A traditional Chinese medicine composition with detoxifying and uterine-warming effects and its application in the preparation of external products.

Abstract

This invention belongs to the field of traditional Chinese medicine (TCM) technology, specifically relating to a TCM composition with detoxifying and uterus-warming effects and its application in the preparation of external products. The medicinal component of this external TCM product is composed of fenugreek, amethyst, rose, pomegranate seed, centella asiatica, long pepper, five-finger peach, lycopodium, litchi seed, and achyranthes bidentata. Animal experiments show that this product can significantly reduce the number of writhing movements in animals with cold-induced blood stasis type dysmenorrhea, lower COX-2 and PGE2 levels in the uterus, and improve peritoneal inflammation, demonstrating good detoxifying, blood stasis-removing, menstruation-regulating, and pain-relieving effects. Regarding blood rheology, it exhibits the effects of inhibiting platelet aggregation, dilating blood vessels, reducing blood viscosity, and balancing TXA2 and PGI2 levels, reflecting its effects of warming the kidneys and uterus, and strengthening the body's foundation. In summary, the TCM composition of this invention and its prepared external product can warm the kidneys and uterus, promote diuresis and eliminate turbidity, providing a novel TCM external application solution for the clinical treatment of cold-induced blood stasis type dysmenorrhea.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a traditional Chinese medicine composition with detoxifying and warming effects on the uterus and its application in the preparation of external products. Background Technology

[0002] Primary dysmenorrhea is a common and frequently occurring gynecological condition. Symptoms typically include spasmodic pain in the lower abdomen, sometimes radiating to the lumbosacral region. In severe cases, the pain can be excruciating, accompanied by nausea, vomiting, dizziness, and fainting, significantly impacting a woman's normal work and life. Traditional Chinese medicine classifies primary dysmenorrhea into four types based on its etiology: cold-induced blood stasis, qi stagnation and blood stasis, qi and blood deficiency, and kidney and blood deficiency. The cold-induced blood stasis type is the most common clinically, often caused by exposure to dampness and cold during menstruation, excessive consumption of cold foods, or cold invading the Chong and Ren meridians, leading to qi and blood stagnation and poor blood flow to the uterus, thus triggering dysmenorrhea.

[0003] Current medical treatments for dysmenorrhea often use nonsteroidal anti-inflammatory drugs (NSAIDs) and birth control pills, which only provide temporary pain relief and do not address the underlying cause, and also have numerous side effects. For example, long-term use of NSAIDs in the treatment of primary dysmenorrhea may cause digestive system abnormalities and central nervous system damage, leading to symptoms such as abdominal discomfort, nausea, and vomiting. Birth control pills are used to relieve dysmenorrhea symptoms, but long-term use may cause side effects such as irregular bleeding, nausea, and headaches.

[0004] Traditional Chinese medicine (TCM) can achieve holistic regulation and treat both the symptoms and root cause of dysmenorrhea through the rational combination of herbs. Whether in improving dysmenorrhea-related symptoms, enhancing clinical efficacy, or reducing drug side effects and recurrence rates, Chinese herbal medicines have demonstrated good effects and play a positive regulatory role in the body. Therefore, researching and preparing TCM preparations for the prevention and treatment of dysmenorrhea has practical significance for TCM. Summary of the Invention

[0005] (a) Technical problems to be solved

[0006] To address the shortcomings of existing technologies, this invention provides a traditional Chinese medicine composition with detoxifying and uterine-warming effects and its application in the preparation of external products for dysmenorrhea caused by cold stagnation and blood stasis.

[0007] (II) Technical Solution

[0008] To achieve the above objectives, the present invention provides the following technical solution:

[0009] In a first aspect, the present invention provides a traditional Chinese medicine composition with detoxifying and uterine-warming effects, wherein the traditional Chinese medicine composition is made from the following raw materials in parts by weight: fenugreek 5-30 parts, amethyst 6-25 parts, rose 3-20 parts, pomegranate seed 1-15 parts, centella asiatica 2-16 parts, long pepper 3-12 parts, Ficus hirta 10-30 parts, Lycopodium clavatum 5-20 parts, litchi seed 8-28 parts, and Achyranthes bidentata 6-24 parts.

[0010] Specifically, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 8-20 parts fenugreek, 10-20 parts amethyst, 6-18 parts rose, 4-10 parts pomegranate seeds, 5-12 parts centella asiatica, 5-10 parts long pepper, 12-22 parts five-finger peach, 8-16 parts lycopodium clavatum, 10-20 parts litchi seeds, and 8-20 parts Sichuan achyranthes bidentata.

[0011] Specifically, the traditional Chinese medicine composition is made from the following raw materials in parts by weight: 10 parts fenugreek, 15 parts amethyst, 9 parts rose, 6 parts pomegranate seeds, 9 parts centella asiatica, 6 parts long pepper, 18 parts five-finger peach, 10 parts lycopodium clavatum, 12 parts litchi seeds, and 12 parts Sichuan achyranthes bidentata.

[0012] Secondly, the present invention provides the application of a traditional Chinese medicine composition with detoxifying and warming effects in the preparation of a topical product for treating or improving dysmenorrhea caused by cold stagnation and blood stasis, wherein the topical product is a topical plaster.

[0013] Specifically, the traditional Chinese medicine external plaster product for treating or improving dysmenorrhea due to cold stagnation and blood stasis is prepared according to the following steps:

[0014] (1) Take amethyst, crush it into coarse powder, and pass it through a 60-mesh sieve; add 15-20g of vinegar to every 100g of amethyst and mix well; let it sit until the vinegar is absorbed, heat it over a low flame and stir-fry until it turns slightly red, then let it cool to obtain the amethyst processed product.

[0015] (2) Take pomegranate seeds and rose petals, crush them into coarse powder, and pass them through a 40-mesh sieve; add 8-12 times the amount of 95% ethanol to soak for 24-48 hours, filter, and concentrate the filtrate under reduced pressure until there is no alcohol taste, and the active components of pomegranate seeds and rose petals are obtained.

[0016] (3) Mix fenugreek, centella asiatica, litchi seed, long pepper, lycopodium, achyranthes bidentata, and five-finger peach, crush them into coarse powder, and pass them through a 100-120 mesh sieve to obtain mixed medicinal powder;

[0017] (4) After thoroughly mixing the amethyst processed product from step (1), the active component obtained from step (2), and the mixed powder obtained from step (3), add them to a hydrophilic matrix containing 20-30 parts of glycerin, 10-15 parts of gelatin, 5-8 parts of polyvinyl alcohol, 1-3 parts of carbomer, 0.5-1.5 parts of lauryl acetone, and 40-60 parts of purified water at a ratio of 1:6. Stir at 40°C for 30 minutes, coat the mixture onto the non-woven fabric backing layer with a thickness of 0.5-1.0 mm, cover with release paper, and cut into circles or ovals to obtain a topical plaster of traditional Chinese medicine composition.

[0018] Preferably, the hydrophilic matrix consists of the following parts by weight: 25 parts glycerol, 12 parts gelatin, 6 parts polyvinyl alcohol, 2 parts carbomer, 1 part lauryl acetone, and 50 parts purified water.

[0019] The external plaster of the traditional Chinese medicine composition of the present invention has the release paper removed, and the hydrophilic ointment layer is applied to the navel or the area below the navel.

[0020] The pharmacological effects of each herbal raw material in the herbal composition of this invention are as follows:

[0021] Fenugreek: The mature seed of *Trigonella foenum-graecum* L., a plant belonging to the genus *Trigonella* of the legume family. It has a bitter taste and warm properties; it enters the kidney meridian. It has the effects of warming the kidneys and tonifying yang, dispelling cold and relieving pain. It is used to treat kidney yang deficiency, lower abdominal coldness, lower abdominal pain due to cold, hernia pain, and cold-damp beriberi.

[0022] Amethyst: a fluorite group of halide minerals. It has a sweet taste and warm properties; it enters the kidney, heart, and lung meridians. It has the effects of warming the kidneys and uterus, calming the mind and soothing the nerves, and warming the lungs and relieving asthma. It is used for kidney yang deficiency, infertility due to cold uterus, palpitations, insomnia, and cough and asthma due to deficiency and cold.

[0023] Rose: The dried flower of *Rosa chinensis* Jacq., a plant belonging to the genus *Rosa* in the family Rosaceae. It has a sweet taste and warm nature, and enters the liver meridian. It has the effects of promoting blood circulation and regulating menstruation, soothing the liver and relieving depression. It is used for qi stagnation and blood stasis, irregular menstruation, dysmenorrhea, amenorrhea, and chest and rib pain.

[0024] Pomegranate seeds: The dried seeds of the pomegranate tree (Punica granatum), a plant in the Punicaceae family. They are sour, sweet, warm, and moistening. They have the effects of promoting saliva production, aiding digestion, strengthening the spleen, and benefiting the stomach. They are used for treating cold-related ailments, stomach coldness, and other stomach problems.

[0025] Centella asiatica (L.) Urb., a plant in the Apiaceae family, is the whole herb. It has the effects of clearing heat and dampness, detoxifying and reducing swelling. It is used for damp-heat jaundice, heatstroke diarrhea, urinary stones and hematuria, carbuncles and boils, and injuries from falls.

[0026] Long pepper (Litsea cubeba CLour. Pers.), a plant in the Lauraceae family, is the dried, ripe fruit of the plant. It is warm in nature and pungent in taste; it enters the spleen, stomach, kidney, and bladder meridians. It has the effects of warming the middle jiao (spleen and stomach), dispelling cold, promoting qi circulation, and relieving pain. It is used to treat stomach cold and abdominal pain, vomiting, hiccups, and abdominal pain due to cold hernia.

[0027] Five-finger Ficus hirta Vahl, the dried root of the plant (Ficus hirta Vahl, Moraceae family). It has a sweet taste and neutral properties, entering the spleen, lung, and liver meridians. It functions to strengthen the spleen and lungs, promote qi circulation and eliminate dampness, and relax muscles and tendons. It is used for spleen deficiency edema, poor appetite and weakness, pulmonary tuberculosis cough, night sweats, leukorrhea, edema, and rheumatic pain.

[0028] Lycopodium japonicum Thunb., a plant belonging to the genus Lycopodium in the family Lycopoaceae, is dried whole.

[0029] It tastes bitter and slightly pungent, and is warm in nature; it enters the liver, spleen, and kidney meridians. It has the effects of dispelling wind and dampness, and relaxing muscles and tendons. It is used for joint pain and difficulty in flexion and extension.

[0030] Litchi seed: The dried, mature seed of *Litchi chinensis* Sonn., a plant belonging to the Sapindaceae family. It is warm in nature, pungent and slightly bitter in taste, and enters the liver and stomach meridians. It has the effects of promoting qi circulation, dispersing stagnation, dispelling cold, and relieving pain. It is used for abdominal pain due to cold hernia and testicular swelling and pain.

[0031] Achyranthes bidentata: The dried root of *Cyathula officinalis* Kuan, a plant in the Amaranthaceae family. It has a sweet and slightly bitter taste, and is neutral in nature; it enters the liver and kidney meridians. It has the effects of removing blood stasis and promoting menstruation, facilitating joint movement, and promoting urination. It is used for amenorrhea, abdominal masses, retained placenta, traumatic injuries, rheumatic pain, foot weakness and muscle spasms, and hematuria.

[0032] (III) Beneficial Effects

[0033] This invention provides a traditional Chinese medicine external plaster for treating or improving dysmenorrhea caused by cold stagnation and blood stasis. The plaster is made from the following traditional Chinese medicine ingredients: fenugreek, amethyst, rose, pomegranate seed, centella asiatica, lychee seed, long pepper, lycopodium, five-finger peach, and achyranthes bidentata. Fenugreek and amethyst are the principal ingredients. Fenugreek dispels cold pathogens in the lower abdomen, relieving spasms and blockages caused by "cold causing contraction," thus acting as the core for warming the uterus. Amethyst, with its strong downward-moving properties, guides the medicine into the uterus, enhancing its warming and consolidating effect on the lower abdomen. The two ingredients together are warm but not harsh, forming a "source of fire" for warming the uterus. Rose and pomegranate seed are the assistant ingredients. Rose invigorates blood circulation, removes blood stasis, regulates menstruation, relieves pain, and resolves uterine stagnation. Pomegranate seed warms the stomach and kidneys, generates fluids, strengthens the spleen, and restores uterine yang energy. The combination of these two ingredients warms and unblocks without depleting blood, and invigorates blood circulation without harming yang. The assistant herbs inherit the warmth of the principal herbs, transforming it into the driving force for "detoxification." The adjuvant herbs include five ingredients: lychee seed, long pepper, *Lycopodium clavatum*, *Ficus hirta*, and *Centella asiatica*. Among them, lychee seed promotes qi circulation, disperses stagnation, relieves cold and pain, specifically targeting the liver meridian to regulate qi and alleviate stagnation; long pepper warms the middle jiao, disperses cold, promotes qi circulation, and relieves pain, enhancing the qi-regulating effect of pomegranate seed; *Lycopodium clavatum* dispels wind and dampness, relaxes muscles and tendons, and can alleviate pelvic adhesions and fallopian tube spasms; *Ficus hirta* strengthens the spleen and lungs to eliminate the source of dampness and toxins, promotes qi circulation and eliminates dampness to aid detoxification, while preventing the warming and drying properties of the herbs and blood-activating herbs from depleting the body's vital energy; the addition of *Centella asiatica* ensures the entire formula is warm without being drying. These herbs work synergistically to assist the principal and assistant herbs in clearing blockages at the "qi" and "meridian" levels, ensuring unobstructed detoxification pathways. *Achyranthes bidentata* serves as the guiding herb, dispelling blood stasis and unblocking the meridians, leading the other herbs into the uterus and expelling stagnant fluids downwards.

[0034] This study constructed an animal model of dysmenorrhea due to cold stagnation and blood stasis by using ice water immersion combined with estradiol glutarate (to induce platelet aggregation) and oxytocin (to induce uterine spasms). The efficacy of this traditional Chinese medicine external plaster was verified by comparing the effects of different groups. By comparing the efficacy differences among the traditional Chinese medicine external plaster (complete formula group), the uterus-warming group (containing only drugs with kidney-warming and uterus-warming effects), and the detoxification group (containing only drugs with meridian-clearing and detoxification effects), the results showed that neither the uterus-warming group nor the detoxification group formed a good efficacy loop, exhibiting significant functional deficiencies. Specifically, the uterus-warming group tended to dispel cold pathogens but lacked detoxification power, while the detoxification group often lacked the effect of clearing stagnation and nourishing the uterus. In contrast, the traditional Chinese medicine external plaster (complete formula group) fully demonstrated the advantages of synergistic effects and scientific compatibility between drugs, achieving integrated regulation that combines warming and clearing, addressing both the symptoms and the root cause, and exhibiting superior comprehensive efficacy.

[0035] The ibuprofen group (Western medicine positive control) significantly reduced uterine contractions and vasospasm-related indicators, while also lowering the level of inflammatory factors in the uterus, thus relieving pain. However, it did not show significant efficacy in promoting blood circulation and removing blood stasis. The dysmenorrhea relief group (traditional Chinese medicine positive control) focused more on improving blood rheology and reducing platelet aggregation and the risk of thrombosis, but its anti-inflammatory and antispasmodic effects were relatively weak. In contrast, this traditional Chinese medicine external plaster (comprehensive formula group) combines the advantages of the above two groups, comprehensively exerting its anti-inflammatory, antispasmodic, blood-activating and stasis-removing, lower abdominal cold pain relief, and pelvic stasis metabolic product excretion effects. It achieves a multi-target synergistic effect of anti-inflammatory, antispasmodic, blood-activating, meridian-warming, and detoxifying properties. This traditional Chinese medicine external plaster not only compensates for the "insufficient blood-activating" deficiency of ibuprofen but also enhances the "anti-inflammatory and antispasmodic" weakness of the dysmenorrhea relief group, fully demonstrating the comprehensive advantages of traditional Chinese medicine compound external preparations in treating dysmenorrhea caused by cold stagnation and blood stasis. Attached Figure Description

[0036] Figure 1 The number of writhing movements in each group of rats was compared with that in the control group. a P<0.05, b P<0.01; compared with the model group, c P<0.05, d P<0.01; compared with the traditional Chinese medicine external plaster group, e P<0.05, f P<0.01.

[0037] Figure 2 The blood rheology of each group of rats was compared with that of the control group. a P<0.05, b P<0.01; compared with the model group, c P<0.05, d P<0.01; compared with the traditional Chinese medicine external plaster group, e P<0.05, f P<0.01.

[0038] Figure 3 The levels of TXA2 and PGI2 in the serum of rats in each group were compared with those in the control group. a P<0.05, b P<0.01; compared with the model group, c P<0.05, d P<0.01; compared with the traditional Chinese medicine external plaster group, e P<0.05, f P<0.01.

[0039] Figure 4 The levels of COX-2, PGE2, IL-6, and TNF-α in the uterus of rats in each group were compared with those in the control group.a P<0.05, b P<0.01; compared with the model group, c P<0.05, d P<0.01; compared with the traditional Chinese medicine external plaster group, e P<0.05, f P<0.01. Detailed Implementation

[0040] 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.

[0041] Example 1

[0042] A traditional Chinese medicine external plaster for treating or relieving dysmenorrhea due to cold stagnation and blood stasis is made from the following traditional Chinese medicine composition in the indicated weights: 10g fenugreek, 15g amethyst, 9g rose, 6g pomegranate seed, 9g centella asiatica, 6g long pepper, 18g five-finger peach, 10g lycopodium clavatum, 12g lychee seed, and 12g achyranthes bidentata.

[0043] Example 2

[0044] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 5g fenugreek, 6g amethyst, 3g rose, 1g pomegranate seed, 2g centella asiatica, 3g long pepper, 10g five-finger peach, 5g lycopodium clavatum, 8g lychee seed, and 6g achyranthes bidentata.

[0045] Example 3

[0046] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 30g fenugreek, 25g amethyst, 20g rose, 15g pomegranate seed, 6g centella asiatica, 12g long pepper, 30g five-finger peach, 20g lycopodium clavatum, 28g lychee seed, and 24g achyranthes bidentata.

[0047] Example 4

[0048] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 8g fenugreek, 10g amethyst, 6g rose, 4g pomegranate seed, 5g centella asiatica, 5g long pepper, 12g five-finger peach, 8g lycopodium clavatum, 10g lychee seed, and 8g achyranthes bidentata.

[0049] Example 5

[0050] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 20g fenugreek, 20g amethyst, 18g rose, 10g pomegranate seed, 12g centella asiatica, 10g long pepper, 22g five-finger peach, 16g lycopodium clavatum, 20g lychee seed, and 20g achyranthes bidentata.

[0051] Example 6

[0052] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 25g fenugreek, 18g amethyst, 15g rose, 12g pomegranate seed, 14g centella asiatica, 8g long pepper, 25g five-finger peach, 18g lycopodium clavatum, 25g lychee seed, and 22g achyranthes bidentata.

[0053] Example 7

[0054] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 15g fenugreek, 12g amethyst, 9g rose, 8g pomegranate seed, 10g centella asiatica, 8g long pepper, 15g five-finger peach, 12g lycopodium clavatum, 14g lychee seed, and 15g achyranthes bidentata.

[0055] Example 8

[0056] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 5g fenugreek, 25g amethyst, 3g rose, 15g pomegranate seed, 2g centella asiatica, 12g long pepper, 10g five-finger peach, 5g lycopodium clavatum, 8g lychee seed, and 6g achyranthes bidentata.

[0057] Example 9

[0058] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 5g fenugreek, 6g amethyst, 20g rose, 1g pomegranate seed, 9g centella asiatica, 3g long pepper, 30g five-finger peach, 20g lycopodium clavatum, 28g lychee seed, and 24g achyranthes bidentata.

[0059] Examples 1-9: Weigh the ingredients according to the stated weight and prepare the traditional Chinese medicine external plaster using the following steps:

[0060] (1) Take amethyst, crush it into coarse powder, and pass it through a 60-mesh sieve; add 18g of vinegar to every 100g of amethyst and mix well; let it sit until the vinegar is absorbed, heat it over a low flame until it turns slightly red, and let it cool to obtain amethyst extract.

[0061] (2) Take pomegranate seeds and rose petals, crush them into coarse powder, and pass them through a 40-mesh sieve; add 12 times the amount of 95% ethanol and soak for 48 hours, filter, and concentrate the filtrate under reduced pressure until there is no alcohol taste, and the active components of pomegranate seeds and rose petals are obtained.

[0062] (3) Mix fenugreek, centella asiatica, litchi seed, long pepper, lycopodium, achyranthes bidentata, and five-finger peach, crush them into coarse powder, and pass them through a 100-120 mesh sieve to obtain mixed medicinal powder;

[0063] (4) Add the amethyst extract obtained in step (1), the active component obtained in step (2), and the mixed powder obtained in step (3) in a ratio of 1:6 to a hydrophilic matrix containing 25g of glycerin, 12g of gelatin, 6g of polyvinyl alcohol, 2g of carbomer, 1g of lauryl acetone, and 50g of purified water. Stir at 40°C for 30 minutes. Coat the mixture onto the non-woven fabric backing layer with a thickness of 0.5-1.0mm. Cover with release paper and cut into circles or ovals to obtain a traditional Chinese medicine external plaster.

[0064] Comparative Example 10

[0065] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 10g fenugreek, 15g amethyst, 6g pomegranate seeds, and 6g long pepper.

[0066] Comparative Example 11

[0067] The difference between this embodiment and Embodiment 1 is that the herbal external plaster is made from the following herbal composition in the indicated weights: 9g of rose petals, 9g of centella asiatica, 18g of five-finger peach, 10g of lycopodium clavatum, 12g of lychee seed, and 12g of achyranthes bidentata.

[0068] Comparative Examples 10-11 were weighed according to the stated weight and prepared as traditional Chinese medicine external plasters with reference to the preparation steps of Examples 1-9.

[0069] Experimental Example 1

[0070] 1. Materials

[0071] 1.1 Experimental Drugs

[0072] The external application plaster of the traditional Chinese medicine composition of the present invention is prepared according to the formula described in Example 1.

[0073] Warming Uterus Formula: Prepare an external plaster according to the formula described in Comparative Example 10.

[0074] Detoxification formula: Prepare an external plaster according to the formula described in Comparative Example 11.

[0075] The dysmenorrhea relief patch was prepared according to the dysmenorrhea relief patch formula reported in the literature (leech 3 g, corydalis 15 g, cynanchum paniculatum 15 g, achyranthes bidentata 10 g, and cattail pollen 10 g) and the external plaster preparation process described in Examples 1-9 of this invention.

[0076] Ibuprofen sustained-release capsules were purchased from Sino-American Tianjin SmithKline Pharmaceutical Co., Ltd.

[0077] 1.2 Laboratory Animals

[0078] SPF-grade female SD rats, weighing 180-220g, were purchased from Henan Spekes Biotechnology Co., Ltd. They were housed in an SPF-grade animal facility under the following conditions: temperature 22-25℃, relative humidity 50%-60%, circadian rhythm 12h / 12h, and free access to food and water. After one week of acclimatization, subsequent experiments were conducted.

[0079] 2. Methods

[0080] 2.1 Animal modeling, grouping, and drug administration

[0081] After one week of acclimatization, eight rats were randomly selected as the control group, and the remaining rats were used for modeling. The modeling rats were placed in ice water at 0-1℃ for 10 minutes, once daily, and all rats were orally administered estradiol glutarate suspension for 12 consecutive days (see Table 1 for details). The control group was given the same volume of physiological saline.

[0082] Simultaneous drug administration during modeling: Rats were randomly divided into four groups (n=8 per group): Model group, Traditional Chinese Medicine (TCM) external plaster group (ZYWY), Uterus warming group (NG), Detoxification group (PD), Dysmenorrhea relief group (TJA), and Ibuprofen group. Prior to modeling, the abdominal hair of the rats was removed. The TCM external plaster group, Uterus warming group, Detoxification group, and Dysmenorrhea relief group received daily application of the plaster to the corresponding areas. The ibuprofen group (0.06 g / kg / day) was administered orally via gavage. Blank medical adhesive tape was applied to the same areas in both the control group and the model group. One hour after the last drug administration on day 12 of modeling, except for the control group, each rat in all groups was intraperitoneally injected with 20 U of oxytocin, and the following experiments were then conducted.

[0083]

[0084] 2.2 Detection Indicators

[0085] 2.2.1 Torsional response

[0086] Within 30 minutes after oxytocin injection, the number of writhing responses in each group of rats was observed and recorded. The writhing response was defined as changes in body posture such as abdominal concavity, body twisting, hind limb extension, hip elevation, and crawling. The writhing latency and number of writhing responses were observed within 30 minutes.

[0087] 2.2.2 Hemorheology

[0088] After the writhing phase, the patient was anesthetized, and blood was drawn from the abdominal aorta. 2 ml of whole blood was collected using a blood collection tube containing sodium heparin. The viscosity of the whole blood was measured using a blood rheometer. After centrifugation, the plasma was separated and its viscosity was measured.

[0089] 2.2.3 Detection of thromboxane (TXA2) and prostacyclin (PGI2) in the serum of rats in each group

[0090] Animals were anesthetized, and whole blood was collected using blood collection tubes without sodium heparin. After centrifugation, serum was separated and tested according to the kit instructions.

[0091] 2.2.4 Detection of COX-2, PGE2, IL-6, and TNF-α in the uterus of rats in each group

[0092] After anesthetizing the animals and collecting blood, uterine tissue was extracted for relevant tests. PGE2, IL-6, and TNF-α were detected using kit methods; COX-2 was detected by Western blot followed by grayscale analysis.

[0093] 2.3 Statistical Methods

[0094] All experimental data were analyzed using GraphPad Prism 8.0 statistical software, and one-way ANOVA was used for comparisons between groups. A p-value < 0.05 was considered statistically significant, and a p-value < 0.01 was considered extremely statistically significant.

[0095] 3 Results

[0096] 3.1 Observation of writhing response

[0097] The results are shown below. Figure 1 Compared with the blank group, the number of writhing movements in the model group rats increased significantly (P<0.01), and the writhing latency was shorter (P<0.01). After drug treatment, the dysmenorrhea symptoms of rats in each group were improved to varying degrees. Among them, the traditional Chinese medicine external plaster group and the ibuprofen group had significant effects (P<0.01), and the analgesic effects of the two were basically equivalent.

[0098] 3.2 Blood rheology in each group

[0099] In Traditional Chinese Medicine (TCM) theory, "blood stasis syndrome" is closely related to the body's hemorheological state. When blood stasis syndrome occurs, blood flow slows down due to changes in blood composition. Therefore, this study detected hemorheological parameters in experimental animals. The results showed... Figure 2 Compared with the control group, the blood rheology-related indices (whole blood high-shear, medium-shear, and low-shear reduced viscosity, plasma viscosity, and erythrocyte aggregation index) of the model group rats were significantly increased (P<0.01), indicating that ice-water baths can lead to increased blood viscosity in the model group rats, which is consistent with the traditional Chinese medicine theory of "cold coagulation and blood stasis," further confirming the successful preparation of the pathological model of cold coagulation and blood stasis syndrome. After different drug interventions, the above indices of rats in the traditional Chinese medicine external plaster group, the uterus warming group, and the dysmenorrhea relief group all showed varying degrees of improvement, with the traditional Chinese medicine external plaster group showing the best effect, followed by the uterus warming group. Especially in terms of whole blood low-shear reduced viscosity, the traditional Chinese medicine external plaster group showed a significant difference compared with the other groups (P<0.01). The above results suggest that this traditional Chinese medicine external plaster has a significant therapeutic effect in promoting blood circulation. It is worth noting that using the blood-activating and stasis-removing traditional Chinese medicine in the formula alone did not enhance its blood-activating effect.

[0100] 3.3 Serum levels of thromboxane (TXA2) and prostacyclin (PGI2) in each group of rats

[0101] TXA2 is mainly synthesized and released by platelet mitochondria, and has the effects of vasoconstriction, promoting platelet aggregation, and inducing thrombus formation; PGI2, on the other hand, can inhibit platelet aggregation and dilate blood vessels. Results are shown below. Figure 3 Compared with the control group, the TXA2 content in the model group rats was significantly increased, while the PGI2 content was significantly decreased (P<0.01), indicating enhanced vasoconstriction and decreased blood flow. After drug intervention, the TXA2 content in all groups of rats decreased significantly, while the PGI2 content increased accordingly, especially in the traditional Chinese medicine external plaster group, the uterus warming group, and the dysmenorrhea relief group (P<0.01). These results indicate that these drug interventions can promote the release of PGI2 in the serum of rats with cold coagulation and blood stasis model, inhibit the production of TXA2, and thus exert the effects of dilating blood vessels, increasing uterine blood flow, and relieving pain caused by cold coagulation.

[0102] 3.4 Levels of COX-2, PGE2, IL-6, and TNF-α in the uterus of rats in each group

[0103] Studies have shown that women with dysmenorrhea have significantly higher levels of IL-6 and TNF-α secretion during menstruation compared to normal women. IL-6 is closely related to COX-2 regulation, and PGE2, as one of the most important downstream products of COX-2, participates in the contraction of the uterus and arcuate vessels, and is a direct driver of local pain and inflammation. PGE2 is produced by elevated COX-2 catalysis, directly stimulating uterine smooth muscle spasm, which is the core mechanism triggering dysmenorrhea. Therefore, this study detected and compared these indicators. Experimental results are shown in […]. Figure 4 Compared with the control group, the inflammatory markers, COX-2 protein expression, and PGE2 levels in the model group rats were significantly increased (P<0.01). After drug intervention, the traditional Chinese medicine external plaster group and the ibuprofen group showed good improvement effects, significantly improving the levels of the above indicators (P<0.01). The above results indicate that the traditional Chinese medicine external plaster can achieve analgesic effects comparable to ibuprofen and has a protective effect on the uterine cavity microenvironment.

[0104] 4. Conclusion

[0105] Cold-induced blood stasis is the most common TCM syndrome type in primary dysmenorrhea. This external herbal plaster treats cold-induced blood stasis dysmenorrhea through "warming," "unblocking," and "tonifying." Warming dispels cold, unblocking clears stagnant blood, and tonifying strengthens qi and blood, allowing the uterus to flow smoothly and thus relieving pain. In animal experiments, rats were subjected to cold stimulation using an ice-water bath to allow cold pathogens to enter the body; simultaneously, adrenaline was administered to constrict blood vessels, reduce capillary permeability, and increase blood viscosity. Based on this, an animal model of cold-induced blood stasis combined with dysmenorrhea was prepared by combining estradiol glutarate and oxytocin. The results of drug intervention in each group showed that ibuprofen could reduce the number of writhing responses in the model group rats, prolong the writhing latency, and reduce the levels of inflammatory factors and improve the levels of pain-inducing factors, indicating that it has the effect of relieving pain and inhibiting inflammatory response, but the improvement effect on blood-activating and stasis-removing related indicators was not significant. While Tongjing'an (a traditional Chinese medicine plaster) can reduce whole blood viscosity and plasma viscosity at various cutting rates, it has no significant effect on the levels of inflammatory factors, COX-2, and PGE2 in the uterus, suggesting that its main function is to promote blood circulation and remove blood stasis, while its ability to relieve pain and inhibit inflammatory response is relatively weak. This study further compared the efficacy differences of the traditional Chinese medicine external plaster (full formula group), the uterus-warming group (containing only the warming ingredients), and the detoxification group (containing only the detoxification ingredients), selecting indicators that reflect the traditional efficacy of "promoting blood circulation and removing blood stasis" for evaluation. The results showed that both the traditional Chinese medicine external plaster group and the uterus-warming group improved blood flow; the detoxification group was superior to the uterus-warming group in reducing COX-2, PGE2, IL-6, and TNF-α in the uterus, but the effects of both groups were not as good as those of the traditional Chinese medicine external plaster group (full formula group). The comprehensive experimental results indicate that the traditional Chinese medicine external plaster group has multiple effects, including promoting blood circulation and removing blood stasis, dispelling cold and relieving pain, warming the kidneys and uterus, and clearing the meridians and removing turbidity. This traditional Chinese medicine external plaster not only constructs a "balanced" warming structure for the uterus by regulating both cold and heat, but also effectively integrates a "three-level pathway" detoxification system, indicating that the drugs contained in the warming group and the detoxification group have a significant synergistic or synergistic effect.

[0106] In summary, the formulation of this traditional Chinese medicine external plaster is scientifically sound, with synergistic effects among its various medicinal components. Using only a portion of the ingredients would not achieve the desired overall therapeutic effect. Furthermore, this traditional Chinese medicine external plaster achieves comparable analgesic and anti-inflammatory effects to existing Western medicines. In addition, because this formula is based on traditional Chinese medicine, it has a high safety profile and is suitable for long-term use, thus compensating for the limitations of long-term use of Western medicines.

[0107] 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 traditional Chinese medicine composition with detoxifying and uterine-warming effects, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 5-30 parts fenugreek, 6-25 parts amethyst, 3-20 parts rose, 1-15 parts pomegranate seed, 2-16 parts centella asiatica, 3-12 parts long pepper, 10-30 parts five-finger peach, 5-20 parts lycopodium clavatum, 8-28 parts litchi seed, and 6-24 parts Sichuan achyranthes bidentata.

2. The traditional Chinese medicine composition for detoxification and uterine warming according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 8-20 parts fenugreek, 10-20 parts amethyst, 6-18 parts rose, 4-10 parts pomegranate seeds, 5-12 parts centella asiatica, 5-10 parts long pepper, 12-22 parts five-finger peach, 8-16 parts lycopodium clavatum, 10-20 parts litchi seeds, and 8-20 parts Sichuan achyranthes bidentata.

3. The traditional Chinese medicine composition for detoxification and uterine warming according to claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 10 parts fenugreek, 15 parts amethyst, 9 parts rose, 6 parts pomegranate seed, 9 parts centella asiatica, 6 parts long pepper, 18 parts five-finger peach, 10 parts lycopodium clavatum, 12 parts litchi seed, and 12 parts Sichuan achyranthes bidentata.

4. The application of a traditional Chinese medicine composition with detoxifying and uterine-warming effects as described in any one of claims 1 to 3 in the preparation of a topical product for treating or improving dysmenorrhea caused by cold stagnation and blood stasis, characterized in that... The external product is prepared by using the above-mentioned weight proportions of Chinese herbal medicines as raw materials, supplemented with pharmaceutically acceptable excipients, into an external plaster product.

5. The application of the traditional Chinese medicine composition with detoxifying and uterine-warming effects as described in claim 4 in the preparation of a topical plaster for treating or improving dysmenorrhea caused by cold stagnation and blood stasis, characterized in that... The topical plaster product used to treat or improve dysmenorrhea caused by cold stagnation and blood stasis is composed of a hydrophilic ointment layer and a backing layer stacked in sequence.

6. The application of the traditional Chinese medicine composition with detoxifying and uterine-warming effects as described in claim 5 in the preparation of a topical plaster for treating or improving dysmenorrhea caused by cold stagnation and blood stasis, characterized in that... The topical plaster is prepared according to the following steps: (1) Take amethyst, crush it into coarse powder, and pass it through a 60-mesh sieve; add 15-20g of vinegar to every 100g of amethyst and mix well; let it sit until the vinegar is absorbed, heat it over a low flame and stir-fry until it turns slightly red, then let it cool to obtain the amethyst processed product. (2) Take pomegranate seeds and rose petals, crush them into coarse powder, and pass them through a 40-mesh sieve; add 8-12 times the amount of 95% ethanol to soak for 24-48 hours, filter, and concentrate the filtrate under reduced pressure until there is no alcohol taste, and the active components of pomegranate seeds and rose petals are obtained. (3) Mix fenugreek, centella asiatica, litchi seed, long pepper, lycopodium, achyranthes bidentata, and five-finger peach, crush them into coarse powder, and pass them through a 100-120 mesh sieve to obtain mixed medicinal powder; (4) After thoroughly mixing the amethyst processed product from step (1), the active component obtained from step (2), and the mixed powder obtained from step (3), add them to the hydrophilic matrix at a ratio of 1:5 to 1:8, stir at 40°C for 30 minutes, coat the mixture onto the nonwoven fabric backing layer with a thickness of 0.5-1.0 mm, cover with release paper, and cut into circles or ovals to obtain the external plaster of the traditional Chinese medicine composition.

7. The application of the traditional Chinese medicine composition with detoxifying and uterine-warming effects as described in claim 6 in the preparation of a topical plaster for treating or improving dysmenorrhea caused by cold stagnation and blood stasis, characterized in that... The hydrophilic matrix is ​​composed of the following parts by weight: 20-30 parts glycerol, 10-15 parts gelatin, 5-8 parts polyvinyl alcohol, 1-3 parts carbomer, 0.5-1.5 parts lauryl acetone, and 40-60 parts purified water.

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