Application of Corydalis yanhusuo-Angelica dahurica extract in preparing medicine for treating rhinitis

Abstract

The invention discloses the application of Yanhusuo-Angelica extract in the preparation of rhinitis treatment drugs, and belongs to the field of anti-rhinitis drug preparation. Yanhusuo-Angelica extract has a clear therapeutic effect on improving rhinitis symptoms, and the effect is better than dexamethasone, a commonly used clinical drug. By comparing the number of nasal scratching, the number of sneezes, and the IgE release of nasal lavage fluid, the therapeutic effect of the drug on rhinitis is evaluated, and it is determined that the Yanhusuo-Angelica extract formed when the mass ratio of vinegar Yanhusuo:Angelica is 1:1 can improve allergic rhinitis symptoms, and can be used for the preparation of rhinitis drugs. The drug combination of 1:1 ratio is better than the use of vinegar Yanhusuo and Angelica alone or the drug combination of 2:1, and plays a synergistic role; the toxicity is lower than that used alone, and the effect of attenuation is played.

Description

Technical Field

[0001] The invention belongs to the field of anti-rhinitis drug preparation and relates to application of a Corydalis yanhusuo-Angelica dahurica extract in preparing a drug for treating rhinitis. Background Art

[0002] Yuanhuzhitongfang is composed of Corydalis yanhusuo and Angelica dahurica. It is clinically used to treat various pains caused by qi stagnation and blood stasis, including stomachache, rib pain and headache. Corydalis yanhusuo is pungent, dispersing, warming and unblocking. It is good at promoting blood circulation and removing blood stasis, and can promote qi and relieve pain. It is the main drug of this prescription. Angelica dahurica is pungent, dispersing, warming and unblocking. It is good at dispelling wind and cold, drying dampness and relieving pain. It is the assistant drug of this prescription, which helps Corydalis yanhusuo to promote blood circulation, promote qi and relieve pain. The whole prescription is used together to play the role of regulating qi, promoting blood circulation and relieving pain.

[0003] Allergic rhinitis, also known as allergic rhinitis, refers to a chronic inflammatory disease of the nasal mucosa, which is mainly mediated by immunoglobulin E (IgE) and involves the body's immune active cells and cytokines after susceptible individuals come into contact with allergens. Epidemiological surveys of rhinitis show that the prevalence of the disease in adults is increasing year by year. Allergens in the environment can induce the production of specific IgE antibodies and react with them. Among them, exposure to inhaled allergens is the main cause of allergic rhinitis, mainly including dust mites, pollen, animal dander and fungi. The disease is characterized by nasal itching, paroxysmal sneezing, clear watery nasal discharge and nasal congestion. The main manifestations and severity of patients with different types of rhinitis are different. At the same time, the disease can be accompanied by eye symptoms, including itchy eyes, tears, red and swollen eyes and burning sensation; patients with pollen allergies may also be accompanied by lower respiratory tract symptoms such as itchy throat, chest tightness, cough and asthma attacks.

[0004] The treatment principle of rhinitis is to avoid allergen exposure as much as possible and use antihistamines and glucocorticoids reasonably; in addition, monoclonal antibodies against IgE have shown good effects on severe rhinitis. However, current drugs can only relieve symptoms and have significant side effects, so they cannot be used for a long time. There is no drug that can completely cure rhinitis, and new safe and effective drugs for the treatment of rhinitis are urgently needed.

[0005] Currently, there are no reports on the application of Corydalis-Angelica Dahurica as a drug for treating rhinitis. Summary of the invention

[0006] In order to overcome the above-mentioned shortcomings of the prior art, the object of the present invention is to provide an application of Corydalis yanhusuo-Angelica dahurica extract in the preparation of a drug for treating rhinitis.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] The invention discloses the application of a corydalis yanhusuo-angelica dahurica extract in preparing a drug for treating rhinitis. The corydalis yanhusuo-angelica dahurica extract is obtained by crushing corydalis yanhusuo and angelica dahurica dahurica in a mass ratio of (1-2):1, soaking in ethanol, extracting by heating and refluxing, and then filtering.

[0009] Preferably, the Corydalis yanhusuo-Angelica dahurica extract is obtained by crushing Corydalis yanhusuo and Angelica dahurica dahurica in a mass ratio of 1:1, soaking in ethanol, extracting under heating reflux and then filtering.

[0010] Preferably, the specific steps of ethanol soaking and heating reflux are: soak the crushed Corydalis yanhusuo and Angelica dahurica in three times the amount of 60% ethanol for 24 hours, heat under reflux for 3 hours, collect the extract, add twice the amount of 60% ethanol, heat under reflux for 2 hours, and collect the extract.

[0011] Preferably, the drug is a drug for reducing the frequency of nose scratching due to rhinitis.

[0012] Preferably, the drug is a drug for reducing the number of sneezes caused by rhinitis.

[0013] Preferably, the drug is a drug for reducing IgE in nasal lavage fluid.

[0014] Preferably, based on the crude drug of Corydalis yanhusuo or Angelica dahurica, when the drug is used to treat rhinitis, the dosage is 5-10 mg / kg.

[0015] Preferably, the toxicity of the Corydalis yanhusuo-Angelica dahurica extract is lower than that of the single administration, and Corydalis yanhusuo and Angelica dahurica dahurica synergistically exert a toxicity-reducing effect.

[0016] Preferably, Corydalis yanhusuo and Angelica dahurica exert a synergistic effect at a mass ratio of 1:1.

[0017] The present invention also discloses a medicine for treating rhinitis, comprising a corydalis yanhusuo-angelica dahurica extract and a pharmaceutically acceptable auxiliary material. The corydalis yanhusuo-angelica dahurica extract is obtained by crushing corydalis yanhusuo and angelica dahurica in a mass ratio of (1-2):1, soaking in ethanol, extracting by heating and refluxing, and then filtering.

[0018] Preferably, the Corydalis yanhusuo-Angelica dahurica extract is obtained by crushing Corydalis yanhusuo and Angelica dahurica dahurica in a mass ratio of 1:1, soaking in ethanol, extracting under heating reflux and then filtering.

[0019] Preferably, the dosage form of the drug is nasal drops.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] The invention discloses the use of a Corydalis yanhusuo-Angelica dahurica extract in preparing a drug for treating rhinitis. Experiments show that the Corydalis yanhusuo-Angelica dahurica extract ((1-2):1) has a clear therapeutic effect on improving rhinitis symptoms, especially when the Corydalis yanhusuo and Angelica dahurica are extracted in a mass ratio of 1:1, the therapeutic effect on rhinitis is better. After administering the extract of Corydalis yanhusuo and Angelica dahurica (1:1), firstly, the number of nasal scratching, the number of sneezes and the IgE content in the nasal lavage fluid of the rhinitis model mice were effectively inhibited; secondly, Angelica dahurica and Corydalis yanhusuo could synergistically enhance the effect, and the effect was better than that of using Angelica dahurica or Corydalis yanhusuo alone; thirdly, compared with using Angelica dahurica or Corydalis yanhusuo extract alone, Angelica dahurica and Corydalis yanhusuo could reduce the weight of mice, indicating that the two ingredients have the effect of reducing toxicity; fourthly, the therapeutic effect of Angelica dahurica and Corydalis yanhusuo was better than that of an equal proportion mixture of the active ingredients of Angelica dahurica and Corydalis yanhusuo - imperatorin and drupein - in relieving the symptoms of rhinitis in mice; fifthly, compared with the mixture of other doses, the number of nose scratching of mice with the extract of Corydalis yanhusuo and Angelica dahurica (1:1) was less, indicating that the extract of Corydalis yanhusuo and Angelica dahurica could synergistically enhance the effect and could be used in the preparation of rhinitis drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is the result of the inhibition of Yanhusuo-Angelica extract on the number of nose scratching in mice induced by OVA;

[0023] Figure 2 This is the result of the inhibition of the number of sneezing in mice induced by OVA by the extract of Corydalis yanhusuo and Angelica dahurica;

[0024] Figure 3 This is the result of the inhibition of the Yanhusuo-Angelica extract on the increase of IgE in the nasal lavage fluid of mice induced by OVA;

[0025] Figure 4 The results of the number of times mice scratched their noses showed that the effect of Corydalis yanhusuo-Angelica dahurica extract was better than that of Angelica dahurica and Corydalis yanhusuo alone;

[0026] Figure 5 The figure shows the number of sneezes in mice, showing that the effect of Corydalis yanhusuo-Angelica dahurica extract is better than that of Angelica dahurica and Corydalis yanhusuo alone.

[0027] Figure 6 This is the result graph showing that the toxicity of the extract of Corydalis yanhusuo and Angelica dahurica is less than that of Angelica dahurica and Corydalis yanhusuo when used alone;

[0028] Figure 7 The results of the Yanhusuo-Angelica extract being superior to the 1:1 mixture of imperatorin and dihydropalmatine in the mice scratching their noses;

[0029] Figure 8 This is a graph showing the results of the number of times mice scratched their noses, with the effect of Corydalis yanhusuo-Angelica dahurica extract (1:1) being better than that of Corydalis yanhusuo-Angelica dahurica extract (2:1). DETAILED DESCRIPTION

[0030] In order to enable those skilled in the art to understand the characteristics and effects of the present invention, the following is a general description and definition of the terms and expressions mentioned in the specification and claims. Unless otherwise specified, all technical and scientific terms used in the text are the common meanings understood by those skilled in the art for the present invention. In the event of a conflict, the definition in this specification shall prevail.

[0031] The theories or mechanisms described and disclosed herein, whether correct or incorrect, should not limit the scope of the present invention in any way, that is, the present invention can be implemented without being limited by any specific theory or mechanism.

[0032] Herein, all features such as values, quantities, contents and concentrations defined in the form of numerical ranges or percentage ranges are for simplicity and convenience only. Accordingly, the description of numerical ranges or percentage ranges should be considered to have included and specifically disclosed all possible secondary ranges and individual values ​​within the range (including integers and fractions).

[0033] In this document, unless otherwise specified, “includes,” “including,” “contains,” “has,” or similar terms cover the meanings of “consisting of” and “mainly consisting of,” for example, “A includes a” covers the meanings of “A includes a and other” and “A only includes a.”

[0034] In this document, in order to make the description concise, not all possible combinations of various technical features in various embodiments or examples are described. Therefore, as long as there is no contradiction in the combination of these technical features, the various technical features in various embodiments or examples can be combined arbitrarily, and all possible combinations should be considered to be within the scope of this specification.

[0035] The invention provides application of Corydalis yanhusuo-Angelica dahurica extract in preparing medicine for treating rhinitis.

[0036] The present invention will be further described below in conjunction with specific embodiments. It should be understood that these embodiments are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall within the scope limited by the appended claims of the application equally.

[0037] The following examples use conventional instruments and equipment in the art, and the various raw materials and reagents (e.g., organic solvents, inorganic solvents, kinases, substrates, antibodies, buffers, reaction solutions, etc.) used are, unless otherwise specified, conventional commercial products, and their specifications are conventional specifications in the art, or can be prepared or formulated by known methods or reagent instructions. The experimental methods in the following examples where specific conditions are not specified are usually carried out under conventional conditions or under conditions recommended by the manufacturer.

[0038] In the specification of the present invention and the following examples, unless otherwise specified, "%" means percentage by weight, "part" means part by weight, and "ratio" means weight ratio.

[0039] In the specification of the present invention and the following examples, if not otherwise specified, the term "effective amount" refers to the dosage that can achieve the purpose of preventing and / or treating the diseases described in the present invention in a subject. Those skilled in the art can easily determine the dosage of Corydalis yanhusuo and Angelica dahurica based on the context of the present invention. In particular, the term "effective amount" can be understood as Corydalis yanhusuo and Angelica dahurica (or in the form of a plant extract containing Corydalis yanhusuo and Angelica dahurica, or in the form of a plant extract containing vinegar Corydalis yanhusuo and Angelica dahurica) to treat the disorder in a reasonable effect / risk ratio suitable for any medical treatment. However, it should be recognized that the total daily dosage of Corydalis yanhusuo and Angelica dahurica or their compositions of the present invention can be determined by those skilled in the art within the scope of reliable medical judgment. For any specific subject, the specific preventive effective dose level must be determined according to a variety of factors, including the age, weight, general health, sex and diet of the subject, the specific composition used, other therapeutically active substances used in combination with Corydalis yanhusuo and Angelica dahurica or used simultaneously, and similar factors known in the medical field.

[0040] In the specification of the present invention and the following examples, unless otherwise specified, the term "preparation form" is also referred to as "dosage form", "medicament", "drug preparation" and the like.

[0041] In the specification of the present invention and the following examples, if not otherwise specified, the term "plant extract" or "extract", if not otherwise specified, refers to an "extract" containing Corydalis yanhusuo or Angelica dahurica extracted from, for example, but not limited to, the plants described herein. It is understood by those skilled in the art that Corydalis yanhusuo and Angelica dahurica described in the present invention can be chemically synthesized or can be derived from plants such as the plant extracts described herein. In addition, it is known to those skilled in the art that people extract Corydalis yanhusuo or Angelica dahurica from plants, and it is also known to those skilled in the art that Corydalis yanhusuo or Angelica dahurica are obtained by chemical synthesis.

[0042] The present invention provides a drug for treating rhinitis comprising Rhizoma Corydalis and Radix Angelicae Dahuricae formulated with one or more non-toxic pharmaceutically acceptable carriers. The drug for treating rhinitis can be specially formulated for oral administration or rectal administration in solid or liquid form, or formulated for injection or nasal administration. Solid dosage forms for oral administration include but are not limited to capsules, tablets, pills, powders and granules. In such solid dosage forms, the active compound may be mixed with at least one inert pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate and / or the following: a) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinyl pyrrolidone, sucrose and gum arabic; c) humectants such as glycerol; d) disintegrants such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates and sodium carbonate; e) solution retarder such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glyceryl monostearate; h) adsorbents such as kaolin and bentonite; i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof. In the case of capsules, tablets and pills, the dosage form may also contain a buffer. Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, solutions, suspensions, syrups and elixirs. In addition to the active compound, the liquid dosage form may also contain an inert diluent commonly used in the art, such as water or other solvents, solubilizers and emulsifiers such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil and sesame oil), glycerol, tetrahydrofuran alcohol, polyethylene glycol and fatty acid esters of sorbitan and mixtures thereof.

[0043] Example 1: Yanhusuo-Angelica Dahurica Extract (Vinegar Yanhusuo:Angelica Dahurica = 1:1) Inhibits OVA-Induced Rhinitis Symptoms in Mice

[0044] 1. Experimental Materials

[0045] Vinegar-corydalis and Angelica dahurica were purchased from Ningxia Mingde Chinese Medicine Pieces Co., Ltd.; OVA (ovalbumin) was purchased from SIGMA; 6-8 week old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0046] 2. Experimental methods

[0047] Prepare 400g each of vinegar Corydalis and Angelica dahurica. Take 166g of Angelica dahurica and crush it into fine powder. Crush the remaining Angelica dahurica and vinegar Corydalis into coarse powder. Mix the fine powder with the coarse powder to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat and reflux for 3 hours, collect the extract, add two times the amount of 60% ethanol and heat and reflux for 2 hours, collect the extract, combine the secondary extracts, filter, and concentrate the filtrate into a thick paste. According to the content determination method of Yuanhu Pain Relief Tablets included in the 2020 edition of the Chinese Pharmacopoeia, the Corydalis-Angelica extract was determined by high performance liquid chromatography. Taking imperatorin and tetrahydropalmatine as indicator components, when the crude drug amount is 10mg / kg, the content of imperatorin in the Corydalis-Angelica extract is 400μg / mL and the content of tetrahydropalmatine is 90μg / mL.

[0048] Mice were divided into negative control group (NC), blank control group (Vehicle), positive control group (DEX) and groups treated with different concentrations of Corydalis yanhusuo-Angelica dahurica extract. Mice in the blank control group, positive control group and groups treated with different concentrations of Corydalis yanhusuo-Angelica dahurica extract were sensitized by intraperitoneal injection of OVA (10 μg / day on the 1st, 7th and 14th days), and mice in the negative control group were not treated. After sensitization, Corydalis yanhusuo-Angelica dahurica extract solutions of different concentrations (5 mg / kg and 10 mg / kg, respectively) were prepared with normal saline and administered intranasally to mice in different concentrations of Corydalis yanhusuo-Angelica dahurica extract groups. Mice in the negative control group and blank control group were given equal doses of normal saline intranasally; mice in the positive control group were given equal doses of dexamethasone. 30 minutes after the end of administration in each group, 200 μg / mL OVA intranasally induced rhinitis (on the 21st, 23rd, 25th and 27th days). After the last challenge, the number of nose scratching and sneezing of mice in each group was counted; the mice were killed within 24 hours, and the nasal lavage fluid was collected and the IgE content was detected by ELISA.

[0049] 3. Experimental results

[0050] Results Figure 1 , Figure 2 and Figure 3 .

[0051] Figure 1 , Figure 2 and Figure 3 As can be seen, the blank control group OVA intranasal mice showed significant rhinitis symptoms, including increased nasal scratching, sneezing and nasal lavage fluid IgE content, indicating that the model was successfully established. Compared with the control group, intranasal administration of Corydalis yanhusuo-Angelica dahurica extract in a ratio of 1:1 can effectively inhibit the number of nasal scratching ( Figure 1 ), number of sneezes( Figure 2 ) and nasal lavage fluid IgE content ( Figure 3) and relieved the symptoms of rhinitis in mice. 10mg / kg of Yanhusuo-Angelica extract nasal drops significantly inhibited the symptoms of rhinitis, and its therapeutic effect was better than that of dexamethasone, a commonly used clinical drug.

[0052] The dosage of Corydalis yanhusuo and Angelica dahurica in the drug combination is lower than that of using them alone, which plays a role in reducing toxicity and increasing efficacy. The examples are as follows.

[0053] Example 2 The efficacy of Corydalis yanhusuo-Angelica dahurica extract (vinegar Corydalis yanhusuo:Angelica dahurica = 1:1) in inhibiting OVA-induced rhinitis in mice is better than that of single use

[0054] 1. Experimental Materials

[0055] Vinegar-corydalis and Angelica dahurica were purchased from Ningxia Mingde Chinese Medicine Pieces Co., Ltd.; OVA was purchased from SIGMA; 6-8 week old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0056] 2. Experimental methods

[0057] Prepare 400g each of vinegar Corydalis and Angelica dahurica. Take 166g of Angelica dahurica and crush it into fine powder. Crush the remaining Angelica dahurica and vinegar Corydalis into coarse powder. Mix the fine powder with the coarse powder to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat and reflux for 3 hours, collect the extract, add two times the amount of 60% ethanol and heat and reflux for 2 hours, collect the extract, combine the secondary extracts, filter, and concentrate the filtrate into a thick paste. According to the content determination method of Yuanhu Pain Relief Tablets included in the 2020 edition of the Chinese Pharmacopoeia, the Corydalis-Angelica extract was determined by high performance liquid chromatography. Taking imperatorin and tetrahydropalmatine as indicator components, when the crude drug amount is 10mg / kg, the content of imperatorin in the Corydalis-Angelica extract is 400μg / mL and the content of tetrahydropalmatine is 90μg / mL.

[0058] The mice were divided into negative control group (NC), blank control group (Vehicle), positive control group (DEX), Corydalis yanhusuo-Angelica dahurica extract group (prescription 1:1), Corydalis yanhusuo group (vinegar Corydalis yanhusuo) and Angelica dahurica group (Angelica dahurica). The mice in the blank control group, positive control group and different concentrations of Corydalis yanhusuo-Angelica dahurica extract groups were sensitized by intraperitoneal injection of OVA (10 μg / day on the 1st, 7th and 14th days), and the mice in the negative control group were not treated. After the sensitization, 10 mg / kg Corydalis yanhusuo-Angelica dahurica extract solution with vinegar Corydalis yanhusuo:Angelica dahurica = 1:1, 10 mg / kg vinegar Corydalis yanhusuo solution and 10 mg / kg Angelica dahurica solution were prepared with normal saline, and the mice in the Corydalis yanhusuo-Angelica dahurica extract group, Corydalis yanhusuo group and Angelica dahurica group were nasally administered. Among them, Corydalis yanhusuo-Angelica dahurica extract and Angelica dahurica solution contained 400 μg / mL of imperatorin, and Corydalis yanhusuo-Angelica dahurica extract and vinegar Corydalis yanhusuo solution contained 150 μg / mL of tetrahydropalmatine.

[0059] 30 minutes after the end of administration, 200 μg / mL OVA was dripped into the nose to induce rhinitis (days 21, 23, 25 and 27). After the last challenge, the number of nose scratching and sneezing of mice in each group was counted.

[0060] 3. Experimental results

[0061] Results Figure 4 and Figure 5 .

[0062] Figure 4 and Figure 5 It can be seen that the blank control group OVA nasal drop mice showed significant rhinitis symptoms, including the number of nasal scratching, the number of sneezes and the IgE content of nasal lavage fluid increased, indicating that the model was successfully established. Compared with the control group, the dosage of vinegar corydalis and angelica was lower than that of single use. The intranasal administration of corydalis-angelica extract, angelica solution and corydalis solution to mice can effectively inhibit the number of nasal scratching ( Figure 4 ) and sneeze( Figure 5 ) times, relieved the symptoms of rhinitis in mice. The nasal drops of Corydalis yanhusuo and Angelica dahurica in a ratio of 1:1 significantly inhibited the symptoms of rhinitis, played a role in reducing toxicity and increasing efficacy, and its therapeutic effect was better than that of Angelica dahurica or Corydalis yanhusuo alone.

[0063] Example 3 The toxicity of the extract of Corydalis yanhusuo and Angelica dahuricae Dahuricae (vinegar Corydalis yanhusuo: Angelica dahuricae Da ...

[0064] 1. Experimental Materials

[0065] Vinegar-corydalis and Angelica dahurica were purchased from Ningxia Mingde Chinese Medicine Pieces Co., Ltd.; OVA was purchased from SIGMA; 6-8 week old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0066] 2. Experimental methods

[0067] Prepare 400g each of vinegar Corydalis and Angelica dahurica. Take 166g of Angelica dahurica and crush it into fine powder. Crush the remaining Angelica dahurica and vinegar Corydalis into coarse powder. Mix the fine powder with the coarse powder to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat and reflux for 3 hours, collect the extract, add two times the amount of 60% ethanol and heat and reflux for 2 hours, collect the extract, combine the secondary extracts, filter, and concentrate the filtrate into a thick paste. According to the content determination method of Yuanhu Pain Relief Tablets included in the 2020 edition of the Chinese Pharmacopoeia, the Corydalis-Angelica extract was determined by high performance liquid chromatography. Taking imperatorin and tetrahydropalmatine as indicator components, when the crude drug amount is 10mg / kg, the content of imperatorin in the Corydalis-Angelica extract is 400μg / mL and the content of tetrahydropalmatine is 90μg / mL.

[0068] The mice were divided into negative control group (NC), blank control group (Vehicle), Yanhusuo-Angelica extract group (prescription 1:1), vinegar Yanhusuo group, Angelica dahurica group and positive control group (DEX). The mice in the blank control group, Yanhusuo-Angelica extract group, vinegar Yanhusuo group, Angelica dahurica group and positive control group were sensitized by intraperitoneal injection of OVA, and the mice in the negative control group were not treated. After the sensitization, 10 mg / kg Yanhusuo-Angelica extract solution, 10 mg / kg Yanhusuo solution and 10 mg / kg Angelica dahurica solution were prepared with normal saline, and the mice in the Yanhusuo-Angelica extract group, vinegar Yanhusuo group and Angelica dahurica group were intranasally administered, respectively. The mice in the negative control group and blank control group were given the same dose of normal saline; the mice in the positive control group were given the same dose of dexamethasone. Among them, the Yanhusuo-Angelica extract group and Angelica dahurica solution contained 400 μg / mL of imperatorin, and the Yanhusuo-Angelica extract group and vinegar Yanhusuo solution contained 150 μg / mL of tetrahydropalmatine.

[0069] 30 minutes after the end of the administration, 200 μg / mL OVA was dripped into the nose to induce rhinitis. The weight changes of mice were recorded every day.

[0070] 3. Experimental results

[0071] Results Figure 6 .

[0072] Figure 6 As can be seen, the weight of the OVA-treated mice in the blank control group decreased significantly, indicating that the model was successfully established. Compared with the control group, dexamethasone and the 1:1 formula both reduced the weight loss of mice. However, the Angelica dahurica extract alone and the vinegar-corydalis extract alone could not reduce the weight loss of mice. Therefore, the 1:1 mixture of Angelica dahurica and vinegar-corydalis has the effect of reducing toxicity.

[0073] Example 4 The efficacy of Corydalis yanhusuo-Angelica dahurica extract (vinegar Corydalis yanhusuo:Angelica dahurica = 1:1) in inhibiting OVA-induced rhinitis in mice is better than that of imperatorin and tetrahydropalmatine mixed in a ratio of 1:1

[0074] 1. Experimental Materials

[0075] Vinegar-corydalis and Angelica dahurica were purchased from Ningxia Mingde Chinese Medicine Pieces Co., Ltd.; OVA was purchased from SIGMA; 6-8 week old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0076] 2. Experimental methods

[0077] Prepare 400g each of vinegar Corydalis and Angelica dahurica. Take 166g of Angelica dahurica and crush it into fine powder. Crush the remaining Angelica dahurica and vinegar Corydalis into coarse powder. Mix the fine powder with the coarse powder to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat and reflux for 3 hours, collect the extract, add two times the amount of 60% ethanol and heat and reflux for 2 hours, collect the extract, combine the secondary extracts, filter, and concentrate the filtrate into a thick paste. According to the content determination method of Yuanhu Pain Relief Tablets included in the 2020 edition of the Chinese Pharmacopoeia, the Corydalis-Angelica extract was determined by high performance liquid chromatography. Taking imperatorin and tetrahydropalmatine as indicator components, when the crude drug amount is 10mg / kg, the content of imperatorin in the Corydalis-Angelica extract is 400μg / mL and the content of tetrahydropalmatine is 90μg / mL.

[0078] The mice were divided into negative control group (NC), blank control group (Vehicle), positive control group (DEX), group administered with Corydalis yanhusuo-Angelica dahurica extract (prescription 1:1), and group administered with imperatorin and dihydropalmatine (component 1:1). Mice in the blank control group, positive control group, group administered with Corydalis yanhusuo-Angelica dahurica extract, and group administered with imperatorin and dihydropalmatine were sensitized by intraperitoneal injection of OVA (10 μg / day on the 1st, 7th, and 14th days), and mice in the negative control group were not treated. After sensitization, 10 mg / kg of Corydalis yanhusuo-Angelica dahurica extract solution with vinegar Corydalis yanhusuo:Angelica dahurica = 1:1 and 10 mg / kg of 1:1 mixed solution of imperatorin and dihydropalmatine were prepared with normal saline, and the mice in the Corydalis yanhusuo-Angelica dahurica extract group and the mixed group administered with imperatorin and dihydropalmatine were administered intranasally, respectively. Mice in the negative control group and blank control group were given the same dose of normal saline; mice in the positive control group were given the same dose of dexamethasone. Among them, the 1:1 mixed solution of Corydalis yanhusuo-Angelica dahurica extract and imperatorin and corydalis butylene both contained 400 μg / mL of imperatorin, and the 1:1 mixed solution of Corydalis yanhusuo-Angelica dahurica extract and imperatorin and corydalis butylene both contained 150 μg / mL of corydalis butylene.

[0079] 30 minutes after the end of administration, 200 μg / mL OVA was dripped into the nose to induce rhinitis (days 21, 23, 25 and 27). After the last challenge, the number of times the mice in each group scratched their nose was counted.

[0080] 3. Experimental results

[0081] Results Figure 7 .

[0082] Figure 7As can be seen, the blank control group OVA nasal drops mice showed significant rhinitis symptoms, indicating that the model was successfully established. Compared with the control group, nasal drops of Corydalis-Angelica extract to mice can effectively inhibit the number of nose scratching and relieve the symptoms of rhinitis in mice, while the effect of a 1:1 mixture of imperatorin and corydalis butylene was poor. Nasal drops of Corydalis-Angelica extract with vinegar Corydalis: Angelica dahurica = 1:1 significantly inhibited the symptoms of rhinitis, and its therapeutic effect was better than a solution of imperatorin and corydalis butylene mixed at equal concentrations.

[0083] Example 5 The efficacy of the extract of Corydalis yanhusuo and Angelica dahuricae Dahuricae (vinegar Corydalis yanhusuo: Angelica dahuricae Da ...

[0084] 1. Experimental Materials

[0085] Vinegar-corydalis and Angelica dahurica were purchased from Ningxia Mingde Chinese Medicine Pieces Co., Ltd.; OVA was purchased from SIGMA; 6-8 week old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0086] 2. Experimental methods

[0087] Prepare vinegar Corydalis (400g or 800g) and Angelica dahurica (400g). Take 166g of Angelica dahurica and crush it into fine powder. The remaining Angelica dahurica and vinegar Corydalis dahurica are crushed into coarse powder. The fine powder is mixed with the coarse powder to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat and reflux for 3 hours, collect the extract, add two times the amount of 60% ethanol and heat and reflux for 2 hours, collect the extract, combine the secondary extracts, filter, and concentrate the filtrate into a thick paste. According to the content determination method of Yuanhu Pain Relief Tablets included in the 2020 edition of the Chinese Pharmacopoeia, the Corydalis dahurica-Angelica extract was determined by high performance liquid chromatography. Taking imperatorin and tetrahydropalmatine as indicator components, when the crude drug amount is 10mg / kg, the content of imperatorin in the Corydalis dahurica-Angelica extract is determined to be 400μg / mL and the content of tetrahydropalmatine is 90μg / mL.

[0088] The mice were divided into negative control group (NC), blank control group (Vehicle), positive control group (DEX), Yanhusuo-Angelica extract administration group (prescription 1:1) and Yanhusuo-Angelica extract administration group (prescription 2:1). The mice in the blank control group, positive control group, Yanhusuo-Angelica extract administration group (prescription 1:1) and Yanhusuo-Angelica extract administration group (prescription 2:1) were sensitized by intraperitoneal injection of OVA (10 μg / day on the 1st, 7th and 14th days), and the mice in the negative control group were not treated. After the sensitization, 10 mg / kg vinegar Yanhusuo:Angelica = 1:1 and 2:1 Yanhusuo-Angelica extract solution was prepared with normal saline, and the Yanhusuo-Angelica extract administration group (prescription 1:1) and Yanhusuo-Angelica extract administration group (prescription 2:1) mice were intranasally administered, and the negative control group and blank control group mice were given the same dose of normal saline; the positive control group mice were given the same dose of dexamethasone.

[0089] 30 minutes after the end of administration, 200 μg / mL OVA was dripped into the nose to induce rhinitis (days 21, 23, 25 and 27). After the last challenge, the number of times the mice scratched their noses was counted.

[0090] 3. Experimental results

[0091] Results Figure 8 .

[0092] Figure 8 As can be seen, the blank control group OVA nasal drops mice showed significant rhinitis symptoms, indicating that the model was successfully established. Compared with the control group, nasal drops of 1:1 or 2:1 Corydalis yanhusuo-Angelica dahurica extracts to mice can effectively inhibit the number of nose scratching and relieve the symptoms of rhinitis in mice, and the 1:1 mixture of Corydalis yanhusuo-Angelica dahurica extracts has a better effect.

[0093] The technical idea of ​​the present invention is to illustrate the technical idea of ​​the present invention, but it cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. The use of Corydalis yanhusuo-Angelica dahurica extract in the preparation of a drug for treating rhinitis, characterized in that: The Corydalis yanhusuo-Angelica dahurica extract is obtained by crushing Corydalis yanhusuo and Angelica dahurica dahurica in a mass ratio of (1-2):1, soaking in 60% ethanol and heating under reflux, extracting and filtering.

2. The use according to claim 1, characterized in that The Corydalis yanhusuo-Angelica dahurica extract is prepared by crushing Corydalis yanhusuo and Angelica dahurica in a mass ratio of (1-2):1, soaking them in 60% ethanol three times the amount of the crushed Corydalis yanhusuo and Angelica dahurica, heating and refluxing, collecting the extract, then adding 60% ethanol twice the amount of the crushed Corydalis yanhusuo and Angelica dahurica, heating and refluxing, and collecting the extract.

3. The use according to claim 1 or 2, characterized in that: The mass ratio of Corydalis yanhusuo and Angelica dahurica is 1:

1.

4. A drug for treating rhinitis, characterized in that: The invention is prepared from Corydalis yanhusuo-Angelica dahurica extract and pharmaceutically acceptable excipients. The Corydalis yanhusuo-Angelica dahurica extract is obtained by crushing Corydalis yanhusuo and Angelica dahurica dahurica in a mass ratio of 1:1, soaking in 60% ethanol and heating under reflux, and filtering after extraction. The drug is administered through the nose and the dosage form is nasal drops.

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