A composition with the effect of regulating menstruation and activating blood and its application in preparing external products

Abstract

This invention provides a composition with menstrual regulating and blood-activating effects and its application in the preparation of external products, relating to the field of biomedical technology. This invention utilizes a composition composed of Chinese herbal raw materials including *Cephalotaxus fortunei* bark, star anise, *Erigeron breviscapus*, *Piper longum*, *Caulis thunbergii*, *Radix Achyranthis Bidentatae*, *Radix Scutellariae*, *Radix Achyranthis Bidentatae*, *Radix Panax notoginseng*, *Radix Bambusae in Taeniam*, and *Radix Achyranthis Bidentatae* to prepare a traditional Chinese medicine acupoint patch for treating or improving primary dysmenorrhea. The herbal acupoint patch can inhibit the expression of inflammatory factors, downregulate the expression level of COX-2, thereby inhibiting PGF2α, increasing the level of PGE2, and reducing uterine tissue inflammation, achieving multi-target treatment of primary dysmenorrhea. The herbal acupoint patch utilizes the power of the medicine through the acupoint, and the acupoint utilizes the properties of the medicine. The meridians are the channels, and the acupoints are the gateways. The medicinal power directly reaches the Chong and Ren meridians and the uterus, so that cold is warmed and dispelled, blood stasis is cleared and eliminated, and qi and blood flow smoothly, thus curing dysmenorrhea. It plays a role in warming the meridians and dispelling cold, promoting qi and blood circulation, removing blood stasis and relieving pain, providing a new direction for the external treatment strategy of traditional Chinese medicine for primary dysmenorrhea.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a composition with menstrual regulating and blood-activating effects and its application in the preparation of topical products. Background Technology

[0002] Primary dysmenorrhea refers to menstrual cramps without any organic lesions in the female reproductive system. It manifests as lower abdominal distension or dull pain before, during, or after menstruation, radiating to the groin, inner thigh, or lumbosacral region. A feeling of heaviness or pressure may also be present. Some women experience accompanying symptoms such as lower back pain, dizziness, headache, nausea, vomiting, fatigue, diarrhea, abdominal distension, palpitations, and in severe cases, paleness, cold extremities, cold sweats, convulsions, or even fainting. It accounts for over 90% of dysmenorrhea cases and significantly impacts women's mood, work, and quality of life. Currently, Western medicine primarily treats primary dysmenorrhea with nonsteroidal anti-inflammatory drugs (NSAIDs) and contraceptives. These drugs mainly work by inhibiting the synthesis and release of prostaglandins, thereby reducing or eliminating menstrual cramps. However, they often come with a high risk of adverse reactions affecting the digestive and central nervous systems, and a significant recurrence rate.

[0003] Primary dysmenorrhea, known as "dysmenorrhea" or "menstrual abdominal pain" in Traditional Chinese Medicine (TCM), is characterized by lower abdominal pain during menstruation, occurring with the menstrual cycle, and is a common clinical condition. Currently, external TCM therapies are widely used in the clinical treatment of dysmenorrhea, with significant efficacy, high acceptance, and safety. Acupoint application of Chinese medicine is one of the traditional external therapies in TCM. Based on the principles of TCM theory and meridian theory, Chinese medicine is applied to acupoints to prevent disease and relieve symptoms through the combined action of the medicine and the acupoints. Acupoint application of Chinese medicine is highly safe, has few side effects, treats both the symptoms and the root cause, is convenient to operate, has good clinical efficacy, and is widely used. It has significant advantages for patients who are insensitive to or tolerant of Western medicine and are prone to adverse reactions such as gastrointestinal discomfort and liver and kidney damage. Based on this background, this invention aims to provide a Chinese herbal composition with menstrual regulating and blood-activating effects and its application in the preparation of Chinese herbal acupoint application products, in order to provide a better solution for patients with primary dysmenorrhea. Summary of the Invention

[0004] (a) Technical problems to be solved

[0005] To address the shortcomings of existing technologies, this invention provides a traditional Chinese medicine composition with the functions of regulating menstruation and promoting blood circulation, promoting qi circulation and relieving pain, and dispelling cold and removing blood stasis, and its application in the preparation of traditional Chinese medicine acupoint patch products for treating or improving primary dysmenorrhea.

[0006] (II) Technical Solution

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] In a first aspect, the present invention provides a composition having the effect of regulating menstruation and promoting blood circulation, the composition being made from the following Chinese herbal medicines in parts by weight: 20-50 parts of *Cephalotaxus fortunei* bark, 20-50 parts of star anise, 20-50 parts of *Erigeron breviscapus*, 20-50 parts of *Piper longum*, 20-50 parts of *Cephalotaxus fortunei*, 20-50 parts of *Gnaphalium affine*, 20-50 parts of *Spatholobus suberectus*, 20-50 parts of *Bletilla striata*, 20-50 parts of *Hypericum perforatum*, 20-50 parts of *Panax notoginseng*, 20-50 parts of bamboo shavings, and 20-50 parts of *Gnaphalium affine*.

[0009] Furthermore, the composition is made from the following Chinese herbal medicines in parts by weight: 25-45 parts of *Acer buergerianum* bark, 25-45 parts of star anise, 25-45 parts of *Erigeron breviscapus*, 25-45 parts of *Piper longum*, 25-45 parts of *Caulis thunbergii*, 25-45 parts of *Radix et Rhizoma Scutellariae ... and 25-45 parts of *Radix et Rhizoma Scutellariae*.

[0010] Furthermore, the composition is made from the following Chinese herbal medicines in parts by weight: 40 parts of ground maple bark, 40 parts of star anise, 35 parts of scutellaria baicalensis, 40 parts of long pepper, 35 parts of vine, 30 parts of clematis, 35 parts of spatholobus suberectus, 30 parts of white ox gall, 30 parts of spatholobus suberectus, 30 parts of red ginseng, 35 parts of bamboo shavings, and 35 parts of ground blood incense.

[0011] Secondly, the present invention provides the application of a composition having the effect of regulating menstruation and promoting blood circulation in the preparation of a topical product for treating or improving primary dysmenorrhea, wherein the topical product is a traditional Chinese medicine acupoint patch product.

[0012] Specifically, the traditional Chinese medicine acupoint patch product for treating or causing primary dysmenorrhea is prepared according to the following steps:

[0013] (1) Take each of the Chinese medicinal materials in the above composition, clean and dry them, and then coarsely grind and ultra-finely grind each medicinal material into fine powder, pass them through a 100-120 mesh sieve, and obtain various medicinal material fine powders for use.

[0014] (2) Weigh each medicinal material powder according to the above composition parts by weight, and mix each medicinal material powder evenly by equal incremental method to ensure that the color of the composition powder is uniform after tempering. Then pass it through a 100-120 mesh sieve to obtain the composition powder.

[0015] (3) Mix the powdered medicine and honey in a weight ratio of 1:1-1.2, then add 1-3% azone, 15-20% propylene glycol and 15-20% glycerin by weight of the powdered medicine and mix evenly to make a thick paste that is soft and hard, malleable but not runny, for later use.

[0016] (4) The thick paste prepared in step (3) is made into a round medicated cake with a thickness of 1-5cm and 0.2-0.3cm. The medicated cake is placed in the center of medical tape or medical non-woven fabric, covered with release paper, and sealed in packaging to obtain the Chinese medicine acupoint patch product.

[0017] Specifically, the traditional Chinese medicine acupoint patch product for treating or causing primary dysmenorrhea can also be prepared according to the following steps:

[0018] (1) Weigh each Chinese medicinal material according to the above weight proportions, clean and dry them, coarsely crush each medicinal material, mix them evenly, extract them 2-3 times by alcohol extraction, collect the alcohol extract, concentrate it under reduced pressure to a thick extract with a relative density of 1.2-1.3, and set it aside for later use;

[0019] (2) Take 2-3 times the weight of glycerol and 0.3-0.6 times the weight of sodium acrylate of the Chinese herbal extract and mix them thoroughly. Add tartaric acid solution of 0.02-0.04 times the weight of the Chinese herbal extract dissolved in purified water and stir well. Then add aluminum hydroxide solution of 0.04-0.06 times the weight of the Chinese herbal extract dissolved in purified water and stir for more than 15 minutes. Then add polyvinylpyrrolidone of 0.5-0.7 times the weight of the Chinese herbal extract dissolved in purified water and stir for more than 10 minutes. Then add azone of 0.1-0.2 times the weight of the Chinese herbal extract and propylene glycol of 1.5-2 times the weight of the Chinese herbal extract and stir thoroughly to form a homogeneous colloidal matrix without particles.

[0020] (3) The matrix prepared in step (2) is evenly coated on medical nonwoven fabric with a coating thickness of 0.8-1.0 mm, covered with release paper to protect the adhesive layer, and left to stand at room temperature for more than 24 hours until fully cured. Then it is cut into round or square patches. The cut patches are placed at 45°C or below to dry for 2-4 hours, with the moisture content controlled at 15-20%. The patches are then sealed and packaged to obtain the Chinese medicine acupoint patch product.

[0021] The herbal acupoint patch of this invention is applied to acupoints such as Zhongji, Guanyuan, Shenque, Qihai, Xuehai, Sanyinjiao, and Zigong, and is used once a day for 3 days before menstruation and during menstruation, for at least 2 hours each time.

[0022] The herbal acupoint patch of this invention is prepared using pure Chinese herbal medicines as raw materials. The source, properties, meridian tropism, efficacy, and indications of the Chinese herbal medicine raw materials are described below:

[0023] Illicium difengpi (KIBet KIM): The dried bark of Illicium difengpi, a plant of the Magnoliaceae family; slightly pungent, astringent, and warm; slightly toxic; enters the bladder and kidney meridians; has the functions of dispelling wind and dampness, promoting qi circulation and relieving pain; used for rheumatic pain, lumbago due to overwork, lumbar muscle strain, centipede bites, etc.

[0024] Star anise: The dried, mature fruit of Illicium verum Hook.f., a plant of the Magnoliaceae family; pungent and warm; enters the liver, kidney, spleen, and stomach meridians; has the functions of warming yang and dispelling cold, regulating qi and relieving pain; used for symptoms such as abdominal pain due to cold hernia, lower back pain due to kidney deficiency, vomiting due to stomach cold, and cold pain in the epigastrium and abdomen.

[0025] Erigeron breviscapus (Vant.) Hand.-Mazz., a plant of the Asteraceae family, is a dried whole herb. It is pungent, slightly bitter, and warm in nature. It enters the heart and liver meridians. It has the functions of promoting blood circulation, relieving pain, dispelling wind and cold, and is used for stroke hemiplegia, chest pain, rheumatic pain, headache, toothache, and other symptoms.

[0026] Piper longum: The dried, nearly mature or mature fruit spike of Piper longum L., a plant in the Piperaceae family. It is pungent and hot in nature; it enters the stomach and large intestine meridians; it has the functions of warming the middle jiao and dispelling cold, lowering qi and relieving pain; it is used for cold pain in the epigastrium and abdomen, vomiting, diarrhea, cold stagnation of qi, chest pain, headache, and toothache.

[0027] Guangxiangteng: The root of Fissistigma oldhamii (Hemsl.) Merr., a plant in the Annonaceae family. It is pungent and neutral in nature; it enters the liver and stomach meridians; it has the functions of dispelling wind and dampness, promoting blood circulation and relieving pain, and is used for rheumatic pain, lower back pain, stomach pain, and traumatic injuries.

[0028] Silene aprica Turcz. [Melandrium apricum (Turcz.) Rohrb.], a plant in the Caryophyllaceae family. It is pungent, bitter, and neutral in nature. It enters the liver and spleen meridians; it has the functions of promoting blood circulation and regulating menstruation, promoting lactation, strengthening the spleen, eliminating dampness, and detoxifying; it is used for irregular menstruation, insufficient lactation, infantile malnutrition, spleen deficiency edema, and boils and carbuncles.

[0029] Small Blood Vine: The stems or roots of *Schisandra propinqua* (Wall.) Baill. var. *sinensis* Oliv., a plant in the Magnoliaceae family. It has the effects of dispelling wind and promoting blood circulation, detoxifying and reducing swelling, and stopping bleeding. It is mainly used to treat rheumatism and numbness, muscle and bone pain, traumatic injuries, irregular menstruation, stomach pain, abdominal distension, carbuncles and boils, and hemoptysis due to overexertion.

[0030] White Ox Gallbladder: The whole herb of Inula cappa (Buch.-Ham.) DC., a plant of the genus Inula in the family Asteraceae; pungent, slightly bitter, and warm; enters the liver, lung, spleen, and stomach meridians; has the effects of dispelling cold and relieving exterior syndromes, dispelling wind and reducing swelling, promoting qi circulation and relieving pain; used for colds due to wind-cold, cough, rheumatic joint pain, nervous headache, stomachache, chest tightness, irregular menstruation, and abnormal leukorrhea.

[0031] Cynanchum amplexicaule (Sieb. et Zucc.) Hemsl., a plant of the Asclepiadaceae family; bitter, pungent, and neutral in nature; enters the lung and spleen meridians; has the functions of clearing heat and detoxifying, dispelling wind and dampness, promoting blood circulation and reducing swelling; used for rheumatic pain, migraine, back pain, acute gastroenteritis, acute hepatitis, irregular menstruation, mastitis, hematochezia, carbuncles, and eczema.

[0032] Red Sanqi: The rhizome of *Polygonum suffultum* Maxim., a plant in the Polygonaceae family. Its functions and indications include: dispersing blood stasis, stopping bleeding, promoting qi circulation, and regulating menstruation. It is used to treat injuries from falls and blows, hematemesis due to overexertion, hematochezia, metrorrhagia, and irregular menstruation.

[0033] Bamboo yellow: the stroma of the fungus Shiraia bambusicola P. Henn.; warm, bland; enters the lung and liver meridians; has the functions of resolving phlegm and relieving cough, dispelling wind and dampness, promoting blood circulation and relieving pain; used for cough with excessive phlegm, whooping cough, infantile convulsions, rheumatic pain, numbness of the limbs, excessive leukorrhea, stomach pain, toothache, and traumatic injuries.

[0034] *Kadsura heteroclita* (Roxb.) Craib, a plant in the Schisandraceae family, is a medicinal herb. It has a pungent and bitter taste, and is warm in nature. It enters the spleen, stomach, and liver meridians. It has the effects of dispelling wind and dampness, promoting qi circulation and relieving pain, and relaxing muscles and tendons. It is commonly used for rheumatic pain, stomachache, abdominal pain, dysmenorrhea, postpartum abdominal pain, traumatic injuries, and chronic lower back and leg pain.

[0035] (III) Beneficial Effects

[0036] This invention fully considers the mutual influence, interaction, and complementarity between "acupoint properties" and "medicinal properties." Starting from the pathogenesis of primary dysmenorrhea caused by cold stagnation, qi stagnation, and blood stasis, it utilizes the transdermal penetration characteristics of acupoint patches to allow the medicine to reach the uterus directly through specific acupoints and meridians. This demonstrates the precise correspondence between "medicine-acupoint-meridian-disease" and realizes the advantages of traditional Chinese medicine acupoint patch therapy for the targeted treatment of primary dysmenorrhea.

[0037] This invention relates to a traditional Chinese medicine acupoint patch prepared from the following raw materials: *Cephalotaxus fortunei* bark, star anise, *Erigeron breviscapus*, *Piper longum*, *Caulis thunbergii*, *Radix Achyranthis Bidentatae*, *Caulis Spatholobi*, *Radix Achyranthis Bidentatae*, *Radix Achyranthis Bidentatae*, *Radix Achyranthis Bidentatae*, *Radix Achyranthis Bidentatae*, and *Radix Achyranthis Bidentatae*. *Piper longum* is warm and potent, with a strong dispersing and penetrating effect. It effectively warms the middle burner, dispels cold, lowers qi, and relieves pain. When applied to acupoints, it can quickly warm and unblock the cold stagnation in the Ren and Chong meridians of the abdomen. *Cephalotaxus fortunei* bark is effective in dispelling wind and dampness, promoting qi circulation, and relieving pain. It can also guide other herbs downwards to the kidneys and bladder. The kidneys govern reproduction, and the uterus is connected to the kidneys. *Cephalotaxus fortunei* bark guides the herbs to the kidneys, directly directing the medicinal power down to the lower burner. The two herbs work synergistically; their pungent and warm properties descend along the Ren meridian, warming and melting the cold blood, and dispersing the stagnation in the Chong and Ren meridians. This is considered the principal herb.

[0038] Guangxiangteng is effective in dispelling wind and dampness, promoting blood circulation and relieving pain. Its nature is mild, and it is good at entering the blood aspect of the liver meridian, promoting qi and activating blood circulation without being dry. Xiaoxueteng is good at regulating qi and activating blood circulation, dispelling wind and removing dampness. Matched with Guangxiangteng, it promotes qi to assist blood circulation. Dixuexiang can pass through the twelve meridians, is good at entering the thoroughfare and conception vessels in the lower jiao, and helps the monarch drug disperse the cold in the uterine cavity and dredge the stagnation of the blood sea. Dengzhan Xixin is specialized in promoting blood circulation to dredge collaterals, dispelling wind and cold, and is good at entering the blood aspect, being an important drug for treating stasis pain syndromes. The four together serve as ministerial drugs, penetrating the skin and entering the collaterals through acupoints, ascending and descending along the Stomach Meridian of Foot-Yangming and the Spleen Meridian of Foot-Taiyin, enabling the qi and blood to flow smoothly without obstruction, the uterine cavity to be dredged, and the pain to stop automatically. When the ministerial drugs are matched with the monarch drug, the monarch drug warms and disperses, and the ministerial drugs activate and dredge. The cold is dispersed and the stasis is eliminated, complementing each other and synergistically enhancing the effect.

[0039] Silene aprica promotes blood circulation to regulate menstruation, invigorates the spleen and removes dampness. Its nature is mild, it can promote blood circulation without consuming blood, and regulate menstruation without being overly dry and fierce, assisting in preventing the excessive heat of the monarch and ministerial drugs. Inula cappa dispels cold and relieves the exterior, regulates qi and relieves pain. Its nature is warm but not intense, it not only helps the monarch and ministerial drugs dispel cold, but also regulates qi and soothes the middle, preventing the medicinal power from stagnating in the middle jiao. Cynanchum amplexicaule has a relatively cool nature, can clear and relieve depression-heat, prevent the whole formula from being overly hot and dry, and can also reduce swelling and relieve pain, relieving the distending pain and stasis pain in the lower abdomen during dysmenorrhea. Hongsanqi is cool and astringent. Its function of promoting qi and activating blood circulation is used to treat stasis, and its hemostatic power can prevent excessive blood circulation resulting in excessive menstrual flow. Dysmenorrhea is often accompanied by qi stagnation and the production of phlegm-dampness. Bambusa tuldoides can resolve phlegm and relieve cough, dispel wind and remove dampness, promote blood circulation and relieve pain. Its nature is warm but not hot, assisting in promoting blood circulation and resolving phlegm to dredge the collaterals. Illicium verum has the functions of aromaticity and running through, guiding the meridian and reporting the envoy. It is good at entering the spleen, stomach, liver and kidney meridians, can lead the medicinal power of the whole formula to enter the uterine cavity along the meridians, and it also has the effects of warming yang and dispelling cold, regulating qi and relieving pain, assisting the monarch and ministerial drugs. The five together serve as assistant and guiding drugs, distributing the power of regulating menstruation, clearing heat, stopping bleeding and resolving phlegm along the meridians. Matched with the monarch and ministerial drugs, they jointly achieve the effects of warming the meridian and dispelling cold, promoting qi and activating blood circulation, removing stasis and relieving pain. The traditional Chinese medicine acupoint application of the present invention uses the power of the drug through the acupoints, and the nature of the drug through the acupoints. The meridians are used as the channels, and the acupoints are used as the portals. The medicinal power directly reaches the thoroughfare and conception vessels and the uterine cavity, enabling the cold to be warmed and dispersed, the stasis to be dredged and eliminated, and the qi and blood to flow smoothly, and the dysmenorrhea to heal itself.

[0040] Based on the theory of traditional Chinese medicine, the pharmaceutical efficacy experiments have also verified that the components of the traditional Chinese medicine acupoint application of the present invention complement each other and synergistically enhance the effect, and jointly achieve the therapeutic effect on primary dysmenorrhea with a specific compatibility relationship. Changing some of the medicinal flavors or deleting some of the medicinal flavors cannot achieve the above technical effects. The traditional Chinese medicine acupoint application of the present invention can inhibit the expression of inflammatory factors, down-regulate the expression level of COX-2, thereby inhibiting PGF2α and increasing the level of PGE2, reducing the inflammation of uterine tissue, and achieving multi-target treatment of primary dysmenorrhea. It has significant advantages compared with other drugs in relieving the symptoms of dysmenorrhea. The traditional Chinese medicine acupoint application of the present invention provides a new direction for the external treatment strategy of traditional Chinese medicine for primary dysmenorrhea. Brief Description of the Drawings

[0041] Figure 1 Results of the writhing latency (A), number of writhing (B) and writhing behavior score (C) of rats in each group; compared with the blank group, * P<0.05,** P<0.01; compared with the model group, # P<0.05, ## P<0.01; compared with the experimental group, & P<0.05, && P<0.01.

[0042] Figure 2 The levels of inflammatory factors TNF-α (A), IL-2 (B), and IL-1β (C) in the serum of rats in each group were measured; compared with the control group, * P<0.05, ** P<0.01; compared with the model group, # P<0.05, ## P<0.01; compared with the experimental group, & P<0.05, && P<0.01.

[0043] Figure 3 The levels of COX-2 (A), PGF2α (B), and PGE2 (C) in the serum of rats in each group were compared with those in the control group. * P<0.05, ** P<0.01; compared with the model group, # P<0.05, ## P<0.01; compared with the experimental group, & P<0.05, && P<0.01. Detailed Implementation

[0044] 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 in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0045] Example 1

[0046] A traditional Chinese medicine acupoint patch for treating or improving primary dysmenorrhea is prepared according to the following steps:

[0047] (1) Take the raw materials of Chinese medicinal materials such as ground maple bark, star anise, scutellaria baicalensis, long pepper, sedum, scutellaria barbata, scutellaria barbata, scutellaria barbata, scutellaria barbata, scutellaria barbata, red ginseng, bamboo yellow, and ground blood fragrance. After cleaning and drying, each medicinal material is coarsely crushed and ultra-finely crushed into fine powder. The powder is then passed through a 100-120 mesh sieve to obtain various fine powders for later use.

[0048] (2) Weigh out the fine powder of each medicinal material according to the following weight parts: 40 parts of ground maple bark, 40 parts of star anise, 35 parts of scutellaria baicalensis, 40 parts of long pepper, 35 parts of vine vine, 30 parts of vine vine, 35 parts of vine vine, 30 parts of white ox gall, 30 parts of scutellaria barbata, 30 parts of red ginseng, 35 parts of bamboo yellow, and 35 parts of ground blood incense. Mix the fine powder of each medicinal material evenly using the equal amount increasing method to ensure that the color of the combined medicinal powder is uniform after mixing. Then pass it through a 100-mesh sieve to obtain the combined medicinal powder.

[0049] (3) Mix the powdered medicine and honey in a 1:1 weight ratio, then add 2% azone, 15% propylene glycol and 20% glycerin by weight of the powdered medicine and mix well to make a thick paste that is soft and hard, malleable but not runny, for later use.

[0050] (4) The thick paste prepared in step (3) is made into a round medicated cake with a thickness of 1-5cm and 0.2cm. The medicated cake is placed in the center of medical tape or medical non-woven fabric, covered with release paper, and sealed in packaging to obtain the Chinese medicine acupoint patch product.

[0051] Example 2

[0052] A traditional Chinese medicine acupoint patch for treating or improving primary dysmenorrhea is prepared according to the following steps:

[0053] (1) Weigh out the following parts by weight: 40 parts of ground maple bark, 40 parts of star anise, 35 parts of scutellaria baicalensis, 40 parts of long pepper, 35 parts of vine vine, 30 parts of scutellaria barbata, 35 parts of spatholobus suberectus, 30 parts of white ox gall, 30 parts of spatholobus suberectus, 30 parts of red ginseng, 35 parts of bamboo yellow, and 35 parts of ground blood incense. After cleaning and drying, coarsely crush each medicinal material, mix them evenly, extract them three times by alcohol extraction, collect the alcohol extract, and concentrate it under reduced pressure to a thick extract with a relative density of 1.25 for later use.

[0054] (2) Take glycerol and sodium acrylate, which are 2 times the weight of the Chinese herbal extract, and mix them thoroughly. Add tartaric acid solution, which is 0.02 times the weight of the Chinese herbal extract, dissolved in purified water. Stir well. Then add aluminum hydroxide, which is 0.04 times the weight of the Chinese herbal extract, dissolved in purified water. Stir for more than 15 minutes. Then add polyvinylpyrrolidone, which is 0.5 times the weight of the Chinese herbal extract, dissolved in purified water. Stir for more than 10 minutes. Then add azone, which is 0.1 times the weight of the Chinese herbal extract, and propylene glycol, which are 1.5 times the weight of the Chinese herbal extract. Stir well to form a homogeneous colloidal matrix without particles.

[0055] (3) The matrix prepared in step (2) is evenly coated on medical nonwoven fabric with a coating thickness of 0.8-1.0 mm, covered with release paper to protect the adhesive layer, and left to stand at room temperature for more than 24 hours until fully cured. Then it is cut into round or square patches. The cut patches are placed at 45°C or below to dry for 2-4 hours, with the moisture content controlled at 15%. The patches are then sealed and packaged to obtain the Chinese medicine acupoint patch product.

[0056] Example 3

[0057] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 20 parts of ground maple bark, 20 parts of star anise, 20 parts of scutellaria baicalensis, 20 parts of long pepper, 20 parts of vine, 20 parts of spatholobus suberectus, 20 parts of small spatholobus suberectus, 20 parts of white ox gall, 20 parts of purslane, 20 parts of red ginseng, 20 parts of bamboo shavings, and 20 parts of ground spatholobus.

[0058] Example 4

[0059] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 50 parts of ground maple bark, 50 parts of star anise, 50 parts of scutellaria baicalensis, 50 parts of long pepper, 50 parts of vine, 50 parts of sedge, 50 parts of small spatholobus suberectus, 50 parts of white ox gall, 50 parts of purslane, 50 parts of red ginseng, 50 parts of bamboo shavings, and 50 parts of ground spatholobus.

[0060] Example 5

[0061] The difference between this embodiment and Embodiment 2 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 20 parts of ground maple bark, 20 parts of star anise, 20 parts of scutellaria baicalensis, 20 parts of long pepper, 20 parts of vine, 20 parts of purslane, 20 parts of small spatholobus suberectus, 20 parts of white ox gall, 20 parts of purslane, 20 parts of red ginseng, 20 parts of bamboo shavings, and 20 parts of ground spatholobus.

[0062] Example 6

[0063] The difference between this embodiment and Embodiment 2 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 20 parts of ground maple bark, 20 parts of star anise, 20 parts of scutellaria baicalensis, 20 parts of long pepper, 20 parts of vine, 20 parts of purslane, 20 parts of small spatholobus suberectus, 20 parts of white ox gall, 20 parts of purslane, 20 parts of red ginseng, 20 parts of bamboo shavings, and 20 parts of ground spatholobus.

[0064] Example 7

[0065] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint patch are as follows: 25 parts of ground maple bark, 25 parts of star anise, 25 parts of scutellaria baicalensis, 25 parts of long pepper, 25 parts of vine, 25 parts of spatholobus suberectus, 25 parts of small spatholobus suberectus, 25 parts of white ox gall, 25 parts of purslane, 25 parts of red ginseng, 25 parts of bamboo shavings, and 25 parts of ground spatholobus.

[0066] Example 8

[0067] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 45 parts of ground maple bark, 45 parts of star anise, 45 parts of scutellaria baicalensis, 45 parts of long pepper, 45 parts of vine, 45 parts of spatholobus suberectus, 45 parts of small spatholobus suberectus, 45 parts of white ox gall, 45 parts of purslane, 45 parts of red ginseng, 45 parts of bamboo shavings, and 45 parts of ground spatholobus.

[0068] Example 9

[0069] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 30 parts of ground maple bark, 35 parts of star anise, 30 parts of scutellaria baicalensis, 35 parts of long pepper, 30 parts of vine, 25 parts of spatholobus suberectus, 30 parts of ox gall, 25 parts of purslane, 30 parts of purslane, 25 parts of purslane, 30 parts of red ginseng, 30 parts of bamboo shavings, and 30 parts of ground maple.

[0070] Example 10

[0071] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 35 parts of ground maple bark, 40 parts of star anise, 28 parts of scutellaria baicalensis, 38 parts of long pepper, 32 parts of vine vine, 30 parts of spatholobus suberectus, 30 parts of spatholobus suberectus, 30 parts of ox gall, 35 parts of purslane, 30 parts of red notoginseng, 32 parts of bamboo shavings, and 32 parts of ground maple.

[0072] Example 11

[0073] The difference between this embodiment and Embodiment 2 is that the weight parts of each Chinese herbal medicine in the herbal acupoint patch are as follows: 25 parts of ground maple bark, 25 parts of star anise, 25 parts of scutellaria baicalensis, 25 parts of long pepper, 25 parts of vine, 25 parts of spatholobus suberectus, 25 parts of spatholobus suberectus, 25 parts of white ox gall, 25 parts of purslane, 25 parts of red ginseng, 25 parts of bamboo shavings, and 25 parts of ground spatholobus.

[0074] Example 12

[0075] The difference between this embodiment and Embodiment 2 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 45 parts of ground maple bark, 45 parts of star anise, 45 parts of scutellaria baicalensis, 45 parts of long pepper, 45 parts of vine, 45 parts of spatholobus suberectus, 45 parts of small spatholobus suberectus, 45 parts of white ox gall, 45 parts of purslane, 45 parts of red ginseng, 45 parts of bamboo shavings, and 45 parts of ground spatholobus.

[0076] Example 13

[0077] The difference between this embodiment and Embodiment 2 is that the weight parts of each Chinese herbal medicine in the herbal acupoint patch are as follows: 30 parts of ground maple bark, 35 parts of star anise, 30 parts of scutellaria baicalensis, 35 parts of long pepper, 30 parts of vine, 25 parts of spatholobus suberectus, 30 parts of ox gall, 25 parts of purslane, 30 parts of purslane, 25 parts of purslane, 30 parts of red ginseng, 30 parts of bamboo shavings, and 30 parts of ground maple.

[0078] Example 14

[0079] The difference between this embodiment and Embodiment 2 is that the weight parts of each Chinese herbal medicine in the herbal acupoint application are as follows: 35 parts of ground maple bark, 40 parts of star anise, 28 parts of scutellaria baicalensis, 38 parts of long pepper, 32 parts of vine vine, 30 parts of spatholobus suberectus, 30 parts of spatholobus suberectus, 30 parts of ox gall, 35 parts of purslane, 30 parts of red notoginseng, 32 parts of bamboo shavings, and 32 parts of ground maple.

[0080] Comparative Example 1

[0081] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint patch are as follows: 40 parts of Qianghuo, 40 parts of dried ginger, 35 parts of Dengzhanxixin, 40 parts of Wuzhuyu, 35 parts of Guangxiangteng, 30 parts of Nuloucai, 35 parts of Xiaoxueteng, 30 parts of Bainiudan, 30 parts of Hezhangxiao, 30 parts of Hongsanqi, 35 parts of Zhuhuang, and 35 parts of Dixuexiang.

[0082] Comparative Example 2

[0083] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint patch are as follows: 40 parts of ground maple bark, 40 parts of star anise, 35 parts of salvia miltiorrhiza, 40 parts of long pepper, 5 parts of clematis chinensis, 30 parts of purslane, 35 parts of sea bream, 30 parts of white ox gall, 30 parts of claspings, 30 parts of red notoginseng, 35 parts of bamboo shavings, and 35 parts of ground sap.

[0084] Comparative Example 3

[0085] The difference between this embodiment and Embodiment 1 is that the weight parts of each Chinese herbal medicine in the herbal acupoint patch are as follows: 40 parts of ground maple bark, 40 parts of star anise, 35 parts of scutellaria baicalensis, 40 parts of long pepper, 35 parts of vine, 35 parts of spatholobus suberectus, 30 parts of spatholobus suberectus, and 30 parts of red ginseng.

[0086] Test case

[0087] Evaluation of the effects of traditional Chinese medicine acupoint application in a rat model of primary dysmenorrhea.

[0088] 1. Materials and Methods

[0089] 1.1 Materials

[0090] 1.1.1 Animals

[0091] SPF-grade female SD rats aged 6-8 weeks with a body weight of (200±10) g were selected. They were fed for one week before the experiment at a temperature of 18-26 ℃ and a humidity of 40%-65%. The lighting was artificially controlled (12h / 12h light and dark alternation). During this period, the rats were allowed free access to food and water. Rats that showed no abnormal behavior were included in the experiment.

[0092] 1.1.2 Experimental Drugs

[0093] The traditional Chinese medicine acupoint patches prepared in Examples 1, 1, 2, and 3. Ibuprofen capsules (0.3g / capsule).

[0094] 1.2 Methods

[0095] 1.2.1 Modeling and Grouping

[0096] After one week of acclimatization, 56 rats with regular estrous cycles were selected by vaginal smears and randomly divided into four groups (NC, Model, Positive Control Group, ibuprofen, Experimental Group, and Control Groups 1-3, with 8 rats in each group) using a random number table. Except for the NC group, all other groups received subcutaneous injections of estradiol benzoate (2.5 mg / kg on days 1 and 14, and 1.0 mg / kg on days 2-13). One hour after the last estradiol injection, oxytocin 2 U / rat was injected intraperitoneally. The rats' writhing response was observed and recorded within 30 minutes. A successful PD model was defined as the rat exhibiting typical writhing responses such as unilateral limb internal rotation. The NC group received an equal volume of saline simultaneously.

[0097] 1.2.2 Drug administration

[0098] Intervention began on day 8 of model establishment. The experimental group (using traditional Chinese medicine acupoint application as described in Example 1) and control groups 1-3 (corresponding to Comparative Examples 1, 2, and 3, respectively, using traditional Chinese medicine acupoint application) were located according to the "Shenque, Qihai, and Guanyuan" acupoints as described in *Experimental Acupuncture*. Hair was removed and routine disinfection was performed at the application sites. Starting on day 8 of model establishment, each group received traditional Chinese medicine acupoint application for 4 hours per day for 7 consecutive days. Blank medical adhesive tape was simultaneously applied to the same sites in the blank control group and the model group. The positive control group received ibuprofen capsule solution via gavage at a dose of 0.06 g / kg starting on day 8 of model establishment for 7 consecutive days.

[0099] 1.2.3 Detection Indicators and Methods

[0100] 1.2.3.1 Detection of rat writhing latency, number of writhing episodes, and scoring.

[0101] Timing began on day 14 of modeling with oxytocin injection. The time from oxytocin injection to the appearance of a writhing response (latency period) was recorded for each group of rats. If no writhing response appeared within 30 minutes, the latency period was recorded as 30 minutes. The number of writhing movements within 30 minutes was also recorded. Writhing behavior was scored according to behavioral scoring criteria: 0 points, normal posture, forepaws flat or normal exploring behavior; 1 point, trunk tilted to one side, abdomen concave due to contraction; 2 points, hind limbs extended, hind paws dorsiflexed, trunk extended with pelvic rotation; 3 points, abdominal muscle contraction, hind limbs extended.

[0102] 1.2.3.2 ELISA detection of inflammatory factors and levels of COX-2, PGF2α, and PGE2

[0103] After the above observations were completed, blood was collected from anesthetized rats via the abdominal aorta. The blood was allowed to stand at room temperature for 2 hours, then centrifuged at 3000 r / min for 15 minutes at 4 ℃. The supernatant serum was collected, and the levels of IL-1β, IL-2, TNF-α, COX-2, PGF2α, and PGE2 were detected using ELISA.

[0104] 1.2.4 Statistical Methods

[0105] Statistical analysis was performed on the data using GraphPad Prism 8.0 software. Quantitative data are expressed as mean ± standard deviation. This indicates that a one-way ANOVA test was used for comparisons among multiple groups.

[0106] 2 Results

[0107] 2.1 Effects of the herbal acupoint application of the present invention on the latency, number of writhing movements, and scores of PD model rats

[0108] Compared with the control group, the writhing latency of rats in the model group was significantly reduced (P<0.01), while the number of writhing movements and the writhing behavior score were significantly increased (P<0.01), indicating that the PD model rat was successfully established. Compared with the model group, the writhing latency of rats in each drug-treated group was significantly increased (P<0.01), while the number of writhing movements and the writhing behavior score were significantly reduced (P<0.01). Among them, the writhing latency of rats in the positive control group and control groups 1-3 was significantly lower than that in the experimental group (P<0.01), while the number of writhing movements was significantly higher than that in the experimental group (P<0.01); the writhing behavior score of rats in control groups 1 and 3 was significantly higher than that in the experimental group (P<0.05, P<0.01). The results are as follows. Figure 1 As shown.

[0109] 2.2 Effects of the herbal acupoint application of this invention on inflammatory factors in the serum of PD model rats

[0110] Compared with the blank group, the serum levels of inflammatory factors TNF-α, IL-2, and IL-1β in the model group rats were significantly increased (P<0.01). Compared with the model group, the serum levels of inflammatory factors TNF-α, IL-2, and IL-1β in all treatment groups rats were significantly decreased (P<0.01); among them, the serum levels of inflammatory factors TNF-α, IL-2, and IL-1β in the experimental group rats were significantly lower than those in the positive control group and control groups 1-3 (P<0.05, P<0.01). Results are as follows. Figure 2 As shown.

[0111] 2.3 Effects of the herbal acupoint application of the present invention on the serum levels of COX-2, PGF2α, and PGE2 in PD model rats

[0112] Compared with the control group, the serum levels of COX-2 and PGF2α in the model group rats were significantly increased (P<0.01), while the PGE2 level was significantly decreased (P<0.01). Compared with the model group, the serum levels of COX-2 and PGF2α in all treatment groups rats were significantly decreased (P<0.01), while the PGE2 level was significantly increased (P<0.01). Among them, the serum levels of COX-2 and PGF2α in the experimental group rats were significantly lower than those in the positive control group and control groups 1-3 (P<0.05, P<0.01), while the PGE2 level was significantly higher than that in the positive control group and control groups 1-3 (P<0.01). The results are as follows. Figure 3 As shown.

[0113] 3. Conclusion

[0114] This invention successfully established a dysmenorrhea model in rats using estradiol benzoate combined with oxytocin to induce dysmenorrhea. The rats in the model group exhibited significant symptoms of increased writhing response and shortened writhing latency, indicating successful model establishment. After administration of the herbal acupoint patch of this invention, the writhing latency of the PD model rats significantly increased, and the number of writhing movements significantly decreased, significantly improving the dysmenorrhea symptoms in the PD model rats. Moreover, its improvement effect was significantly superior to that of ibuprofen or other herbal acupoint patches composed of specific drugs (Comparative Examples 1-3).

[0115] Furthermore, we explored the mechanism of action of the herbal acupoint application of this invention. According to relevant research reports, inflammatory response is an important factor in the occurrence of dysplasia radiata (PD). TNF-α, IL-2, and IL-1β, as common pro-inflammatory factors, play a role in this process. After the release of pro-inflammatory factors, they can induce the production of COX-2. When PD occurs, COX-2 will show pathologically high expression. As a key catalytic enzyme, COX-2 can convert arachidonic acid into prostaglandins (PGs), further affecting the levels of PGF2α and PGE2. PGF2α and PGE2 have different effects. PGE2 can decrease the tension of uterine smooth muscle, while PGF2α can increase the amplitude of uterine smooth muscle contraction. When PD occurs, the release of PGF2α increases and the release of PGE2 decreases, thereby causing abnormal contraction of uterine smooth muscle and blood vessels, leading to uterine ischemia and pain. In the above experiments, compared with the blank group, the serum levels of inflammatory factors, COX-2, and PGF2α in the model group rats were significantly increased, while PGE2 was significantly decreased. After administration of the herbal acupoint patch of the present invention, the levels of inflammatory factors, COX-2, and PGF2α in the serum of the model rats were significantly reduced, and the PGE2 level was significantly increased. Moreover, the regulatory effect of the herbal acupoint patch of the present invention on the above indicators was significantly better than that of the herbal acupoint patch composed of ibuprofen or other specific drugs (comparative examples 1-3).

[0116] In summary, this invention fully considers the mutual influence, interaction, and complementarity between the properties of acupoints and medicinal herbs. Starting from the pathogenesis of primary dysmenorrhea due to cold stagnation and blood stasis, it scientifically and rationally formulates a traditional Chinese medicine composition consisting of *Gnaphalium affine* bark, star anise, *Erigeron breviscapus*, *Piper longum*, *Caulis thunbergii*, *Radix Achyranthis Bidentatae*, *Radix Scutellariae*, *Radix Cynodon dactylis*, *Radix Achyranthis Bidentatae*, *Radix Panax notoginseng*, *Radix Bambusae in Taeniam*, and *Radix Achyranthis Bidentatae*. This composition is used as the raw material to prepare the acupoint patch of this invention. The components in the above-mentioned traditional Chinese medicine composition complement each other, synergistically enhancing their effects. Through a specific compatibility relationship, they jointly achieve the therapeutic effect on primary dysmenorrhea. Changing or deleting some of the medicinal ingredients would not achieve the above-mentioned technical effect. The herbal acupoint patch of this invention can inhibit the expression of inflammatory factors, downregulate the expression level of COX-2, thereby inhibiting PGF2α, increasing the level of PGE2, and reducing uterine tissue inflammation, thus achieving multi-target treatment of primary dysmenorrhea. Compared with other drugs, it has significant advantages in relieving dysmenorrhea symptoms. The herbal acupoint patch of this invention provides a new direction for the external treatment strategy of traditional Chinese medicine for primary dysmenorrhea.

[0117] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A composition having the effect of regulating menstruation and promoting blood circulation, characterized in that, The composition is made from the following Chinese herbal medicines in parts by weight: 20-50 parts of ground maple bark, 20-50 parts of star anise, 20-50 parts of scutellaria baicalensis, 20-50 parts of long pepper, 20-50 parts of vine, 20-50 parts of purslane, 20-50 parts of small spatholobus suberectus, 20-50 parts of white ox gall, 20-50 parts of purslane, 20-50 parts of red ginseng, 20-50 parts of bamboo shavings, and 20-50 parts of ground sap.

2. The composition with menstrual regulating and blood-activating effects according to claim 1, characterized in that, The composition is made from the following Chinese herbal medicines in parts by weight: 25-45 parts of ground maple bark, 25-45 parts of star anise, 25-45 parts of scutellaria baicalensis, 25-45 parts of long pepper, 25-45 parts of vine, 25-45 parts of purslane, 25-45 parts of small blood vine, 25-45 parts of white ox gall, 25-45 parts of purslane, 25-45 parts of red ginseng, 25-45 parts of bamboo yellow, and 25-45 parts of ground blood shavings.

3. The composition with menstrual regulating and blood-activating effects according to claim 1, characterized in that, The composition is made from the following Chinese herbal medicines in parts by weight: 40 parts of ground maple bark, 40 parts of star anise, 35 parts of scutellaria baicalensis, 40 parts of long pepper, 35 parts of vine, 30 parts of clematis, 35 parts of spatholobus suberectus, 30 parts of white ox gall, 30 parts of spatholobus suberectus, 30 parts of red ginseng, 35 parts of bamboo shavings, and 35 parts of ground blood incense.

4. The use of the composition with menstrual regulating and blood-activating effects as described in any one of claims 1 to 3 in the preparation of a traditional Chinese medicine product for treating or improving primary dysmenorrhea, characterized in that, The external product is a traditional Chinese medicine acupoint patch made from the above-mentioned weight proportions of Chinese herbal medicines as raw materials, supplemented with pharmaceutically acceptable excipients.

5. The application of the composition with menstrual regulating and blood-activating effects as described in claim 4 in the preparation of a traditional Chinese medicine product for treating or improving primary dysmenorrhea, characterized in that... The traditional Chinese medicine acupoint patch product for treating or treating primary dysmenorrhea is prepared according to the following steps: (1) Take each of the Chinese medicinal materials in the above composition, clean and dry them, and then coarsely grind and ultra-finely grind each medicinal material into fine powder, pass them through a 100-120 mesh sieve, and obtain various medicinal material fine powders for use. (2) Weigh each medicinal material powder according to the above composition parts by weight, and mix each medicinal material powder evenly by equal incremental method to ensure that the color of the composition powder is uniform after tempering. Then pass it through a 100-120 mesh sieve to obtain the composition powder. (3) Mix the powdered medicine and honey in a weight ratio of 1:1-1.2, then add 1-3% azone, 15-20% propylene glycol and 15-20% glycerin by weight of the powdered medicine and mix evenly to make a thick paste that is soft and hard, malleable but not runny, for later use. (4) The thick paste prepared in step (3) is made into a round medicated cake with a thickness of 1-5cm and 0.2-0.3cm. The medicated cake is placed in the center of medical tape or medical non-woven fabric, covered with release paper, and sealed in packaging to obtain the Chinese medicine acupoint patch product.

6. The application of the composition with menstrual regulating and blood-activating effects as described in claim 4 in the preparation of a traditional Chinese medicine product for treating or improving primary dysmenorrhea, characterized in that... The traditional Chinese medicine acupoint patch product for treating or treating primary dysmenorrhea is prepared according to the following steps: (1) Weigh each Chinese medicinal material according to the above weight proportions, clean and dry them, coarsely crush each medicinal material, mix them evenly, extract them 2-3 times by alcohol extraction, collect the alcohol extract, concentrate it under reduced pressure to a thick extract with a relative density of 1.2-1.3, and set it aside for later use; (2) Take 2-3 times the weight of glycerol and 0.3-0.6 times the weight of sodium acrylate of the Chinese herbal extract and mix them thoroughly. Add tartaric acid solution of 0.02-0.04 times the weight of the Chinese herbal extract dissolved in purified water and stir well. Then add aluminum hydroxide solution of 0.04-0.06 times the weight of the Chinese herbal extract dissolved in purified water and stir for more than 15 minutes. Then add polyvinylpyrrolidone of 0.5-0.7 times the weight of the Chinese herbal extract dissolved in purified water and stir for more than 10 minutes. Then add azone of 0.1-0.2 times the weight of the Chinese herbal extract and propylene glycol of 1.5-2 times the weight of the Chinese herbal extract and stir thoroughly to form a homogeneous colloidal matrix without particles. (3) The matrix prepared in step (2) is evenly coated on medical nonwoven fabric with a coating thickness of 0.8-1.0 mm, covered with release paper to protect the adhesive layer, and left to stand at room temperature for more than 24 hours until fully cured. Then it is cut into round or square patches. The cut patches are placed at 45°C or below to dry for 2-4 hours, with the moisture content controlled at 15-20%. The patches are then sealed and packaged to obtain the Chinese medicine acupoint patch product.

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