Rhizoma corydalis and radix angelicae dahuricae steaming dew nanofiber membrane as well as preparation method and application thereof

The preparation of the nanofiber membrane of Yuanhu Baizhi Zhenlu through high-voltage electrospinning method has solved the problems of unstable drug release and liver first pass effect in the drug delivery process in the prior art, and achieved rapid absorption of nanofiber membrane on the mucosal surface and nasal and brain pathway, significantly improving the bioavailability and therapeutic effect of drug efficacy.

CN119633043AActive Publication Date: 2025-03-18SHANTOU UNIV MEDICAL COLLEGE
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Patent Information

Application Number
CN202510169446.5
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-02-17
Publication Date
2025-03-18
Estimated Expiration
2045-02-17

AI Technical Summary

Technical Problem

The prior art is difficult to effectively utilize the active ingredients of Yuanhu and Baizhi, especially during drug delivery, which is difficult to release the drug effect quickly and stably, and there is a problem of liver first pass effect.

Method used

The high-pressure electrospinning method was used to prepare the nanofiber membrane of the Chrysanthemum and Chrysanthemum nanofiber membrane was prepared. By mixing the Chrysanthemum and Chrysanthemum nanofiber membrane with N-vinylpyrrolidone solution, adding water and ethanol solvent, adjusting the pH value, adding poloxamer F-127 to form an electrospinning liquid, and then high-pressure electrospinning preparation was carried out to obtain the nanofiber membrane loaded with the active ingredients of the Chrysanthemum.

Benefits of technology

The nanofiber membrane is quickly fitted and absorbed on the surface of the nasal mucosa or oral mucosa, avoiding the liver first pass effect, significantly improving the bioavailability of the drug effect, and quickly acting on the blood vessels in the brain through the nasal and brain pathway, with significant analgesic, anti-depressant, and improving insulin resistance.

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Abstract

The invention relates to a rhizoma corydalis and radix angelicae dahuricae steaming dew nanofiber membrane as well as a preparation method and application thereof. The preparation method comprises the following steps: adding N-vinyl pyrrolidone into rhizoma corydalis and radix angelicae dahuricae steaming dew in a mass ratio of (2-3): 1; adding a mixed solvent of water and ethanol, adjusting the pH value to 6.0, adding poloxamer, and uniformly mixing to obtain a rhizoma corydalis and radix angelicae steaming-dew electrostatic spinning solution; and preparing the rhizoma corydalis and radix angelicae steaming dew nanofiber membrane by adopting a high-voltage electrostatic spinning method. Under the action of poly (N-vinyl pyrrolidone), poloxamer and the like, the rhizoma corydalis and radix angelicae rice steamer is converted into dry nanofibers through a high-voltage electrostatic spinning method to obtain the nanofiber membrane, and the nanofiber membrane has the characteristics of being porous, soft, large in specific surface area and the like, can be rapidly adsorbed on the nose, oral mucosa or skin surface and rapidly releases essence components, and can be used for preparing a mask. The composition can be effectively absorbed by mucous membranes and skin surfaces, and the bioavailability of plant distilled components is increased. The compound can be applied to antidepressant, analgesic, diabetes mellitus and other metabolic disease treatment preparations, smoking cessation and alcohol cessation preparations or sleep aiding preparations and the like.
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Description

Technical Field

[0001] The invention belongs to the field of biomedicine, and specifically relates to a Yuanhu Baizhi Zhenlu nanofiber membrane and a preparation method and application thereof. Background Art

[0002] Yuanhu, also known as Yanhusuo, Chuanwu, and Chuanyanhusuo, is a Chinese medicinal material belonging to the poppy family. Its medicinal part is the rhizome extending from the underground stem. Yanhusuo has been widely used in traditional Chinese medicine since ancient times for analgesia, sedation, wind-dispelling, and blood circulation. Yuanhu contains a variety of active ingredients, the main ingredients of which include yanhusuol, yanhuketone, and fumaric acid. These ingredients are believed to have analgesic, sedative, anti-inflammatory, wind-dispelling, and blood circulation effects. Among them, yanhusuol B is considered to be the main component of Yuanhu's analgesic effect. The analgesic mechanism of Yuanhu may involve anti-inflammatory effects, regulation of the central nervous system, the influence of active sites of medicinal properties, the interaction of endogenous pain regulation systems, and the influence of neural conduction pathways. In today's clinical practice, Yuanhu is still widely used in analgesic treatments including: rheumatic pain, headache, dysmenorrhea, visceral pain, pain caused by trauma, such as sprains, contusions, etc., and some cancer pain. Scientific research in recent years has also shown that Yuanhu plays an important role in the treatment of neuropsychiatric, cardiovascular, endocrine metabolism and drug addiction diseases.

[0003] Angelica dahurica: White in color, warm in nature, pungent in taste, slightly bitter, it has the effects of dispersing wind and dampness, relieving pain, reducing swelling and draining pus. It is widely used in clinical treatment of colds, headaches, brow pain, nasal congestion, sinusitis, toothache, leucorrhea, abscesses and other diseases, and has good curative effect. One of the main components of Angelica dahurica is coumarin compounds, which have a dilating effect on coronary arteries and also have an antagonistic effect on calcium ions. Therefore, it can be used to treat hypertension. In addition, the isoimperatorin contained in Angelica dahurica has the effect of promoting blood circulation and removing blood stasis, which can prevent cardiovascular and cerebrovascular diseases. In addition, the coumarin components contained in Angelica dahurica, such as prickly ash toxin, imperatorin, water and oxidized imperatorin, etc., can inhibit the effect of insulin-induced triglyceride synthesis from glucose, thereby indirectly promoting fat decomposition and inhibiting fat synthesis. Summary of the invention

[0004] The purpose of the present invention is to provide a Yuanhu Baizhi Zhenlu nanofiber membrane and a preparation method and application thereof, so as to solve the problems existing in the prior art.

[0005] A method for preparing a Yuanhu Baizhi Zhenlu nanofiber membrane comprises the following steps: (1) preparing Yuanhu Zhenlu and Baizhi Zhenlu respectively; (2) adding Rhizoma Corydalis and Angelica Dahuricae Zhenlu to the N-vinyl pyrrolidone solution in a mass ratio of (2-3):1; (3) then adding a mixed solvent of water and ethanol and adjusting the pH to 6.0; (4) adding poloxamer and mixing evenly at room temperature to obtain Yuanhu Baizhi Zhenlu electrospinning solution; (5) The Yuanhu Baizhi Zhenlu electrospinning liquid was used to prepare Yuanhu Baizhi Zhenlu nanofiber membrane by high-voltage electrospinning method.

[0006] Furthermore, the process parameters of the high-voltage electrospinning method are: the feeding rate of Yuanhu Baizhi Zhenlu electrospinning solution is 1.5-3mL / h, the drum speed is 200-400 RPM, and the spinning time is 2-4 hours. More preferably, the electrospinning process parameters are adjusted as follows: (1) the feeding rate of the spinning solution on the single-needle spinning electrospinning machine is 1.5mL / h, (2) the spinning solution spinneret is 21G in diameter, (3) the electric field strength is 18kV, (4) the fiber collection distance is 15cm, (5) the temperature is room temperature, the relative humidity of the environment is 45%, and (6) the spinning time is two hours.

[0007] Furthermore, the mass content of N-vinyl pyrrolidone in the Yuanhu Baizhi Zhenlu electrospinning solution is 45-50%, the mass content of Yuanhu and Baizhi Zhenlu is 9-10%, the mass content of poloxamer is 0.1-0.12%, and the viscosity at room temperature is 350-650 cP.

[0008] Furthermore, the molecular weight of the N-vinyl pyrrolidone is 43000-50000 g / mol.

[0009] Furthermore, the mass ratio of water to ethanol in the water-ethanol mixed solvent is 90: 10. When a mixed solvent with a mass ratio of water to ethanol of 90: 10 is selected, the dissolution rate of the fat-soluble substances in Rhizoma Corydalis and Radix Angelicae Dahuricae is the highest and the drug effect is the strongest.

[0010] N-vinyl pyrrolidone (molecular weight 43000g / mol) was added to Yuanhu and Baizhi Zhenlu (2:1). It has good biocompatibility, bioabsorbability, and aqueous solution spinnability, and is used as a matrix polymer to realize the electrospinning process. A certain proportion of water and ethanol solvent mixture (mass ratio 90 / 10) was added, the pH was adjusted to 6.0, and poloxamer F-127 was added and mixed evenly to obtain a uniform solution at room temperature. The mass concentration of the polymer was 45%, the mass concentration of Yuanhu and Baizhi Zhenlu was 9%, the mass concentration of poloxamer was 0.1%, and the ethanol solvent mixture was 45.9%. The viscosity at room temperature was 350cP.

[0011] Poloxamer F-127 is a highly effective surfactant that plays two roles in the nanomembrane: 1) It makes the distribution of Yuanbai Zhenlu more even and more stable; 2) It helps penetration.

[0012] The Yuanhu Zhenlu of the present invention has the best solubility under slightly acidic conditions, especially when the pH value is 6.

[0013] The Yuanhu Baizhi Zhenlu nanofiber membrane obtained by the above preparation method is loaded with all the effective components of Zhenlu, and is a loose and porous nanofiber membrane with uniform fiber size and a soft membrane layer that is easy to be applied to the nasal mucosa, oral mucosa or skin surface.

[0014] A micropatch comprises the Yuanhu Baizhi Zhenlu nanofiber membrane prepared above, and the micropatch includes a nasal mucosa micropatch, an oral mucosa micropatch and a skin micropatch.

[0015] The application of the above-mentioned Yuanhu Baizhi Zhenlu nanofiber membrane in the preparation of antidepressant preparations.

[0016] The above-mentioned Yuanhu Baizhi Zhenlu nanofiber membrane is used in the preparation of preparations for treating insulin metabolic diseases.

[0017] The above-mentioned Yuanhu Baizhi Zhenlu nanofiber membrane is used in the preparation of preparations for quitting smoking, quitting drinking or quitting addiction.

[0018] The above-mentioned Yuanhu Baizhi Zhenlu nanofiber membrane is used in the preparation of analgesics and sleeping aids.

[0019] The present invention uses the intermolecular hydrogen bonding between the polar groups of the macromolecular poly (N-vinyl pyrrolidone) and the mucosal surface, and this nanofiber membrane is easy to fit and adhere to the surface of the nasal mucosa or oral mucosa. Under the normal humidity provided by the nasal breathing process, the membrane absorbs a small amount of water on the surface of the nasal mucosa and gradually dissolves. The released small molecules of the effective essence components of Yuanhu and Baizhi Zhenlu are rapidly absorbed by the nasal mucosa and quickly act on the blood vessels in the brain with the help of the nose-brain pathway. At the same time, the water-soluble polymer part is absorbed, degraded and excreted by the body, and the rest follows the nasal mucosal secretions and leaves the nasal cavity. Therefore, loading the effective ingredients of Yuanhu and Baizhi Zhenlu on the nanofiber membrane is a new drug delivery technology, which is cleverly applied to the nasal mucosa and absorbed by the body through the mucosal layer, avoiding the first-pass effect of the liver, and is used to prevent and treat various diseases.

[0020] Compared with the prior art, the nanofiber membrane of the present invention mainly includes the following significant advantages: (1) The nanofiber membrane can effectively load the full spectrum components of Yuanhu and Baizhi Zhenlu essence, especially the alkaloid components that play an important role in medical and health care, which can be dissolved in an acidic mixed solution mainly composed of water and ethanol.

[0021] (2) During the electrospinning process at room temperature, the Yuanhu Baizhi Zhenlu electrospinning liquid is directly converted into dry nanofibers, thereby being evenly retained and mixed in the main polymer matrix of the nanofibers; the nanofiber membrane is extremely porous and has a very large specific surface area, which greatly increases the effective contact area with the surface of the nasal mucosa, can be quickly adsorbed on the surface of the nasal mucosa and quickly release the essence components, which are effectively absorbed by the surface of the nasal mucosa, thereby increasing the bioavailability of the Zhenlu components; the nanomembrane is overall soft and highly porous, and is easy to fit and adhere to the surface of the nasal mucosa, oral mucosa or skin.

[0022] (3) Polar polymer poly (N-vinyl pyrrolidone) has the ability to quickly adhere to mucous membranes and skin. The matrix polymers all have good aqueous spinnability and are used as matrix polymers to realize electrospinning process, and have good adhesion to oral and nasal mucosa.

[0023] (4) Penetration enhancer: Poloxamer F-127, a commonly used commodity in the food industry and biomedicine, helps promote the penetration of the Zhenlu Essence components released from the fiber membrane patch through the oral or nasal mucosa and be absorbed.

[0024] (5) A mild and environmentally friendly aqueous solution system is used in the preparation of the nanofiber membrane, and a small amount of ethanol is used. The entire process is safe, non-toxic, environmentally friendly, and can retain all the effective components of the Zhenlu Essence. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 is a SEM image of the nanofiber membrane prepared by the present invention; Figure 2 The diagrams are of the effect of the Yuanhu Baizhi Zhenlu nanofiber membrane of the present invention on the pain threshold of mice, wherein (A) is the hot plate method for measuring the skin pain threshold of mice, (B) is the acetic acid writhing method for measuring the visceral pain threshold, and (C) is the cilia method for measuring the pain response of pain model mice; Figure 3 Graph showing the effect of the Yuanhu Baizhi Zhenlu nanofiber membrane of the present invention on the depressive-like behavior of chronic depression model mice, wherein (A) is the open field movement distance, (B) is the immobility time during forced swimming, and (C) is the immobility time during tail suspension measurement; Figure 4 The effects of the Yuanhu Baizhi Zhenlu nanofiber membrane of the present invention on insulin resistance (A), blood sugar (B), insulin (C) and blood lipids (D) in diabetic model mice, as well as the weight of the model mice after 10 days of treatment (E), and the pathological changes of fat cells and muscle cells (F); Figure 5 This is a diagram showing the effect of the Yuanhu Baizhi Zhenlu nanofiber membrane of the present invention on nicotine and alcohol addiction behaviors in mice, wherein (A) is nicotine-induced, and (B) is alcohol-induced place preference response.

[0026] Figure 6 This is the effect of applying the Yuanhu Baizhi Zhenlu nanofiber membrane oral mucosa of the present invention on the sleep of mice; in the figure, (A) is the normal saline nanofiber membrane control group, (B) the Yuanhu Baizhi Zhenlu nanofiber membrane group, and (C) the performance comparison of the normal saline nanofiber membrane for 4 minutes and the Yuanhu Baizhi Zhenlu nanofiber membrane for 4 minutes. DETAILED DESCRIPTION

[0027] In order to make the objectives, technical solutions and advantages of the present invention more clear, the present invention will be further described in detail below with reference to the accompanying drawings.

[0028] Example 1 A method for preparing a Yuanhu Baizhi Zhenlu nanofiber membrane comprises the following steps: (1) Preparation of electrospinning solution. Prepare a solution of poly(N-vinyl pyrrolidone) (molecular weight: 43000 g / mol), add Yuanhu Zhenlu and Baizhi Zhenlu in a mass ratio of 2:1, the solvent is a mixture of water and ethanol (90 / 10 mass ratio), and adjust the pH value to 6.0 with citric acid. Add poloxamer F-127 and mix well to obtain a uniform solution at room temperature. The mass concentration of high molecular weight poly(N-vinyl pyrrolidone) in the electrospinning solution is 45%, the mass concentration of Yuanhu and Baizhi Zhenlu is 9%, the mass concentration of poloxamer is 0.1%, and the viscosity at room temperature is 350 cP.

[0029] (2) Preparation of nanofiber membrane by high-voltage electrospinning.

[0030] Using an electrospinning machine, at room temperature, this solution was used as an electrospinning solution for high-voltage electrospinning. The feeding rate of the spinning solution on the single-needle spinning electrospinning machine was 1.5 mL / h, the spinning solution spray needle was 21G in diameter, the electric field strength was 18 kV, the fiber collection distance was 15 cm, the temperature was room temperature, and the relative humidity of the environment was 45%. Aluminum foil was used as a receiving substrate on the drum surface to receive the nanofiber membrane, and the drum speed was 200 RPM. After spinning for two hours, a dry, loose and porous nanofiber membrane was obtained. The obtained nanofiber membrane is loaded with all the effective components of Zhenlu, and the fiber size is uniform. Under an electron microscope, it was observed that the fiber diameter was 900 nanometers, the nanofiber membrane was loose and porous, and the overall thickness was 100 microns. The membrane layer is soft and easy to apply to the surface of the nasal mucosa. Figure 1 The SEM photo shows the microscopic morphology of the nanofiber membrane. The diameter of the nanofiber is uniform, about 900 nanometers, and the Zhenlu essence components are loaded in the fibers of the polymer main body.

[0031] Example 2 A method for preparing a Yuanhu Baizhi Zhenlu nanofiber membrane comprises the following steps: (1) Preparation of electrospinning solution. Prepare a solution of poly(N-vinyl pyrrolidone) (molecular weight: 43000 g / mol), add Yuanhu Zhenlu and Baizhi Zhenlu in a mass ratio of 2:1, the solvent is a mixture of water and ethanol (90 / 10 mass ratio), and adjust the pH value to 6.0 with citric acid. Add poloxamer F-127 and mix well to obtain a uniform solution at room temperature. The mass concentration of high molecular weight poly(N-vinyl pyrrolidone) in the obtained electrospinning solution is 50%, the mass concentration of Yuanhu and Baizhi Zhenlu is 10%, the mass concentration of poloxamer is 0.12%, and the viscosity at room temperature is 650 cP.

[0032] (2) Preparation of nanofiber membrane by high-voltage electrospinning.

[0033] Using an electrospinning machine, at room temperature, this solution was used as the electrospinning solution for high-voltage electrospinning. The feeding rate of the spinning solution on the single-needle spinning electrospinning machine was 1.5 mL / h, the spinning solution spray needle was 21G in diameter, the electric field strength was 18 kV, the fiber collection distance was 15 cm, the temperature was room temperature, and the relative humidity of the environment was 45%. Aluminum foil was used as the receiving substrate on the drum surface to receive the nanofiber membrane, and the drum speed was 200 RPM. After spinning for two hours, a dry, loose and porous nanofiber membrane was obtained. The obtained nanofiber membrane is loaded with all the effective components of Zhenlu, and the fiber size is uniform. Under an electron microscope, it was observed that the fiber diameter was 900 nanometers, the nanofiber membrane was loose and porous, and the overall thickness was 120 microns. The membrane layer is soft and easy to apply to the surface of the nasal mucosa.

[0034] Performance test and data 1. Effect of Yuanhu Baizhi Zhenlu (abbreviated as Yuanbai Zhenlu) nanofiber membrane on pain threshold of mice The prepared tiny Yuanbaizhenlu nanofiber membrane (1x1 mm) was placed in the nasal cavity of C57BL / 6 mice for 2-4 minutes, and then the skin pain threshold of the mice was measured (hot plate method, Figure 2 (A)) and visceral pain threshold (acetic acid writhing test, Figure 2 Middle (B), as shown in the figure, compared with the control group (normal saline membrane), the Yuanbai Zhenlu nanofiber membrane treatment significantly increased the pain threshold to the level of the positive control drug (lidocaine), and the effect was better than that of Yuanbai Zhenlu gavage. Figure 2 Middle (C) The effect of Yuanbai Zhenlu nanofiber membrane on the pain response of pain model mice was tested. The results showed that after applying Yuanbai Zhenlu nanofiber membrane for 10 and 30 seconds, Yuanbai Zhenlu nanofiber membrane could significantly reduce the pain response of mice (i.e., enhance the analgesic effect) compared with the control group (solvent group).

[0035] 2. Effect of Yuanbaizhenlu Nanofiber Membrane on Depressive Behavior of Depression Model Mice The prepared tiny Yuanbai Zhenlu nanofiber membrane (1x1 mm) was placed in the nasal cavity of C57BL / 6 mice for 2 minutes, and then the depressive-like behaviors of the chronic depression model mice were tested, including open field movement distance, immobility time during forced swimming, and immobility time during tail suspension test. Figure 3 As shown, the treatment of Yuanbaizhenlu nanofiber membrane significantly improved the depressive-like behavior of depression model mice, and the effect of Yuanbaizhenlu nanofiber membrane was better than that of Yuanhu membrane or Angelica dahurica membrane alone, and was also better than that of Yuanbaizhenlu oral administration. This shows that Yuanbaizhenlu nanofiber membrane has a good anti-depression effect.

[0036] 3. Effects of Yuanbaizhenlu Nanofiber Membrane on Insulin Resistance, Blood Glucose, Blood Lipids and Body Weight in Diabetic Mice The prepared micro-sized Yuanbai Zhenlu nanofiber membrane (1x1 mm) was placed in the nasal cavity of one side of the insulin resistance model rat (SD) induced by high sugar / high fat for 2 minutes / day, and the insulin resistance index, blood sugar, blood insulin and blood lipid levels were measured after 10 days of treatment. Figure 4 As shown in the results, one week of treatment with Yuanbaizhenlu nanofiber membrane can significantly improve insulin resistance, reduce blood sugar, blood insulin and blood lipids. Figure 4 As shown in (E), the body weight of the model mice decreased significantly after 10 days of treatment with the Yuanbaizhenlu nanofiber membrane; and pathological examination revealed that the lesions of the liver cells, adipocytes and muscle cells of the model mice were improved (see Figure 2). Figure 4 The experimental results showed that in the insulin resistance model mice, the treatment with Yuanbaizhenlu nanofiber membrane showed significant effects of improving insulin resistance, lowering blood sugar, blood lipids, and reducing body weight.

[0037] 4. Effects of Yuanbaizhenlu Nanofiber Membrane on Nicotine and Alcohol Addiction Behavior in Mice In the nicotine or alcohol induced conditioned place preference behavior experiment of mice, the prepared tiny Yuanbai Zhenlu nanofiber membrane (1x1 mm) was placed in the nasal cavity of C57BL / 6 mice for 2 minutes, and then nicotine (0.5 kg / kg) or alcohol (2g / kg) was intraperitoneally injected, and then the nicotine and alcohol addiction behaviors (place preference behaviors) of the mice were tested respectively. The results are as follows Figure 5 As shown, simultaneous treatment of Yuanbai Zhenlu nanofiber membrane with nicotine or alcohol can prevent the formation of nicotine and alcohol place preference behavior, and the effect of Yuanbai Zhenlu nanofiber membrane is better than that of Yuanhu Zhenlu oral administration. The experimental results show that treatment with Yuanbai Zhenlu nanofiber membrane has the effect of assisting smoking and alcohol cessation.

[0038] 5. Effect of oral mucosal treatment with Yuanbaizhenlu nanofiber membrane on sleep in mice C57BL / J6 mice were surgically implanted with EEG recording electrodes, and then the EEG and EMG of freely moving mice were recorded. After the oral mucosa of the mice was treated with the Yuanbai Zhenlu nanofiber membrane for 10 minutes, sleep waves appeared in the EEG of the mice and the EMG activity was significantly weaker ( Figure 6 (B) shows that compared with the control group (normal saline, Figure 6 In (A), treatment of oral mucosa with Yuanbaizhenlu nanofiber membrane can promote sleep. Figure 6 In (C), it can be seen that the proportion of REM sleep in the control group is much greater than that of NREM sleep; the proportion of REM sleep in the Yuanbai nanofilm group is less than that of NREM sleep, indicating that Yuanbai nanofilm has a sleep-inducing effect.

[0039] Comparative Example 1 The mass ratio of Corydalis yanhusuo and Angelica dahurica extract added in Example 1 was changed to 1:1, and the other ingredients remained unchanged. It was found that the sleep-aiding effect was weakened.

[0040] Comparative Example 2 Poloxamer F-127 was not added, and the rest was the same as in Example 1. It was found that the comprehensive effect of the obtained Yuanbaizhenlu nanofilm was reduced.

[0041] Comparative Example 3 The pH in Example 1 was changed to 7.0, and the other parameters remained unchanged. The solubility of Corydalis yanhusuo in the obtained electrospinning solution was low.

[0042] Comparative Example 4 When the water and ethanol mixture (90 / 10 mass ratio) in Example 1 was replaced with water, and other ingredients remained unchanged, it was found that the dissolution rate of the fat-soluble substances in Rhizoma Corydalis and Radix Angelicae Dahuricae was reduced, and the efficacy was weakened.

Claims

1. A method for preparing a Yuanhu Baizhi Zhenlu nanofiber membrane, characterized in that: The following steps are involved: (1) preparing Yuanhu Zhenlu and Baizhi Zhenlu respectively; (2) adding Rhizoma Corydalis and Radix Angelicae Dahuricae Zhenlu into the N-vinyl pyrrolidone solution in a mass ratio of (2-3):1; (3) then adding a mixed solvent of water and ethanol and adjusting the pH to 6.0; (4) adding poloxamer and mixing evenly at room temperature to obtain Yuanhu Baizhi Zhenlu electrospinning solution; (5) The Yuanhu Baizhi Zhenlu electrospinning liquid was prepared into Yuanhu Baizhi Zhenlu nanofiber membrane by high-voltage electrospinning method.

2. The preparation method according to claim 1, characterized in that: The process parameters of the high-voltage electrospinning method are as follows: the feeding rate of the Yuanhu Baizhi Zhenlu electrospinning solution is 1.5-3 mL / h, the drum speed is 200-400 RPM, and the spinning time is 2-4 hours.

3. The preparation method according to claim 1, characterized in that: The viscosity of the Yuanhu Baizhi Zhenlu electrospinning solution at room temperature is 350-650 cP, the mass content of N-vinyl pyrrolidone is 45-50%, the total mass content of Yuanhu and Baizhi Zhenlu is 9-10%, and the mass content of poloxamer is 0.1-0.12%.

4. The preparation method according to claim 1, characterized in that: The molecular weight of the N-vinyl pyrrolidone is 43000-50000 g / mol.

5. The preparation method according to claim 1, characterized in that: The mass ratio of water to ethanol in the mixed solvent is 90:

10.

6. The Yuanhu Baizhi Zhenlu nanofiber membrane obtained by the preparation method according to any one of claims 1 to 5.

7. A micro patch, characterized in that: It comprises the Yuanhu Baizhi Zhenlu nanofiber membrane according to claim 6, and the micro-patch includes a nasal mucosa micro-patch, an oral mucosa micro-patch and a skin micro-patch.

8. Use of the Yuanhu Baizhi Zhenlu nanofiber membrane according to claim 6 in the preparation of antidepressant, analgesic or sleep-inducing preparations.

9. Use of the Yuanhu Baizhi Zhenlu nanofiber membrane according to claim 6 in preparing a preparation for treating diabetic metabolic diseases.

10. Use of the Yuanhu Baizhi Zhenlu nanofiber membrane according to claim 6 in preparing preparations for quitting smoking, quitting drinking or quitting addiction.

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