Use of corydalis rhizoma–angelicae dahuricae radix extract in preparation of drug for treating rhinitis

Abstract

The present invention belongs to the field of the preparation of anti-rhinitis drugs. Disclosed in the present invention is the use of a Corydalis rhizoma–Angelicae dahuricae radix extract in the preparation of a drug for treating rhinitis. The Corydalis rhizoma–Angelicae dahuricae radix extract has a clear therapeutic effect on improving symptoms of rhinitis, and the effect is superior to that of the common clinical drug dexamethasone. The therapeutic effect of the drug on rhinitis is evaluated by means of comparing the number of times of nasal scratching, the number of sneezes and the IgE release amount of a nasal lavage fluid; and it is determined that a Corydalis rhizoma–Angelicae dahuricae radix extract formed from Corydalis rhizoma praeparatum and Angelicae dahuricae radix at a mass ratio of 1:1 can improve the symptoms of allergic rhinitis, and can be used in the preparation of a drug for treating rhinitis. The pharmaceutical combination at the ratio of 1:1 has a better effect than Corydalis rhizoma processed with vinegar and Angelicae dahuricae radix alone or a pharmaceutical combination at the ratio of 2:1, thereby exerting a synergistic role, and has lower toxicity than using one drug component alone, thereby exerting an effect of reducing toxicity.

Description

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

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

[0002] The Yuanhuzhitong prescription, composed of Corydalis yanhusuo and Angelica dahurica, is clinically used to treat various pains caused by qi stagnation and blood stasis, including stomachache, rib pain, and headache. Corydalis yanhusuo, with its pungent, dispersing, warming, and unblocking properties, is effective in promoting blood circulation and removing blood stasis, while also promoting qi and relieving pain. It serves as the main ingredient in the prescription. Angelica dahurica, with its pungent, dispersing, warming, and unblocking properties, is adept at dispelling wind and cold, drying dampness, and relieving pain. It serves as the auxiliary ingredient in the prescription, assisting Corydalis yanhusuo in promoting blood circulation, promoting qi, and relieving pain. The entire prescription, when used together, achieves the benefits of regulating qi, activating blood circulation, and relieving pain.

[0003] Allergic rhinitis, also known as allergic rhinitis, is a chronic inflammatory disease of the nasal mucosa caused by exposure to allergens in susceptible individuals. This disease is primarily mediated by immunoglobulin E (IgE) and involves the production of immune-competent cells and cytokines. Epidemiological surveys of rhinitis show an increasing prevalence among adults. Environmental allergens induce the production and reaction of specific IgE antibodies. Exposure to inhaled allergens, including dust mites, pollen, animal dander, and fungi, is the primary cause of allergic rhinitis. The disease is characterized by nasal itching, paroxysmal sneezing, watery nasal discharge, and nasal congestion. The primary manifestations and severity vary among different types of rhinitis. Ocular symptoms may also be present, including itching, tearing, redness, swelling, and burning sensation. Pollen allergy sufferers may also experience lower respiratory symptoms such as throat itching, chest tightness, coughing, and asthma attacks.

[0004] The treatment principles for rhinitis are to minimize allergen exposure and to use antihistamines and glucocorticoids appropriately. Furthermore, monoclonal antibodies targeting IgE have shown promising results for severe rhinitis. However, current medications only alleviate symptoms and have significant side effects, making long-term use unsuitable. There is no drug that completely cures rhinitis, and the development of new, safe, and effective treatments is urgently needed.

[0005] Currently, there are no reports on the use of Corydalis-Angelica dahurica as a drug for treating rhinitis. Technical issues

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

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

[0008] The invention discloses an application of a Corydalis yanhusuo-Angelica dahurica extract in preparing a medicine 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 under reflux, 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, heating under reflux extraction and then filtering.

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

[0011] Preferably, the drug is a drug that reduces the frequency of nose scratching caused by rhinitis.

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

[0013] Preferably, the drug is a drug that reduces IgE in nasal lavage fluid.

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

[0015] Preferably, the toxicity of the Corydalis yanhusuo-Angelica dahurica extract is lower than that of the single administration, and the 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 excipient. 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, heating under reflux, 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, heating under reflux extraction and then filtering.

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

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

[0021] The present invention discloses the use of a Corydalis yanhusuo-Angelica dahurica extract in the preparation of a medicament for treating rhinitis. Experiments have shown that the Corydalis yanhusuo-Angelica dahurica extract ((1-2):1) has a clear therapeutic effect on improving rhinitis symptoms, and in particular, the Corydalis yanhusuo and Angelica dahurica extract have a better therapeutic effect on rhinitis when the mass ratio of the extract is 1:1. After administering the extract of Corydalis yanhusuo and Angelica dahurica (1:1), firstly, the number of nasal scratching, sneezing and IgE content in the nasal lavage fluid of mice with rhinitis model were effectively inhibited; secondly, Angelica dahurica and Corydalis yanhusuo could synergistically enhance their effects, and the effect was better than that of using Angelica dahurica or Corydalis yanhusuo alone; thirdly, Angelica dahurica and Corydalis yanhusuo could reduce the weight of mice compared with using Angelica dahurica or Corydalis yanhusuo extract alone, 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 - imperatorin and dihydropalmatine - in relieving the symptoms of rhinitis in mice; fifthly, compared with the mixture of other doses, mice scratched their noses less frequently with the extract of Corydalis yanhusuo and Angelica dahurica (1:1), indicating that the extract of Corydalis yanhusuo and Angelica dahurica could synergistically enhance their effects and could be used in the preparation of rhinitis drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] FIG1 is a graph showing the results of the inhibition of the Yanhusuo-Angelica extract on the number of nose scratching in mice induced by OVA;

[0023] FIG2 is a graph showing the inhibition of the Corydalis yanhusuo-Angelica dahurica extract on the number of sneezing in mice induced by OVA;

[0024] FIG3 is a graph showing the inhibitory effect of Corydalis yanhusuo-Angelica dahurica extract on the increase of IgE in the nasal lavage fluid of mice induced by OVA;

[0025] FIG4 shows the results of the number of nose scratching in mice using the extract of Corydalis yanhusuo and Angelica dahuricae Da ... and Corydalis yanhusuo alone;

[0026] FIG5 shows that the effect of Corydalis yanhusuo-Angelica dahurica extract is better than that of Angelica dahurica or Corydalis yanhusuo alone in the number of sneezes in mice;

[0027] FIG6 shows that the toxicity of the Corydalis yanhusuo-Angelica dahurica extract is less than that of Angelica dahurica or Corydalis yanhusuo when used alone;

[0028] FIG7 shows the results of the nasal scratching frequency of mice given a 1:1 mixture of imperatorin and tetrahydropalmatine, which showed a better effect of the extract of Corydalis yanhusuo and Angelica dahurica than that of mice given a 1:1 mixture of imperatorin and tetrahydropalmatine;

[0029] Figure 8 shows the results of the number of times mice scratched their noses, showing that the effect of Corydalis yanhusuo-Angelica dahurica extract (1:1) was better than that of Corydalis yanhusuo-Angelica dahurica extract (2:1). Modes for Carrying Out the Invention

[0030] To facilitate understanding of the features and effects of the present invention by those skilled in the art, the following provides a general description and definition of the terms and expressions used in the specification and claims. Unless otherwise indicated, all technical and scientific terms used herein have the ordinary meanings as understood by those skilled in the art regarding the present invention. In the event of conflict, the definitions 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] All features, such as values, amounts, contents, and concentrations, described herein as numerical ranges or percentage ranges are provided for simplicity and convenience only. Accordingly, the description of numerical ranges or percentage ranges should be considered to include and specifically disclose all possible subranges and individual values ​​within the range (including integers and fractions).

[0033] In this document, unless otherwise specified, “include,” “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, for the sake of brevity, not all possible combinations of the various technical features in each embodiment or example are described. Therefore, as long as there are no contradictions in the combination of these technical features, the various technical features in each embodiment or example can be combined in any way, and all possible combinations should be considered to be within the scope of this specification.

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

[0036] Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiments are only used to illustrate the present invention and are not used in limiting the scope of the present invention.In addition, 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 equally within the scope limited by the appended claims of the application.

[0037] The following examples utilize conventional equipment in the art. Unless otherwise noted, all raw materials and reagents (e.g., organic solvents, inorganic solvents, kinases, substrates, antibodies, buffers, reaction solutions, etc.) are commercially available products, with specifications conventional in the art, or can be prepared or formulated according to known methods or reagent instructions. Experimental procedures in the following examples, where specific conditions are not specified, were generally performed under conventional conditions or according to the manufacturer's recommendations.

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

[0039] Throughout the present description and the following examples, unless otherwise specified, the term "effective amount" refers to an amount effective to prevent and / or treat the conditions described herein in a subject. A person skilled in the art can readily determine the dosage of Corydalis yanhusuo and Angelica dahurica based on the present disclosure. Specifically, the term "effective amount" should be understood as a sufficient amount of Corydalis yanhusuo and Angelica dahurica (or in the form of a plant extract comprising Corydalis yanhusuo and Angelica dahurica, or in the form of a plant extract comprising vinegared Corydalis yanhusuo and Angelica dahurica) to treat the condition at a reasonable benefit / risk ratio applicable to any medical treatment. However, it should be understood that the total daily dosage of Corydalis yanhusuo and Angelica dahurica, or their combination, can be determined by a person skilled in the art within the scope of sound medical judgment. For any particular subject, the specific prophylactically effective dosage level will depend on a variety of factors, including the subject's age, weight, general health, sex, and diet, the specific composition used, other therapeutically active substances used in combination with or concurrently with Corydalis yanhusuo and Angelica dahurica, 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 present specification and the following examples, unless otherwise specified, the term "plant extract" or "extract" refers to an "extract" extracted from, for example, but not limited to, the plants described herein, including Corydalis yanhusuo or Angelica dahurica. Those skilled in the art will appreciate that the Corydalis yanhusuo and Angelica dahurica described herein may be chemically synthesized or may be plant extracts derived from plants, such as those described herein. Furthermore, it is known to those skilled in the art that plant extracts containing Corydalis yanhusuo or Angelica dahurica can be obtained by extracting from plants, and it is also known to those skilled in the art that Corydalis yanhusuo or Angelica dahurica can be obtained by chemical synthesis.

[0042] The present invention provides a medicament for treating rhinitis comprising Rhizoma Corydalis and Radix Angelicae Dahuricae, formulated together with one or more non-toxic pharmaceutically acceptable carriers. The medicament for treating rhinitis can be specifically formulated for oral or rectal administration in solid or liquid form, or 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 retarding agents such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as cetyl alcohol and glycerol monostearate; h) adsorbents such as kaolin and bentonite; i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, 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 contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers such as ethanol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (particularly cottonseed oil, peanut oil, corn oil, germ oil, olive oil, castor oil, and sesame oil), glycerol, tetrahydrofuranol, polyethylene glycol, and fatty acid esters of sorbitan, and mixtures thereof.

[0043] Example 1: Corydalis yanhusuo-Angelica dahurica extract (vinegar Corydalis yanhusuo:Angelica dahurica = 1:1) inhibits OVA-induced rhinitis symptoms in mice

[0044] 1. Experimental Materials

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

[0046] 2. Experimental methods

[0047] Prepare 400 g each of vinegared Corydalis yanhusuo and Angelica dahurica. Grind 166 g of Angelica dahurica into a fine powder. Grind the remaining Angelica dahurica and vinegared Corydalis yanhusuo into a coarse powder. Mix the fine and coarse powders to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat under reflux for 3 hours, collect the extract, then add twice the amount of 60% ethanol and heat under reflux for 2 hours. Collect the extract, combine the two extracts, filter, and concentrate the filtrate into a thick paste. The Corydalis yanhusuo-Angelica dahurica extract was determined using high-performance liquid chromatography according to the content determination method for Yuanhu analgesic tablets in the 2020 edition of the Chinese Pharmacopoeia. Using imperatorin and tetrahydropalmatine as indicator components, the Corydalis yanhusuo-Angelica dahurica extract, at a crude drug dosage of 10 mg / kg, showed imperatorin content of 400 μg / mL and tetrahydropalmatine content of 90 μg / mL.

[0048] Mice were divided into a negative control (NC), a blank control (Vehicle), a positive control (DEX), and groups treated with different concentrations of Corydalis yanhusuo-Angelica dahurica extract. Mice in the blank, positive, and DEX groups were sensitized with intraperitoneal injection of OVA (10 μg / day on days 1, 7, and 14). Mice in the negative control group received no treatment. After sensitization, different concentrations of Corydalis yanhusuo-Angelica dahurica extract solutions (5 mg / kg and 10 mg / kg, respectively) prepared with saline were administered intranasally to the mice in the DEX groups. Mice in the negative and blank control groups received an equal dose of saline intranasally; mice in the positive control group received an equal dose of dexamethasone. Thirty minutes after the end of drug administration, rhinitis was induced by intranasal administration of 200 μg / mL OVA on days 21, 23, 25, and 27. 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] The results are shown in Figures 1, 2 and 3.

[0051] As shown in Figures 1, 2, and 3, mice receiving intranasal administration of the OVA extract in the blank control group developed significant symptoms of rhinitis, including increased nasal scratching, sneezing, and IgE levels in nasal lavage fluid, demonstrating successful model establishment. Compared to the control group, intranasal administration of a 1:1 ratio of vinegared Corydalis yanhusuo to Angelica dahurica extract effectively suppressed increases in nasal scratching (Figure 1), sneezing (Figure 2), and IgE levels in nasal lavage fluid (Figure 3), alleviating rhinitis symptoms in mice. Intranasal administration of 10 mg / kg of the Corydalis yanhusuo to Angelica dahurica extract significantly suppressed rhinitis symptoms, demonstrating superior therapeutic efficacy to the commonly used clinical drug dexamethasone.

[0052] The dosage of Corydalis yanhusuo and Angelica dahurica in the drug combination is lower than that when used 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 either extract alone

[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- to 8-week-old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0056] 2. Experimental methods

[0057] Prepare 400 g each of vinegared Corydalis yanhusuo and Angelica dahurica. Grind 166 g of Angelica dahurica into a fine powder. Grind the remaining Angelica dahurica and vinegared Corydalis yanhusuo into a coarse powder. Mix the fine and coarse powders to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat under reflux for 3 hours, collect the extract, then add twice the amount of 60% ethanol and heat under reflux for 2 hours. Collect the extract, combine the two extracts, filter, and concentrate the filtrate into a thick paste. The Corydalis yanhusuo-Angelica dahurica extract was determined using high-performance liquid chromatography according to the content determination method for Yuanhu analgesic tablets in the 2020 edition of the Chinese Pharmacopoeia. Using imperatorin and tetrahydropalmatine as indicator components, the Corydalis yanhusuo-Angelica dahurica extract, at a crude drug dosage of 10 mg / kg, showed imperatorin content of 400 μg / mL and tetrahydropalmatine content of 90 μg / mL.

[0058] Mice were divided into a negative control (NC), a blank control (Vehicle), a positive control (DEX) group, a Corydalis yanhusuo-Angelica dahurica extract group (prescription 1:1), a Corydalis yanhusuo group (vinegar Corydalis yanhusuo), and an Angelica dahurica group (Angelica dahurica). Mice in the blank, positive, and different concentrations of Corydalis yanhusuo-Angelica dahurica extract groups were sensitized with intraperitoneal injection of OVA (10 μg / day on days 1, 7, and 14). Mice in the negative control group received no treatment. After sensitization, a 10 mg / kg Corydalis yanhusuo-Angelica dahurica extract solution (vinegar Corydalis yanhusuo:Angelica dahurica) with a ratio of 1:1, a 10 mg / kg Corydalis yanhusuo solution, and a 10 mg / kg Angelica dahurica solution were prepared in normal saline and administered intranasally to the mice in the Corydalis yanhusuo-Angelica dahurica extract, Corydalis yanhusuo, and Angelica dahurica extract groups, respectively. The Corydalis yanhusuo-Angelica dahurica extract and Angelica dahurica extract solutions contained 400 μg / mL of imperatorin, and the Corydalis yanhusuo-Angelica dahurica extract and Angelica dahurica extract solutions contained 150 μg / mL of tetrahydropalmatine.

[0059] Thirty minutes after the end of drug administration, rhinitis was induced by intranasal administration of 200 μg / mL OVA (on days 21, 23, 25, and 27). After the final challenge, the number of nose scratches and sneezes in each group of mice was counted.

[0060] 3. Experimental results

[0061] The results are shown in Figures 4 and 5.

[0062] As shown in Figures 4 and 5, mice receiving OVA intranasal drops in the blank control group developed significant rhinitis symptoms, including increased nasal scratching, sneezing, and IgE levels in nasal lavage fluid, demonstrating successful model establishment. Compared to the control group, the doses of vinegared Corydalis yanhusuo and Angelica dahurica were lower than those used alone. Intranasal administration of Corydalis yanhusuo-Angelica dahurica extract, Angelica dahurica solution, and Corydalis yanhusuo solution effectively reduced nasal scratching (Figure 4) and sneezing (Figure 5), alleviating rhinitis symptoms in mice. Intranasal administration of Corydalis yanhusuo-Angelica dahurica extract in a 1:1 ratio significantly suppressed rhinitis symptoms, demonstrating a toxicity-reducing and efficacy-enhancing effect, surpassing the therapeutic efficacy of Angelica dahurica or Corydalis yanhusuo alone.

[0063] Example 3: The toxicity of Corydalis yanhusuo-Angelica dahurica extract (vinegar Corydalis yanhusuo:Angelica dahurica = 1:1) is less than that of Angelica dahurica and vinegar Corydalis yanhusuo alone.

[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- to 8-week-old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0066] 2. Experimental methods

[0067] Prepare 400 g each of vinegared Corydalis yanhusuo and Angelica dahurica. Grind 166 g of Angelica dahurica into a fine powder. Grind the remaining Angelica dahurica and vinegared Corydalis yanhusuo into a coarse powder. Mix the fine and coarse powders to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat under reflux for 3 hours, collect the extract, then add twice the amount of 60% ethanol and heat under reflux for 2 hours. Collect the extract, combine the two extracts, filter, and concentrate the filtrate into a thick paste. The Corydalis yanhusuo-Angelica dahurica extract was determined using high-performance liquid chromatography according to the content determination method for Yuanhu analgesic tablets in the 2020 edition of the Chinese Pharmacopoeia. Using imperatorin and tetrahydropalmatine as indicator components, the Corydalis yanhusuo-Angelica dahurica extract, at a crude drug dosage of 10 mg / kg, showed imperatorin content of 400 μg / mL and tetrahydropalmatine content of 90 μg / mL.

[0068] Mice were divided into a negative control (NC), a blank control (Vehicle) group, a Corydalis yanhusuo-Angelica dahurica extract group (prescription 1:1), a Corydalis yanhusuo vinegar group, an Angelica dahurica group, and a positive control (DEX) group. Mice in the blank, Corydalis yanhusuo-Angelica dahurica extract, Corydalis yanhusuo vinegar group, Angelica dahurica group, and the positive control group were sensitized with intraperitoneal injection of OVA. Mice in the negative control group received no treatment. After sensitization, 10 mg / kg Corydalis yanhusuo-Angelica dahurica extract, 10 mg / kg Corydalis yanhusuo solution, and 10 mg / kg Angelica dahurica solution were prepared in normal saline and administered intranasally to the mice in the Corydalis yanhusuo-Angelica dahurica extract, Corydalis yanhusuo vinegar, and Angelica dahurica groups, respectively. Mice in the negative and blank controls received an equal dose of normal saline, and mice in the positive control group received an equal dose of dexamethasone. The Corydalis yanhusuo-Angelica dahurica extract and Angelica dahurica solutions contained 400 μg / mL of imperatorin, while the Corydalis yanhusuo-Angelica dahurica extract and Angelica dahurica vinegar solutions contained 150 μg / mL of tetrahydropalmatine.

[0069] Thirty minutes after the end of drug administration, 200 μg / mL OVA was administered intranasally to induce rhinitis. The body weight of the mice was recorded daily.

[0070] 3. Experimental results

[0071] The results are shown in Figure 6.

[0072] As shown in Figure 6, the blank control group, mice receiving intranasal OVA drops, showed significant weight loss, demonstrating successful model establishment. Dexamethasone and the 1:1 ratio of the formula both reduced weight loss compared to the control group. However, Angelica dahurica extract alone and Corydalis yanhusuo extract alone did not reduce weight loss. Therefore, a 1:1 ratio of Angelica dahurica and Corydalis yanhusuo extract has the potential to mitigate toxicity.

[0073] Example 4 The efficacy of the extract of Corydalis yanhusuo and Angelica dahurica (vinegar Corydalis yanhusuo: Angelica dahurica = 1:1) in inhibiting OVA-induced rhinitis in mice is superior to that of the mixed administration of imperatorin and tetrahydropalmatine 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- to 8-week-old female C57 mice were purchased from the Experimental Animal Center of Xi'an Jiaotong University.

[0076] 2. Experimental methods

[0077] Prepare 400 g each of vinegared Corydalis yanhusuo and Angelica dahurica. Grind 166 g of Angelica dahurica into a fine powder. Grind the remaining Angelica dahurica and vinegared Corydalis yanhusuo into a coarse powder. Mix the fine and coarse powders to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat under reflux for 3 hours, collect the extract, then add twice the amount of 60% ethanol and heat under reflux for 2 hours. Collect the extract, combine the two extracts, filter, and concentrate the filtrate into a thick paste. The Corydalis yanhusuo-Angelica dahurica extract was determined using high-performance liquid chromatography according to the content determination method for Yuanhu analgesic tablets in the 2020 edition of the Chinese Pharmacopoeia. Using imperatorin and tetrahydropalmatine as indicator components, the Corydalis yanhusuo-Angelica dahurica extract, at a crude drug dosage of 10 mg / kg, showed imperatorin content of 400 μg / mL and tetrahydropalmatine content of 90 μg / mL.

[0078] Mice were divided into a negative control (NC), a blank control (Vehicle), a positive control (DEX) group, a group receiving a Corydalis yanhusuo-Angelica extract (prescription ratio 1:1), and a group receiving a mixture of imperatorin and tetrahydropalmatine (component ratio 1:1). Mice in the blank, positive, Corydalis yanhusuo-Angelica extract, and imperatorin and tetrahydropalmatine groups were sensitized with intraperitoneal injection of OVA (10 μg / day on days 1, 7, and 14). Mice in the negative control group received no treatment. After sensitization, a 10 mg / kg solution of Corydalis yanhusuo-Angelica extract (prescription ratio 1:1) and a 10 mg / kg solution of imperatorin and tetrahydropalmatine (prescription ratio 1:1) were prepared in normal saline and administered intranasally to the mice in the Corydalis yanhusuo-Angelica extract and imperatorin and tetrahydropalmatine groups, respectively. Mice in the negative and blank control groups received an equal dose of normal saline; mice in the positive control group received an equal dose of dexamethasone. Among them, the 1:1 mixed solution of Corydalis yanhusuo-Angelica dahurica extract and imperatorin and tetrahydropalmatine both contained 400 μg / mL of imperatorin, and the 1:1 mixed solution of Corydalis yanhusuo-Angelica dahurica extract and imperatorin and tetrahydropalmatine both contained 150 μg / mL of tetrahydropalmatine.

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

[0080] 3. Experimental results

[0081] See Figure 7 for the results.

[0082] As shown in Figure 7, the blank control group OVA-administered nasal drops showed significant rhinitis symptoms, indicating successful modeling. Compared with the control group, intranasal administration of the Corydalis-Angelica extract to mice effectively reduced nasal scratching and alleviated rhinitis symptoms in mice, while a 1:1 mixture of imperatorin and tetrahydropalmatine was less effective. Intranasal administration of the Corydalis-Angelica extract in a 1:1 ratio of vinegared Corydalis:Tera delta-delta significantly suppressed rhinitis symptoms, demonstrating a therapeutic effect superior to a solution containing equal concentrations of imperatorin and tetrahydropalmatine.

[0083] Example 5 The efficacy of the extract of Corydalis yanhusuo and Angelica dahurica (vinegar Corydalis yanhusuo: Angelica dahurica = 1:1) in inhibiting OVA-induced rhinitis in mice is better than that of the extract of Corydalis yanhusuo and Angelica dahurica (vinegar Corydalis yanhusuo: Angelica dahurica = 2:1)

[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 400 g or 800 g of vinegared Corydalis yanhusuo and 400 g of Angelica dahurica. Grind 166 g of Angelica dahurica into a fine powder. Grind the remaining Angelica dahurica and vinegared Corydalis yanhusuo into a coarse powder. Mix the fine and coarse powders to obtain a mixed powder. Soak the mixed powder in three times the amount of 60% ethanol for 24 hours, heat under reflux for 3 hours, and collect the extract. Add two times the amount of 60% ethanol and heat under reflux for 2 hours. Collect the extract, combine the two extracts, filter, and concentrate the filtrate into a thick paste. The Corydalis yanhusuo-Angelica dahurica extract was determined using high-performance liquid chromatography (HPLC) according to the content determination method for Yuanhu analgesic tablets in the 2020 edition of the Chinese Pharmacopoeia. Using imperatorin and tetrahydropalmatine as indicator components, the Corydalis yanhusuo-Angelica dahurica extract, at a crude drug dosage of 10 mg / kg, showed imperatorin to be 400 μg / mL and tetrahydropalmatine to be 90 μg / mL.

[0088] Mice were divided into a negative control (NC), a blank control (Vehicle), a positive control (DEX), a group receiving a Corydalis yanhusuo-Angelica dahurica extract (prescription 1:1), and a group receiving a Corydalis yanhusuo-Angelica dahurica extract (prescription 2:1). Mice in the blank, positive, Corydalis yanhusuo-Angelica dahurica extract (prescription 1:1), and Corydalis yanhusuo-Angelica dahurica extract (prescription 2:1) were sensitized with OVA (10 μg / day on days 1, 7, and 14). Mice in the negative control group received no treatment. After sensitization, 10 mg / kg vinegar Corydalis yanhusuo:Angelica dahurica extract solutions (1:1 and 2:1) were prepared in saline and administered intranasally to mice in the Corydalis yanhusuo-Angelica dahurica extract (prescription 1:1) and Corydalis yanhusuo-Angelica dahurica extract (prescription 2:1) groups, respectively. Mice in the negative and blank controls received an equal dose of saline; mice in the positive control group received an equal dose of dexamethasone.

[0089] Thirty minutes after the end of drug administration, 200 μg / mL OVA was administered intranasally to induce rhinitis (days 21, 23, 25, and 27). After the final challenge, the number of times the mice scratched their noses was counted.

[0090] 3. Experimental results

[0091] See Figure 8 for the results.

[0092] As shown in Figure 8, mice in the blank control group receiving OVA intranasal drops developed significant rhinitis symptoms, demonstrating successful model establishment. Compared to the control group, intranasal administration of either a 1:1 or 2:1 ratio of Corydalis yanhusuo to Angelica dahurica extract effectively reduced nasal scratching and alleviated rhinitis symptoms in mice, with the 1:1 ratio of Corydalis yanhusuo to Angelica dahurica extract being even more effective.

[0093] The technical idea of ​​the present invention is to illustrate the technical idea of ​​the present invention, and the protection scope of the present invention cannot be limited by this. 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 ethanol, heating under reflux extraction and then filtering.

2. The use according to claim 1, characterized in that 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, heat reflux, collect the extract, add twice the amount of 60% ethanol, heat reflux, and collect the extract.

3. The use according to claim 1 or 2, characterized in that: The medicine is a medicine for reducing the number of times of scratching the nose due to rhinitis.

4. The use according to claim 1 or 2, characterized in that: The medicine is a medicine for reducing the number of sneezing caused by rhinitis.

5. The use according to claim 1 or 2, characterized in that: The medicine is a medicine for reducing IgE in nasal lavage fluid.

6. The use according to claim 1 or 2, characterized in that: Calculated on the basis of the raw drug of Corydalis yanhusuo or Angelica dahurica, when the drug is used to treat rhinitis, the dosage is 5-10 mg / Kg.

7. The use according to claim 1 or 2, characterized in that: The toxicity of the extract of Corydalis yanhusuo and Angelica dahurica is lower than that of single administration, and Corydalis yanhusuo and Angelica dahurica synergistically play a toxicity-reducing role.

8. The use according to claim 1 or 2, characterized in that: Corydalis yanhusuo and angelica dahurica exert synergistic effects at a mass ratio of 1:

1.

9. A drug for treating rhinitis, characterized in that: The invention comprises a corydalis yanhusuo-angelica dahurica extract and pharmaceutically acceptable auxiliary materials. 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 under reflux and then filtering.

10. A drug for treating rhinitis according to claim 9, characterized in that: The dosage form of the medicine is nasal drops.

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