CN113813249A

CN113813249A - Application of emodin in preparing medicine for treating migraine

Info

Publication number: CN113813249A
Application number: CN202111125076.3A
Authority: CN
Inventors: 张春凤; 孙淑汀
Original assignee: China Pharmaceutical University
Current assignee: China Pharmaceutical University
Priority date: 2021-09-25
Filing date: 2021-09-25
Publication date: 2021-12-21

Abstract

The invention discloses an application of emodin in preparing a medicine for treating migraine. The research of the invention finds that: 1. emodin can inhibit NO production, relieve excessive blood vessel dilation, and prevent and treat migraine from source; 2. emodin reduces the release of inflammatory factor TNF-alpha, thereby inhibiting inflammatory response; 3. emodin can reduce release of blood vessel neuropeptide CGRP and P substance; 4. emodin can inhibit the expression of PKG protein of migraine rat and reduce vasodilatation. Therefore, the invention shows the possibility of the emodin serving as an anti-migraine drug in various ways, and the emodin is hopeful to become a novel small molecular drug for clinically treating migraine.

Description

Application of emodin in preparing medicine for treating migraine

The technical field is as follows:

the invention belongs to the field of medicines, and particularly relates to application of emodin in preparation of a medicine for treating migraine.

Background art:

migraine (migrine) is a primary central nervous system dysfunction disease with unilateral or bilateral throbbing headache, the etiology is complex, the mainstream theory at present is trigeminal neurovascular theory, and the theory considers that after trigeminal nerve endings around cerebral blood vessels are stimulated, neuropeptides such as Substance P (SP), neurokinin A (NKA) and Calcitonin Gene Related Peptide (CGRP) are released, so that the blood vessel walls of adjacent intracranial blood vessels are over-expanded to generate fluctuating headache.

The current drugs for treating migraine are: calcium ion antagonist, 5-HT1B/1D receptor agonist, alpha adrenergic receptor blocker, CGRP receptor antagonist, non-steroidal anti-inflammatory drug and the like, but all have certain toxic and side effects. The prior different types of treatment medicines for migraine can not meet the treatment requirements due to the problems of insufficient curative effect, obvious adverse reaction, poor compliance, medicine accessibility and the like. Therefore, there is an urgent need to find new migraine therapies. There is increasing clinical and preclinical evidence that botanical drug or botanical drug formulations have promising potential for the treatment of migraine disease, and many patients are turning to traditional Chinese and botanical drugs instead of current conventional drug therapies for migraine treatment.

Emodin is a plant-derived hydroxyanthraquinone, is an active ingredient separated from rhubarb, Polygonum, Rhus and senna leaves, and has potential activity for treating cardiovascular diseases and various nervous system diseases. In recent years, extensive and intensive research on the pharmacological action mechanism of emodin has found that emodin has wide pharmacological action and mainly focuses on the aspects of inhibiting cell proliferation, resisting inflammation, contracting smooth muscle and the like. In addition, emodin can reduce the release of CGRP in trigeminal ganglia and inhibit the pain of mouth and face, but no study on emodin for treating migraine exists.

Disclosure of Invention

The invention aims to provide application of emodin in preparation of a medicine for treating migraine based on a cGMP-PKG pathway.

The purpose of the invention can be realized by the following technical scheme:

an application of emodin in preparing medicine for treating migraine is disclosed. Emodin has the following structural formula:

the drug is a drug for treating migraine based on cGMP-PKG pathway. Studies have shown that emodin, via the cGMP-PKG pathway, attenuates PKG protein expression in brain tissue, attenuates C-fos activation, and modulates vasoactive substances such as NO, CGRP, substance P, TNF- α and cGMP, thereby alleviating migraine symptoms.

The medicine is capable of resisting inflammation and inhibiting vasodilatation and is used for treating migraine.

The medicine is a pharmaceutical composition prepared from emodin serving as an active ingredient and a pharmaceutically acceptable carrier or auxiliary material. The dosage form of the drug includes, but is not limited to, oral dosage forms or dosage forms suitable for nasal administration.

The invention has the beneficial effects that:

the research result of the invention shows that the emodin can be used as a potential migraine therapeutic compound with low side effect. The research has important significance on the development of anti-migraine drugs.

Drawings

FIG. 1 is a graph of the effect of emodin on the nitroglycerin-induced pain response in migraine rats;

wherein, the emodin has the influence on the cage climbing times, and the emodin has the influence on the head bending times. And respectively recording the times of cage climbing and head bending within 2h after nitroglycerin injection by taking 30min as a unit. Data are expressed as mean ± SD (n ═ 12);^##p<0.01, with a very significant difference compared to the blank group;^**p<0.01, with a very significant difference compared to the model group.

FIG. 2 is a graph showing the effect of emodin on vasoactive substances in the plasma of rats with nitroglycerin-induced migraine;

wherein (A) Nitric Oxide (NO), (B) calcitonin gene-related peptide (CGRP), (C) Substance P (SP), (D) tumor necrosis factor-alpha (TNF-alpha), and (E) cyclic guanosine monophosphate (cGMP). Data are expressed as mean ± SD (n ═ 6);^##p<0.01, significant difference compared to blank group; 0.01<^*p<0.05 indicated a significant difference compared to the model group,^**p<0.01, there was a significant difference compared to the model group.

FIG. 3 is a graph of the effect of emodin on C-fos neurons in the cortex after nitroglycerin injection;

wherein, immunohistology photograph: (A) blank group, (B) dieA group of (A), (B), (C) and (D) an ibuprofen group; bar graph: (E) the number of C-fos-positive cells; (F) an integrated optical density value (IOD); photographs were taken under a microscope at 200 × magnification: scale bar 20 μm; data mean ± SD to represent (n ═ 6);^##p<0.01, which is significantly different from the blank group;^**p<0.01, there was a significant difference compared to the model group.

FIG. 4 is a graph of the effect of emodin on C-fos neurons in the brainstem following nitroglycerin injection;

wherein, immunohistology photograph: (A) blank group, (B) model group, (C) ibuprofen group, (D) emodin group; bar graph: (E) the number of C-fos-positive cells; (F) an integrated optical density value (IOD); photographs were taken under a microscope at 200 × magnification: scale bar 20 μm; data mean ± SD to represent (n ═ 6);^##p<0.01, significant difference compared to blank group;^**p<0.01, there was a significant difference compared to the model group.

FIG. 5 is a graph of the effect of emodin on levels of PKG proteins in nitroglycerin-induced brain tissue;

wherein the content of the first and second substances,^##p<0.01, which is significantly different from the blank group;^**p<0.01, which is significantly different from the model group.^Δp<0.05, there was a statistical difference between the emodin group and the ibuprofen group.

Detailed Description

The invention is further described below in conjunction with specific embodiments, the advantages and features of which will become apparent from the description. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be within the scope of the invention.

The invention provides an application of emodin in preparing a medicine for treating migraine based on a cGMP-PKG channel, wherein the emodin is a single active ingredient in the medicine for treating the migraine. In the present invention, the emodin is derived from conventional commercial sources.

Example 1

Materials and methods

1. Test materials

Emodin 98% pure, purchased from Beijing Miruida technologies, Inc. (batch No. M026282); ibuprofen granules were purchased from stone pharmaceutical group ltd (batch No. 363200601); sodium carboxymethylcellulose was purchased from pharmaceutic adjuvant, inc (lot 160511) of shanhe, anhui; uratan was purchased from national pharmaceutical group chemical Co., Ltd (batch No. 20190419); the glycerin nitrate injection is purchased from Beijing Yimin pharmaceutical Co., Ltd (batch No. 20200310); emodin and ibuprofen granules were dissolved in 0.5% sodium carboxymethylcellulose for administration. SD rats (180-. According to the literature method, the breeding is carried out under the environment with the temperature (19-21 ℃), the humidity (40-70%) and the illumination time of 8:00 to 20:00, and the environment is adapted to 7 days by freely taking food and drinking water. All procedures and feedings involved in animals were performed according to the guidelines for laboratory animal care and use of the national institutes of health.

2. Animal grouping and administration

After one week of adaptive feeding, rats of different sexes were randomly divided into four groups (6 females +6 males/group, females divided into cages): blank, model, ibuprofen and emodin groups. The blank and model groups were treated with the corresponding 0.5% (w/w, mass fraction) CMC-Na for 7 days, and the ibuprofen and emodin groups were pretreated with the corresponding drug solutions at fixed doses for 7 days. The last day of administration was performed separately, fasting was performed 12 hours in advance, and gavage (ibuprofen: 36 mg/kg; emodin: 27.3mg/kg) was performed, and Nitroglycerin (NTG) was subcutaneously injected into each group except the blank group.

3. Animal behavioural study

At 30min after the last administration, the model group, ibuprofen group and emodin group were injected subcutaneously with a nitroglycerin solution at a dose of 10mg/kg for migraine modeling, except for the blank group. After about 3-5min, the animals developed dysphoric symptoms with many typical symptoms, such as red ears, cage climbing, body shaking and head grabbing. These symptoms may last for about 2 hours. Scratching the head and climbing the cage are more responsive than other pain symptoms, and therefore scratching the head and climbing the cage is considered a positive response. The number of pain responses (n-12) was recorded for each rat over 2h, and the animals were not known to humans for group treatment.

4. Biochemical detection

After 2h of behavioral observation, random numbering is carried out in each group of rats, 20% urethane is injected intraperitoneally for anesthesia (5mL/kg), the rats are fixed on a plate in a supine mode, abdominal aorta blood collection is carried out, blood is naturally coagulated for 30min, centrifugation is carried out for 10min at 3000 r, and supernatant is taken, so that serum is obtained. The nitric oxide level in plasma was measured by colorimetry according to the instructions of the nitric oxide biochemical kit (Nanjing institute of bioengineering), and the levels of NO, CGRP, substance P, TNF- α and cGMP in serum were measured by using an Elisa kit (trade names: CGRP, SP, TNF- α and cGMP kit, Nanjing Carmilo bioengineering Co., Ltd.).

5. Immunohistochemistry

After blood collection, the chest was opened, 300 mL/mouse of normal saline (0.9% (w/w, mass fraction) sodium chloride +20U/mL heparin sodium) containing heparin sodium was perfused into the heart, the head was rapidly cut off, the brain was removed on ice, the brain was fixed with 4% mass fraction paraformaldehyde solution for 24h, then the brain was dehydrated with 20% (w/w, mass fraction) sucrose solution, embedded in tissue freezing medium (OTC) medium, and cut into 40 μm slices (coronal slice containing hippocampal tissue and sagittal slice containing medulla oblongata). Brain sections were washed 3 times with PBS, incubated in 3% hydrogen peroxide solution for 30min, and then washed clean again. Then, the sections were pretreated for 30min with 5% (v/v) normal goat serum (25 ℃) containing 0.3% (v/v) Triton X-100. Sections from all groups were incubated with rabbit anti-rat C-fos antibody (37 ℃, 2-4h) and blanks were pretreated with PBS under the same conditions. After washing, the sections were incubated with biotinylated goat anti-rabbit antibody and horseradish peroxide compound for 1h, respectively. The color was developed using 3, 3' -diaminobenzidine substrate solution and counterstained with hematoxylin, and finally the mounting was dehydrated. Pictures were taken with a Leica microscope and stained sections were viewed at 200x magnification. The positive C-fos-ir neurons were brownish yellow, and the negative neurons were bluish purple. Finally, the number of positive cells, the integrated optical density value IOD of the positive staining was recorded using Image-Pro Plus. Each rat was counted three times and the average was taken as the measurement (n-6).

6. Western blot

After 20% urethane injection in abdominal cavity of rat, perfusing heart (same as above), cutting head rapidly, collecting brain on ice, rapidly placing in liquid nitrogen, and storing in refrigerator at-80 deg.C for use. Placing brain tissue in a ceramic mortar, adding liquid nitrogen for grinding, taking about 100mg of broken brain tissue, adding protein lysate for extracting total protein according to the instruction of the kit, calculating the protein concentration of a sample according to the instruction of the BCA kit, uniformly adjusting the protein concentration by RAPI, and denaturing the protein sample at-20 ℃ for later use. The protein was electrophoresed by SDS-PAGE and subsequently transferred to nitrocellulose. The blot was blocked with 5% skim milk and incubated with corresponding concentrations of primary anti-PKG 1(1: 1000; protein inter ch; catalog number:21646-1-AP), GAPDH (1: 1000; cell signaling Technology; catalog number; 2118) and secondary antibody (1: 4000; Handzhou de Biological Technology Co., LTD, catalog number:3256751), respectively. Development photography was performed using ECL enhanced luminescence, tannon-5200 gel imager.

7. Statistical analysis

Data were statistically processed using Graph Pad Prism 6.0 software, and results are expressed as Mean ± standard deviation (Mean ± SD). The mean comparisons between groups were statistically different using IBM SPSS Statistics 19.0 software for One-way ANOVA (One-way ANOVA) with p < 0.05.

Second, result in

1. Animal behavioural study

After 3-5min of molding, the rats have pain symptoms such as red ears, head bending, cage climbing and the like. As can be seen from fig. 1(B), the subcutaneous injection of nitroglycerin significantly increased the number of times of head bending in rats (p <0.01) compared to the blank rats, and the model rats showed a longer head bending time (p <0.01) within 90min after the injection. Compared with a model group, the ibuprofen granules can remarkably relieve the pain response of the rat in the flexible head within 0 to 90min (p < 0.01); in addition, the use of emodin extremely reduces the number of times of head bending within 60min after injection (p < 0.01); from 60 to 90min, the number of times of head bending of rats (p <0.01) is extremely obviously weakened, and the blank group, the ibuprofen group and the emodin group have no statistical difference. Thereafter, all rats eventually appeared tired and dysphoric. Also, as shown in FIG. 1(A), the number of cage climbs peaked within 0-30min and lasted for about 90 min. Pretreatment of ibuprofen and emodin significantly reduced the number of cage climbs (p <0.01) from 0 to 90min compared to the model group. Ibuprofen granules and emodin rats showed a peak of cage climbing within 0 to 30min and appeared to be tired at 60 min.

2. Emodin inhibits nitroglycerin-induced increase in NO levels in migraine rats

As shown in fig. 2(a), NO levels in the model group rats were very significantly increased (p <0.01) compared to the blank group; compared with the model group, the ibuprofen granules and the emodin can remarkably reduce the level of NO (p is less than 0.01), and the inhibition effect of the ibuprofen group is stronger than that of the emodin group. Consistent with the results of the behavioral studies.

3. Emodin inhibits nitroglycerin-induced increase in CGRP levels in migraine rats

As can be seen from fig. 2(B), CGRP levels of the model group rats were significantly higher than those of the blank group (p < 0.01). The ibuprofen and emodin pretreatment can remarkably inhibit the increase of the CGRP level (p <0.01), and the ibuprofen group and the emodin group have no remarkable difference (p > 0.05).

4. Emodin inhibits nitroglycerin-induced increase in substance P levels in migraine rats

As shown in fig. 2(C), compared with the blank group, the level of substance P in the model group rats was significantly higher than that in the blank group rats (P <0.01), and there was no statistical difference in substance P in both the ibuprofen group and the emodin group (P > 0.05); compared with the model group, the ibuprofen group and the emodin group can remarkably inhibit the increase of the content of P substances (P is less than 0.01); there was no statistical difference between the ibuprofen and emodin groups (p > 0.05).

5. Emodin inhibits nitroglycerin-induced increase in TNF-alpha levels in migraine rats

As can be seen from FIG. 2(D), the TNF-. alpha.levels in the model rats were significantly higher than those in the blank group (p <0.01) and there was no statistical difference between TNF-. alpha.in the ibuprofen and emodin groups (p >0.05) as compared with the blank group; compared with the model group, the ibuprofen group and the emodin group can obviously inhibit the increase of the content of TNF-alpha (p is less than 0.05); there was no statistical difference between the ibuprofen and emodin groups (p > 0.05).

6. Emodin inhibits nitroglycerin-induced cGMP (cgMP) level elevation in migraine rats

As can be seen from fig. 2(E), compared to the blank group, the cGMP levels in the model group rats were significantly higher than those in the blank group (p <0.01), and there was no statistical difference in cGMP in both the ibuprofen and emodin groups (p > 0.05); compared with the model group, the ibuprofen group and the emodin group can obviously inhibit the increase of the content of cGMP (p <0.01), and the inhibition effect of the ibuprofen group is slightly stronger than that of the emodin group (p < 0.05).

7. Emodin-attenuated nitroglycerin-induced C-fos immunoreaction neuron activation

The number and the integrated optical density of the C-Fos immunocompetent cells in different brain tissue areas (cortex, hippocampus, cerebellum and brain stem) are analyzed, and the difference of C-Fos expression between different groups is mainly reflected in the cortex and brain stem areas, and the result is shown in figure 3 and figure 4.

As can be seen from FIG. 3(E), the number of C-fos-positive cells in the model rats was greater than that in the blank rats (p <0.01), and this increase was reversed by pretreatment with ibuprofen and emodin (p <0.01), which had no significant difference between the ibuprofen particles and emodin in attenuating nitroglycerin-induced activation of C-fos neurons (p > 0.05). As shown in FIG. 3(F), the integrated optical density was much greater for the model group compared to the blank group (p <0.01), whereas ibuprofen and emodin significantly reduced the integrated optical density of C-fos positive cells (p < 0.01). The results are in agreement with those shown in FIGS. 3 (A-D). NTG-activated C-fos immunoreactive positive neurons were brownish yellow, while negative cells were bluish purple. In FIG. 3(B), there was a large number of areas of brown-yellow positive cells, while in FIG. 3(A), there was a small number of areas of brown-yellow positive cells in the blank stained section. The tan areas in fig. 3(C and D) are much smaller than the tan areas in fig. 3(B), indicating that ibuprofen and emodin pretreatment may reduce C-fos neuron overexpression in the cortex.

As can be seen from FIG. 4(E), the number of C-fos-positive cells in the model rats was greater than that in the blank rats (p <0.01), and this increase was reversed by pretreatment with ibuprofen and emodin (p <0.01), which had no significant difference between the ibuprofen particles and emodin in attenuating nitroglycerin-induced activation of C-fos neurons (p > 0.05). As can be seen from FIG. 4(F), the IOD of the stained area was larger in the model group (p <0.01) compared to the blank group, but the IOD of the stained area was significantly reduced after the pretreatment with ibuprofen and emodin (p <0.01), and there was no significant statistical difference between the IOD of the ibuprofen group and the emodin group (p > 0.05). The results are in agreement with those shown in FIGS. 4 (A-D). NTG-activated C-fos immunoreactive positive neurons were brownish yellow, while negative cells were bluish purple. In FIG. 4(B), there was a large area of brown-yellow positive cells, while in FIG. 4(A), the blank stained section had a small area of brown-yellow positive cells. The tan areas in fig. 4(C and D) are much smaller than the tan areas in fig. 4(B), indicating that ibuprofen and emodin pretreatment can reduce C-fos neuron overexpression in the brainstem.

8. Effect of emodin on nitroglycerin-induced PKG proteins

In order to study the effect of emodin on nitroglycerin-induced PKG proteins, western blot analysis was performed on brain tissue proteins. As shown in fig. 5, compared to the blank group, the expression of PKG proteins was very significantly increased in the model group (p < 0.01); compared with the model group, the ibuprofen and the emodin can obviously inhibit the increase of the PKG protein (p <0.01), and the inhibition strength comparison between the ibuprofen and the emodin has no statistical significance (p > 0.05).

The research result shows that: emodin, through the cGMP-PKG pathway, attenuates the expression of PKG protein in the brain tissue of rats induced by nitroglycerin, attenuates the activation of C-fos, and regulates vasoactive substances such as NO, CGRP, substance P, TNF-alpha and cGMP, thereby alleviating the symptoms of migraine.

EXAMPLE 2 preparation of a drug for treating migraine

Materials and methods

1. Test materials

Isopropyl myristate (IPM, Linyi LvSen), isopropyl palmitate (IPP, Linyi LvSen), castor oil polyoxyethylene (EL-40, Aladdin), sodium polyacrylate 700(NP700, International specialty Co., USA), carbomer (CP-934, Gallery Polymercuric chemical Co., Ltd.), polyoxyethylene hydrogenated castor oil (RH-40, BASF Co., Ltd.), poloxamer 407(P407), poloxamer 188(P188) was purchased from Shandong Youso chemical technology, Inc., emodin 98% pure, from Beijing Merrill technology, Inc., acetonitrile (chromatographically pure, Shanghai star can be high purity solvent, Inc.), formic acid (chromatographically pure, Aladdin reagent, Inc.), hydroxypropyl methyl fiber (Shanghai Yuye Biotechnology, Inc.), lactose (Zhenjiang city Kangfu bioengineering, Inc.), absolute ethanol (analytical grade, Shanghai Tantan chemistry, Inc.).

2. Preparation of emodin nano-emulsion gel nose drops

Firstly, oil phase Lauroglicol FCC, Labrafac PG, isopropyl myristate, emulsifier Tween 80, polyoxyethylene hydrogenated castor oil (RH-40), castor oil polyoxyethylene (EL-40), co-emulsifier absolute ethyl alcohol, 1, 2-propylene glycol and 1, 3-butylene glycol are selected. Then, a nano-emulsion prescription is optimized by drawing a pseudo-ternary phase diagram and an orthogonal design test method, and then the emodin nano-emulsion is prepared as follows:

weighing 1mg of emodin, placing the emodin in a beaker, adding 1g of isopropyl palmitate to fully dissolve the mixed oil phase, adding 2.8g of polyoxyethylene hydrogenated castor oil (RH-40) and 1.4g of 1, 2-propylene glycol under stirring, and slowly dripping normal-temperature distilled water (about 7.8g) into the mixture under constant-temperature magnetic stirring at 25 ℃ until the system is clear, thereby obtaining the emodin nanoemulsion. The obtained emodin nanoemulsion is light yellow, clear and transparent, has tyndall phenomenon after illumination, and is stable after centrifugation (3000 r. min., 30 min).

Secondly, 1.677g and 0.252g of P407 and P188 respectively are precisely weighed, the mixture is placed into a beaker, 10mL of ice water is added for stirring and dispersing, standing and dissolving are carried out to prepare poloxamer gel matrix, the poloxamer gel matrix is stored and reserved in a refrigerator, and the prepared emodin nanoemulsion and the emodin nanoemulsion are stirred uniformly at 4 ℃ to prepare the emodin nanoemulsion gel nasal drop (the content of the emodin is about 38 mug/mL).

3. Preparation of emodin tablet

The emodin tablet is prepared by adopting a wet granulation tabletting process. Firstly, preparing emodin particles, taking hydroxypropyl methyl fiber as a carrier material, optimizing a prescription by a single-factor investigation method, and evaluating the soft material properties, granulation conditions and particle appearance as indexes; then, the prescription of tablets such as a filling agent, an adhesive and the like is optimized by taking the sticking punch and the tablet hardness in the tabletting process as comprehensive evaluation indexes, and finally, the tabletting is carried out. The existence form of the emodin in the tablet is identified by adopting calorimetric differential scanning and X-ray diffraction methods.

Dissolving emodin 1.8g and hydroxypropyl methylcellulose 6.0g in 50% (v/v) ethanol at room temperature under stirring; weighing 9g of lactose, 0.5g of microcrystalline cellulose and 0.2g of sodium carboxymethyl starch, uniformly mixing, using 95% (v/v) of hydrous ethanol as an adhesive to prepare a soft material, sieving with a 20-mesh sieve, granulating, carrying out forced air drying at 45 ℃ for 60min, adding 0.5g of magnesium stearate, and uniformly mixing; tabletting to obtain the tablet (the weight of the tablet is 100mg, the content of the emodin is 10mg per tablet, and the hardness is 4-6 kg).

Second, result in

1. Parameter determination and evaluation of emodin nanoemulsion gel

Morphology examination is carried out on the prepared emodin nanoemulsion and emodin nanoemulsion gel by using a transmission electron microscope, and the emodin nanoemulsion gel are spheres with round and uniform appearance. The particle size of emodin nanoemulsion and emodin nanoemulsion gel is less than 100nm and the polydispersity index is less than 0.3 by adopting a Malvern dynamic light scattering particle size analyzer. The viscosity of the prepared emodin nanoemulsion does not change along with the change of the shear rate and belongs to Newtonian fluid, and the viscosity of the emodin nanoemulsion gel is reduced along with the increase of the shear rate and is non-Newtonian fluid.

Therefore, the emodin nanoemulsion and the emodin nanoemulsion gel established in the research have simple preparation process and moderate viscosity, and can provide reference for selection of an emodin nasal drop delivery preparation.

2. Evaluation of emodin tablets

The emodin in the emodin tablet exists in an amorphous or molecular state through calorimetric scanning and X-ray diffraction analysis. The emodin tablets prepared by the research have reasonable prescription composition and simple preparation process, and can provide reference for the preparation of the emodin tablets.

Claims

1. An application of emodin in preparing medicine for treating migraine is disclosed.

2. Use according to claim 1, characterized in that: the drug is a drug for treating migraine based on cGMP-PKG pathway.

3. Use according to claim 1, characterized in that: the medicine is capable of resisting inflammation and inhibiting vasodilatation and is used for treating migraine.

4. Use according to any one of claims 1 to 3, characterized in that: the medicine is a pharmaceutical composition prepared from emodin serving as an active ingredient and a pharmaceutically acceptable carrier or auxiliary material.

5. Use according to claim 4, characterized in that: the dosage form of the medicine is oral dosage form or dosage form suitable for nasal administration.