of the experimental animals in each dosage group of the traditional Chinese medicine composition in Example 1.

[0075] Body weight: During the experiment, the dosage groups of the traditional Chinese medicine composition in Example 1 had no significant effect on the overall food intake of female rats compared with the blank control group at the same time.

[0076] Food intake: During the experiment, the average food intake of each dose group of the traditional Chinese medicine composition in Example 1 was compared with that of the blank control group during the same period. It had no significant effect on the overall food intake of female rats.

[0077] Hematological examination: Compared with the blank control group, no toxicological changes were observed in the hematological indicators of each dosage group of the traditional Chinese medicine composition in Example 1. The results indicate that the traditional Chinese medicine composition in Example 1 has no significant effect on the hematological indicators of female rats.

[0078] Blood biochemical tests: Compared with the blank control group, no toxicologically significant changes were observed in the blood biochemical indicators of each dosage group of the traditional Chinese medicine composition in Example 1. The results indicate that the traditional Chinese medicine composition in Example 1 has no significant effect on the blood biochemical indicators of female rats.

[0079] Coagulation test: Compared with the blank control group, no toxicologically significant changes were observed in the coagulation indicators of each dose group of the traditional Chinese medicine composition in Example 1. The results indicate that the traditional Chinese medicine composition in Example 1 has no significant effect on the coagulation indicators of female rats.

[0080] Organ coefficient: Compared with the blank control group at the same time, the organ coefficients of each dosage group of the traditional Chinese medicine composition in Example 1 showed no significant abnormalities. The results indicate that the traditional Chinese medicine composition in Example 1 had no significant effect on the organ coefficients of female rats.

[0081] Gross anatomy and pathological examination: The experimental animals in the high-dose group of the traditional Chinese medicine composition in Example 1 were dissected during the middle, end and recovery periods of drug administration. No significant differences were found between the experimental animals and the blank control group at the same time. No pathological changes of toxicological significance were found.

[0082] Conclusion: Under the conditions of this experiment, the no obvious adverse reaction (NOAEL) in SD rats after oral administration of the traditional Chinese medicine composition of Example 1 for 6 months was 58.65 g crude drug / kg (equivalent to 50 times the clinically intended dose for a 70 kg adult, and 7.9 times the equivalent dose).

[0083] Table 3. Effects of the traditional Chinese medicine composition in Example 1 on the body weight of female experimental animals (g, )

[0084]

[0085]

[0086] Note: Compared with the blank control group, * P<0.05.

[0087] Table 4. Effect of the traditional Chinese medicine composition of Example 1 on the average food intake of female experimental animals (g / animal / day). )

[0088]

[0089]

[0090] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0091] Table 5. Effects of the traditional Chinese medicine composition of Example 1 on the hematology of female experimental animals.

[0092]

[0093]

[0094]

[0095] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0096] Table 6. Effects of the traditional Chinese medicine composition of Example 1 on blood biochemical parameters of female experimental animals.

[0097]

[0098]

[0099] Note: Compared with the blank control group, * P<0.05, ** P<0.01.

[0100] Table 7. Effects of the traditional Chinese medicine composition in Example 1 on coagulation in female experimental animals.

[0101]

[0102] Note: Compared with the blank control group, ** P<0.01.

[0103] Example 4: Animal pharmacodynamic experimental data

[0104] Experiment 1: Effects on a mouse model of dysmenorrhea

[0105] 1. Experimental Objective

[0106] This experiment involved administering the traditional Chinese medicine compositions of Example 1, Comparative Examples 1 and 2 to mice via gavage to observe their effects on dysmenorrhea model mice, providing experimental evidence for clinical application.

[0107] 2. Test materials

[0108] Test substance (test sample): Traditional Chinese medicine compositions of Example 1, Comparative Example 1 and Comparative Example 2 (Guyitang (Hunan) Health Technology Co., Ltd.), 1 g of extract is equivalent to 3.91 g of cut crude drugs, in the form of paste, clinically proposed dosage: 82.50 g of cut crude drugs per day; clinically proposed administration route: oral administration, 1 bag each time, 3 times a day, clinically proposed treatment course: 2 months.

[0109] Positive control drug, name: Wuji Baifeng Pills, specification: 9 g × 10 pills, manufacturer: Tongrentang Pharmaceutical Factory of Beijing Tongrentang Co., Ltd.

[0110] Experimental animals: 60 female KM mice qualified for quarantine, weight range for use: 19.6 - 22.0 g; (Hunan Slack Jingda Experimental Animal Co., Ltd.).

[0111] Main reagents: Name: Oxytocin Injection, manufacturer: NSHF; Name: Estradiol Valerate Tablets, manufacturer: DELPHARMLille S.A.S.

[0112] 3. Grouping, administration and model establishment of experimental animals

[0113] The 60 female KM mice qualified for quarantine were randomly divided into 6 groups according to body weight, namely blank control group, model control group, groups of Example 1, Comparative Example 1 and Comparative Example 2, positive control group (i.e., Wuji Baifeng Pills group), with 10 mice in each group.

[0114] Groups of Example 1, Comparative Example 1 and Comparative Example 2 (10.95, 10.95, 10.95 g of cut crude drugs / kg), positive control group (2.34 g / kg) were given the corresponding dose of liquid medicine by gavage at 20 mL / kg, the blank control group was given an equal volume of pure water by gavage, once a day for 4 consecutive days. After 6 hours of drug administration every day for each group of mice, Estradiol Valerate Tablets 0.5 mg / kg were given by gavage, once a day, and the blank control group was given an equal volume of pure water by gavage at the same time.

[0115] Dose design of test samples and control samples

[0116] The clinically proposed dosage of the traditional Chinese medicine compositions of Example 1, Comparative Example 1 and Comparative Example 2 is 82.50 g of cut crude drugs per day. According to the conversion table of equivalent doses based on body surface area between animal species in "Pharmacological Experimental Methods" edited by Wei Wei, Fourth Edition, it was converted into the equivalent dose for mice according to body surface area: 82.50 g of cut crude drugs per day × 0.0026 / 0.02 kg ≈ 10.95 g of cut crude drugs / kg. The equivalent dose of Wuji Baifeng Pills: 18 g per day × 0.0026 / 0.02 kg = 2.34 g / kg, and the experiment was carried out, as shown in Table 8 for details.

[0117] Table 8 Dose design table for each group

[0118]

[0119] Note: 1.00 g of the extract is equivalent to 3.91 g of the crude drug pieces.

[0120] Drug preparation:

[0121] For the traditional Chinese medicine compositions of Example 1, Comparative Example 1 and Comparative Example 2: Weigh 1.4 g of the extract of the traditional Chinese medicine compositions of Example 1, Comparative Example 1 and Comparative Example 2, and add pure water to make up to 10 mL (0.14 g of extract / mL).

[0122] Wuji Baifeng Pills group: Take 1.17 g of Wuji Baifeng Pills, grind them and add pure water to make up to 10 mL (0.12 g / mL).

[0123] The preparation volume is adjusted according to the change in the body weight of the animals every week.

[0124] Detection indexes:

[0125] (1) General status observation: After administration, closely observe and record the appearance signs, behavioral activities, secretions, excretions, diet conditions, death conditions, etc. of the animals in each group, and weigh them once a week.

[0126] (2) Writhing latency and writhing次数: 30 minutes after the last administration, the blank control group was intraperitoneally injected with 0.2 mL / rat of normal saline, and the other groups were intraperitoneally injected with 2 U / rat of oxytocin. Record the writhing latency of the mice in each group and the number of writhing within 30 minutes after the injection of oxytocin.

[0127] Data statistical analysis

[0128] SPSS 16.0 software was used for data statistics, and the experimental data were expressed as mean ± standard deviation. The results of systematic anatomy and histopathology were judged by qualitative indexes; for measurement data, normality and homogeneity of variance tests were performed. If normality was satisfied, one-way ANOVA was used for statistical analysis, and LSD+Dunnett-t (homogeneous variance) or Tamhane's T2 (heterogeneous variance) was selected for comparative analysis according to the homogeneity of variance; if normality was not satisfied, the Kruskal-Wallis test was used, and the Mann-Whitney test was used for pairwise comparison analysis; where P<0.05 indicates statistical difference or P<0.01 indicates significant statistical difference, and its biological significance was considered during evaluation.

[0129] 4. Experimental results

[0130] 4.1. Effects on the mouse dysmenorrhea model induced by oxytocin (writhing method)

[0131] As shown in Table 9, compared with the blank control group, the writhing latency of mice in the model control group was significantly shortened (P<0.01) and the number of writhing movements was significantly increased (P<0.01), suggesting that intraperitoneal injection of oxytocin induced dysmenorrhea in mice. Compared with the model control group, the writhing latency of mice in Example 1, Comparative Example 1, Comparative Example 2, and the Wuji Baifeng Wan group was significantly prolonged (P<0.01) and the number of writhing movements was significantly reduced (P<0.01). Number of writhing movements: Compared with Comparative Example 1, Comparative Example 2 showed a slight decrease, but it was not significant (P>0.5); Compared with Comparative Example 1, Example 1 showed a significant decrease, which was statistically significant (P<0.05); Compared with Comparative Example 2, Example 1 showed a significant decrease, which was statistically significant (P<0.05). The latency period of writhing was significantly increased in Comparative Example 2 compared to Comparative Example 1 (P<0.05); significantly increased in Example 1 compared to Comparative Example 1 (P<0.01); and significantly increased in Example 1 compared to Comparative Example 2 (P<0.05). The efficacy of Example 1 was comparable to that of Wuji Baifeng Wan (2.34 g / kg).

[0132] Table 9. Effects of oxytocin on a mouse model of dysmenorrhea (writhing test) ( n=10)

[0133]

[0134]

[0135] Note: Compared with the blank control group, "**" indicates P<0.01; compared with the model control group, "**" indicates P<0.01. Δ " indicates P < 0.05, " ΔΔ " " indicates P < 0.01; "#" indicates P < 0.05 compared to Comparative Example 1; "##" indicates P < 0.01; "▲" indicates P < 0.05 compared to Comparative Example 2.

[0136] 6. Conclusion and Evaluation

[0137] Under the experimental conditions, Example 1 and Comparative Example 1 and Comparative Example 2 (10.95, 10.95 and 10.95 g of medicinal slices / kg) had significant analgesic effects on dysmenorrhea model mice, and Comparative Example 2 was more effective than Comparative Example 1. Example 1 was significantly more effective than Comparative Example 1 and Comparative Example 2. Example 1 showed a significant synergistic effect of drugs compared to Comparative Example 1 and Comparative Example 2, and was more effective.

[0138] Experiment 2: Effects on a rat model of qi stagnation and blood stasis

[0139] 1. Experimental Objective

[0140] This experiment involved administering the traditional Chinese medicine compositions of Example 1, Comparative Examples 1 and 2 to mice via gavage to observe their effects on rats with a qi stagnation and blood stasis model, providing experimental evidence for clinical application.

[0141] 2. Test materials

[0142] Test substance (test sample): Traditional Chinese medicine composition of Example 1, Comparative Example 1 and Comparative Example 2 (Guyitang (Hunan) Health Technology Co., Ltd.), 1g extract is equivalent to 3.91g of decoction pieces, ointment, clinically intended dose: 82.50g decoction pieces / day; clinically intended route of administration: oral, 1 sachet at a time, 3 times a day; clinically intended course of treatment: 2 months.

[0143] Positive control drug, name: Wuji Baifeng Wan, specification: 9g×10 pills, manufacturer: Beijing Tongrentang Co., Ltd. Tongrentang Pharmaceutical Factory.

[0144] Experimental animals: 60 female SD rats that passed quarantine, with a weight range of 206.5–237.4 g (Hunan Slack Jingda Experimental Animal Co., Ltd.).

[0145] Main reagent: Name: Epinephrine Hydrochloride Injection; Manufacturer: Shanghai Quanyu Biotechnology (Zhumadian) Animal Pharmaceutical Co., Ltd.

[0146] 3. Grouping, administration, and modeling of experimental animals

[0147] Animal grouping: Sixty qualified female SD rats were randomly divided into 6 groups according to their body weight: blank control group, model control group, Example 1, Comparative Example 1 and Comparative Example 2, and positive control group (i.e. Wuji Baifeng Wan group), with 10 rats in each group.

[0148] Modeling and drug administration: Except for the blank control group, the other groups were modeled according to the following methods: (1) Tail clamping: The tail of the rat was clamped with a large clamp to keep it in an angry state for 30 minutes each time, twice a day, with an interval of 4 hours each time; (2) Restraint: The rat was restrained with a restraint device for 30 minutes each time; (3) The rat cage was tilted at 45° for 2 hours, once a day; (4) Fasting for 24 hours; (5) Subcutaneous injection of adrenaline hydrochloride (0.4 mg / kg) into the back of the rat twice, with an interval of 4 hours; (6) Ice water bath: Ice water bath at 1-4℃ for 5 minutes, twice a day, with an interval of 4 hours each time; 1-2 of the above stimulation methods were given daily for 5 consecutive weeks, and each stimulation was given 3 times in the whole cycle. Starting from day 1 of modeling, the corresponding dose of medicine solution was administered by gavage at 10 mL / kg to the groups of Example 1, Comparative Example 1 and Comparative Example 2 (7.43, 7.43, 7.43 g of medicinal slices / kg) and the Wuji Baifeng Wan group (1.62 g / kg), once a day. The blank control group and the model control group were administered the same volume of pure water by gavage.

[0149] Dosage Design of Test Substances and Control Substances

[0150] The clinically proposed dosage of the traditional Chinese medicine compositions in Example 1, Comparative Example 1, and Comparative Example 2 is 82.50 g of cut crude drugs per day. Converted to the equivalent dosage for rats according to body surface area: 82.50 g of cut crude drugs per day × 0.018 / 0.2 kg = 7.43 g of cut crude drugs per kg. The equivalent dosage of Wuji Baifeng Pills: 18 g per day × 0.018 / 0.2 kg = 1.62 g per kg. The test was carried out, as shown in Table 10 for details.

[0151] Table 10 Dosage Design Table for Each Group

[0152]

[0153] Note: 1.00 g of extract is equivalent to 3.91 g of cut crude drugs.

[0154] Drug Preparation Method

[0155] Traditional Chinese medicine compositions in Example 1, Comparative Example 1, and Comparative Example 2: 5.7 g of the extract of the traditional Chinese medicine compositions in Example 1, Comparative Example 1, and Comparative Example 2 was added with pure water to make up to 30 mL (0.19 g of extract / mL).

[0156] Group of Wuji Baifeng Pills: 4.8 g of Wuji Baifeng Pills was taken, ground and added with pure water to make up to 30 mL (0.16 g / mL).

[0157] The preparation volume was adjusted according to the change in animal body weight every week.

[0158] Detection Indexes

[0159] (1) Body weight: The body weight of the animals was weighed before administration. After administration, the appearance signs, behavioral activities, secretions, excretions, diet conditions, death conditions, etc. of the animals in each group were closely observed and recorded, and the weight was measured once a week.

[0160] (2) Hemorheology indexes and coagulation indexes: Blood was collected from the abdominal aorta the day after the last administration to measure the hemorheology indexes (whole blood viscosity, plasma viscosity) of rats and activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT).

[0161] Data Statistical Analysis

[0162] SPSS 16.0 software was used for data statistics, and the experimental data were expressed as mean ± standard deviation The results of systemic anatomy and histopathology were assessed using qualitative indicators. Quantitative data underwent normality and homogeneity of variance tests. If normality was satisfied, one-way ANOVA was used for statistical analysis, and LSD+Dunnett-t (homogeneous variance) or Tamhane's T2 (unequal variance) was selected for comparison based on the homogeneity of variance. If normality was not satisfied, the Kruskal-Wallis test was used, followed by the Mann-Whitney test for pairwise comparisons. P<0.05 indicated a statistically significant difference, and P<0.01 indicated a statistically significant difference; biological significance was considered during evaluation.

[0163] 4. Experimental results

[0164] 4.1 Effects on hemorheological parameters (whole blood viscosity, plasma viscosity) in rats

[0165] As shown in Table 11, compared with the blank control group, the whole blood viscosity at low, medium, and high shear rates and plasma viscosity in the model control group were significantly increased (P<0.01). Compared with the model control group, the whole blood viscosity at low, medium, and high shear rates and plasma viscosity in Comparative Example 2 and Example 1 were significantly decreased (P<0.05 or P<0.01). The whole blood viscosity at low, medium, and high shear rates and plasma viscosity in Comparative Example 1 showed a decreasing trend, but no statistical difference was observed. The whole blood viscosity at low, medium, and high shear rates and plasma viscosity in the Wuji Baifeng Wan group were significantly decreased (P<0.01). Compared with Comparative Example 1, the whole blood viscosity at low, medium, and high shear rates and plasma viscosity in Comparative Example 2 and Example 1 were significantly or significantly decreased (P<0.05 or P<0.01). Compared with Comparative Example 2, plasma viscosity in Example 1 was significantly decreased (P<0.05). The whole blood viscosity at low, medium, and high shear rates showed a decreasing trend, but no statistical difference was observed.

[0166] Table 11 Effects on hemorheological parameters in rats ( n=10)

[0167]

[0168]

[0169] Note: Compared with the blank control group, "**" indicates P<0.01; compared with the model control group, "**" indicates P<0.01. Δ " indicates P < 0.05, " ΔΔ " " indicates P < 0.01; compared with Comparative Example 1, "#" indicates P < 0.05, and "##" indicates P < 0.01; compared with Comparative Example 2, "▲" indicates P < 0.05.

[0170] 4.2 Effects on coagulation parameters (APTT, PT, TT) in rats

[0171] As shown in Table 12, compared with the blank control group, the APTT, PT, and TT levels of rats in the model control group were significantly decreased (P<0.01). Compared with the model control group, the APTT, PT, and TT levels of rats in Comparative Example 2 and Example 1 were significantly or substantially increased (P<0.05 or P<0.01); compared with Comparative Example 1, the APTT and PT levels of rats in Comparative Example 2 were increased, but there was no statistical difference, while TT was significantly increased (P<0.05); the APTT, PT, and TT levels of rats in Example 1 were significantly increased (P<0.05); compared with Comparative Example 2, the APTT, PT, and TT levels of rats in Example 1 were all increased, but no statistical difference was observed. Compared with the model control group, the APTT, PT, and TT levels of rats in the Wuji Baifeng Wan group were significantly increased (P<0.05).

[0172] Table 12 Effects on coagulation parameters in rats ( n=10)

[0173]

[0174] Note: Compared with the blank control group, "**" indicates P<0.01; compared with the model control group, "**" indicates P<0.01. Δ " indicates P < 0.05, " ΔΔ "#" indicates P < 0.01, compared with Comparative Example 1; "#" indicates P < 0.05.

[0175] 5. Conclusion and Evaluation

[0176] Under the experimental conditions, compared with the blank control group, the whole blood viscosity and plasma viscosity of the model control group were significantly increased, and the APTT, PT and TT levels were significantly shortened, indicating that the rat model of qi stagnation and blood stasis was successfully established. Example 1 and Comparative Example 1 and Comparative Example 2 (7.43, 7.43 and 7.43 g of medicinal slices / kg) all improved the whole blood viscosity, plasma viscosity and coagulation indicators APTT, PT and TT of the rat model of qi stagnation and blood stasis. Among them, Example 1 and Comparative Example 2 showed significant or obvious improvement (P<0.05 or P<0.01). Example 1 was more effective than Comparative Example 1 and Comparative Example 2. The synergistic effect of the drugs in Example 1 was more obvious than that in Comparative Example 1 and Comparative Example 2.

[0177] The pharmacokinetic data of this invention demonstrate that the traditional Chinese medicine composition of this invention has a significant analgesic effect on dysmenorrhea model mice; it also has a good therapeutic effect on qi stagnation and blood stasis model rats, significantly reducing whole blood viscosity (low shear, medium shear, high shear) and plasma viscosity, as well as activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT), and significantly improving blood rheological parameters and coagulation parameters in qi stagnation and blood stasis model rats.

[0178] Example 5: Clinical analysis data of the traditional Chinese medicine composition from Example 1

[0179] 136 patients with menstrual disorders were selected for observation and randomly divided into Example 1 and a control group, with 68 patients in each group. The control group ranged in age from 20 to 39 years, with a mean age of (30.54±3.15) years and a disease duration of 0.5 to 3.0 years, with a mean duration of (1.25±0.37) years. Example 1 group ranged in age from 21 to 39 years, with a mean age of (30.27±2.97) years and a disease duration of 0.5 to 3.0 years, with a mean duration of (1.27±0.38) years. There were no statistically significant differences in general characteristics between the two groups (P>0.05).

[0180] Diagnostic criteria:

[0181] The patient meets the diagnostic criteria for menstrual irregularities due to liver stagnation and spleen deficiency in Traditional Chinese Medicine Gynecology: infrequent menstruation, obesity, chest tightness, dysmenorrhea, breast tenderness, pale red tongue with a white, greasy coating, and a wiry, weak pulse. A normal menstrual cycle is 21–35 days, menstruation lasts 3–7 days, and the total menstrual flow is 50–80 mL. If the menstrual flow exceeds these ranges, it can be diagnosed as menstrual irregularity.

[0182] Inclusion criteria:

[0183] All patients were clinically diagnosed with menstrual disorders; they had no cyclical uterine bleeding, with varying amounts of bleeding, and their menstrual irregularities lasted for more than 3 menstrual cycles. Ultrasound showed no organic lesions in the uterus, and their ages ranged from 20 to 40 years.

[0184] Exclusion criteria:

[0185] Poor mental state; mental or psychological illness; organic lesions requiring treatment or intervention; history of drug allergies; other gynecological diseases; malignant tumors undergoing radiotherapy or chemotherapy.

[0186] Treatment methods:

[0187] The control group received oral norethindrone tablets (produced by Shanghai Xinyi Tianping Pharmaceutical Co., Ltd., specification 0.625mg / tablet) on the 5th day of the menstrual cycle, 3.75mg / time, twice a day; the traditional Chinese medicine group received the traditional Chinese medicine composition in Example 1, one packet (20g per packet, equivalent to 27.5g of decoction pieces) on the 5th day of the menstrual cycle, three times a day; both groups of patients received continuous treatment for 2 months.

[0188] Efficacy evaluation criteria:

[0189] The efficacy was evaluated according to the relevant efficacy standards for menstrual disorders in the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine". Cure: After treatment, the menstrual cycle, menstrual period, menstrual blood color, and bleeding amount were normal; discomfort symptoms such as abdominal pain and fatigue disappeared; and the TCM symptom score decreased by ≥95%. Significantly Effective: After treatment, the menstrual blood color and bleeding amount were significantly improved; the menstrual cycle returned to the range of (28±7) days; the menstrual period returned to within 7 days; and 70% ≤ TCM symptom score decreased by <95%. Effective: After treatment, the menstrual cycle, menstrual period, menstrual blood color, and bleeding amount were somewhat improved; and 30% ≤ TCM symptom score decreased by <70%. Ineffective: After treatment, the menstrual cycle, menstrual period, menstrual blood color, and bleeding amount did not improve; and the TCM symptom score decreased by <30%. Total effective rate = (Number of cured cases + Number of significantly effective cases + Number of effective cases) / Total number of cases.

[0190] Observation indicators

[0191] Traditional Chinese Medicine Symptom Scores: Before and after treatment, the TCM symptom scores of lower abdominal distension, fatigue, lumbosacral pain, and lethargy were calculated for all patients with menstrual disorders. Each score was assigned 0, 2, 4, and 6 points respectively based on the severity of the symptom: none, mild, moderate, and severe.

[0192] Hormone level testing: On day 3 of the menstrual cycle before and after treatment, 5 mL of fasting venous blood was drawn from all patients with menstrual disorders. After appropriate settling, serum was extracted by high-speed centrifugation. The levels of follicle-stimulating hormone (FSH), estradiol, luteinizing hormone (LH), and progesterone were detected using electrochemiluminescence immunoassay.

[0193] Adverse reaction observation: Record all adverse drug reactions in patients with menstrual disorders, mainly observing adverse reactions such as nausea, gastrointestinal discomfort, headache, dizziness, fatigue, and breast tenderness; perform data statistics and analyze the incidence of adverse drug reactions.

[0194] Post-treatment recurrence observation: After the completion of treatment in both groups, a follow-up visit was conducted for 6 months to summarize the post-treatment recurrence situation.

[0195] Statistical methods: SPSS 16.0 statistical software was used for data processing and analysis in this study. The t-test was used to compare continuous data, and the chi-square test was used to compare categorical data. P < 0.05 was considered statistically significant.

[0196] Table 13 Comparison of disease efficacy among patients in 13 groups

[0197]

[0198] Note: Compared with the control group, "*" indicates P<0.05

[0199] Table 14 Comparison of TCM symptom scores among patients in 14 groups

[0200]

[0201] Note: Compared with the pre-treatment values ​​in this group, "*" indicates P<0.05; compared with the post-treatment values ​​in the control group, "#" indicates P<0.05.

[0202] Table 15 Comparison of Hormone Indicators among Patient Groups

[0203]

[0204] Note: Compared with the pre-treatment values ​​in this group, "*" indicates P<0.05; compared with the post-treatment values ​​in the control group, "#" indicates P<0.05.

[0205] Table 16 Comparison of adverse reactions in 16 groups of patients

[0206]

[0207] Note: Compared with the control group, "*" indicates P<0.05

[0208] Table 17: Prognosis and Recurrence of Patient Groups

[0209]

[0210] Note: Compared with the control group, "*" indicates P<0.05

[0211] Clinical analysis data showed that the total effective rate of Example 1 was significantly higher than that of the control group (P<0.05), and the improvement of TCM symptom scores in the treatment group was better than that in the control group (P<0.05). The results of this study showed that after treatment, estradiol and progesterone levels significantly increased in both groups, while FSH and LH levels significantly decreased, and the improvement of various hormones in the treatment group was better than that in the control group (P<0.05). This suggests that Example 1 can effectively regulate hormone levels and improve hormonal imbalances in patients with menstrual disorders. Comparison of adverse reactions between the two groups showed that the incidence of adverse reactions in Example 1 was significantly lower than that in the control group (P<0.05), indicating that Example 1 has a high safety profile in treating menstrual disorders. Comparison of the recurrence rate after 6 months of treatment between the two groups showed that Example 1 had a significantly lower recurrence rate than the control group (P<0.05), indicating that the TCM composition of Example 1 has a low recurrence rate and stable efficacy.

[0212] Example 6

[0213] A traditional Chinese medicine composition for treating menstrual disorders, the formula and proportions by weight are as follows: 12 parts of stir-fried Bupleurum chinense, 12 parts of dried Leonurus japonicus, 9 parts of Ligusticum chuanxiong, 9 parts of Angelica sinensis, 5 parts of wine-processed Ligustrum lucidum, 5 parts of Rubus idaeus, 5 parts of salt-processed Cuscuta chinensis, 5 parts of stir-fried Citrus aurantium, 5 parts of Cinnamomum cassia, 10 parts of Paeonia lactiflora, 10 parts of Carthamus tinctorius, 5 parts of Spatholobus suberectus, 5 parts of Euonymus alatus, 5 parts of Prunella vulgaris, 5 parts of Lycopus lucidus, and 5 parts of Poria cocos.

[0214] Preparation method: The above sixteen herbs are decocted twice with water. The first decoction is decocted with 10 times the amount of water for 2 hours, and the second decoction is decocted with 8 times the amount of water for 1 hour. The decoctions are combined, filtered, and the filtrate is concentrated to a thick paste with a relative density of 1.20-1.25 (60℃). Take an appropriate amount of honey, add an appropriate amount of water, heat and stir to dissolve, mix with the above thick paste, add 1 part of sorbic acid, and concentrate to a thick paste with a relative density of not less than 1.35 (20℃).

[0215] Experiments have shown that the traditional Chinese medicine composition of Example 6 has no obvious toxic side effects and its efficacy is similar to that of Example 1. The experimental data will not be repeated here.

Claims

1. A traditional Chinese medicine composition for treating menstrual disorders, characterized in that, By weight, it consists of the following components: 8-15 parts of stir-fried Bupleurum chinense, 8-15 parts of dried Leonurus japonicus, 6-10 parts of Ligusticum chuanxiong, 6-10 parts of Angelica sinensis, 2-6 parts of wine-processed Ligustrum lucidum, 2-6 parts of Rubus idaeus, 2-6 parts of salt-processed Cuscuta chinensis, 2-6 parts of stir-fried Citrus aurantium, 2-6 parts of Cinnamomum cassia, 6-10 parts of Paeonia lactiflora, 6-10 parts of Carthamus tinctorius, 2-6 parts of Spatholobus suberectus, 2-6 parts of Euonymus alatus, 2-6 parts of Prunella vulgaris, 2-6 parts of Lycopus lucidus, and 2-6 parts of Poria cocos.

2. The traditional Chinese medicine composition for treating menstrual disorders according to claim 1, characterized in that, By weight, it consists of the following components: 10 parts of stir-fried Bupleurum chinense, 10 parts of dried Leonurus japonicus, 8 parts of Ligusticum chuanxiong, 8 parts of Angelica sinensis, 4 parts of wine-processed Ligustrum lucidum, 4 parts of Rubus idaeus, 4 parts of salt-processed Cuscuta chinensis, 4 parts of stir-fried Citrus aurantium, 4 parts of Cinnamomum cassia, 8 parts of Paeonia lactiflora, 8 parts of Carthamus tinctorius, 4 parts of Spatholobus suberectus, 4 parts of Euonymus alatus, 4 parts of Prunella vulgaris, 4 parts of Lycopus lucidus, and 4 parts of Poria cocos.

3. The traditional Chinese medicine composition for treating menstrual disorders according to claim 1, characterized in that, By weight, it consists of the following components: 12 parts of stir-fried Bupleurum chinense, 12 parts of dried Leonurus japonicus, 9 parts of Ligusticum chuanxiong, 9 parts of Angelica sinensis, 5 parts of wine-processed Ligustrum lucidum, 5 parts of Rubus idaeus, 5 parts of salt-processed Cuscuta chinensis, 5 parts of stir-fried Citrus aurantium, 5 parts of Cinnamomum cassia, 10 parts of Paeonia lactiflora, 10 parts of Carthamus tinctorius, 5 parts of Spatholobus suberectus, 5 parts of Euonymus alatus, 5 parts of Prunella vulgaris, 5 parts of Lycopus lucidus, and 5 parts of Poria cocos.

4. A method for preparing the traditional Chinese medicine composition for treating menstrual disorders according to any one of claims 1-3, characterized in that, The preparation method includes selecting the following ingredients according to the above proportions: stir-fried Bupleurum chinense, dried Leonurus japonicus, Ligusticum chuanxiong, Angelica sinensis, wine-processed Ligustrum lucidum, Rubus idaeus, salt-processed Cuscuta chinensis, stir-fried Citrus aurantium, Cinnamomum cassia, Paeonia lactiflora, Carthamus tinctorius, Spatholobus suberectus, Euonymus alatus, Prunella vulgaris, Lycopus lucidus, and Poria cocos. Add water and decoct 2-4 times, adding 8-10 times the amount of water each time and decoct for 1-2 hours. Combine the decoctions, filter, and concentrate the filtrate to a thick paste with a relative density of 1.20-1.

25.

5. The method for preparing the traditional Chinese medicine composition for treating menstrual disorders according to claim 4, characterized in that: Add honey and water to the paste, heat and stir to dissolve, add 1 part sorbic acid, and concentrate to a finished paste with a relative density greater than or equal to 1.

35.

6. The method for preparing the traditional Chinese medicine composition for treating menstrual disorders according to claim 4, characterized in that, The paste may be further formulated into one of the following formulations: tablets, granules, pills, capsules, and oral liquids, using conventional techniques in the art.

7. The use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicine for treating menstrual disorders.

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