Traditional Chinese medicine nasal cavity administration agent for treating migraine and preparation method of traditional Chinese medicine nasal cavity administration agent

Abstract

According to the traditional Chinese medicine nasal cavity administration agent for treating migraine and the preparation method thereof, the defects of traditional Chinese medicine dosage forms and existing western medicine treatment can be overcome, through rapid absorption, precise action and overall adjustment, the traditional Chinese medicine nasal drops integrate rapid, stable and safe effects of migraine treatment, symptom relieving and long-term conditioning are both considered, and the treatment effect is good. And an efficient, safe and convenient treatment choice is provided for patients.

Description

Technical Field

[0001] The invention relates to a Chinese medicinal compound, in particular to a Chinese medicinal nasal administration agent for treating migraine and a preparation method thereof. Background Art

[0002] Migraine is a common neurological disease characterized by recurrent headaches, often accompanied by symptoms such as nausea, vomiting, light sensitivity and sound sensitivity. About 15% of the world's population suffers from it, and the incidence rate in women is significantly higher than that in men. Migraine not only seriously affects the quality of life and work efficiency of patients, but also causes a huge socioeconomic burden. Current treatment methods mainly include acute treatment and preventive treatment. Commonly used drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), triptans, and beta-blockers can relieve symptoms or reduce attacks, but there are problems such as gastrointestinal damage, cardiovascular risks, significant individual differences, and drug resistance. At the same time, since migraine involves complex pathological mechanisms such as neurovascular regulation, inflammatory response, and central pain sensitization, existing therapies are difficult to fully regulate, and their efficacy needs to be improved urgently. There is an urgent need to develop new, safer and more efficient treatment strategies.

[0003] Although modern medicine is constantly updating its drugs for treating migraine, there are still some shortcomings in current clinical use of drugs: (1) oral drugs have a slow onset of action and low bioavailability; (2) long-term efficacy is uncertain; (3) intravenous administration is inconvenient; (4) Chinese medicine preparations are complex in formulation and require large dosages; and (5) chemical drugs are expensive and have a large number of adverse reactions.

[0004] Traditional Chinese medicine has accumulated a long history and rich clinical experience in the treatment of migraine. Traditional Chinese medicine believes that the pathogenesis of migraine is closely related to factors such as wind evil invasion, liver yang hyperactivity, qi stagnation and blood stasis. Its treatment is centered on "treating both the symptoms and the root causes", and fundamentally relieves symptoms and prevents recurrence by regulating systemic functions and improving qi and blood circulation. Traditional Chinese medicine has significant advantages in the treatment of migraine: first, its multi-target effect enables the active ingredients in traditional Chinese medicine to exert comprehensive therapeutic effects from multiple levels by regulating neurovascular function, relieving inflammatory response and reducing pain sensitivity. Secondly, traditional Chinese medicine has low toxicity and side effects, and is particularly suitable for patients who need long-term conditioning, and has obvious advantages in safety. In addition, the overall regulatory effect of traditional Chinese medicine not only helps to relieve migraine symptoms, but also significantly improves the patient's physical condition, thereby reducing the recurrence rate. However, traditional Chinese medicine preparations such as decoctions have shortcomings in actual application, such as single dosage form, cumbersome administration and slow onset, which restricts its clinical promotion and patient compliance. To this end, combining traditional Chinese medicine with modern formulation technology, through innovative dosage forms and optimized administration methods, has become a key way to improve the efficacy of traditional Chinese medicine in treating migraine.

[0005] Nasal administration is a modern form of preparation that utilizes the rich vascular network and high permeability of the nasal mucosa to achieve rapid absorption and high bioavailability of drugs. This route of administration exhibits significant advantages in many aspects. First, nasal administration has the characteristics of rapid onset of action, and the drug can directly enter the systemic circulation without gastrointestinal absorption and first-pass metabolism in the liver, which greatly shortens the duration of action. Secondly, nasal administration is a non-invasive method of administration, which is safer and easier to use than injection, and significantly improves patient compliance. In addition, due to the unique physiological connection between the nasal cavity and the brain, nasal administration can effectively bypass the blood-brain barrier and deliver drugs directly to the central nervous system, thereby enhancing the therapeutic effect on brain diseases. These characteristics make nasal administration show great application potential in rapid disease relief and targeted treatment, especially suitable for the management of diseases such as migraine that require rapid onset and precise treatment. Summary of the invention

[0006] The present invention aims to provide a Chinese medicine nasal administration agent for treating migraine, which can overcome the shortcomings of traditional Chinese medicine dosage forms and existing Western medicine treatments and meet the treatment needs of migraine patients for high safety, rapid onset and convenient use. The present invention is achieved through the following technical solutions: To achieve the above purpose, the present invention provides a Chinese medicine nasal administration agent for treating migraine, comprising the following raw materials in parts by weight: 15-30 parts of white peony root, 10-30 parts of chuanxiong, 10-15 parts of licorice, 5-15 parts of mint, and 3-10 parts of borneol.

[0007] Preferably, the above-mentioned Chinese herbal nasal medicine for treating migraine comprises the following raw materials in parts by weight: 30 parts of white peony root, 15 parts of chuanxiong, 10 parts of licorice, 10 parts of mint, and 3 parts of borneol.

[0008] Preferably, the above-mentioned Chinese medicinal nasal preparation for treating migraine is added with 0.001-0.05 parts of casein phosphopeptide.

[0009] Traditional Chinese medicine believes that the etiology and pathogenesis of migraine are closely related to factors such as wind evil invasion, hyperactivity of liver yang, qi stagnation and blood stasis. Its essence is caused by imbalance of yin and yang in the body and poor circulation of qi and blood. External invasion of wind evil can lead to meridian blockage, hyperactivity of liver yang can easily cause disorder of qi and blood in the head, and qi stagnation and blood stasis further aggravate the pain symptoms. In terms of treatment, Chinese medicine emphasizes "treating both the symptoms and the root causes", regulating the body's functions and restoring the circulation of qi and blood through methods such as dispersing wind and clearing heat, calming the liver and suppressing yang, and promoting blood circulation and removing blood stasis.

[0010] White peony root has the effects of nourishing blood, softening liver, relieving acute pain, and its main ingredient, paeoniflorin, can reduce nerve excitability and vascular spasm. Chuanxiong is known for promoting blood circulation and qi, dispelling wind and relieving pain. Chuanxiongqin can dilate cerebral blood vessels, improve blood flow and inhibit nerve inflammation, which is the key to achieving rapid effect. Licorice harmonizes the medicinal properties through its anti-inflammatory ingredients, relieves inflammation and reduces the irritation of mint and borneol to the mucosa. Mint dispels wind and heat, relieves pain and relieves spasms, and menthol can quickly relieve pain and inhibit inflammation. Borneol is good at opening the mind and relieving pain. Its volatile components are quickly absorbed through the nasal cavity and directly act on the central nervous system, significantly enhancing the speed of drug action and strengthening the cooling effect of mint.

[0011] In addition, adding casein phosphopeptides (CPPs) to nasal drops can effectively solve the problem of short onset time in migraine treatment. Casein phosphopeptides can combine with mineral ions (such as calcium, zinc, and magnesium) to form stable complexes, thereby delaying the dissolution and absorption rate of drugs in the nasal cavity. In addition, casein phosphopeptides have good mucosal adhesion, which can prolong the contact time between drugs and nasal mucosa, enhance the retention effect, and further delay drug release. Its low allergenicity and high safety also make it an ideal additive for nasal preparations.

[0012] The present invention also provides a method for preparing a Chinese medicine nasal drug for treating migraine, the steps of which are as follows: a. Raw material processing: Select the above-mentioned raw materials, wash the herbs, dry them, and crush them into 80 mesh fine powder for later use; b. Extraction and concentration: white peony root, chuanxiong and licorice were mixed in the above ratio, 95% ethanol was added in a volume weight ratio of 10:1, and refluxed at 55-60°C for 2 times, each time for 2 hours, and then the extracts were combined and filtered to remove the residue; mint and borneol were extracted by low temperature extraction: mint and borneol were mixed in the above ratio, 95% ethanol was added in a volume weight ratio of 10:1, and the mixture was refrigerated at 4°C for 48 hours and filtered; the extracts were concentrated under reduced pressure to a relative density of 1.05-1.10 at 50°C to remove ethanol and retain the active ingredients; c. Prepare the drug solution: Mix the main drug extracts: Mix the concentrated white peony root, chuanxiong, and licorice extracts with the mint and borneol extracts in a ratio of 9.375-1.4:1 and stir evenly; d. Adding excipients: adding 0.001-0.05% of casein phosphopeptide by weight of the mixed extract to slow down the dissolution and absorption rate of the drug in the nasal cavity to ensure the durability of the efficacy of the drug solution for migraine; adding 1-2% of the weight of the mixed extract to solubilize the insoluble components in the drug solution; adding 0.1-0.2% of the weight of the mixed extract to stabilize the solution to adjust the viscosity of the drug solution; adding sodium chloride as an osmotic pressure regulator until the osmotic pressure of the drug solution is close to the physiological environment of the nasal cavity, that is, 0.9% NaCl isotonic; e. Dilution and pH adjustment: dilute with sterile purified water to the final concentration and control the pH value of the solution between 5.5-6.5 to adapt to the nasal mucosal environment; f. Filtration and sterilization: Use a 0.22-micron filter membrane to filter the drug solution to remove particles and impurities; place the drug solution in a sterilized container and sterilize it under high temperature and high pressure at 121°C for 15 minutes to ensure sterility; under a sterile environment, dispense the drug solution into sterilized dosing bottles, install droppers and seal the bottle mouths to ensure that they are not contaminated.

[0013] Preferably, the solubilizer is polysorbate 80.

[0014] Preferably, the stabilizer is hypromellose.

[0015] Preferably, the nasal administration agent is a spray or nasal drops.

[0016] The beneficial effects of the present invention are: (1) Rapid onset of effect: Nasal drops are administered through the nasal cavity, relying on the rich vascular network of the nasal mucosa to directly enter the systemic circulation without the need for gastrointestinal absorption and first-pass metabolism in the liver, which greatly shortens the drug's onset time. At the same time, the volatile components of mint and borneol can directly stimulate the nasal nerve endings, providing a rapid cooling sensation and analgesic effect. Chuanxiong further accelerates the process of relieving headaches by improving cerebral blood flow and dilating blood vessels; (2) Long-lasting effect: Adding casein phosphopeptide to migraine nasal drops significantly improves the long-lasting efficacy of the drug through its characteristics of delaying drug release and absorption. Casein phosphopeptide enhances the retention time of the drug in the nasal mucosa, achieving a full range of efficacy from rapid onset to sustained release. It forms a synergistic effect with the blood circulation and qi-promoting effects of Chuanxiong, the rapid analgesic effects of mint and borneol, the anti-inflammatory and analgesic effects of licorice, and the neuromodulatory effects of white peony, which not only prolongs the drug's duration of action, but also stabilizes the migraine relief effect; (3) Safe and efficient: The combination combines the multi-target mechanism of Chinese medicine to regulate the pathological mechanism of migraine as a whole: Chuanxiong - promotes blood circulation and qi circulation, improves cerebral vasospasm and neuroinflammation; White Peony - regulates nerve excitability and relieves tension; Licorice - anti-inflammatory and analgesic, synergistically reduces inflammatory response; Peppermint and Borneol - quickly improve pain symptoms through local sedation and nerve sensitivity inhibition. Since the main ingredients are natural Chinese medicine, compared with Western medicine, it has less toxic side effects and is especially suitable for patients who need long-term management of migraine; (4) Convenient to use: Nasal drops are small and portable, and patients can use them without additional equipment. They are particularly suitable for immediate treatment of sudden migraine attacks. Compared with oral or injectable medications, nasal drops avoid gastrointestinal irritation and the discomfort of injections, significantly improving patient compliance and experience; (5) Targeted effect, alleviating relapse: Ingredients such as borneol and mint can effectively bypass the blood-brain barrier and deliver drugs directly to the central nervous system, playing a precise regulatory role on the core pathological mechanisms of migraine (such as neuroinflammation and pain sensitization). At the same time, white peony root and licorice have the effects of harmonizing qi and blood and stabilizing nerve function, which helps to improve the patient's overall physical condition and reduce the recurrence rate of migraine; (6) Comfort: The properties of mint and borneol provide a cool and comfortable sensory experience while relieving pain. It not only has a direct analgesic effect on the painful area, but also can alleviate the nausea, vomiting and other discomfort symptoms that often accompany migraine, so that the patient's overall symptoms can be improved more quickly; Comprehensive advantages: Through rapid absorption, precise action and overall regulation, this Chinese medicine nasal drops achieves the three-in-one effect of "fast, stable and safe" in the treatment of migraine, taking into account both symptom relief and long-term conditioning, providing patients with an efficient, safe and convenient treatment option. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 The analgesic effect of the present invention on spontaneous pain within 5 minutes after administration; the mean and standard deviation are 15 biological replicates, and the significant differences among the groups were detected by Duncan analysis in SPSS 20.0 (P<0.05), and are represented by letters; Figure 2 The analgesic effect of the mechanical pain threshold of the present invention within 5 minutes after administration; the mean and standard deviation are 15 biological replicates, and the significant differences among the groups were detected by Duncan analysis in SPSS 20.0 (P<0.05), and are represented by letters; Figure 3 The analgesic effect of the present invention on the thermal pain threshold within 5 minutes after administration; the mean and standard deviation are 15 biological replicates, and the significant differences among the groups were detected by Duncan analysis in SPSS 20.0 (P<0.05), and are represented by letters; Figure 4 The analgesic effect of the present invention on spontaneous pain within 60 minutes after administration; the mean and standard deviation are 15 biological replicates, and the significant differences among the groups were detected by Duncan analysis in SPSS 20.0 (P<0.05), and are represented by letters; Figure 5 The analgesic effect of the mechanical pain threshold of the present invention within 60 minutes after administration; the mean and standard deviation are 15 biological replicates, and the significant differences among the groups were detected by Duncan analysis in SPSS 20.0 (P<0.05), and are represented by letters; Figure 6The analgesic effect of the present invention on the thermal pain threshold within 60 minutes after administration; the mean and standard deviation are 15 biological replicates, and the significant differences among the groups were detected by Duncan analysis in SPSS 20.0 (P<0.05), and are represented by letters; Figure 7 This is a comparison of the nasal mucosal tissue morphology of the present invention to evaluate the effects of each treatment on the nasal mucosal structure; Figure 8 The results of the open field experiment on the motor ability of mice in the present invention; Fig. 9 The figure is the result of the rotarod test on the motor ability of mice in the present invention. DETAILED DESCRIPTION

[0018] The following examples are used to more specifically describe the present invention. It should be understood that the implementation of the present invention is not limited to the following examples, and any modifications or changes made to the present invention fall within the scope of protection of the present invention; and the methods in the following examples, unless otherwise specified, are conventional methods in the art.

[0019] Embodiment 1: Preparation method of Chinese medicine nasal drops White peony root, Chuanxiong root, licorice root, mint and borneol that meet the pharmacopoeia standards were selected, washed, dried and crushed into 80 mesh fine powder for use; 30 parts of white peony root, 15 parts of Chuanxiong root and 10 parts of licorice were weighed according to the formula ratio, and 95% ethanol (liquid-solid ratio 10:1) was added to reflux extraction at 55°C twice, each time for 2 hours, and the extracts were filtered and combined; 10 parts of mint and 3 parts of borneol were weighed according to the formula ratio, and 95% ethanol was added, and low-temperature extraction was performed at 4°C for 48 hours, and then filtered to obtain volatile component extracts. The extracts were concentrated to a relative density of 1.05 by reduced pressure to remove excess ethanol and retain the effective components. Subsequently, the concentrated extracts of white peony root, Chuanxiong, and licorice were mixed evenly with the extracts of mint and borneol, and 0.005% of the total weight of casein phosphopeptide was added to ensure the durability of the efficacy of the drug solution for migraine. The solubilizer polysorbate 80 was added to dissolve the fat-soluble components, the stabilizer hydroxypropyl methylcellulose was added to adjust the viscosity, and the osmotic pressure regulator sodium chloride was added to make the solution close to isotonic, and the solution was diluted to the final volume with sterile purified water and the pH value was adjusted to the range of 5.5-6.5. The drug solution was filtered through a 0.22 micron filter membrane and dispensed into sterile containers, and sterilized at 121°C for 15 minutes. Finally, the drug solution was dispensed into sterile nasal drop bottles (1 ml per bottle) in a sterile environment, the dropper was assembled and sealed, and the pH value, viscosity, osmotic pressure and main component content of the drug solution were tested to ensure that it met the drug quality standards, and sterility and microbial limit tests were performed to ensure that the product met the pharmacopoeia requirements.

[0020] Embodiment 2: Preparation method of Chinese medicine nasal drops No casein phosphopeptide was added during the preparation, and the rest was the same as in Example 1.

[0021] Analgesic effect evaluation Construction of migraine model: The Inflammatory Soup (IS) model is a classic model that simulates the inflammatory pathological mechanism of migraine. A solution containing multiple inflammatory mediators (5-hydroxytryptamine, histamine, prostaglandin E2 and bradykinin) is injected around the dura mater to induce local neuroinflammation and vasodilation, thereby activating the trigeminovascular system and triggering pain behaviors similar to migraine.

[0022] Migraine intensity evaluation index: The number of scratches on the head and face: reflects the discomfort caused by migraine, which is a spontaneous pain behavior; mechanical pain threshold of the head and face: the pain threshold of mechanical stimulation of the head and face of mice is detected by von-Frey hairs (Von Frey fiber); facial thermal pain threshold: the pain threshold of thermal stimulation of the head and face of mice is detected by laser irradiation. Evaluation time point: 5 minutes and 60 minutes after administration.

[0023] The von-Frey hairs mechanical stimulation needle can provide tactile stimulation force of 0.008g-300g, and can be used to measure mechanical pain or tactile thresholds in multiple parts of the body of experimental animals such as rats, mice, and beagles.

[0024] The thickness and extension length of the nylon wire of the von-Frey hairs mechanical stimulator determine the magnitude of the tactile von-Frey test stimulus. During the experiment, select the appropriate tactile test von-Frey hairs mechanical stimulator according to the actual situation, adjust the appropriate extension length, and stimulate the skin vertically. The stimulus force can be adjusted by adjusting the extension and replacing the tactile nylon wire until the tactile test nylon wire bends. When the rodent's paw is subjected to a mechanical pain threshold or tactile threshold, they will retract the reflex. This tactile test can be applied to the mechanical pain threshold or tactile threshold test of rats and mice.

[0025] When the von-Frey hairs ciliary mechanical stimulation needle is used for plantar testing of rats and mice, a perforated workbench can be optionally used. The tactile test mesh holes are square holes punched by laser cutting, with a size of 5x5mm 2 The spacing between the tactile test holes is about 1mm, which is a comfortable environment for the test animals and also convenient for operators to observe the tactile sensing area of ​​the animal's sole. The drilling table is coated for easy cleaning and is not easily corroded.

[0026] Experimental groups: 60 C57BL / 6 mice were divided into 4 groups, 15 mice in each group. The groups were as follows: 1. Sham operation group: no migraine model was established, and normal saline was administered to the nose; 2. Model group: migraine model was established and normal saline was administered to the nose; 3. Example 1 group: the model was established and the above-mentioned Chinese medicine nose drops (50 μL) were administered to the nose; 4. Example 2 group: the model was established and the above-mentioned Chinese medicine nose drops were administered to the nose without adding casein phosphopeptide (50 μL); 5. Positive drug control group: migraine model was established and positive drug (triptan, 1 mg / ml, 50 μL) was administered to the nose.

[0027] Result analysis: Figure 1-Figure 6 As shown, 5 minutes after administration, the number of head scratching, mechanical pain threshold and thermal pain threshold of the model group were significantly higher than those of the sham operation group, indicating that the IS model of migraine successfully induced significant pain behavior. The number of head scratching, mechanical pain threshold and thermal pain threshold of Example 1 and Group 2 were significantly lower than those of the model group, indicating that Chinese medicine nasal drops can quickly relieve pain, while the positive control drug has no such effect. 60 minutes after administration, the number of head scratching, mechanical pain threshold and thermal pain threshold of Example 1 group were significantly lower than those of the model group, while the number of head scratching, mechanical pain threshold and thermal pain threshold of Example 2 group were no different from those of the model group, showing that the analgesic effect of the present invention lasted for a long time, while the positive control drug group only had significantly lower number of head scratching and thermal pain threshold than the model group, while the mechanical pain threshold was equivalent to the model group. The above results suggest that the present invention with the addition of casein phosphopeptide can quickly produce analgesic effect after use, and the effect lasts for a long time; while the positive drug triptan does not have a rapid onset of analgesia, and the effect after onset is not as good as the present invention.

[0028] Safety assessment: nasal mucosa Evaluate the safety of Chinese medicine nasal drops on nasal mucosa, observe whether it will cause mucosal damage after long-term use, and compare with positive drug and normal saline control groups. Apply nasal drops twice a day (once in the morning and once in the afternoon) for 28 consecutive days. 50 μL of nasal drops are accurately applied to the nasal cavity through a nasal dropper each time. HE staining: observe pathological changes such as mucosal structural integrity, epithelial shedding, and inflammatory cell infiltration. Experimental groups: control group, positive drug group, Example 1 group, and Example 2 group.

[0029] Result analysis: Figure 7As shown, the image analysis results show that the nasal mucosa structure of the control group is intact, the columnar epithelial cells are closely arranged, there is no inflammation or abnormality, and it shows a normal physiological state; the mucosal morphology of Example 1 and Example 2 groups is close to that of the control group, and no cell shedding or inflammatory cell infiltration is observed, showing good tissue compatibility and safety; the positive drug group has slight shedding of columnar epithelial cells and inflammatory cell infiltration, accompanied by a decrease in the number of goblet cells, indicating that the positive drug has a certain irritation to the nasal mucosa. In summary, the protective effect of the present invention on the nasal mucosa is significantly better than that of the positive drug, indicating that it is safer in long-term use and provides a reliable histological basis for its clinical application.

[0030] Safety Assessment: Exercise Capacity Mine field test: The open field test is also called the open box test. It is a method to evaluate the autonomous behavior, exploratory behavior and tension of experimental animals in a new environment. The frequency and duration of certain behaviors of experimental animals in a new environment reflect the autonomous behavior and exploratory behavior of experimental animals in a strange environment, and the frequency of urination and defecation reflects their tension.

[0031] The experimental device consists of an open field reaction box and an automatic data acquisition and processing system. The rat open field reaction box is 30-40 cm high, 100 cm long at the bottom, with black inner walls. The bottom is evenly divided into 25 small squares of 4 cm × 4 cm. A digital camera is set 2 m above, and its field of view can cover the entire open field. The open field lighting is fully artificial, and "day" and "night" can be set manually. During the day, four energy-saving lamps on the walls on both sides emit a simulation of about 200 lux of illumination, and at night, an infrared light source on one wall provides lighting. Experimenters and computers and other equipment are located in another room to reduce interference to the animals, and the background noise in the laboratory is controlled below 65dB.

[0032] The mouse open field reaction box is 25-30 cm high, 72 cm long at the bottom, with black inner walls and 64 small squares on the bottom. The automatic data acquisition and processing system is the same as above.

[0033] Rotarod test: The rotarod is a widely used performance and behavioral task to assess motor performance in rodents. Motor performance can be considered an indicator of neurological deficits. The rotarod test is based on the fact that many neurological conditions may affect functional motor parameters such as balance, motor coordination or motor learning ability, which directly affect the ability of the animal to remain on a rod. The rotarod test measures the time an animal takes to walk on an accelerating rotating rod, thus allowing the assessment of motor deficits caused by disease models or interventions. For example, deficits in motor function are a common consequence of traumatic brain injury. Therefore, the rotarod is often used as an indicator of injury-induced motor deficits.

[0034] The testing apparatus consists of a rotating rod of fixed diameter that is moved at increasing speeds over a predetermined period of time. As the speed increases, the mouse needs to go faster to maintain its position on the rod. The latency for the animal to fall off the rotating rod or the speed at which the rodent falls off the rod can be recorded and used as a measure of motor performance.

[0035] When testing injured animals, wait at least 24 h to allow for full recovery from the effects of anesthetic drugs.

[0036] Before starting the test, train the animal by placing it on the rotarod for 5 min (e.g., slow constant speed 4 rpm). Allow a 1 h interval before starting the first trial.

[0037] Set the device to the desired acceleration (e.g., initial speed of 4 rpm, acceleration rate of 20 rpm / min until maximum speed of 40 rpm; Deacon, 2013).

[0038] Place the animal on the rod, facing the direction of rotation so that it must walk forward to remain on the rod; start the motor and timer. At the end of each trial, the animal will fall off the rod. When the animal falls, record the latency to fall off the rod as indicated by the timer, as well as the rotation speed at the time of fall. Repeat this process twice.

[0039] The mean latency or mean rotation speed determined from the three trials will be the final result. Both can be used as a measure of motor function and used in subsequent analyses.

[0040] The potential effects of the present invention on the motor ability of mice were evaluated by open field test and rotarod test, including whether it would cause motor inhibition, decreased coordination or other adverse effects. Experimental groups: control group, positive drug group, Example 1 group and Example 2 group.

[0041] Result analysis: Figure 8-Figure 9 As shown, the present invention exhibits good safety in the open field test and the rotating rod test. The open field test shows that Example 1 and Example 2 did not significantly change the total movement distance of the mice, which was equivalent to the control group, indicating that they had no inhibitory effect on the ability of autonomous activities; in the rotating rod test, the retention time of the mice in the Example 1 group and the Example 2 group was consistent with that of the control group, and no adverse effects were produced on the motor coordination and balance ability. Overall, the present invention did not have a significant adverse effect on the motor ability and behavior of mice, reflecting good behavioral safety, and providing support for its further development.

Claims

1. A Chinese medicinal nasal drug for treating migraine, characterized in that: The invention comprises the following raw materials in parts by weight: 15-30 parts of white peony root, 10-30 parts of chuanxiong, 10-15 parts of liquorice, 5-15 parts of mint and 3-10 parts of borneol.

2. A Chinese medicinal nasal preparation for treating migraine according to claim 1, characterized in that: The preparation is composed of the following raw materials in parts by weight: 30 parts of white peony root, 15 parts of chuanxiong, 10 parts of liquorice, 10 parts of mint and 3 parts of borneol.

3. A Chinese medicinal nasal preparation for treating migraine according to claim 1, characterized in that: The raw material medicine also includes 0.001-0.05 parts by weight of casein phosphopeptide.

4. A method for preparing a Chinese medicine nasal drug for treating migraine, characterized in that: Here are the steps: a. Raw material processing: select the raw material drug according to claim 1, wash the medicinal material, dry it, and then grind it into 80 mesh fine powder for standby use; b. Extraction and concentration: white peony root, chuanxiong and licorice are mixed in the ratio of claim 1, 95% ethanol is added in a volume-to-weight ratio of 10:1, and reflux extraction is performed at 55-60°C for 2 times, each time for 2 hours, and then the extracts are combined and filtered to remove the residue; mint and borneol are extracted by low-temperature extraction: mint and borneol are mixed in the ratio of claim 1, 95% ethanol is added in a volume-to-weight ratio of 10:1, and the mixture is refrigerated at 4°C for 48 hours and filtered; the extracts are respectively concentrated under reduced pressure to a relative density of 1.05-1.10 at 50°C to remove ethanol and retain the active ingredients; c. Prepare the drug solution: Mix the main drug extracts: Mix the concentrated white peony root, chuanxiong, and licorice extracts with the mint and borneol extracts in a ratio of 9.375-1.4:1 and stir evenly; d. Adding excipients: adding 0.001-0.05% of the weight of the mixed extract to slow down the dissolution and absorption rate of the drug in the nasal cavity to ensure the durability of the efficacy of the drug solution for migraine; adding 1-2% of the weight of the mixed extract to increase the solubility of the insoluble components in the drug solution; adding 0.1-0.2% of the weight of the mixed extract to increase the viscosity of the drug solution; Sodium chloride, an osmotic pressure regulator, was added until the osmotic pressure of the solution approached the physiological environment of the nasal cavity, i.e., 0.9% NaCl isotonic; e. Dilution and pH adjustment: dilute with sterile purified water to the final concentration and control the pH value of the solution between 5.5-6.5 to adapt to the nasal mucosal environment; f. Filtration and sterilization: Use a 0.22-micron filter membrane to filter the drug solution to remove particles and impurities; place the drug solution in a sterilized container and sterilize it under high temperature and high pressure at 121°C for 15 minutes to ensure sterility; under a sterile environment, dispense the drug solution into sterilized dosing bottles, install droppers and seal the bottle mouths to ensure that they are not contaminated.

5. The method for preparing a Chinese medicine nasal preparation for treating migraine according to claim 4, characterized in that: The solubilizing agent is polysorbate 80.

6. The method for preparing a Chinese medicine nasal preparation for treating migraine according to claim 4, characterized in that: The stabilizer is hypromellose.

7. The method for preparing a Chinese medicine nasal preparation for treating migraine according to claim 4, characterized in that: The nasal administration agent is a spray or nasal drops.

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