New application of fructus arctii-fructus forsythiae medicine pair and medicine containing fructus arctii-fructus forsythiae medicine pair and used for regulating hormone level

Abstract

The invention relates to the technical field of biological medicine, in particular to a novel application of a burdock-fructus forsythiae medicine pair and a medicine containing the burdock-fructus forsythiae medicine pair and used for adjusting the hormone level, and finds that the burdock-fructus forsythiae medicine pair can improve the hormone level of female mice and male rats for the first time. Tests finally find that when the mass ratio of the burdock alcohol extract to the fructus forsythiae alcohol extract is 1: 2, the hormone level adjusting effect is optimal, the inhibition effect of cyclophosphamide on splenic lymphocytes can be effectively relieved, meanwhile, the anti-inflammatory effect is optimal, and the pharmaceutical composition is suitable for clinical application. Therefore, the effect of treating the acne can be achieved by independently using the burdock alcohol extract and the fructus forsythiae alcohol extract, and the problems that a traditional Chinese medicine composition is complex in compatibility, high in medication cost, large in side effect and the like are solved.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biological medicine, in particular to a new use of a Fructus Arctii-Fructus Forsythiae drug pair and a medicine containing the Fructus Arctii-Fructus Forsythiae drug pair for regulating hormone levels. BACKGROUND

[0002] Acne is a common disease occurring on the face, mainly related to sex hormone level disorder, excessive secretion of sebaceous glands and other factors, and its clinical symptoms include papules, pustules, cysts and the like. Acne often occurs in adolescence, with a very high prevalence rate, and is prone to disease recurrence, facial pigmentation and atrophic scarring, etc., which seriously affects the appearance and thus causes psychological damage.

[0003] In traditional Chinese medicine, acne is classified into the categories of acne vulgaris and wine acne, which are caused by vigorous blood and heat, excessive yang heat, fullness of collaterals, internal heat and external blockage, stagnation of yang qi on the body surface, and external wind evil, and are divided into internal heat, lung heat, blood heat, liver heat and internal heat due to yin deficiency, and should be treated by clearing heat, removing dampness, purging the bowels and detoxifying.

[0004] At present, isotretinoin is commonly used in clinical treatment of acne, which can regulate epidermal keratin, improve sebaceous gland inflammation and dissolve comedones, but long-term use can easily induce adverse reactions such as elevated blood lipids and skin tingling, and in addition, it has teratogenic effect, so the use of isotretinoin in clinical treatment has certain limitations. Antibiotics, azelaic acid and hormone drugs can also treat acne, which can reduce the bacterial population on the skin surface and inside the hair follicle to achieve a therapeutic effect, but after use, acne propionibacterium resistance and side effects such as folliculitis are prone to occur. Therefore, seeking a drug with significant efficacy and high safety has become the research focus for the treatment of acne.

[0005] Chinese patent CN 102973779 B discloses a traditional Chinese medicine composition for treating seborrheic dermatitis and acne and a preparation method thereof. It comprises the following components: honeysuckle 16-35 parts, soapberry thorn 16-35 parts, windproof 16-35 parts, baizhi 12-28 parts, chuanbeimu 12-28 parts, dock 12-28 parts, malve 10-25 parts, akebia 10-25 parts, dandelion 10-25 parts, purple flower 10-25 parts, devil's needle grass 8-15 parts, forsythia 8-15 parts, diaphragm 8-15 parts, swollen node wind 6-12 parts, diaphragm 6-12 parts, fuling 5-10 parts, xuchangqing 5-10 parts, weilingxian 5-10 parts, arctium 5-10 parts, pueraria 5-10 parts, old crane grass 5-10 parts, tianhuafen 4-8 parts, pangolin 4-8 parts, dried tangerine or orange skin 4-8 parts, haw 3-8 parts and licorice 2-6 parts. The traditional Chinese medicine composition has significant effect on seborrheic dermatitis or acne and is safe in clinical use.

[0006] Chinese Patent CN 120324552A discloses a traditional Chinese medicine composition for treating severe acne, its preparation method and application. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine monomers according to the weight ratio: 10 - 20 parts of loquat leaf, 8 - 15 parts of honeysuckle flower, 6 - 12 parts of lightyellow sophora root, 5 - 15 parts of chrysanthemum flower, 8 - 15 parts of great burdock achene, 6 - 12 parts of phellodendron bark, 10 - 20 parts of white mulberry root-bark, 15 - 30 parts of oldenlandia diffusa, 15 - 30 parts of dandelion, 10 - 20 parts of lanceolate vein of Chinese pulsatilla, 15 - 30 parts of calcined oyster, 6 - 12 parts of dahurian angelica root, 8 - 15 parts of capillaris, 10 - 20 parts of red peony root, 3 - 9 parts of coptis root, 10 - 20 parts of weeping forsythia, 10 - 20 parts of red-rooted salvia, 15 - 30 parts of viola philippica, 6 - 12 parts of thunberg fritillary bulb, 10 - 20 parts of common selfheal fruit-spike. This traditional Chinese medicine formula combines the effects of multiple traditional Chinese medicines and synergistically plays the roles of clearing heat and drying dampness, cooling blood and detoxifying, dissipating binds and detumescence, and can effectively regulate the constitution of acne patients with damp-heat in the lung and stomach and heat-toxin stasis-binding, and fundamentally improve the pathogenesis of acne.

[0007] Although traditional Chinese medicine can achieve good effects in the treatment of acne, it is mainly formulated based on traditional Chinese medicine theory, and there are problems such as complex compatibility, high medication cost, and large side effects. In addition, burdock achene is added to the existing formula, mainly considering its effects of dispersing wind and heat, dispersing lung qi and promoting eruption, and detumescence and relieving pain; forsythia is added mainly considering its inhibitory effect on Propionibacterium acnes and its effects of clearing heat and detoxifying, dissipating binds and detumescence. Regarding the regulatory effect of the burdock achene - forsythia drug pair on sex hormone level disorders, there is no report in the existing technology. Summary of the Invention

[0008] The first object of the present invention is to provide a new use of the burdock achene - forsythia drug pair, specifically: the application of the burdock achene - forsythia drug pair in the preparation of a drug for improving hormone levels; or, the application in the preparation of a drug for immune regulation; or, the application in the preparation of a drug for preventing and / or treating acne.

[0009] As a preference of the present invention, when the burdock achene - forsythia drug pair is actually used, both burdock achene and forsythia are used in the form of their alcohol extracts, and the mass ratio of the burdock achene alcohol extract to the forsythia alcohol extract is (1 - 3):(1 - 3).

[0010] As a preference of the present invention, when the burdock achene - forsythia drug pair is applied in the preparation of a drug for improving hormone levels, it is used to increase the content of estradiol and decrease the content of testosterone.

[0011] As a preference of the present invention, when the burdock achene - forsythia drug pair is applied in the preparation of a drug for immune regulation, it is used to promote the proliferation of splenic lymphocytes.

[0012] As a preference of the present invention, the mass ratio of the burdock achene alcohol extract to the forsythia alcohol extract is 1:2.

[0013] As a preferred embodiment of the present application, 70% ethanol is selected when preparing the arctiin extract and the forsythia fruit extract. First, the forsythia fruit and the arctium lappa L. are soaked in 70% ethanol, and then extracted by heating and refluxing.

[0014] A second object of the present application is to provide a medicine for regulating hormone levels containing an arctium lappa L.-forsythia fruit pair, wherein the arctium lappa L. and the forsythia fruit are both in the form of alcohol extracts, and the mass ratio of the arctiin extract to the forsythia fruit extract is (1-3):(1-3).

[0015] As a preferred embodiment of the present application, the mass ratio of the arctiin extract to the forsythia fruit extract is 1:2, and 70% ethanol is selected when preparing the arctiin extract and the forsythia fruit extract.

[0016] A third object of the present application is to provide a medicine for preventing and / or treating acne, wherein the effective component is a mixture of an arctiin extract and a forsythia fruit extract, the mass ratio of the arctiin extract to the forsythia fruit extract is 1:2, and 70% ethanol is selected when preparing the arctiin extract and the forsythia fruit extract.

[0017] As a preferred embodiment of the present application, the medicine is prepared by the following method: the forsythia fruit and the arctium lappa L. are respectively placed in a round-bottom flask, 6 times the amount of 70% ethanol is added, and soaked for 10-30 min. Then, the mixture is heated and refluxed for 2-3 h, filtered, and the residue is added with 4 times the amount of 70% ethanol, heated and refluxed for 1-2 h, and the two extracted liquids are combined and evaporated to dryness to obtain the arctiin extract and the forsythia fruit extract. Then, the arctiin extract and the forsythia fruit extract are mixed in a certain proportion.

[0018] The present application has the following advantages and beneficial effects: (1) The arctium lappa L.-forsythia fruit pair can improve the hormone levels of female mice and male rats, and thus can be used in the preparation of a medicine for improving sex hormone levels, and provides a new treatment method for a series of diseases caused by sex hormone level disorders.

[0019] (2) The arctium lappa L.-forsythia fruit pair can effectively alleviate the inhibitory effect of cyclophosphamide on spleen lymphocytes, and thus can be used in the preparation of an immunoregulatory medicine, and provides a new treatment method for people with low immunity caused by radiotherapy and chemotherapy.

[0020] (3) The present application finally finds through experiments that when the mass ratio of arctiin extract and forsythia alcohol extract is 1:2, the effect of adjusting hormone level is optimal, and the inhibition effect of cyclophosphamide on spleen lymphocytes can be effectively relieved, and the anti-inflammatory effect is best, and the level of inflammatory factors can be effectively inhibited; therefore, it can be proved that the use of arctiin extract and forsythia alcohol extract alone can achieve the effect of treating acne, and the problems such as complex composition of traditional Chinese medicine composition, high drug cost, and large side effects can be avoided. BRIEF DESCRIPTION OF DRAWINGS

[0021] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed in the embodiments will be briefly introduced below, and it should be understood that the following drawings only show some embodiments of the present application, and therefore should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can also be obtained without creative labor on the basis of these drawings.

[0022] Figure 1 The present application is used for improving the hormone level of female mice by using arctium lappa and forsythia in combination; wherein A is the uterus organ index, B is the testosterone content, C is the estradiol content, and D is the follicle stimulating hormone content; Figure 2 The present application is used for improving the hormone level of male rats by using arctium lappa and forsythia in combination; wherein A is the testis organ index, B is the accessory organ index, C is the testosterone content, and D is the estradiol content; Figure 3 The present application is used for promoting the lymphocyte transformation of immunocompromised model mice caused by cyclophosphamide by using arctium lappa and forsythia in combination; wherein A is the spleen cell suspension, B is the spleen cell suspension+ConA, and C is the spleen cell suspension+LPS; Figure 4 The present application is used for inhibiting the secretion of inflammatory factors of immunocompromised model mice caused by cyclophosphamide by using arctium lappa and forsythia in combination; wherein A is IL-2, and B is TNF-α; Figure 5 The present application is used for inhibiting the ear swelling of delayed hypersensitivity reaction mice by using arctium lappa and forsythia in combination; Figure 6 The present application is used for improving the toe swelling of rats caused by carrageenan by using arctium lappa and forsythia in combination; wherein A is the swelling degree after 1h, B is the swelling degree after 2h, C is the swelling degree after 4h, and D is the swelling degree after 6h.

[0023] In the figure, AL represents the arctium lappa L. alcohol extraction group; FS represents the forsythia suspensa fruit alcohol extraction group; AL1:FS2(W) represents the arctium lappa L. and forsythia suspensa fruit 1:2 water extraction group, i.e., the mass ratio of the water extracts of the two is 1:2; AL1:FS1 represents the arctium lappa L. and forsythia suspensa fruit 1:1 alcohol extraction group, i.e., the mass ratio of the alcohol extracts of the two is 1:1; AL2:FS1 represents the arctium lappa L. and forsythia suspensa fruit 2:1 alcohol extraction group; AL3:FS1 represents the arctium lappa L. and forsythia suspensa fruit 3:1 alcohol extraction group; AL1:FS2 represents the arctium lappa L. and forsythia suspensa fruit 1:2 alcohol extraction group; AL1:FS3 represents the arctium lappa L. and forsythia suspensa fruit 1:3 alcohol extraction group. DETAILED DESCRIPTION

[0024] In order to make the objectives, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below. If the specific conditions are not specified in the embodiments, the conventional conditions or the conditions recommended by the manufacturers are adopted. If the manufacturers of the reagents or instruments are not specified, the conventional products that can be purchased in the market are adopted.

[0025] The present embodiment provides a new use of the arctium lappa L.-forsythia suspensa fruit drug pair. In the preparation of the medicine, the arctium lappa L. and forsythia suspensa fruit 70% ethanol extracts are prepared respectively, and then the two are mixed.

[0026] In the optional embodiment, the mass ratio of the arctium lappa L. and forsythia suspensa fruit alcohol extracts is (1-3):(1-3), which can be specifically 1:1, 2:1, 3:1, 1:2 or 1:3. Preferably, the mass ratio of the arctium lappa L. and forsythia suspensa fruit alcohol extracts is 1:2, and under the limitation of the mass ratio, the better synergistic effect is obtained.

[0027] The present embodiment provides the use of the arctium lappa L. and forsythia suspensa fruit in the preparation of the medicine for improving the sex hormone level.

[0028] The present embodiment also provides the use of the arctium lappa L. and forsythia suspensa fruit in the preparation of the medicine for anti-inflammation. The arctium lappa L. and forsythia suspensa fruit can effectively inhibit the ear swelling of the delayed hypersensitivity reaction mice and improve the toe swelling of the rats caused by the carrageenan, thereby providing a new approach for the prevention or treatment of the diseases caused by the inflammatory reaction.

[0029] The present embodiment also provides the use of the arctium lappa L. and forsythia suspensa fruit in the preparation of the medicine for immune regulation.

[0030] The present embodiment also provides the use of the arctium lappa L. and forsythia suspensa fruit in the preparation of the medicine for inhibiting the secretion of the inflammatory factors.

[0031] Specifically, the inflammatory factors include but are not limited to at least one of IL-2 and TNF-α. The combined treatment of the arctium lappa L. and forsythia suspensa fruit can effectively inhibit the inflammatory factor level, thereby providing a new treatment or prevention means for the diseases caused by the excessive inflammatory factor level, including but not limited to acne.

[0032] In addition, the present embodiment also provides a medicine for preventing and / or treating acne, wherein an effective component of the medicine is a mixture of arctiin extract and forsythia extract; and a medicine containing the arctiin-forsythia pair for regulating hormone levels.

[0033] The features and properties of the present application are further described in detail below in conjunction with examples.

[0034] Example 1

[0035] Experimental drugs: arctium and forsythia. Arctium and forsythia were respectively placed in round-bottom flasks, soaked in 6 times water or 70% ethanol for 0.5 h, heated and refluxed for 2.5 h, filtered, the residues were added with 4 times water or 70% ethanol, heated and refluxed for 1.5 h, the two extraction liquids were combined and evaporated to dryness to obtain arctium water or ethanol extract and forsythia water or ethanol extract, respectively, and then the two extracts were mixed in proportion.

[0036] Improving hormone levels in female mice: 100 immature Kunming female mice (body weight 10-14 g) were randomly divided into 10 groups, 10 mice in each group. The drug concentrations were prepared as follows: arctium ethanol extraction group (AL, 100 mg / mL), forsythia ethanol extraction group (FS, 200 mg / mL), arctium and forsythia 1:2 water extraction group (AL 100 mg / mL+FS 200 mg / mL), arctium and forsythia 1:1 ethanol extraction group (AL 100 mg / mL+FS 100 mg / mL), arctium and forsythia 2:1 ethanol extraction group (AL 200 mg / mL+FS 100 mg / mL), arctium and forsythia 3:1 ethanol extraction group (AL 300 mg / mL+FS 100 mg / mL), arctium and forsythia 1:2 ethanol extraction group (AL 100 mg / mL+FS 200 mg / mL), arctium and forsythia 1:3 ethanol extraction group (AL 100 mg / mL+FS 300 mg / mL), blank control group (Control, normal saline), estradiol control group (E2, normal saline), each mouse was given corresponding drug or normal saline 10 mL / kg per day. The estradiol control group was subcutaneously injected with benzoic acid estradiol 0.25 mg per mouse, continuously injected for 5 days, and the blood was collected from the eyeball on the 6th day, the serum was collected, and the follicle-stimulating hormone, testosterone and estradiol were detected by ELISA kit. The uterus was removed, the adipose tissue was removed, and the balance was weighed, and the uterus weight (mg) / 10g body weight was expressed. Organ coefficient = organ weight (mg) / animal body weight (g) x 100%.

[0037] Experimental results: Compared with the blank control group, the estradiol control group mice showed a significant increase in uterine weight, a decrease in serum follicle-stimulating hormone (FSH) and testosterone levels, and an increase in estradiol levels. The burdock seed alcohol extract alone decreased serum FSH levels but had no significant effect on uterine weight, testosterone, or estradiol levels. The forsythia fruit alcohol extract alone and the 1:1 burdock seed and forsythia fruit alcohol extract groups increased uterine weight and decreased serum FSH and testosterone levels, but had no significant effect on estradiol levels. The 1:2 burdock seed and forsythia fruit water extract group and the 2:1 and 3:1 burdock seed and forsythia fruit alcohol extract groups had no significant effect on uterine weight, serum testosterone, estradiol, or FSH levels. The 1:2 and 1:3 burdock seed and forsythia fruit alcohol extract groups significantly increased uterine weight and estradiol levels, and decreased serum FSH and testosterone levels, with the 1:2 ratio being superior to the 1:3 ratio. In summary, the combined administration of 1:2 ethanol extracts of burdock seed and forsythia showed significantly better efficacy than either the single-administered or other combined administration groups. Figure 1 ).

[0038] Example 2

[0039] Experimental drugs: Burdock seed and Forsythia. Burdock seed and Forsythia were placed in round-bottom flasks, respectively, and 6 times their volume of water or 70% ethanol were added. The mixture was soaked for 0.5 h, heated under reflux for 2.5 h, filtered, and the residue was then mixed with 4 times its volume of water or 70% ethanol and heated under reflux for 1.5 h. The two extracts were combined and evaporated to dryness to obtain aqueous or ethanolic extracts of burdock seed and Forsythia, respectively. The two extracts were then mixed in a specific ratio.

[0040] Improving the hormone levels of male rats: 60 immature SD male rats (50-60 g) were randomly divided into 10 groups, 6 in each group. The drug concentrations were prepared as follows: arctium lappa alcohol extract group (AL, 100 mg / mL), forsythia suspense alcohol extract group (FS, 200 mg / mL), arctium lappa and forsythia suspense 1:2 water extract group (AL 100 mg / mL+FS 200 mg / mL), arctium lappa and forsythia suspense 1:1 alcohol extract group (AL 100 mg / mL+FS 100 mg / mL), arctium lappa and forsythia suspense 2:1 alcohol extract group (AL 200 mg / mL+FS 100 mg / mL), arctium lappa and forsythia suspense 3:1 alcohol extract group (AL 300 mg / mL+FS 100 mg / mL), arctium lappa and forsythia suspense 1:2 alcohol extract group (AL 100 mg / mL+FS 200 mg / mL), arctium lappa and forsythia suspense 1:3 alcohol extract group (AL 100 mg / mL+FS 300 mg / mL), blank control group (Control, normal saline), model group (Model, normal saline), each rat was given corresponding drug or normal saline 10 mL / kg per day. Except for the blank control group, the rest of the groups were injected intramuscularly with 0.25 mg of testosterone propionate 0.1 mL every other day. The drug administration and modeling time lasted for 14 days. 24 h after the last injection of testosterone propionate, the eyeball was taken for blood collection, and the serum was collected for ELISA kit detection of testosterone and estradiol. At the same time, the testis and accessory organs (epididymis, seminal vesicle, prostate) were removed and weighed, and the organ coefficient = organ weight (mg) / animal body weight (g) x 100%.

[0041] Experimental results: Compared with the blank control group, the weight of testis and accessory organs of the model group rats increased significantly, the serum testosterone content increased, and the estradiol content decreased. Compared with the model group, the rats in the arctium lappa intervention group alone, the arctium lappa and forsythia suspense 1:2 water extract group, the arctium lappa and forsythia suspense 2:1 and 3:1 alcohol extract group had no significant changes in testis and accessory organ weight, serum testosterone and estradiol content; the rats in the forsythia suspense intervention group alone, the arctium lappa and forsythia suspense 1:1 and 1:3 alcohol extract group had decreased serum testosterone content, and no significant change in testis and accessory organ weight, serum estradiol content; the rats in the arctium lappa and forsythia suspense 1:2 alcohol extract group had significantly decreased serum testosterone content and significantly increased estradiol level, and no significant change in testis and accessory organ weight. In summary, the arctium lappa and forsythia suspense 1:2 alcohol extract combined administration group has better efficacy than the single administration and other combined administration groups. Figure 2

[0042] Example 3

[0043] ​Experimental drugs: Fructus Arctii and Forsythia. Fructus Arctii and Forsythia were respectively put in round-bottomed flask, soaked with 6 times water or 70% ethanol for 0.5 h, heated and refluxed for 2.5 h, filtered, the residue was soaked with 4 times water or 70% ethanol, heated and refluxed for 1.5 h, the two times of extraction liquid were combined and evaporated to dryness, and then the two extracts were mixed in proportion.

[0044] Promoting lymphocyte transformation of cyclophosphamide-induced immunosuppression model mice: 100 ICR mice were randomly divided into 10 groups, 10 mice in each group. The drug concentrations were prepared as follows: Fructus Arctii alcohol extract group (AL, 100 mg / mL), Forsythia alcohol extract group (FS, 200 mg / mL), Fructus Arctii and Forsythia 1:2 water extract group (AL 100 mg / mL+FS 200 mg / mL), Fructus Arctii and Forsythia 1:1 alcohol extract group (AL 100 mg / mL+FS 100 mg / mL), Fructus Arctii and Forsythia 2:1 alcohol extract group (AL 200 mg / mL+FS 100 mg / mL), Fructus Arctii and Forsythia 3:1 alcohol extract group (AL 300 mg / mL+FS 100 mg / mL), Fructus Arctii and Forsythia 1:2 alcohol extract group (AL 100 mg / mL+FS 200 mg / mL), Fructus Arctii and Forsythia 1:3 alcohol extract group (AL 100 mg / mL+FS 300 mg / mL), blank control group (Control, normal saline), model group (Model, normal saline), each mouse was given corresponding drug or normal saline 10 mL / kg per day. On the 11th day of administration, except for the blank control group, the rest of the groups were given intraperitoneal injection of cyclophosphamide 50 mg / kg to establish the model. After 15 days of continuous administration, the mice were sacrificed by enucleation and blood collection, the spleen was aseptically removed and ground into a single cell suspension. In a 96-well plate, 100 μL of spleen cell suspension was added to each well, 100 μL of IMDM culture solution was added to the control wells, 100 μL of ConA (10 μg / mL) solution was added to the ConA (concanavalin A) wells, and 100 μL of LPS (lipopolysaccharide) solution was added to the LPS wells. Incubate at 37°C, 5% CO2 for 40 h, then add MTT solution to each well, continue to incubate for 4 h, dissolve with DMSO, measure OD value at 570 nm, and calculate stimulation index (SI). SI = stimulated well OD value (ConA or LPS well) / control well OD value.

[0045] Experimental results: Compared with the blank control group, the model group significantly inhibited the proliferation of splenocytes. Compared with the model group, the intervention groups of Arctium lappa and Forsythia suspensa 1:2 water extract, Arctium lappa and Forsythia suspensa 2:1 and 3:1 alcohol extract had no significant change in the proliferation of splenocytes; the Arctium lappa and Forsythia suspensa 1:1 alcohol extraction group could alleviate the inhibition of cyclophosphamide on splenocytes and increase the proliferation of LPS-stimulated splenocytes, but had no significant effect on the proliferation of ConA-stimulated splenocytes; the Arctium lappa and Forsythia suspensa 1:3 alcohol extraction group could alleviate the inhibition of cyclophosphamide on splenocytes, but had no significant effect on the proliferation of ConA and LPS-stimulated splenocytes; the Arctium lappa and Forsythia suspensa 1:2 alcohol extraction group could alleviate the inhibition of cyclophosphamide on splenocytes and significantly increase the proliferation of ConA and LPS-stimulated splenocytes, and the pharmacodynamic effect was the most obvious. Figure 3

[0046] Example 4

[0047] Inhibition of cyclophosphamide-induced inflammatory factor secretion in immunosuppressed model mice: The serum collected in Example 3 was used for detection by ELISA kit.

[0048] It was found that compared with the blank control group, the serum IL-2 and TNF-α levels of the model group were significantly increased. Compared with the model group, the Arctium lappa alcohol extract group alone and the Arctium lappa and Forsythia suspensa 1:2 water extract group could reduce the serum IL-2 level, but had no significant effect on the TNF-α level; the Forsythia suspensa alcohol extract group alone, the Arctium lappa and Forsythia suspensa 1:1, 2:1, 3:1, 1:2 and 1:3 alcohol extract groups all down-regulated the serum IL-2 and TNF-α levels, and the pharmacodynamic effect of the 1:2 alcohol extract combination administration group was the most obvious. Figure 4

[0049] Example 5

[0050] Experimental drugs: Arctium lappa and Forsythia suspensa. Arctium lappa and Forsythia suspensa were respectively placed in round-bottom flasks, soaked with 6 times water or 70% ethanol for 0.5 h, heated and refluxed for 2.5 h, filtered, and the residues were added with 4 times water or 70% ethanol, heated and refluxed for 1.5 h. The two extraction liquids were combined and evaporated to dryness to obtain Arctium lappa water or alcohol extract and Forsythia suspensa water or alcohol extract, respectively. Then the two extracts were mixed in proportion.

[0051] ​​Inhibition of ear swelling in mice with delayed hypersensitivity: 100 ICR mice were randomly divided into 10 groups, 10 mice in each group. The drug concentrations were prepared as follows: Arctium lappa L. ethanol extract group (AL, 100 mg / mL), Forsythia suspensa (Thunb.) Vahl ethanol extract group (FS, 200 mg / mL), A. lappa L. and F. suspensa (Thunb.) Vahl 1:2 water extract group (AL 100 mg / mL + FS 200 mg / mL), A. lappa L. and F. suspensa (Thunb.) Vahl 1:1 ethanol extract group (AL 100 mg / mL + FS 100 mg / mL), A. lappa L. and F. suspensa (Thunb.) Vahl 2:1 ethanol extract group (AL 200 mg / mL + FS 100 mg / mL), A. lappa L. and F. suspensa (Thunb.) Vahl 3:1 ethanol extract group (AL 300 mg / mL + FS 100 mg / mL), A. lappa L. and F. suspensa (Thunb.) Vahl 1:2 ethanol extract group (AL 100 mg / mL + FS 200 mg / mL), A. lappa L. and F. suspensa (Thunb.) Vahl 1:3 ethanol extract group (AL 100 mg / mL + FS 300 mg / mL), blank control group (Control, normal saline), model group (Model, normal saline), each mouse was given corresponding drug or normal saline 10 mL / kg per day. Except for the blank control group, the remaining groups were depilated with 10% sodium sulfide on the fixed site of the abdomen of the mice 3 cm x 1 cm area one day before the experiment, and washed with warm water. On the 1st and 2nd days (sensitization period), the mice were applied with 1% DNCB on the depilated area of the abdomen, 20 μL per time, once a day, and no drug was applied on the 3rd, 4th and 5th days. On the 6th day (induction period), 20 μL of 0.5% DNCB was applied to the left ear back of the mice to induce dermatitis, and 1:1 acetone glycerol 20 μL was applied to the right ear back as a control. After 24 h of induction, the ears were cut off, and tissue blocks were punched at the same position in the middle of the left and right ears with a puncher with a diameter of 6 mm. The weight of the tissue blocks was measured on a balance, and the difference between the weights of the two ears was calculated as an index of inflammatory reaction intensity.

[0052] Experimental results: Compared with the blank control group, the ear swelling of the model group with delayed hypersensitivity was significantly increased. Compared with the model group, the mice in the A. lappa L. and F. suspensa (Thunb.) Vahl 1:2 water extract group, A. lappa L. and F. suspensa (Thunb.) Vahl 1:1, 2:1 and 3:1 ethanol extract groups showed no significant change in ear swelling; the A. lappa L. and F. suspensa (Thunb.) Vahl 1:2 and 1:3 ethanol extract groups significantly reduced the ear swelling of the mice, and the 1:2 ethanol extract combination group showed the most obvious effect. Figure 5

[0053] Example 6

[0054] Experimental drugs: A. lappa L. and F. suspensa (Thunb.). A. lappa L. and F. suspensa (Thunb.) were respectively placed in a round-bottom flask, soaked with 6 times water or 70% ethanol for 0.5 h, heated and refluxed for 2.5 h, filtered, and the residue was added with 4 times water or 70% ethanol, heated and refluxed for 1.5 h. The two extract solutions were combined and evaporated to dryness to obtain A. lappa L. water or ethanol extract and F. suspensa (Thunb.) water or ethanol extract, respectively. Then the two extracts were mixed in a certain proportion.​

[0055] Improvement of carrageenan-induced paw swelling in rats: 100 rats were randomly divided into 10 groups, with 10 rats in each group. The drug concentrations were prepared as follows: Arctium lappa alcohol extract group (AL, 100 mg / mL), Forsythia suspensa alcohol extract group (FS, 200 mg / mL), Arctium lappa and Forsythia suspensa 1:2 water extract group (AL 100 mg / mL + FS 200 mg / mL), Arctium lappa and Forsythia suspensa 1:1 alcohol extract group (AL 100 mg / mL + FS 100 mg / mL), Arctium lappa and Forsythia suspensa 2:1 alcohol extract group (AL 200 mg / mL + FS 100 mg / mL), Arctium lappa and Forsythia suspensa 3:1 alcohol extract group (AL 300 mg / mL + FS 100 mg / mL), Arctium lappa and Forsythia suspensa 1:2 alcohol extract group (AL 100 mg / mL + FS 200 mg / mL), and Arctium lappa and Forsythia suspensa 1:3 alcohol extract group (AL 100 mg / mL + FS). The rats were divided into three groups: a control group (300 mg / mL) and a model group (saline). Each rat was given the corresponding drug or saline at a dose of 10 mL / kg per day. For seven consecutive days, after the last administration, the thickness of the right hind limb toe was measured using an electronic digital caliper. Thirty minutes after the last administration, 0.1 mL of 3% carrageenan solution was subcutaneously injected into the right hind limb plantar surface of each rat. Toe thickness was then measured at 1, 2, 4, and 6 hours after model establishment to calculate the degree of paw swelling, which served as an indicator of the intensity of the inflammatory response.

[0056] Experimental results: Compared with the blank control group, the model group showed significant toe swelling. Compared with the model group, the burdock seed alcohol extract group alone, the burdock seed and forsythia 1:2 water extract group, and the burdock seed and forsythia 3:1 alcohol extract group had no significant effect on the degree of toe swelling in rats in the first six hours; the forsythia ethanol extract group alone only reduced toe swelling in rats at 1h and 2h, and had no significant effect on toe swelling at 4h and 6h; the burdock seed and forsythia 1:1 and 2:1 alcohol extract groups only reduced toe swelling in rats at 1h, and had no significant effect on toe swelling at 2h, 4h, and 6h; the burdock seed and forsythia 1:3 alcohol extract group reduced toe swelling in rats at 1h, 2h, and 4h, but had no significant effect on toe swelling at 6h; while the burdock seed and forsythia 1:2 alcohol extract group significantly reduced toe swelling in rats in the first six hours, showing the most significant therapeutic effect. Figure 6 ).

[0057] The present application finds through experiments that Arctium lappa, Forsythia suspensa, and Arctium lappa combined with Forsythia suspensa increase the serum estradiol content of female mice and male rats to different degrees, reduce the serum follicle-stimulating hormone and testosterone levels, relieve the inhibitory effect of cyclophosphamide on spleen lymphocytes, increase the proliferation response of ConA and LPS-stimulated spleen lymphocytes, inhibit the secretion of serum inflammatory factors IL-2 and TNF-α, and inhibit the ear swelling of delayed hypersensitivity mice and the paw swelling of rats caused by carrageenan, wherein the mass ratio of Arctium lappa alcohol extract and Forsythia suspensa alcohol extract is 1:2, which is optimal in terms of hormone regulation, immune regulation, and inhibition of inflammatory response. Considering that acne is mainly related to factors such as sex hormone level disorder and inflammatory response, based on the above advantages of 1:2, it can be used for acne. In optional embodiments, the acne includes at least one of comedones, papules, pustules, and cysts.

[0058] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Various modifications and changes can be made by those skilled in the art based on the spirit and principles of the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. The use of the burdock seed-forsythia pair in the preparation of drugs for improving hormone levels; or, in the preparation of drugs for immunomodulation; or, in the preparation of drugs for the prevention and / or treatment of acne.

2. The application according to claim 1, characterized in that, In actual use, the burdock seed-forsythia herb pair uses the alcohol extracts of both burdock seed and forsythia, and the mass ratio of burdock seed alcohol extract to forsythia alcohol extract is (1-3):(1-3).

3. The application according to claim 1, characterized in that, When the burdock seed-forsythia drug pair is used in the preparation of drugs for improving hormone levels, it is used to increase estradiol content and decrease testosterone content.

4. The application according to claim 1, characterized in that, When the burdock seed-forsythia suspensa drug pair is used in the preparation of drugs for immunomodulation, it is used to promote the proliferation of splenic lymphocytes.

5. The application according to claim 2, characterized in that, The mass ratio of the burdock root extract to the forsythia extract is 1:

2.

6. The application according to claim 5, characterized in that, The burdock seed alcohol extract and forsythia alcohol extract are prepared by using 70% ethanol. First, burdock seeds and forsythia are soaked in 70% ethanol, and then extracted by heating and reflux.

7. A drug containing a burdock seed-forsythia suspensa pair for regulating hormone levels, characterized in that, Both burdock seed and forsythia are extracted using their alcoholic extracts, and the mass ratio of burdock seed alcoholic extract to forsythia alcoholic extract is (1-3):(1-3).

8. A drug for regulating hormone levels containing a burdock seed-forsythia pair according to claim 7, characterized in that, The mass ratio of the burdock root extract to the forsythia root extract is 1:2, and 70% ethanol is used in the preparation of the burdock root extract and the forsythia root extract.

9. A medicine for the prevention and / or treatment of acne, characterized in that, The active ingredient of the drug is a mixture of burdock root extract and forsythia root extract, wherein the mass ratio of burdock root extract to forsythia root extract is 1:2, and 70% ethanol is used in the preparation of burdock root extract and forsythia root extract.

10. A medicament for preventing and / or treating acne according to claim 9, characterized in that, The preparation method of the drug is as follows: place burdock fruit and forsythia in a round-bottom flask, add 6 times the amount of 70% ethanol, soak for 10-30 minutes, heat under reflux for 2-3 hours, filter, add 4 times the amount of 70% ethanol to the residue, heat under reflux for 1-2 hours, combine the two extracts, evaporate to dryness, and obtain burdock fruit alcohol extract and forsythia alcohol extract; then mix the burdock fruit alcohol extract and forsythia alcohol extract in a certain proportion.

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