Essential oil composition for improving dysmenorrhea and hyperplasia of mammary glands caused by liver depression and qi stagnation and application of essential oil composition

Abstract

The invention provides an essential oil composition for improving dysmenorrhea and hyperplasia of mammary glands caused by liver depression and qi stagnation. The essential oil composition is prepared from the following raw materials in parts by weight: 0.5-1.5 parts of angelica sinensis essential oil and 0.5-1.5 parts of rhizoma cyperi essential oil. The invention also provides application of the essential oil composition in preparation of external medicines for improving hyperplasia of mammary glands caused by liver depression and qi stagnation. The traditional Chinese medicine composition overcomes the defects of single treatment effect, poor patient compliance, more side effects, inconvenience in use and the like in the prior art, can prevent and treat various diseases such as dysmenorrhea, hyperplasia of mammary glands and the like caused by liver depression and qi stagnation, and is scientific and simple in prescription compatibility, convenient to use, high in safety, fragrant in smell and high in patient compliance.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of essential oil composition for improving dysmenorrhea and fibroadenosis caused by liver stagnation. BACKGROUND

[0002] Gynecological diseases are often caused by liver stagnation. Liver stagnation occurs when the liver's yin blood is insufficient and the liver body is unable to be smooth and compliant. Emotional disorders are an important cause of liver stagnation. Long-term emotional depression, anxiety, anger and other adverse emotions can directly affect the liver's function of dispersion, leading to liver stagnation. Liver stagnation and dysfunction of dispersion can cause poor qi movement, blood flow, and blood stasis, which can block the flow of menstrual blood and cause fibroadenosis. Liver stagnation can affect the liver's function of storing blood, leading to irregular filling of the blood sea, which can affect the normal discharge of menstrual blood during menstruation, causing dysmenorrhea and fibroadenosis.

[0003] Dysmenorrhea is a disease that occurs during menstruation or before and after menstruation, characterized by periodic abdominal pain, accompanied by lumbosacral pain, even severe pain and syncope, affecting normal work and life. Epidemiological studies have shown that primary dysmenorrhea is the most common gynecological disease. According to a domestic survey, the incidence of dysmenorrhea among Chinese women is 33.1%, of which primary dysmenorrhea accounts for 53.2%. Dysmenorrhea seriously affects workers, accounting for 13.55%. Dysmenorrhea has a wide range of symptoms, a large number of patients, obvious symptoms, and easy recurrence, which seriously affects women's physical and mental health, and even affects their happiness index.

[0004] Fibroadenosis is a common benign breast disease, which is a non-malignant state of the breast. Its incidence rate is the highest among breast diseases. In addition to causing pain and affecting life, work and study, it also has the potential to develop into breast cancer. Fibroadenosis belongs to the category of "mastitis" in traditional Chinese medicine, and has many clinical syndromes, but liver stagnation and chong and ren disorders are the most common.

[0005] Traditional Chinese medicine essential oil has strong pharmacological activity, and is aromatic, pungent, warm and unobstructed, can promote blood circulation and unblock meridians. Essential oil molecules are small, volatile and fat-soluble, easily penetrate biological membranes, have high bioavailability, and can be quickly absorbed and take effect. Studies have found that aromatic essential oil can be rapidly absorbed by the gastrointestinal tract, applied topically to the skin, inhaled through the nose, and applied to the oral mucosa to act on specific parts of the body. It is suitable for the prevention and treatment of dysmenorrhea and fibroadenosis.

[0006] CN202311447601.2, the invention name: essential oil composition for preventing and treating blood stasis syndrome and its use, provides an essential oil composition for preventing and treating blood stasis syndrome, which is prepared from essential oil or aromatic water extracted from yujin and chuanmiao, wherein the raw material composition is: yujin essential oil 1.0-10.0 parts, chuanmiao essential oil 1.0-10 parts; The ratio of yujin aromatic water and chuanmiao aromatic water is 1.0-10:1.0-10.0 according to the proportion of raw materials yujin and chuanmiao. The application also provides the use of the essential oil composition. The application also discloses a prescription: yujin essential oil 5.0 parts, chuanmiao essential oil 5.0 parts, guihua essential oil 0.3 parts, danggui essential oil 2.0 parts, xiangfu essential oil 2.0 parts, and eiyeh essential oil 0.5 parts, which has obvious curative effect on cardiovascular diseases, rheumatic pain, dysmenorrhea and the like caused by blood stasis. The prescription is specially used for blood stasis syndrome, yujin and chuanmiao are used as the monarch, a large dose of yujin and chuanmiao is used to break blood and remove stasis, danggui and eiyeh are used to warm and dredge, and xiangfu is used to promote qi and transport. It is powerful and special, and is used for stubborn blood stasis.

[0007] There is no related literature report at present that the essential oil of danggui and xiangfu is compounded and used for mammary gland hyperplasia. SUMMARY

[0008] The application provides an essential oil composition for improving dysmenorrhea and mammary gland hyperplasia caused by liver depression and qi stagnation.

[0009] The application provides an essential oil composition for improving dysmenorrhea and mammary gland hyperplasia caused by liver depression and qi stagnation, which is prepared from the following raw materials in a weight ratio:

[0010] The essential oil of danggui is 0.5-1.5 parts, and the essential oil of xiangfu is 0.5-1.5 parts.

[0011] Preferably, the essential oil composition is prepared from the following raw materials in a weight ratio:

[0012] The essential oil of danggui is 0.5-1.5 parts, and the essential oil of xiangfu is 0.5-1.5 parts.

[0013] The essential oil of danggui is 0.5-1.5 parts, and the essential oil of xiangfu is 0.5-1.5 parts.

[0014] The essential oil of danggui is 0.5-1.5 parts, and the essential oil of xiangfu is 0.5-1.5 parts.

[0015] Preferably, the essential oil composition is prepared from the following raw materials in a weight ratio:

[0016] The essential oil of danggui is 0.5-1.5 parts, and the essential oil of xiangfu is 0.5-1.5 parts.

[0017] The essential oil of danggui is 0.5-1.5 parts, and the essential oil of xiangfu is 0.5-1.5 parts.

[0018] Angelica essential oil 0.5-1.5 parts, Cyperus rotundus essential oil 0.5-1.5 parts, Cortex Moutan essential oil 0.5-1.5 parts, Radix Curcumae essential oil 1.0-3.0 parts, Bupleurum essential oil 0.5-1.5 parts, Rhizoma Corydalis essential oil 1.0-3.0 parts;

[0019] Preferably, the weight ratio of the raw materials is:

[0020] Angelica essential oil 1.0 part, Cyperus rotundus essential oil 1.0 part, Cortex Moutan essential oil 1.0 part, Radix Curcumae essential oil 2.0 parts, Bupleurum essential oil 1.0 part, Rhizoma Corydalis essential oil 2.0 parts.

[0021] Among them, the raw materials also contain lavender essential oil and chamomile essential oil, and the weight ratio is:

[0022] Angelica essential oil 0.5-1.5 parts, Cyperus rotundus essential oil 0.5-1.5 parts, Cortex Moutan essential oil 0.5-1.5 parts, Radix Curcumae essential oil 1.0-3.0 parts, Bupleurum essential oil 0.5-1.5 parts, Rhizoma Corydalis essential oil 1.0-3.0 parts, lavender essential oil 0.5-1.5 parts, chamomile essential oil 0.5-1.5 parts;

[0023] Preferably, the weight ratio of the raw materials is:

[0024] Angelica essential oil 1.0 part, Cyperus rotundus essential oil 1.0 part, Cortex Moutan essential oil 1.0 part, Radix Curcumae essential oil 2.0 parts, Bupleurum essential oil 1.0 part, Rhizoma Corydalis essential oil 2.0 parts, lavender essential oil 1.0 part, chamomile essential oil 1.0 part.

[0025] Among them, the raw materials also contain fennel or dried ginger or clove or cinnamon essential oil, and the weight ratio is:

[0026] Angelica essential oil 0.5-1.5 parts, Cyperus rotundus essential oil 0.5-1.5 parts, Cortex Moutan essential oil 0.5-1.5 parts, Radix Curcumae essential oil 1.0-3.0 parts, Bupleurum essential oil 0.5-1.5 parts, Rhizoma Corydalis essential oil 1.0-3.0 parts, lavender essential oil 0.5-1.5 parts, chamomile essential oil 0.5-1.5 parts, fennel or dried ginger or clove or cinnamon essential oil 0.5-1.5 parts;

[0027] Preferably, the weight ratio of the raw materials is:

[0028] Angelica essential oil 1.0 part, Cyperus rotundus essential oil 1.0 part, Cortex Moutan essential oil 1.0 part, Radix Curcumae essential oil 2.0 parts, Bupleurum essential oil 1.0 part, Rhizoma Corydalis essential oil 2.0 parts, lavender essential oil 1.0 part, chamomile essential oil 1.0 part, fennel essential oil 1.0 part, clove essential oil 1.0 part.

[0029] The essential oil composition of the present application is prepared into a commonly used external preparation by adding acceptable adjuvants or auxiliary ingredients to the raw materials as active ingredients.

[0030] Wherein, the external preparation is essential oil, patch, cream, microemulsion gel, suspension.

[0031] The present invention also provides use of the essential oil composition in preparing an external-use medicine for improving dysmenorrhea caused by liver depression and qi stagnation.

[0032] The present invention also provides use of the essential oil composition in preparing a medicine for improving breast hyperplasia caused by liver depression and qi stagnation.

[0033] The external medicine is administered at acupoints; preferably, it is administered at any one of Taichong acupoint, Guanyuan acupoint, Qihai acupoint, and Xuehai acupoint, or a combination of two or more acupoints.

[0034] Angelica sinensis is one of the most commonly used medicinal herbs in my country and is known as the "holy medicine of the blood family." Its medicinal use has a long history, first recorded in the Shennong Bencao Jing (Shen Nong's Herbal Classic), where it was classified as a medium-grade herb. It is warm in nature, sweet and pungent in flavor, and enters the heart, spleen, and liver meridians. It has the effects of nourishing and activating blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting bowel movements. It is clinically used for symptoms such as blood deficiency and sallow complexion, menstrual irregularities, amenorrhea and dysmenorrhea, constipation due to dryness and intestinal dryness, abdominal pain due to deficiency and cold, and epilepsy caused by rheumatism, where it serves as the main herb. Paeonia suffruticosa bark (Mudan Cork) is cold in nature, pungent and bitter in flavor. It has the effects of clearing heat and cooling blood, activating blood circulation and removing blood stasis. It assists the main herb in clearing the blood heat caused by liver stagnation and fire. When liver stagnation persists and qi stagnation transforms into fire, it can lead to blood heat. Moutan Cork can cool blood and remove blood stasis, preventing heat from burning the blood vessels. It also dissipates blood stasis and prevents its formation. Bupleurum chinense (Bupleurum) has the effects of harmonizing the exterior and interior, soothing the liver and relieving depression, primarily assisting the main and auxiliary herbs in soothing the liver and regulating qi. It can guide various herbs into the liver meridian, enhancing the prescription's therapeutic effect on liver depression, allowing liver qi to flow freely and regulating the liver's drainage function, thereby improving the poor flow of qi and blood caused by liver depression. Cyperus rotundus promotes qi and relieves depression, regulates menstruation and relieves pain, and also clears blood stasis, effectively eliminating breast lumps. It is the "general manager" of qi disorders and the "chief" of gynecology. It assists herbs such as Bupleurum in soothing the liver and regulating qi, while also directly acting on the uterus to regulate menstruation. It is a key gynecological herb for regulating menstruation, promoting qi and blood circulation, and relieving dysmenorrhea caused by qi stagnation and blood stasis. Curcuma zedoaria has the effects of promoting blood circulation, relieving depression and clearing the heart. It primarily assists herbs such as Angelica sinensis in promoting blood circulation and removing stasis, while also clearing the heart heat caused by liver depression and fire. It can dissolve blood stasis, clear stagnant internal heat, and disperse stasis in the milk vessels. The three herbs serve as adjuvants: Corydalis yanhusuo, clove, and fennel, which warm the kidneys, dispel cold, relieve pain, and activate blood circulation and qi, enhancing the analgesic effect of the entire formula. Lavender and chamomile can alleviate the mental tension, anxiety, irritability, insomnia, and pain sensitivity associated with liver qi stagnation. The combination of these herbs is highly effective in treating symptoms such as dysmenorrhea and breast hyperplasia caused by liver qi stagnation.

[0035] The prescription of the present invention mainly regulates liver depression, qi stagnation and blood stasis, with bupleurum and cyperus as the core to soothe the liver and regulate qi, while turmeric and corydalis promote blood circulation and relieve pain, and also calm the mind and stabilize the spirit, while moutan bark is used to prevent stagnation and heat, taking into account the emotions and treating the syndrome of qi stagnation and blood stasis.

[0036] The present application overcomes the shortcomings of the prior art, such as single treatment effect, poor patient compliance, more side effects, inconvenience of use and the like, can prevent and treat various diseases caused by liver stagnation and qi stagnation, such as dysmenorrhea, breast hyperplasia and the like, has scientific and simple prescription compatibility, is convenient to use, has high safety, has a fragrance, and has high patient compliance. DETAILED DESCRIPTION

[0037] Example 1 Preparation of the essential oil composition of the present application

[0038] Composition 1: Angelica essential oil 1.0 part, Cyperus rotundus essential oil 1.0 part

[0039] Composition 2: Angelica essential oil 1.0 part, Cyperus rotundus essential oil 1.0 part, Tree peony bark essential oil 1.0 part, Curcuma essential oil 2.0 parts, Bupleurum essential oil 1.0 part, Corydalis essential oil 2.0 parts

[0040] Composition 3: Angelica essential oil 1.0 part, Cyperus rotundus essential oil 1.0 part, Tree peony bark essential oil 1.0 part, Curcuma essential oil 2.0 parts, Bupleurum essential oil 1.0 part, Corydalis essential oil 2.0 parts, Lavender essential oil 1.0 part, Chamomile essential oil 1.0 part

[0041] Composition 4: Angelica essential oil 1.0 part, Cyperus rotundus essential oil 1.0 part, Tree peony bark essential oil 1.0 part, Curcuma essential oil 2.0 parts, Bupleurum essential oil 1.0 part, Corydalis essential oil 2.0 parts, Lavender essential oil 1.0 part, Chamomile essential oil 1.0 part, Fennel essential oil 1.0 part, Clove essential oil 1.0 part

[0042] The single essential oil is extracted by steam distillation, supercritical CO2 extraction, solvent extraction, pressing, redistillation and the like, or can be directly purchased from the market.

[0043] The Bupleurum essential oil is extracted by supercritical CO2 method: the Bupleurum is respectively crushed and passed through a 40-mesh sieve, is placed in an extraction tank, the extraction tank pressure is 30 MPa, the extraction temperature is 50℃, the separation pressure is 6 MPa, the extraction time is 2 h, and the essential oil is collected.

[0044] The Angelica, Cyperus rotundus and Curcuma are extracted by steam distillation: the Angelica, Cyperus rotundus and Curcuma are respectively crushed into coarse powder, are placed in a volatile oil extraction tank, are subjected to steam distillation for 2-4 h, are left to stand for a period of time until the oil and water are separated in an oil-water separator, and the essential oil is respectively collected.

[0045] The optimal ratio of the essential oil is selected by comprehensively considering the treatment effect and factors such as the smell acceptability, properties, safety and irritability of the essential oil after compounding.

[0046] The beneficial effects of the present application are proved by the following efficacy tests.

[0047] Test Example 1 Influence on liver stagnation and qi stagnation dysmenorrhea rats

[0048] A rat model of dysmenorrhea due to liver depression and qi stagnation was established using a composite modeling method. The writhing inhibitory effect of the compound essential oil on dysmenorrhea in rats was observed. Serum sex hormones and pain factors in rats were detected by ELISA.

[0049] 1. Model replication

[0050] A combined modeling method was used to establish a rat model of liver depression and qi stagnation-induced dysmenorrhea. Following the "Draft Standard for the Preparation of Dysmenorrhea Animal Models," female rats were injected with estradiol benzoate and oxytocin to induce a dysmenorrhea-like reaction. Following the reference "Chronic Mild Stress (CMS) Revisited: Consistency and Behavioral-Neurobiological Concordance in the Effects of CMS," rats were subjected to chronic unpredictable stress combined with solitary housing (one rat per cage) to induce a liver depression and qi stagnation syndrome. Modeling Methods: After 7 days of adaptive housing, rats were subjected to tail clamping for 30 minutes at random times daily for 21 consecutive days. The combined model of liver depression and qi stagnation-induced dysmenorrhea was then established by subcutaneous injection of estradiol benzoate and intraperitoneal injection of oxytocin (see Table 1). From day 11 to day 21 of modeling, estradiol benzoate was administered subcutaneously daily, with a dose of 2.5 mg / kg on the first and last day and 1.25 mg / kg on the remaining days. One hour after the last injection of estradiol benzoate, oxytocin was administered to each modeling group at a dose of 10 U / kg.

[0051] Table 1 Stimulation method for rat model of dysmenorrhea with liver depression and qi stagnation

[0052]

[0053] 2. Grouping and Dosing

[0054] One hundred SPF female SD rats, weighing 200±20 g, were housed in the laboratory for 7 days and randomly divided into a blank group, a model group, an angelica essential oil group, a cyperus rotundus essential oil group, a turmeric essential oil group, a compound essential oil group 1 (angelica-cyperus rotundus 1:1), a compound essential oil group 2 (angelica-cyperus rotundus-paeony bark-turmeric 1:1:1:2), a compound essential oil group 3 (angelica-cyperus rotundus-paeony bark-turmeric-bupleurum-corydalis 1:1:1:2), a compound essential oil group 4 (angelica-cyperus rotundus-paeony bark-turmeric-bupleurum-corydalis 1:1:1:2), a compound essential oil group 5 (angelica-cyperus rotundus-paeony bark-turmeric-bupleurum-corydalis 1:1:1:2), a compound essential oil group 6 (angelica-cyperus rotundus-paeony bark-turmeric-bupleurum-corydalis 1:1:1:2), a compound essential oil group 7 (angelica-cyperus rotundus-paeony bark-turmeric-bupleurum-corydalis 1:1:1:2), a compound essential oil group 8 (angelica- 1:1:1:2:1:2:1:2), compound essential oil group 4 (Angelica sinensis-Cyperus rotundus-Paeonia suffruticosa-Curcuma aromatica-Bupleurum chinense-Yorhusuo suo-Lavender-Chamomile 1:1:1:2:1:2:1:1:1), compound essential oil group 5 (Angelica sinensis-Cyperus rotundus-Paeonia suffruticosa-Curcuma aromatica-Bupleurum chinense-Yorhusuo suo-Lavender-Chamomile-Fennel-Clove 1:1:1:2:1:2:1:1:1:1), 10 rats in each group.

[0055] All rats were normally fed, from the 11th day of modeling, the blank group and the model group were smeared with 0.1 ml of normal saline at the uterus; the angelica essential oil group, the cyperus rotundus essential oil group, the curcuma aromatica essential oil group, the compound essential oil 1 group, the compound essential oil 2 group, the compound essential oil 3 group, the compound essential oil 4 group, the compound essential oil 5 group, respectively, 0.1 ml of 20% massage oil containing essential oil diluted with base oil was smeared on the abdomen, all groups were massaged for 2 min after smearing to promote absorption, and each group was smeared once a day, and the continuous administration lasted for 10 d.

[0056] 3. Writhing response

[0057] After the 21st day of modeling, 1 h after administration in the morning, all groups except the blank group were subcutaneously injected with estradiol benzoate, and 40 min later, oxytocin was injected intraperitoneally, the writhing state of rats in each group was observed within 30 min, and the writhing latency and analgesic rate of each group were recorded. The writhing response was used as an indicator of strong uterine contraction, i.e. dysmenorrhea, and directly reflected whether the liver stagnation and qi stagnation type of dysmenorrhea model was successfully established.

[0058] Pain relief rate = (model group writhing times - drug group writhing times) / model group writhing times x 100%.

[0059] 4. Serum sex hormones and pain factors of rats

[0060] After the observation of the writhing response was completed, the rats in each group were anesthetized with 20% urethane, blood was taken from the abdominal aorta, and serum was obtained by centrifugation. According to the operation instruction of the ELISA kit, the multifunctional enzyme label instrument was used for detection, the absorbance was measured, and the content was calculated. The levels of E2, PROG and OT 3 sex hormone indicators and PGE2, IL-6 pain factor indicators in the serum of rats were detected to further evaluate the dysmenorrhea state of rats.

[0061] 5. Experimental results and conclusions of liver stagnation and qi stagnation dysmenorrhea rats

[0062] 5.1 Writhing response results

[0063] Compared with the blank group, the writhing response frequency of the model group of rats was significantly increased (P<0.01), and the writhing latency was short, and the rest of the rats had a significant writhing frequency, indicating that the model was successfully modeled. Compared with the model group, the writhing response frequency of each administration group was significantly reduced (P<0.01), among which the compound essential oil group 4 was better than the rest of the essential oil groups; the latency of each administration group was significantly increased (P<0.01), among which each compound essential oil group was better than each single essential oil group, and the compound essential oil 4 was better than the rest of the compound essential oil groups. The results are shown in Table 2.

[0064] Table 2 Effect of essential oil on writhing frequency and latency of dysmenorrhea rats

[0065]

[0066] Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, & P<0.05, && P<0.01.

[0067] 5.2 Effects of essential oils on serum sex hormones of dysmenorrhea rats

[0068] Compared with the blank group, the PROG level of the model group was significantly reduced (P<0.01), and the E2 and OT levels were significantly increased (P<0.05), indicating that the sex hormone levels in the model group rats changed, and may cause sex hormone disorders in the uterus of rats to produce symptoms such as uterine pain; compared with the model group, the E2 level of each essential oil group was significantly reduced (P<0.05) and the PROG level was significantly increased (P<0.05), but there was no significant difference in the regulation of OT level. The influence of compound essential oil 4 on E2 level and PROG level was significantly higher than that of other essential oil groups. It is shown that each administration group adjusts the sex hormone indicators to different degrees, promotes the stable level of sex hormones in the body, and relieves the symptoms of "liver stagnation and qi stagnation" type dysmenorrhea. The results are shown in Table 3

[0069] Table 3 Effects of essential oils on E2, PROG, and OT of dysmenorrhea rats

[0070]

[0071] Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, & P<0.05, && P<0.01.

[0072] 5.3 Effects of essential oils on pain factors of dysmenorrhea rats

[0073] Compared with the blank group, the PGE2 and IL-6 levels of the model group were significantly increased (P<0.05), indicating that the pain factor levels in the model group rats changed significantly, which may cause the rats to have uterine pain and other symptoms; compared with the model group, the IL-6 level of each essential oil group was significantly reduced (P<0.01), and compound essential oil 3 and compound essential oil 4 had significant differences in PGE2 level (P<0.05), and the rest of the essential oil groups had no significant difference in PGE2 level (P>0.05). It is shown that each administration group adjusts the pain factor indicators to different degrees, inhibits the pain effect of the body, and relieves the symptoms of "liver stagnation and qi stagnation" type dysmenorrhea in rats. The results are shown in Table 4

[0074] Table 4 Effects of essential oils on PGE2 and IL-6 of dysmenorrhea rats

[0075]

[0076]

[0077] Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, & P<0.05, && P<0.01.

[0078] Effects of compound essential oil on liver stagnation and qi stagnation breast hyperplasia rats

[0079] The liver stagnation and qi stagnation type amenorrhea model of rats was established by intramuscular injection of estradiol benzoate and progesterone. The effects of compound essential oil on liver stagnation and qi stagnation breast hyperplasia rats were evaluated by measuring the nipple diameter and height, determining the serum estradiol and progesterone content by enzyme-linked immunosorbent assay, and determining the serum prolactin content by enzyme radioassay.

[0080] 1. Model replication

[0081] 100 SPF level SD female rats, weighing 200±20g, were bred in the laboratory for 7 days. Except for the blank group, all groups of rats were injected with estradiol benzoate 0.5mg / kg intramuscularly in the hind limbs once a day for 25 days, and then injected with progesterone 5mg / kg intramuscularly once a day for 5 days. The blank group of rats was injected with 0.5ml / kg of normal saline intramuscularly in the hind limbs once a day for 30 days.

[0082] 2. Grouping and administration

[0083] 100 SPF level SD female rats, weighing 200±20g, were bred in the laboratory for 7 days. They were randomly divided into a blank group, a model group, an angelica essential oil group, a cyperus rotundus essential oil group, a curcuma aromatica essential oil group, a compound essential oil group 1 (angelica-cyperus rotundus 1:1), a compound essential oil group 2 (angelica-cyperus rotundus-mangnolia officinalis-curcuma aromatica 1:1:1:2), a compound essential oil group 3 (angelica-cyperus rotundus-mangnolia officinalis-curcuma aromatica-bupleurum chinense-corydalis yanhusuo 1:1:1:2:1:2), a compound essential oil group 4 (angelica-cyperus rotundus-mangnolia officinalis-curcuma aromatica-bupleurum chinense-corydalis yanhusuo-lavandula officinalis-chamomile 1:1:1:2:1:2:1:1), and a compound essential oil group 5 (angelica-cyperus rotundus-mangnolia officinalis-curcuma aromatica-bupleurum chinense-corydalis yanhusuo-lavandula officinalis-chamomile-cuminum cyminum-syzygium aromaticum 1:1:1:2:1:2:1:1:1:1), with 10 rats in each group.

[0084] From the first day of modeling, the second and third pairs of nipples of all essential oil groups of rats were respectively smeared with 0.1 ml of 20% massage oil diluted with base oil, and the second and third pairs of nipples of the blank group and the model group of rats were respectively smeared with 0.1 ml of normal saline, all groups were given drugs once a day, for 30 days.

[0085] 3. Measurement of rat nipple diameter and height

[0086] On the 30th day of intervention, the diameter and height of the breast of SD rats in all groups were measured, the diameter (i.e. the horizontal maximum diameter of the nipple) and height (i.e. the distance from the tip of the nipple to the base of the nipple) of the second pair of nipples of SD rats were measured with an electronic vernier caliper, and the appearance of the breast was observed.

[0087] 4. Determination of serum hormone content

[0088] Serum estradiol and serum progesterone were detected by enzyme-linked immunosorbent assay according to the operation steps of the kit.

[0089] Serum prolactin was detected by enzyme radioassay according to the operation steps of the kit.

[0090] 5. Results and conclusions of liver stagnation and breast hyperplasia rats

[0091] 5.1 Effect of essential oil on rat nipple diameter and height

[0092] Compared with the blank group, the nipple diameter and height of the model group increased significantly (P<0.01); compared with the model group, the nipple diameter and height of each essential oil group decreased significantly (P<0.05), indicating that each drug group could inhibit the growth of nipple diameter and height to varying degrees, and all compound essential oil groups had higher inhibition than single essential oil groups, and compound essential oil group 4 had better effect than the rest, indicating that each essential oil group could relieve the symptoms of liver stagnation and breast hyperplasia in rats to varying degrees. The results are shown in Table 5

[0093] Table 5 Effect of essential oil on nipple diameter and height of breast hyperplasia rats

[0094]

[0095]

[0096] Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, & P<0.05, && P<0.01.

[0097] 5.2 Effect of essential oil on serum hormone content of rats

[0098] Compared with the blank group, the progesterone level of the model group was significantly reduced (P<0.01), and the serum prolactin and estradiol levels were significantly increased (P<0.01), indicating that the serum hormone levels in the model group rats changed significantly, which may cause the rats to develop symptoms such as mammary gland hyperplasia; compared with the model group, the progesterone level of each essential oil group was significantly increased (P<0.05), and the serum prolactin and estradiol levels were significantly reduced (P<0.01), indicating that the essential oils in each group could affect the hormone content to varying degrees, and the reduction degree of progesterone in all compound essential oil groups was higher than that in the single essential oil group, and the effect of compound essential oil group 4 was better than that of the remaining compound essential oil groups; the increase degree of serum prolactin and estradiol in all compound essential oil groups was higher than that in the single essential oil group, and the effect of compound essential oil group 4 was better than that of the remaining compound essential oil groups. The results are shown in Table 6

[0099] Table 6 Effect of essential oils on serum prolactin, estradiol and progesterone of dysmenorrhea rats

[0100]

[0101] Compared with the blank group, # P<0.05, ## P<0.01; compared with the model group, & P<0.05, && P<0.01.

[0102] Test Example 3 Clinical efficacy of essential oil composition of the application

[0103] 1. Alleviating effect on dysmenorrhea caused by liver stagnation

[0104] 1.1 Sixty patients diagnosed with dysmenorrhea caused by liver stagnation were selected from a hospital in Yibin City from June 2024 to October 2024. The age was 25-35 years old, and the average age was (27.91±4.64) years old; the disease duration was 6-10 months, and the average disease duration was (7.57±2.13) months; the menstrual cycle was 21-35 days, and the average was (27.21±5.87) days. They were randomly divided into a control group and an experimental group, and there was no statistically significant difference (P>0.05) in gender, age, disease duration, and past medical history between the two groups, which were comparable.

[0105] 1.2 Inclusion criteria ① Meet the diagnostic criteria for dysmenorrhea caused by liver stagnation in TCM Gynecology, and be diagnosed by examination; ② Age 25-35 years old; ③ No relevant treatment history within 1 month, and voluntarily participate and sign the informed consent form.

[0106] 1.3 Exclusion criteria ① Patients with dysmenorrhea caused by other reasons such as organic lesions; ② Patients with gynecological diseases such as cervical cancer; ③ Patients with coagulation dysfunction or severe organic lesions; ④ Patients with fertility plans in the past 3 months; ⑤ Patients with cognitive dysfunction who cannot cooperate with the study.

[0107] 1.4 Administration of the drug The control group was given ibuprofen sustained-release capsules, 300 mg per capsule, orally, 300 mg per time, 2 times per day, starting on the first day of the menstrual period, and taking for one week. The experimental group was given massage oil diluted with base oil containing 0.05% vanillyl butyl ether to a concentration of 10%, starting 7 days before the onset of menstruation, and applying the compound essential oil 4 massage oil to Taichong acupoint, Guanyuan acupoint, Qihai acupoint, and Xuehai acupoint, once in the morning and once in the evening, about 2 ml each time, and massaging each acupoint for about 2 min, until the onset of menstruation. After continuous treatment for 3 menstrual cycles, follow-up was conducted until the 6th month.

[0108] 1.5 Therapeutic efficacy criteria

[0109] According to the Guiding Principles for Clinical Research on New Drugs of Traditional Chinese Medicine, the efficacy index = [(pre-treatment score - post-treatment score) ÷ pre-treatment score] × 100%.

[0110] The treatment index was calculated by scoring method

[0111] 0 points: no pain;

[0112] 1-3 points: slight pain, tolerable;

[0113] 4-6 points: pain affecting sleep, still tolerable;

[0114] 7-10 points: gradually strong pain, unbearable, affecting appetite and sleep

[0115] Cure: after treatment, the symptoms of lower abdominal pain, nausea, vomiting, and other symptoms completely disappeared, and no recurrence was observed in 3 menstrual periods after drug withdrawal, and the EI was ≥90%; Significant improvement: after treatment, the patient's lower abdominal pain was significantly reduced, and the symptoms of nausea, vomiting, and other symptoms completely disappeared, and 75% ≤ EI < 90%; Improvement: after treatment, the patient's abdominal pain, nausea, vomiting, and other symptoms were all reduced, and 40% ≤ EI < 75%; Ineffective: not meeting the above standards. The total effective rate = (cure + significant improvement + improvement) / total number of cases × 100%.

[0116] 2. Relief effect on breast hyperplasia caused by liver stagnation and qi stagnation

[0117] 2.1 Fifty-two patients diagnosed with dysmenorrhea caused by liver stagnation and qi stagnation were selected from a hospital in Yibin City from May 2024 to December 2024. The age was 28-48 years old, and the average age was (30.56 ± 3.67) years old. The disease duration was 10-20 months, and the average disease duration was (14.77 ± 3.73) months. The patients were randomly divided into a control group and an experimental group. There was no statistically significant difference in gender, age, disease duration, and past medical history between the two groups (P > 0.05), and they were comparable.

[0118] 2.2 Diagnostic criteria

[0119] The liver stagnation type of syndrome differentiation standard refers to the Chinese Medicine Society of China <Guidelines for Diagnosis and Treatment of Common Diseases in TCM Surgery>: more common in young women, breast pain is the main performance, mostly distending pain, occasional sharp pain, mass, pain and menstrual cycle, emotional changes are closely related, before or after the menstrual period, emotional worse, after the menstrual period, often accompanied by chest distending pain, irritability, tongue pale red or red, thin white or thin yellow, pulse string.

[0120] 2.3 Inclusion criteria

[0121] (1) age 20-50 years old; (2) meet the diagnostic criteria and syndrome differentiation criteria of this disease; (3) patients have good compliance, can adhere to the treatment for more than 3 months; (4) patients know and agree to participate in the research

[0122] 2.4 Exclusion criteria

[0123] There is inflammation of the breast, breast cancer; (2) in lactation or pregnancy; (3) there is mental illness or combined organ disease; (4) during treatment, do not cooperate or poor compliance.

[0124] 2.5 Administration

[0125] The control group was given Chaihu Shugan pills, specifications 10g / pill, oral, 10g / time, 2 times / d, starting from the menstrual period, continuous treatment for 3 menstrual cycles. The experimental group was given massage oil containing 0.05% vanillyl butyl ether, diluted to a concentration of 10%, starting from 7 days before the menstrual period, and applying compound essential oil 3 massage oil on Guanmen acupoint, Dantian acupoint, Taichong acupoint, milk root acupoint, Zusanli acupoint, morning and evening once, each about 2ml, each about 2min, until the menstrual period, continuous treatment for 3 menstrual cycles.

[0126] 2.6 Efficacy criteria

[0127] After 3 months of treatment, the efficacy was evaluated according to the relevant literature. (1) Cure: symptoms and signs disappeared, and the reduction of TCM syndrome score was ≥90%; (2) Improvement: symptoms and signs basically subsided, and the reduction of TCM syndrome score was 70%-89%; (3) Effect: symptoms and signs were relieved, and the reduction of TCM syndrome score was 30%-69%; (4) Ineffective: symptoms and signs were not improved, and the reduction of TCM syndrome score was <30%. The sum of cure rate, significant efficiency and effective rate was the total effective rate. 2) According to the "TCM Disease Diagnosis and Treatment Routine" 081, the TCM syndrome scores before and after treatment were evaluated, including 3 aspects: breast lumps (diameter <1 cm (1 point), diameter 1-2 cm (2 points), diameter >2 cm (3 points)); breast pain (no tenderness, 1 point; dull pain, 2 points; dull pain with tenderness, 3 points; obvious pain or tenderness, 4 points; severe pain and unable to touch, 4 points); and 4 items of systemic accompanying symptoms, each scoring 3 points, with higher scores indicating more severe symptoms.

[0128] 3. Clinical efficacy analysis

[0129] 3.1 Efficacy on dysmenorrhea caused by liver stagnation and qi stagnation

[0130] After 3 months of treatment, the total effective rate of the experimental group was higher than that of the control group, and the total effective rate of the experimental group was 93.33%. After six months of follow-up, the total effective rate of the experimental group was higher than that of the control group, and the cure rate increased, indicating that the essential oil of the experimental group had good therapeutic effect on dysmenorrhea caused by liver stagnation and qi stagnation. The results are shown in Tables 7 and 8.

[0131] Table 7 3-month efficacy evaluation

[0132]

[0133]

[0134] Table 8 6-month efficacy evaluation

[0135]

[0136] 3.2 Efficacy on fibroadenosis caused by liver stagnation and qi stagnation

[0137] After 3 months of treatment, the total effective rate of the experimental group was higher than that of the control group, and the total effective rate of the experimental group was 96.67%. The scores of breast lumps, breast pain and systemic accompanying symptoms were significantly reduced in both groups after treatment, and the TCM syndrome score in the observation group was significantly lower than that in the control group (P<0.05). The results are shown in Tables 9 and 10.

[0138] Table 9 Comparison of clinical efficacy

[0139]

[0140] Table 10 Comparison of TCM syndrome scores before and after treatment

[0141]

[0142] Compared with the treatment before this group, # P<0.05; compared with the control group, & P<0.05.

Claims

1. An essential oil composition for improving dysmenorrhea and breast hyperplasia caused by liver depression and qi stagnation, characterized in that: It is prepared from the following raw materials in the following weight ratio: 0.5-1.5 parts of angelica essential oil and 0.5-1.5 parts of cyperus rotundus essential oil.

2. The essential oil composition for improving dysmenorrhea and breast hyperplasia caused by liver depression and qi stagnation according to claim 1, characterized in that: It is prepared from the following raw materials in the following weight ratio: 0.5-1.5 parts of angelica essential oil and 0.5-1.5 parts of cyperus rotundus essential oil.

3. The essential oil composition for improving dysmenorrhea and breast hyperplasia caused by liver depression and qi stagnation according to claim 1 or 2, characterized in that: The raw materials also contain peony bark essential oil and turmeric essential oil, and the weight ratio of the raw materials is: 0.5-1.5 parts of angelica essential oil, 0.5-1.5 parts of cyperus rotundus essential oil, 0.5-1.5 parts of peony bark essential oil, 1.0-3.0 parts of turmeric essential oil; Preferably, the weight ratio of the raw materials is: 1.0 part of Chinese angelica essential oil, 1.0 part of cyperus rotundus essential oil, 1.0 part of peony bark essential oil, and 2.0 parts of turmeric essential oil.

4. The essential oil composition for improving dysmenorrhea and mammary gland hyperplasia caused by liver depression and qi stagnation according to claim 3, characterized in that: The raw materials also contain bupleurum essential oil and yanhusuo essential oil, and the weight ratio is: 0.5-1.5 parts of Chinese Angelica essential oil, 0.5-1.5 parts of Cyperus rotundus essential oil, 0.5-1.5 parts of Paeonia suffruticosa essential oil, 1.0-3.0 parts of Curcuma aromatica essential oil, 0.5-1.5 parts of Bupleurum essential oil, and 1.0-3.0 parts of Corydalis yanhusuo essential oil; Preferably, the weight ratio of the raw materials is: 1.0 part of Chinese Angelica Sinensis essential oil, 1.0 part of Cyperus rotundus essential oil, 1.0 part of Paeonia Suffruticosa Andrews essential oil, 2.0 parts of Curcuma aromatica essential oil, 1.0 part of Bupleurum Root essential oil, and 2.0 parts of Corydalis yanhusuo essential oil.

5. The essential oil composition for improving dysmenorrhea and breast hyperplasia caused by liver depression and qi stagnation according to claim 4, characterized in that: The raw materials also contain lavender essential oil and chamomile essential oil, and the weight ratio is: 0.5-1.5 parts of Chinese Angelica essential oil, 0.5-1.5 parts of Cyperus rotundus essential oil, 0.5-1.5 parts of Paeonia suffruticosa essential oil, 1.0-3.0 parts of Curcuma aromatica essential oil, 0.5-1.5 parts of Bupleurum chinense essential oil, 1.0-3.0 parts of Corydalis yanhusuo essential oil, 0.5-1.5 parts of lavender essential oil, and 0.5-1.5 parts of chamomile essential oil; Preferably, the weight ratio of the raw materials is: 1.0 part of Chinese angelica essential oil, 1.0 part of cyperus rotundus essential oil, 1.0 part of peony bark essential oil, 2.0 parts of turmeric essential oil, 1.0 part of bupleurum essential oil, 2.0 parts of corydalis quinoa essential oil, 1.0 part of lavender essential oil, and 1.0 part of chamomile essential oil.

6. The essential oil composition for improving dysmenorrhea and breast hyperplasia caused by liver depression and qi stagnation according to claim 5, characterized in that: The raw materials also contain fennel, dried ginger, cloves or cinnamon essential oils, and the weight ratio is: 0.5-1.5 parts of angelica essential oil, 0.5-1.5 parts of cyperus rotundus essential oil, 0.5-1.5 parts of peony bark essential oil, 1.0-3.0 parts of turmeric essential oil, 0.5-1.5 parts of bupleurum essential oil, 1.0-3.0 parts of corydalis essential oil, 0.5-1.5 parts of lavender essential oil, 0.5-1.5 parts of chamomile essential oil, 0.5-1.5 parts of fennel, dried ginger, cloves, or cinnamon essential oil; Preferably, the weight ratio of the raw materials is: 1.0 part of Chinese angelica essential oil, 1.0 part of cyperus rotundus essential oil, 1.0 part of peony bark essential oil, 2.0 parts of turmeric essential oil, 1.0 part of bupleurum essential oil, 2.0 parts of corydalis quinoa essential oil, 1.0 part of lavender essential oil, 1.0 part of chamomile essential oil, 1.0 part of fennel essential oil, and 1.0 part of clove essential oil.

7. The essential oil composition for improving dysmenorrhea and breast hyperplasia caused by liver depression and qi stagnation according to any one of claims 1 to 6, characterized in that: The raw materials are used as active ingredients, and acceptable excipients or auxiliary ingredients are added to prepare a common external preparation; preferably, the external preparation is an essential oil, a patch, an ointment, a microemulsion gel, or a suspension.

8. Use of the essential oil composition according to any one of claims 1 to 7 in the preparation of an external-applied medicament for improving dysmenorrhea caused by liver depression and qi stagnation.

9. Use of the essential oil composition according to any one of claims 1 to 7 in the preparation of an external-use medicament for improving breast hyperplasia caused by liver depression and qi stagnation.

10. The use according to claim 8 or claim 9, characterized in that: The external medicine is administered at acupoints; preferably, it is administered at any one of Taichong acupoint, Guanyuan acupoint, Qihai acupoint, and Xuehai acupoint, or a combination of two or more acupoints.

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