Traditional Chinese medicine composition for treating primary dysmenorrhea and preparation method and application thereof

Abstract

The invention provides a traditional Chinese medicine composition for treating primary dysmenorrhea and a preparation method and application thereof.The traditional Chinese medicine composition is prepared from, by weight, 3-15 parts of rhizoma corydalis, 6-15 parts of angelica sinensis, 3-15 parts of ligusticum wallichii, 3-10 parts of rhizoma zingiberis, 1.5-6 parts of fennel and 3-12 parts of cassia twigs, and the traditional Chinese medicine composition is prepared from, by weight, 3-15 parts of rhizoma corydalis, 6-15 parts of angelica sinensis, 3-15 parts of ligusticum wallichii, 3-10 parts of rhizoma zingiberis, 1.5-6 parts of fennel and 3-12 parts of cassia twigs. The traditional Chinese medicine composition is prepared by grinding and uniformly mixing the raw materials, all the components have a synergistic effect, and the traditional Chinese medicine composition has the effects of resisting inflammation, resisting oxidative stress, regulating the estrogen level, improving the pathological morphology of the uterus and easing pain, and has a remarkable effect on treating primary dysmenorrhea; the traditional Chinese medicine composition is used for treating primary dysmenorrhea in the form of a traditional Chinese medicine patch, and by combining traditional Chinese medicine application and thermal therapy, local skin blood flow can be remarkably increased, the diffusivity and solubility of medicine in cuticle can be improved, the skin absorption capacity can be enhanced, the medicine absorption and permeation amount can be increased, local blood circulation can be improved, and pain can be relieved; and no anaphylactic reaction is caused to the skin.

Description

Technical Field

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

[0002] Primary dysmenorrhea (PD) refers to lower abdominal pain that occurs during the menstrual cycle in the absence of organic pelvic lesions. The symptoms of PD usually first appear within 6 - 12 months after the onset of menstruation. When severe, it causes symptoms such as nausea, vomiting, diarrhea, and sleep disorders, and increases the risk of anxiety and depression, having a strong negative impact on both the body and mind.

[0003] As one of the common gynecological diseases, PD is an important cause that prevents women from studying or working normally, seriously affecting the quality of life of women. Currently, Western medicine for treating PD mainly uses non - steroidal anti - inflammatory drugs and contraceptives. Ibuprofen can effectively inhibit cyclooxygenase, reduce the production of prostaglandins, and achieve immediate pain relief, but long - term use may cause gastritis and kidney function damage. Contraceptives reduce the thickness of the endometrium by inhibiting ovulation, thereby reducing the production of prostaglandins and effectively relieving pain. However, long - term use may cause side effects such as menstrual disorders and vaginal bleeding, and in severe cases, may even lead to infertility. China is rich in Chinese herbal medicine resources, and the research and development of traditional Chinese medicine for treating primary dysmenorrhea has important clinical application value. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition for treating primary dysmenorrhea.

[0005] Another technical problem to be solved by the present invention is to provide a preparation method of the above - mentioned traditional Chinese medicine composition for treating primary dysmenorrhea.

[0006] Another technical problem to be solved by the present invention is to provide the application of the above - mentioned traditional Chinese medicine composition for treating primary dysmenorrhea.

[0007] The technical solution adopted by the present invention is as follows:

[0008] A traditional Chinese medicine composition for treating primary dysmenorrhea is composed of Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare Mill. and Cinnamomum cassia Presl. By weight, it is 3 - 15 parts of Corydalis yanhusuo, 6 - 15 parts of Angelica sinensis, 3 - 15 parts of Ligusticum wallichii, 3 - 10 parts of Drynaria fortunei, 1.5 - 6 parts of Foeniculum vulgare Mill. and 3 - 12 parts of Cinnamomum cassia Presl.

[0009] Preferably, for the above - mentioned traditional Chinese medicine composition for treating primary dysmenorrhea, the weight ratio of Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare Mill. and Cinnamomum cassia Presl. is 1:1:1:1:1:1.

[0010] The preparation method of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea is to weigh Corydalis yanhusuo, Angelica sinensis, Ligusticum chuanxiong, Drynaria fortunei, Fructus Foeniculi and Ramulus Cinnamomi according to the formula amount, powder and mix them evenly to obtain the composition.

[0011] Preferably, for the preparation method of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea, after powdering and mixing evenly, it is sieved through a 100-mesh sieve.

[0012] The application of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea in the preparation of drugs for treating primary dysmenorrhea.

[0013] The above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea can be prepared into various external medicine dosage forms according to actual application needs.

[0014] Preferably, for the application of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea, the drug is a traditional Chinese medicine patch.

[0015] Preferably, for the application of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea, the traditional Chinese medicine patch is prepared by the following method:

[0016] (1) Weigh Corydalis yanhusuo, Angelica sinensis, Ligusticum chuanxiong, Drynaria fortunei, Fructus Foeniculi and Ramulus Cinnamomi according to the formula amount, powder and mix them evenly, then sieve (preferably through a 100-mesh sieve), and put the evenly mixed medicinal powder into a non-woven traditional Chinese medicine bag and seal it;

[0017] (2) Put iron powder, activated carbon, vermiculite and NaCl into a sealed bag and shake well to make a solid material, with 20 - 40 parts by weight of iron powder, 1 - 6 parts by weight of activated carbon, 1 - 5 parts by weight of vermiculite and 1 - 5 parts by weight of NaCl;

[0018] (3) Add a water-absorbing resin to water to make a liquid gel, pour the solid material into a mortar and stir, then pour the liquid gel into the mortar, and grind with a pestle until completely mixed evenly and there are no obvious lumps visible to the naked eye to obtain a uniformly mixed material;

[0019] (4) Take the uniformly mixed material and put it into a composite non-woven bag, and complete vacuum packaging with a vacuum packaging machine to obtain a heat patch.

[0020] Preferably, for the application of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea, in step (2), there are 30 parts by weight of iron powder, 4 parts by weight of activated carbon, 1.2 parts by weight of vermiculite and 1.2 parts by weight of NaCl.

[0021] Preferably, for the application of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea, when making a 3 cm * 3 cm heat patch, put 5 g of the uniformly mixed material into a composite non-woven bag.

[0022] Preferably, for the application of the above-mentioned traditional Chinese medicine composition for treating primary dysmenorrhea, when making a 5 cm * 5 cm heat patch, put 15 g of the uniformly mixed material into a composite non-woven bag.

[0023] Preferably, for the application of the above traditional Chinese medicine composition for treating primary dysmenorrhea, the heat patch and the non-woven traditional Chinese medicine bag containing the medicinal powder (traditional Chinese medicine composition) are placed separately, and the two are superposed and combined together by adhesive tape or double-sided tape during administration.

[0024] The beneficial effects of the present invention are as follows:

[0025] For the above traditional Chinese medicine composition for treating primary dysmenorrhea, each component acts synergistically, having the effects of anti-inflammatory, anti-oxidative stress, regulating estrogen level, improving uterine pathological morphology and analgesia, and having a significant effect on treating primary dysmenorrhea; applying the traditional Chinese medicine composition to treat primary dysmenorrhea in the form of a traditional Chinese medicine patch, the combination of traditional Chinese medicine application and heat therapy (physical penetration promotion therapy) can significantly increase local skin blood flow, improve the diffusion rate and solubility of the drug in the stratum corneum, enhance skin absorption ability, increase the drug absorption and penetration amount, improve local blood circulation, relieve pain, play a synergistic therapeutic role, and has no allergic reaction to the skin. Description of the Drawings

[0026] Figure 1 : Effect of the dysmenorrhea formula on the number of acetic acid-induced writhing in mice Note: Compared with the Control group, * P < 0.05;

[0027] Figure 2 : Effect of the dysmenorrhea formula on the writhing behavior of rats Note: Compared with the Control group, ** P < 0.01, *** P < 0.001; compared with the Model group, # P < 0.05;

[0028] Figure 3 : Effect of the dysmenorrhea formula on the uterine coefficient Note: Compared with the Control group, *** P < 0.001; compared with the Model group, # P < 0.05;

[0029] Figure 4 : Effect of the dysmenorrhea formula on the uterine morphology of rats;

[0030] Figure 5 : Effect of the dysmenorrhea formula on the uterine pathological tissue of rats Note: The blue arrow indicates glandular cavity dilation, the black arrow indicates vacuolar degeneration of endometrial epithelial cells, the red arrow indicates congestion, and the yellow arrow indicates neutrophil infiltration;

[0031] Figure 6 : Effect of the dysmenorrhea formula on the serum estrogen level Note: Compared with the Control group, ** P < 0.01; compared with the Model group, # P < 0.05;

[0032] Figure 7 : Effects of Dysmenorrhea Prescription on the Serum TNF-α Level in Rats Note: Compared with the Control group, ** P < 0.01; compared with the Model group, # P < 0.05;

[0033] Figure 8 : Effects of Dysmenorrhea Prescription on the Serum Prostaglandin Level in PD Rats Note: Compared with the Control group, * P < 0.05, ** P < 0.01; compared with the Model group, # P < 0.05;

[0034] Figure 9 : Effects of Dysmenorrhea Prescription on the Uterine Prostaglandin Level in PD Rats Note: Compared with the Control group, ** P < 0.01; compared with the Model group, # P < 0.05;

[0035] Figure 10 : Effects of Dysmenorrhea Prescription on the Substance P Level in the Serum of Rats Note: Compared with the Control group, * P < 0.05; compared with the Model group, # P < 0.05, ## P < 0.01;

[0036] Figure 11 : Effects of Dysmenorrhea Prescription on the Serum Oxidative Stress Level in PD Rats Note: Compared with the Control group, ** P < 0.01, *** P < 0.001; compared with the Model group, # P < 0.05;

[0037] Figure 12 : Effects of Dysmenorrhea Prescription on the Skin Erythema and Edema in Guinea Pigs;

[0038] Figure 13 : Effects of Dysmenorrhea Prescription on the Blood Routine of Guinea Pigs. Specific Embodiments

[0039] In order to enable those skilled in the art to better understand the technical solutions of the present invention, the following further details the technical solutions of the present invention in conjunction with the accompanying drawings and specific embodiments.

[0040] Example 1

[0041] A traditional Chinese medicine composition (dysmenorrhea formula) for treating primary dysmenorrhea, which is composed of Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia. Among them, there are 10g of Corydalis yanhusuo, 10g of Angelica sinensis, 10g of Ligusticum wallichii, 10g of Drynaria fortunei, 10g of Foeniculum vulgare and 10g of Cinnamomum cassia.

[0042] The preparation method of the above traditional Chinese medicine composition for treating primary dysmenorrhea is as follows: Weigh Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia according to the prescription amount, powder and mix them evenly, then pass through a 100-mesh sieve. Accurately weigh 0.2g of the evenly mixed medicinal powder, put it into a non-woven traditional Chinese medicine bag and seal it.

[0043] Example 2

[0044] A traditional Chinese medicine composition for treating primary dysmenorrhea, which is composed of Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia. Among them, there are 3g of Corydalis yanhusuo, 6g of Angelica sinensis, 3g of Ligusticum wallichii, 10g of Drynaria fortunei, 6g of Foeniculum vulgare and 12g of Cinnamomum cassia.

[0045] The preparation method of the above traditional Chinese medicine composition for treating primary dysmenorrhea is as follows: Weigh Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia according to the prescription amount, powder and mix them evenly, then you will get it.

[0046] Example 3

[0047] A traditional Chinese medicine composition for treating primary dysmenorrhea, which is composed of Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia. Among them, there are 15g of Corydalis yanhusuo, 15g of Angelica sinensis, 15g of Ligusticum wallichii, 3g of Drynaria fortunei, 1.5g of Foeniculum vulgare and 3g of Cinnamomum cassia.

[0048] The preparation method of the above traditional Chinese medicine composition for treating primary dysmenorrhea is as follows:

[0049] (1) Weigh Corydalis yanhusuo, Angelica sinensis, Ligusticum wallichii, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia according to the prescription amount, powder and mix them evenly, then pass through a 100-mesh sieve. Accurately weigh 0.2g of the evenly mixed medicinal powder, put it into a non-woven traditional Chinese medicine bag and seal it;

[0050] (2) Put 30g of iron powder, 4g of activated carbon, 1.2g of vermiculite and 1.2g of NaCl into a sealed bag and shake well to make a solid material;

[0051] (3) Add a water-absorbing resin to water to make a liquid gel. Pour the solid material into a mortar and stir, then pour the liquid gel into the mortar and grind it with a pestle until it is completely mixed evenly and there is no obvious caking to the naked eye, obtaining a uniformly mixed material;

[0052] (4) Take 5g of the uniformly mixed material and put it into a composite non-woven bag, and complete the vacuum packaging with a vacuum packaging machine to make a 3cm*3cm heating patch.

[0053] Example 4

[0054] A traditional Chinese medicine composition for treating primary dysmenorrhea, which is composed of Corydalis yanhusuo, Angelica sinensis, Ligusticum chuanxiong, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia. Among them, there are 9 g of Corydalis yanhusuo, 10 g of Angelica sinensis, 8 g of Ligusticum chuanxiong, 6 g of Drynaria fortunei, 3 g of Foeniculum vulgare and 8 g of Cinnamomum cassia.

[0055] The preparation method refers to Example 3, the difference is that in step (4), 15 g of the uniformly mixed materials are put into a composite non-woven bag and vacuum-packed by a vacuum packaging machine to obtain a heating patch of 5 cm * 5 cm.

[0056] Example 5

[0057] A traditional Chinese medicine composition for treating primary dysmenorrhea, which is composed of Corydalis yanhusuo, Angelica sinensis, Ligusticum chuanxiong, Drynaria fortunei, Foeniculum vulgare and Cinnamomum cassia. Among them, there are 12 g of Corydalis yanhusuo, 8 g of Angelica sinensis, 11 g of Ligusticum chuanxiong, 10 g of Drynaria fortunei, 4 g of Foeniculum vulgare and 10 g of Cinnamomum cassia.

[0058] The preparation method refers to Example 3.

[0059] Analysis of the formula of the traditional Chinese medicine composition in the above examples:

[0060] In the composition, Angelica sinensis is sweet, pungent and warm in nature, and has the effect of enriching blood and promoting blood circulation; Ligusticum chuanxiong is pungent and warm in nature, can enhance the blood-activating effect of Angelica sinensis, and is good at dispersing, moving but not staying, dredging qi and blood; Drynaria fortunei is pungent and hot in nature, can warm the spleen and stomach and dispel cold pathogens; Foeniculum vulgare is pungent and warm in nature, and has the effects of dispelling cold and relieving pain, regulating qi and harmonizing the stomach; Corydalis yanhusuo is pungent, bitter and warm in nature, can enhance the effect of promoting blood circulation, promoting qi movement and relieving pain; Cinnamomum cassia is pungent, sweet and warm in nature, can warm the meridians, promote blood circulation, and cooperate with other herbs to dispel cold. The various components act synergistically, having the effects of anti-inflammatory, antioxidant stress, regulating estrogen levels, improving the pathological morphology of the uterus and analgesia, and having a significant effect on treating primary dysmenorrhea.

[0061] Experimental Example 1

[0062] Anti-inflammatory and analgesic experiment on mice

[0063] (1) Hot plate experiment

[0064] After 60 Kunming mice were adaptively fed for 3 days, the thermal pain thresholds of each group of mice were detected: A beaker was placed in a water bath preheated to 55 °C, and the thermometer ensured that the temperature was 55 ± 0.5 °C. The mice were placed in the beaker, and the time when they showed the behavior of licking the hind paw (lifting the hind paw) was recorded as the pain threshold. Those with a time less than 5 s or greater than 30 s were discarded. The measurement was repeated three times, with an interval of 20 min each time, and the average of the three times was taken as the basic pain threshold.

[0065] Forty mice with qualified pain thresholds were randomly divided into four groups of 10 mice each, namely the blank (Control) group, the hot pack group, the Tongjing formula (TJF) group, and the warm uterus patch group. In the Hot pack group, a 3x3 cm hot pack (prepared by the method described in steps (2)-(4) of Example 3) was applied to the abdomen of the mice. In the TJF group, a 3x3 cm hot pack + 2 packages of Tongjing formula medicine bags (the traditional Chinese medicine composition described in Example 1) were applied to the abdomen of the mice. In the Warm uterus group, a 3x3 cm hot pack + 2 packages of warm uterus patch medicine bags (the warm uterus patch medicine bag was a positive control drug, prepared by removing the medicine bag of the commercially available Beijing Tongrentang warm uterus hot compress patch and filling 0.2 g of the medicine powder into a non-woven fabric bag) were applied to the abdomen of the mice, each time for 3 hours, for 3 consecutive days, once a day. The blank (Control) group was only wrapped around the abdomen with medical tape for one week, and the winding time was the same as that of the drug administration group.

[0066] After the last administration, the thermal pain thresholds of the mice in each group were measured, repeated three times, with an interval of 20 min each time. For those exceeding 30 s, the pain threshold was calculated as 30 s. The results showed that compared with before administration, the Tongjing formula could significantly prolong the thermal pain threshold of the mice (P < 0.05). Compared with the Control group after administration, the Tongjing formula could significantly prolong the thermal pain threshold of the mice (P < 0.01), as shown in Table 1.

[0067] Table 1 Effects of the Tongjing formula on the thermal pain threshold of mice

[0068]

[0069]

[0070] Note: Compared with the Control group after administration, * P < 0.05, ** P < 0.01; compared with before administration in the same group, # P < 0.05

[0071] (2) Cold plate experiment

[0072] After 3 days of adaptive feeding of 60 Kunming mice, the cold pain thresholds of the mice in each group were detected: Sufficient crushed ice cubes were put into a foam box and compacted, and a beaker was placed on the ice to keep the bottom of the beaker at 4 ± 1 °C. The mice were put into the beaker, and the reaction time of quickly lifting the hind paw was recorded as the pain threshold. Those with a time greater than 60 s were not used. The measurement was repeated three times, with an interval of 20 min each time, and the average of the three times was taken as the basic pain threshold.

[0073] Forty mice with qualified pain thresholds were randomly divided into four groups of 10 each, namely the blank (Control) group, the hot pack group, the TJF (dysmenorrhea formula) group, and the warm uterus patch group. In the hot pack group, a 3x3 cm hot pack was applied to the abdomen of the mice; in the TJF group, a 3x3 cm hot pack + 2 packs of dysmenorrhea formula medicine bags were applied to the abdomen of the mice; in the warm uterus patch group, a 3x3 cm hot pack + 2 packs of warm uterus patch medicine bags were applied to the abdomen of the mice, each time for 3 hours, for 3 consecutive days, once a day. The blank (Control) group was only wrapped around the abdomen with medical tape for one week, and the wrapping time was the same as that of the drug administration group.

[0074] After the last administration, the cold pain thresholds of the mice in each group were measured, repeated three times, with an interval of 20 minutes each time. For those exceeding 60 s, the pain threshold was calculated as 60 s. The results showed that compared with before administration, the TJF could significantly prolong the cold pain threshold of the mice (P < 0.01). Compared with the Control group after administration, the TJF could significantly prolong the cold pain threshold of the mice (P < 0.001), as shown in Table 2.

[0075] Table 2 Effects of TJF on the cold pain threshold of mice

[0076]

[0077]

[0078] Note: Compared with the Control group after administration, * P < 0.05, ** P < 0.01; compared with before administration in the same group, ## P < 0.01, ### P < 0.001

[0079] (3) Acetic acid writhing test

[0080] Forty Kunming mice were randomly divided into four groups of 10 each, namely the blank (Control) group, the hot pack group, the TJF (dysmenorrhea formula) group, and the warm uterus patch group. In the hot pack group, a 3x3 cm hot pack was applied to the abdomen of the mice; in the TJF group, a 3x3 cm hot pack + 2 packs of dysmenorrhea formula medicine bags were applied to the abdomen of the mice; in the warm uterus patch group, a 3x3 cm hot pack + 2 packs of warm uterus patch medicine bags were applied to the abdomen of the mice, each time for 3 hours, for 3 consecutive days, once a day.

[0081] After the last administration, 0.2 ml of 0.6% glacial acetic acid was intraperitoneally injected into each mouse, and the number of writhing times within 20 minutes was immediately observed. If Figure 1As shown, the results indicated that compared with the Control group, Tongjing Recipe could significantly reduce the writhing times of mice (P < 0.05).

[0082] Experimental Example 2

[0083] Experiment on primary dysmenorrhea in rats

[0084] (1) Establishment of primary dysmenorrhea model and administration

[0085] The modeling and administration plan is shown in Table 3. Seventy-two rats were randomly divided into 6 groups, with 12 rats in each group, namely the blank (Control) group, the model (Model) group, the hot pack (Hot pack) group, the low-dose Tongjing Recipe (TJF-L) group, the high-dose Tongjing Recipe (TJF-H) group, and the warm uterus patch (Warm uterus) group. The rats were continuously subcutaneously injected with estradiol benzoate for 10 days (subcutaneously injected with 0.5 mg / rat on the 1st and 10th days, and 0.2 mg / rat on the 2nd - 9th days), once a day. The Control group was intraperitoneally injected with an equal volume of normal saline. Since the 8th day of injection, the hair on the lower abdomen of the rats in the Hot pack group, TJF-L group, TJF-H group, and Warm uterus group was shaved. The Hot pack group was applied with a 3x3 cm heating patch (prepared by the method described in steps (2) - (4) of Example 3), the TJF-L group was applied with a 3x3 cm heating patch + 1 package of Tongjing Recipe medicine bag (the traditional Chinese medicine composition described in Example 1), the TJF-H group was applied with a 3x3 cm heating patch + 2 packages of Tongjing Recipe medicine bag (the traditional Chinese medicine composition described in Example 1), and the Warm uterus group was applied with a 3x3 cm heating patch + 2 packages of warm uterus patch medicine bag. The abdomen of the rats was wound around with medical adhesive tape for one week to make the medicine bag close to the lower abdomen of the rats, continuously for 3 days, 2 times a day, 4 hours each time. The rats in the Model group and the Control group were only wound around the abdomen with medical adhesive tape for one week, and the winding time was the same as that of the administration group. 3 hours after application in each group on the 11th day of modeling, the rats in the Model group, Hot pack group, TJF-L group, TJF-H group, and Warm uterus group were all intraperitoneally injected with 2 U / rat (0.4 ml / rat) of oxytocin, and the Control group was intraperitoneally injected with an equal volume of normal saline. The samples were taken 1 hour later.

[0086] Table 3 Modeling and administration plan

[0087]

[0088] (2) Effect of Tongjing Recipe on the writhing behavior of rats

[0089] Record the time (i.e., latent period) from the injection of oxytocin to the occurrence of writhing response in each group of rats and the number of writhing times within 30 min. The scores are independently recorded by two experimenters. The writhing score is carried out according to the ethological scoring criteria, as shown in Table 4. Writhing score = number of times at grade 0 × 0 (points) + number of times at grade 1 × 1 (points) + number of times at grade 2 × 2 (points) + number of times at grade 3 × 3 (points).

[0090] Table 4 Writhing score table

[0091]

[0092] As Figure 2 shown, the results indicate that compared with the Control group, the writhing latent period of rats in the Model group was significantly reduced (P < 0.001), the number of writhing times was significantly increased (P < 0.001), and the writhing score was significantly increased (P < 0.01); compared with the Model group, the number of writhing times in the TJF-L group was significantly reduced (P < 0.05), and the writhing score was significantly reduced (P < 0.05); the writhing latent period in the TJF-H group was significantly prolonged (P < 0.05), the number of writhing times was significantly reduced (P < 0.05), and the writhing score was significantly reduced (P < 0.05).

[0093] (3) Effects of Dysmenorrhea Prescription on Uterine Pathological Morphology in Rats

[0094] After the observation of writhing response ended, anesthetize the rats and excise the uterine tissues. Separate the fat and connective tissues on the tissues, wash them in PBS buffer, blot the excess water with absorbent paper, and record the weight (g) of the uterine tissues on an electronic balance. Calculation method of uterine coefficient: uterine weight (g) / rat body weight (g) * 100%.

[0095] Take the uterine tissues at the same segment on the same side of the rats, fix them with formalin, and then dehydrate, impregnate with wax, embed, section, and stain them successively after 24 h.

[0096] As Figure 3 、 Figure 4 shown, the results show that compared with the Control group, the uterine coefficient of rats in the Model group was significantly increased (P < 0.001), and the uterine body was enlarged; compared with the Model group, the uterine coefficients of the TJF-L group and the TJF-H group were significantly reduced (P < 0.05), and there was no significant difference in the uterine coefficients of the Hot pack group and the Warm uterus group (P > 0.05).

[0097] The uterine tissues of normal rats consist of adventitia, muscular layer, and endometrium; the adventitia is serosa, the muscular layer is relatively thick and the stratification is not obvious, the endometrium is composed of endometrial epithelium and lamina propria, the endometrial epithelium is simple columnar epithelial cells, and the epithelium invaginates into the lamina propria to form many tubular uterine glands.

[0098] AsFigure 5 As shown, no abnormalities were observed in the uterine tissues of rats in the Control group. In the Model group, degenerative or necrotic endometrial epithelial cells were visible in the uterine tissues, the number of uterine glands in the lamina propria increased, the glandular lumens dilated, neutrophil granulocytes infiltrated, and the lamina propria was congested. In the Hotpack group, TJF-L group, and Warm uterus group, degenerative or necrotic endometrial epithelial cells were still visible in the uterine tissues, the number of uterine glands in the lamina propria increased, the glandular lumens dilated, the lamina propria was congested, and no neutrophil infiltration was observed; in the TJF-H group, necrosis of endometrial epithelial cells and congestion of the lamina propria decreased, the dilation of glandular lumens decreased, and no neutrophil infiltration was observed.

[0099] (4) Effects of Tongjing Prescription on Serum Estrogen Levels in Rats

[0100] The content of estradiol in the serum of rats was detected by ELISA method. As Figure 6 shown, the results showed that compared with the Control group, the estradiol level in the serum of rats in the Model group was significantly increased (P < 0.01); compared with the Model group, the estradiol level in the TJF-H group was significantly decreased (P < 0.05).

[0101] (5) Effects of Tongjing Prescription on Serum Inflammatory Pain-causing Factors in Rats

[0102] The levels of TNF-α, PGF2α, PGE2, and SP in the serum of rats, as well as the levels of PGF2α and PGE2 in the uterine tissues, were detected by ELISA method.

[0103] As Figure 7 shown, the results showed that compared with the Control group, the TNF-α level in the Model group was significantly increased (P < 0.01); compared with the Model group, the TNF-α level in the TJF-H group was significantly decreased (P < 0.05).

[0104] As Figure 8 shown, compared with the Control group, the concentration of PGF2α in the serum of rats in the Model group was significantly increased (P < 0.01), and the concentration of PGE2 was significantly increased (P < 0.05); compared with the Model group, the concentration of PGF2α in the serum of rats in the TJF-L group, TJF-H group, and Warm uterus group was significantly decreased (P < 0.05).

[0105] As Figure 9 shown, compared with the Control group, the concentration of PGE2 in the uterus of rats in the Model group was significantly increased (P < 0.05); compared with the Model group, the concentration of PGE2 in the uterus of rats in the TJF-L group and TJF-H group was significantly decreased (P < 0.05).

[0106] As Figure 10As shown, compared with the Control group, the level of SP in the serum of rats in the Model group was significantly increased (P < 0.05); compared with the Model group, the level of SP in the serum of the TJF-L group was significantly decreased (P < 0.05), and the level of SP in the serum of the TJF-H group was significantly decreased (P < 0.01). There was no significant difference in the level of SP in the serum between the Hot pack group and the Warm uterus group (P > 0.05).

[0107] (6) Effects of Dysmenorrhea Prescription on Serum Oxidative Stress Indexes in Rats

[0108] The levels of SOD and MDA in the serum of rats were detected by biochemical method. As Figure 11 shown, the results showed that compared with the Control group, the activity of SOD in the serum of rats in the Model group was significantly decreased (P < 0.001), and the content of MDA was significantly increased (P < 0.01); compared with the Model group, the activity of SOD in the TJF-H group was significantly increased (P < 0.05), and the content of MDA was significantly decreased (P < 0.05).

[0109] Experimental Example 3

[0110] Guinea Pig Skin Allergy Experiment

[0111] (1) Administration Method and Evaluation of Sensitization Reaction

[0112] Nine guinea pigs were randomly divided into a blank (Control) group, a Dysmenorrhea Prescription (TJF) group, and a 2,4-dinitrochlorobenzene (DNCB) group, with 3 guinea pigs in each group.

[0113] ① Sensitization contact: The hair on the left back of the guinea pigs was removed. In the Control group, a 5x5 cm heat patch (prepared by the method described in steps (2)-(4) of Example 4) was applied. In the TJF group, a 5x5 cm heat patch + 2 packs of Dysmenorrhea prescription medicine bags (the traditional Chinese medicine composition described in Example 1) were applied. They were fixed with medical adhesive tape to make the administration in each group fully contact with the skin. In the DNCB group, 0.2 ml of 1% 2,4-dinitrochlorobenzene solution was applied to the depilated skin. After 6 hours, the heat patch and medicine bags were removed, and the administration was carried out once on the 1st, 8th, and 15th days of the experiment. ② Challenge contact: 14 days after the last administration, the Control group, the TJF group, and the DNCB group were administered again, and the administration method was the same as that of "sensitization contact". The skin erythema, edema of guinea pigs, and the occurrence of systemic symptoms such as unsteady standing, dyspnea, and anaphylactic shock were recorded at 1 hour, 24 hours, 48 hours, and 72 hours after the challenge contact.

[0114] The scoring and evaluation criteria for skin sensitization reactions are shown in Tables 5 and 6.

[0115] Average score of sensitization reaction = (total score of erythema formation + total score of edema formation) / total number of animals. Incidence of sensitization reaction (%) = number of animals with skin erythema, edema or systemic allergic reaction / total number of test animals × 100%.

[0116] Table 5 Scoring criteria for sensitization reaction

[0117]

[0118] Table 6 Evaluation criteria for sensitization

[0119]

[0120] After 72 hours of observation after challenge contact, no allergic reactions occurred in the Control group and the TJF group, and the skin was smooth without erythema or edema. All guinea pigs in the DNCB group showed erythema of varying degrees, indicating extreme sensitization, and the incidence of sensitization was 100%, as shown in Table 7. Figure 12 。

[0121] Table 7 Average score of skin sensitization reaction of Tongjing Recipe

[0122]

[0123]

[0124] (3) Effects of Tongjing Recipe on blood routine of guinea pigs

[0125] As Figure 13 shown, compared with the Control group, there were no significant differences in the levels of red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin content (MCH), mean corpuscular hemoglobin concentration (MCHC), platelets (PLT), and procalcitonin (PCT) in the whole blood of guinea pigs in the TJF group and the DNCB group (P > 0.05).

[0126] In summary, the traditional Chinese medicine composition described in the present invention can significantly exert anti-inflammatory, antioxidant stress, regulate estrogen levels, improve uterine pathological morphology, and analgesic effects, effectively relieve the symptoms of primary dysmenorrhea, and has no allergic reaction to the skin.

[0127] The above embodiments are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention should fall within the protection scope determined by the claims of the present invention.

Claims

1. A Chinese medicine composition for treating primary dysmenorrhea, characterized in that: The invention is composed of corydalis, angelica, chuanxiong, dried ginger, fennel and cassia twig, which are 3-15 parts of corydalis, 6-15 parts of angelica, 3-15 parts of chuanxiong, 3-10 parts of dried ginger, 1.5-6 parts of fennel and 3-12 parts of cassia twig in parts by weight.

2. The Chinese medicine composition for treating primary dysmenorrhea according to claim 1, characterized in that: The weight ratio of the Rhizoma Corydalis, Radix Angelicae Sinensis, Rhizoma Chuanxiong, Dry Ginger, Fennel and Cinnamon Twig is 1:1:1:1:1:

1.

3. The method for preparing the Chinese medicine composition for treating primary dysmenorrhea according to claim 1 or 2, characterized in that: Weigh Corydalis yanhusuo, angelica sinensis, chuanxiong, dried ginger, fennel and cassia twig according to the recipe quantity, grind into powder and mix evenly to obtain the medicine.

4. The method for preparing the Chinese medicine composition for treating primary dysmenorrhea according to claim 3, characterized in that: After beating the powder and mixing evenly, pass through a 100-mesh sieve.

5. Use of the Chinese medicine composition for treating primary dysmenorrhea according to claim 1 or 2 in the preparation of a medicine for treating primary dysmenorrhea.

6. The use according to claim 5, characterized in that: The medicine is a traditional Chinese medicine patch.

7. The use according to claim 6, characterized in that: The Chinese medicine patch is prepared by the following method: (1) Weigh corydalis, angelica, chuanxiong, dried ginger, fennel and cassia twig according to the formula, grind and mix well, then sieve, and put the mixed powder into a non-woven traditional Chinese medicine bag and seal it; (2) putting iron powder, activated carbon, vermiculite and NaCl into a sealed bag and shaking them well to prepare a solid material, wherein the iron powder comprises 20-40 parts, the activated carbon comprises 1-6 parts, the vermiculite comprises 1-5 parts and the NaCl comprises 1-5 parts by weight; (3) adding a water-absorbing resin to water to prepare a liquid gel, pouring the solid material into a mortar and stirring it, then pouring the liquid gel into the mortar and grinding it with a pestle until it is completely mixed and uniform, with no obvious lumps to the naked eye, to obtain a uniformly mixed material; (4) The uniformly mixed materials are placed in a composite non-woven bag and vacuum packed using a vacuum packaging machine to obtain a heating patch.

8. The use according to claim 7, characterized in that: In the step (2), the iron powder is 30 parts, the activated carbon is 4 parts, the vermiculite is 1.2 parts and the NaCl is 1.2 parts by weight.

9. The use according to claim 7, characterized in that: When making a 3cm*3cm heating patch, put 5g of the evenly mixed material into a composite non-woven bag; when making a 5cm*5cm heating patch, put 15g of the evenly mixed material into a composite non-woven bag.

10. The use according to claim 7, characterized in that: The heating patch is placed separately from the non-woven Chinese medicine bag containing medicine powder, and the two are superimposed and combined together by adhesive tape or double-sided tape during medication.

Images