Traditional Chinese medicine sleep-aiding soluble microneedle patch and preparation method thereof

Abstract

The invention discloses a traditional Chinese medicine sleep-aiding soluble microneedle patch and a preparation method thereof, and belongs to the technical field of microneedle patches. The traditional Chinese medicine sleep-aiding soluble microneedle patch comprises a microneedle array prepared from sleep-aiding medicine and hyaluronic acid, the mass ratio of the sleep aiding medicine to the hyaluronic acid is 1: 9; the molecular weight of the hyaluronic acid is 500 kDa. The sleep-aiding micro-needle patch with high mechanical strength, good elasticity and flexibility and ideal drug loading effect is prepared by screening the molecular weight of the drug loading material in the micro-needle patch, the size of the micro-needle and the mixing ratio of the drug loading material to the drug. The sleep-aiding microneedle patch takes traditional Chinese medicine components as effective substances, can obviously improve the sleep quality, and is convenient to use and operate. Due to the fact that the patch is a microneedle array, the requirement for acupoint positioning is reduced, and serious dependence of traditional acupuncture on experience is avoided.

Description

Technical Field

[0001] The present invention relates to the technical field of microneedle patches, and in particular to a Chinese medicine sleep-aiding soluble microneedle patch and a preparation method thereof. Background Art

[0002] Insomnia is a common health problem worldwide, and deteriorating sleep quality poses a serious threat to public health. Studies have shown that severe insomnia is closely related to a significant decline in physical function and quality of life, mental and physical morbidity, and accidents. With the sharp increase in the number of people with insomnia worldwide, related sleep-aiding methods have become increasingly important. Common treatments for insomnia include drug therapy and non-drug treatments.

[0003] Drug treatments for insomnia mainly include benzodiazepine receptor agonists and non-benzodiazepine hypnotics, antidepressants with hypnotic effects, antihistamines, melatonin receptor agonists, and novel orexin receptor antagonists. Although the above drugs are effective quickly, due to the large side effects of prescription drugs, drug abuse will have other negative effects on the human body. Traditional Chinese medicine can fundamentally regulate insomnia patients systematically and has been proven to be an effective sleep aid. For example, sour jujube seeds, polygala, schisandra chinensis, and cypress seeds are often used to treat insomnia. These Chinese herbal medicines have almost no side effects and are widely available and easy to obtain. However, Chinese herbal soup is the most common among Chinese medicine preparations. The preparation of Chinese herbal soup is a complicated process, and Chinese herbal soup cannot achieve high patient compliance in terms of color, smell, and taste.

[0004] Non-drug treatments mainly include psychotherapy and physical therapy. For psychotherapists, cognitive behavioral therapy for insomnia (CBTI) is widely used; for physical therapy, non-invasive brain stimulation (NIBS), such as auditory stimulation, transcranial current stimulation (TCS) and transcranial magnetic stimulation (TMS), can also regulate sleep rhythm. Acupuncture, as a physical therapy, has been used to treat sleep problems in my country since ancient times. In traditional Chinese medicine theory, acupuncture works by regulating the brain system and helps treat diseases such as insomnia, stroke, and Alzheimer's disease. Commonly used acupuncture points include Yintang, Anmian, Shenting, Baihui, Shenmen, Sanyinjiao and other acupoints. Although acupuncture helps sleep, traditional acupuncture methods have high technical requirements, and this technology cannot be widely developed. Summary of the invention

[0005] The purpose of the present invention is to provide a Chinese medicine sleep-aiding soluble microneedle patch and a preparation method thereof, so as to solve the problems existing in the above-mentioned prior art. The present invention prepares a sleep-aiding microneedle patch with high mechanical strength, good elasticity and flexibility, and ideal drug loading effect. The sleep-aiding microneedle patch uses Chinese medicine ingredients as effective substances, can significantly improve sleep quality, is easy to use, and is convenient to operate.

[0006] To achieve the above object, the present invention provides the following solutions:

[0007] The present invention provides a Chinese medicine sleep-aiding microneedle patch, comprising a microneedle array prepared from a sleep-aiding drug and hyaluronic acid; the mass ratio of the sleep-aiding drug to the hyaluronic acid is 1:9; and the molecular weight of the hyaluronic acid is 200-500 kDa.

[0008] Furthermore, the microneedle array is composed of a plurality of microneedles arranged in an array, and the gap between the microneedles is 750-850 μm.

[0009] Furthermore, the height of the microneedle is 270-300 μm.

[0010] Furthermore, the bottom diameter of the microneedle is 130-150 μm.

[0011] Furthermore, the tip radius of the microneedle is 7.5-10 μm.

[0012] Furthermore, the ingredients of the sleep-aiding medicine include a sleep-aiding Chinese medicine composition, and the sleep-aiding Chinese medicine composition includes the following components in parts by weight:

[0013] 6-11 parts of Coptis chinensis, 5-10 parts of lotus seed core, 15-20 parts of Poria cocos, 20-25 parts of stir-fried Ziziphus jujuba seeds, 10-15 parts of Albizzia julibrissin flowers, 20-25 parts of Polygala tenuifolia, and 9-14 parts of processed Polygala tenuifolia.

[0014] Furthermore, the sleep-aiding Chinese medicine composition comprises the following components in parts by weight:

[0015] 6 parts of Coptis chinensis, 10 parts of Lotus Seed Heart, 15 parts of Poria, 25 parts of stir-fried Ziziphus jujuba seeds, 10 parts of Flos Albizia Julibrissin, 25 parts of Caulis Polygoni Multiflori, and 9 parts of processed Polygala tenuifolia.

[0016] Stir-fried Chinese date seeds are used to nourish the liver, calm the nerves, and reduce sweating. Prepared Polygala root is used to calm the nerves, improve intelligence, remove phlegm, and reduce swelling. Albizzia julibrissin is used to treat restlessness, depression, and insomnia. Polygonum multiflorum is used to nourish the heart and dispel wind, calm the nerves and promote menstruation. Poria is used to treat palpitations, forgetfulness, and insomnia. Lotus seed heart is used to strengthen the spleen and kidney, nourish the heart and calm the nerves. Coptis chinensis is used to clear heat, reduce inflammation, detoxify, stop diarrhea, lower blood sugar, lower blood lipids, and is antibacterial and antiviral.

[0017] The present invention also provides a method for preparing the Chinese medicine sleep-aiding microneedle patch, comprising the following steps:

[0018] Extracting the active ingredient of the sleep-aiding drug, mixing and dissolving the active ingredient with hyaluronic acid at a mass ratio of 1:9 to obtain a basic solution;

[0019] The basic solution is defoamed, atomized and dried under high pressure to prepare a microneedle array, which is then adhered to the patch to prepare the traditional Chinese medicine sleep-aiding microneedle patch.

[0020] The present invention discloses the following technical effects:

[0021] The present invention prepares a sleep-aiding microneedle patch with high mechanical strength, good elasticity and flexibility and ideal drug-carrying effect by screening the molecular weight of the drug-carrying material, the size of the microneedles and the mixing ratio of the drug-carrying material and the drug in the microneedle patch. The sleep-aiding microneedle patch uses Chinese medicine ingredients as effective substances, can significantly improve sleep quality, is easy to use and easy to operate. Since the patch is a microneedle array, the requirements for acupoint positioning are reduced, avoiding the heavy reliance on experience of traditional acupuncture. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 The design principle and product schematic diagram of the Chinese herbal sleep-aiding microneedle patch; among them, (a) is the finished product picture of the Chinese herbal sleep-aiding microneedle patch; (b) is the actual picture of the Chinese herbal sleep-aiding microneedle patch; (c) is a microscopic magnified picture of the soluble microneedle array; (d) is an enlarged picture of a single soluble microneedle; (e) is the design principle and mechanism of action of the Chinese herbal sleep-aiding microneedle patch. DETAILED DESCRIPTION

[0024] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0025] It should be understood that the terms described in the present invention are only for describing a particular embodiment and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. The intermediate value in any stated value or stated range, and each smaller range between any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0026] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0027] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0028] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0029] The present invention provides a Chinese medicine sleep-aiding microneedle patch, comprising a microneedle array prepared from a sleep-aiding drug and hyaluronic acid; the mass ratio of the sleep-aiding drug to the hyaluronic acid is 1:9; and the molecular weight of the hyaluronic acid is 200-500 kDa.

[0030] In a specific embodiment, the molecular weight of hyaluronic acid is 500 kDa for microneedle preparation and drug loading ratio analysis, and hyaluronic acid with a molecular weight of 200 to 500 kDa can produce equivalent effects.

[0031] Optionally, the microneedle array is composed of a plurality of microneedles arranged in an array, and the gap between the microneedles is 750-850 μm.

[0032] In a specific embodiment, the gap between the microneedles is 810 μm.

[0033] Optionally, the height of the microneedle is 270-300 μm.

[0034] In a specific embodiment, the height of the microneedle is 270 μm.

[0035] Optionally, the bottom diameter of the microneedle is 130-150 μm.

[0036] In a specific embodiment, the bottom diameter of the microneedle is 135 μm.

[0037] Optionally, the tip radius of the microneedle is 7.5-10 μm.

[0038] In a specific embodiment, the tip radius of the microneedle is 10 μm.

[0039] Furthermore, the ingredients of the sleep-aiding medicine include a sleep-aiding Chinese medicine composition, and the sleep-aiding Chinese medicine composition includes the following components in parts by weight:

[0040] 6-11 parts of Coptis chinensis, 5-10 parts of lotus seed core, 15-20 parts of Poria cocos, 20-25 parts of stir-fried Ziziphus jujuba seeds, 10-15 parts of Albizzia julibrissin flowers, 20-25 parts of Polygala tenuifolia, and 9-14 parts of processed Polygala tenuifolia.

[0041] In a specific embodiment, the sleep-aiding Chinese medicine composition comprises the following components in parts by weight:

[0042] 6 parts of Coptis chinensis, 10 parts of Lotus Seed Heart, 15 parts of Poria, 25 parts of stir-fried Ziziphus jujuba seeds, 10 parts of Flos Albizia Julibrissin, 25 parts of Caulis Polygoni Multiflori, and 9 parts of processed Polygala tenuifolia.

[0043] The present invention is described in detail below with reference to specific embodiments.

[0044] Example

[0045] 1. Selection of Chinese medicine composition

[0046] The present invention uses coptis root, lotus seed core, poria, stir-fried spiny jujube seeds, julibrissin flowers, smilax glabra, polygala tuberosa, and processed polygala as a microneedle patch. In parts by weight, the composition includes 6 parts of coptis root, 10 parts of lotus seed core, 15 parts of poria, 25 parts of stir-fried spiny jujube seeds, 10 parts of julibrissin flowers, 25 parts of polygala tuberosa, and processed polygala.

[0047] 2. Extraction of active ingredients from Chinese medicine compositions

[0048] Select 100g of Chinese medicine according to the proportion, immerse the medicine in distilled water, soak for 3 hours, and then extract it in a microwave at 85℃ for 1 hour. After the medicine solution is cooled to room temperature, add twice the volume of distilled water for alcohol precipitation. The alcohol precipitation solution is placed at 0℃~5℃ for more than 12 hours. Finally, impurities are filtered out and the effective ingredients of the Chinese medicine composition are obtained by rotary evaporation, spray drying or freeze drying.

[0049] 3. Selection of drug carriers for microneedle patches

[0050] Hyaluronic acid (HA) is a glycosaminoglycan, a major component of connective tissue and dermis, with high clinical value, and has been widely used in various ophthalmic surgeries, such as lens implantation, corneal transplantation, and glaucoma surgery. It can also be used to treat arthritis and accelerate wound healing. It is also used in cosmetics to keep the skin moisturized, smooth, and elastic, and has anti-wrinkle and whitening effects. It can be dissolved in the skin, but the degradation residue is very safe, making it very suitable as a drug carrier. Therefore, HA is selected as the drug carrier for the microneedle patch in this aspect.

[0051] 4. Size design of microneedle patch

[0052] To facilitate penetration through the skin and increase drug loading, the microneedles are in the shape of bullets. Figure 1 As shown in (a). The diameter of each patch is set to 1.5×(1±0.05)cm, and the diameter of the microneedle array is 1.0×(1±0.05)cm, and the corresponding area is sufficient to cover the entire acupuncture point. Figure 1 As shown in (b), the enlarged image of the microneedle obtained under a microscope is shown in Figure 1 As shown in (c). The gap of the microneedle array is set to 750-850 μm. Considering the thickness of the epidermis and dermis, the length (i.e., height) of each microneedle is set to 270-300 μm. The diameter of the bottom of the microneedle is set to 130-150 μm.

[0053] 4.1. Selection of microneedle tip radius

[0054] Only when the tip of the microneedle can penetrate the skin smoothly can the drug carried by the microneedle enter the body. Therefore, the designed microneedle must have sufficient mechanical strength to penetrate the skin without breaking or bending. Through mechanical simulation analysis of microneedle tips with different radii, it is found that when the tip radius is 5mm, its skin piercing force and microneedle buckling force are 0.014N and 0.008N respectively. The piercing force is greater than the buckling force, so the microneedle cannot penetrate the skin smoothly. When the tip radius is 10mm, its skin piercing force and microneedle buckling force are 0.023N and 0.038N respectively. The piercing force is less than the buckling force, so the microneedle can penetrate the skin smoothly. Therefore, the tip radius is selected as 10×(1±0.05)μm, such as Figure 1 as shown in (d).

[0055] 4.2 Selection of molecular weight of microneedle drug carrier (HA)

[0056] The molecular weight of hyaluronic acid has a significant impact on its performance in microneedle patches, including the strength, elasticity, drug loading performance and release performance of the microneedles. Therefore, based on the above dimensions, hyaluronic acid with different molecular weights was selected to prepare the corresponding microneedles to verify the strength and elasticity of the microneedles prepared by hyaluronic acid with different molecular weights.

[0057] (1) Preparation of microneedle array:

[0058] Hyaluronic acid of different molecular weights (100 kDa, 500 kDa, 1000 kDa and 2000 kDa) was dissolved in deionized water to obtain a basic solution. Then, the basic solution was uniformly stirred and vacuumed to quickly defoam, and the basic solution was sprayed into a polydimethylsiloxane (PDMS) mold using a high-pressure atomizer. After drying at room temperature for 40 minutes, demoulding was performed to obtain a microneedle array prepared from hyaluronic acid of different molecular weights.

[0059] (2) Strength analysis of microneedle arrays:

[0060] 100kDa microneedle array: This microneedle array exhibits strong flexibility and large deformation, can quickly recover to its original shape, shows good comfort, and is suitable for applications with high requirements for softness.

[0061] 200kDa microneedle array: exhibits strong flexibility, moderate hardness, moderate deformation, can withstand external forces well and recover quickly, and is suitable for most application scenarios.

[0062] 500kDa microneedle array: exhibits a good balance between flexibility and hardness, with moderate deformation, can withstand external forces well and recover quickly, and is suitable for most application scenarios.

[0063] 1000kDa microneedle array: This set of microneedle arrays has less deformation and higher mechanical strength, but sacrifices flexibility. It is suitable for applications that require stronger penetration, but may be less comfortable.

[0064] 2000kDa microneedle array: This group of microneedle arrays exhibits very high hardness and low deformation, but lacks flexibility. It is suitable for use under high-intensity load conditions, but may cause greater irritation to the skin.

[0065] (3) Elasticity analysis of microneedle arrays:

[0066] 100kDa microneedle array: This group of microneedles has excellent elastic recovery ability and can quickly return to its original shape after repeated loading, with a fast elastic recovery speed.

[0067] 200kDa microneedle array: good elastic recovery ability and fast recovery speed, with no significant difference from the 100kDa group.

[0068] 500kDa microneedle array: good elastic recovery ability and moderate recovery speed, but slightly inferior to the 100kDa group.

[0069] 1000kDa microneedle array: poor recovery ability. Although it has higher strength, it does not perform as well as the low molecular weight microneedle array in elastic recovery.

[0070] 2000kDa microneedle array: The elastic recovery speed is slow and it shows a higher elastic modulus, but the recovery ability is poor after repeated use. It is suitable for special occasions with stronger penetration requirements.

[0071] Comprehensive analysis:

[0072] The above shows that when the molecular weight of hyaluronic acid is 200-500 kDa, the strength and elasticity of the microneedle array are most ideal. HA with this molecular weight has good biocompatibility and is suitable for drug delivery systems; HA with this molecular weight usually provides better mechanical strength in the microneedle structure and can effectively penetrate the skin; the degradation rate and drug release characteristics of HA with this molecular weight are between those of low molecular weight and high molecular weight HA, which is suitable for certain specific drug release needs; HA with this molecular weight has good permeability and can effectively promote drug absorption.

[0073] 5. Choice of drug loading ratio

[0074] According to the above parameter analysis results, microneedles were made using hyaluronic acid with a molecular weight of 500 kDa as an example. The gap between the microneedles was set to 810 μm, the height of the microneedles was set to 270 μm, the bottom diameter of the microneedles was set to 135 μm, and the tip radius of the microneedles was set to 10 μm. The ratio of hyaluronic acid and drug components in the microneedle array was optimized to obtain the optimal drug loading ratio.

[0075] Several different ratios of hyaluronic acid (HA) and Chinese herbal extracts were designed, taking into account the drug release rate and skin permeability. The experimental group design is as follows:

[0076] Group 1: hyaluronic acid 100% / traditional Chinese medicine extract 0% (control group);

[0077] Group 2: hyaluronic acid 90% / traditional Chinese medicine extract 10%;

[0078] Group 3: hyaluronic acid 80% / traditional Chinese medicine extract 20%;

[0079] Group 4: hyaluronic acid 70% / traditional Chinese medicine extract 30%;

[0080] The percentages in Group 1 to Group 4 are all mass percentages.

[0081] (1) Drug release rate test

[0082] Drug release experiment is an important step to evaluate the effect of microneedle arrays with different ratios. The microneedle array is immersed in simulated body fluids, and samples are taken at different time points to analyze the release of the drug. The experimental results show that at the ratio of 90% hyaluronic acid / 10% Chinese herbal extract, the drug release curve is stable, the release rate is ideal, and the duration is long.

[0083] (2) In vitro pig skin penetration test

[0084] In order to evaluate the penetration effect of drugs in the skin, an in vitro pig skin model was used for penetration experiments. Pig skin is often used to simulate the penetration process of drugs in the skin because its structure and properties are similar to those of human skin. The pig skin was cut into suitable sizes, and the microneedle array was gently applied to the surface of the pig skin, and the pig skin was punctured by the microneedle array. In order to track the penetration effect of the drug, a fluorescently labeled Chinese herbal extract was used for observation. The distribution of the drug in different layers of the pig skin was analyzed by fluorescence microscopy. The experimental results showed that the depth of drug penetration was most significant at the ratio of 90% hyaluronic acid / 10% Chinese herbal extract, and the drug could be evenly distributed in the epidermis and dermis of the skin.

[0085] From the above, it can be seen that when the mass ratio of drug components to hyaluronic acid is 1:9, the drug loading effect is the best. Figure 1 As shown in (e).

[0086] 6. Processing of Chinese medicine microneedle patches

[0087] 10wt% of Chinese medicine extract and 90wt% of hyaluronic acid were dissolved in deionized water to obtain a base solution, which was uniformly stirred and vacuumed for rapid defoaming, and the base solution was sprayed into a polydimethylsiloxane (PDMS) mold using a high-pressure atomizer. After drying at room temperature for 40 minutes, the sticky hydrocolloid patch was finally adhered to the DMN array, and a Chinese medicine soluble microneedle patch was obtained after it was separated from the mold. In this work, the PDMS mold was made on a metal master mold.

[0088] 7. Safety of Chinese medicine microneedle patches

[0089] (1) Multiple skin irritation tests

[0090] 24 hours before the test, the hair on both sides of the back of 4 New Zealand rabbits was cut off, and the hair removal area on both sides was about 3cm*3cm. Take an appropriate amount of Chinese medicine microneedle patch and cut it into 2.5cm*2.5cm size, apply it directly to the skin of one side of the animal, and then cover it with two layers of gauze (2.5cm*2.5cm) and a layer of cellophane, and then fix it with non-irritating tape and bandage. The other side was not treated as a control. Apply once a day for 14 consecutive days. Starting from the second day, cut the hair before each application and use pure water to remove the residual test substance. Observe the results after 1 hour, and score according to the skin irritation / corrosion test table 1 of the "Safety Technical Specifications for Cosmetics" (2015 edition). The control area and the test area are treated in the same way. Calculate the average score of each animal per day according to the following formula, and determine the skin irritation intensity according to the skin irritation / corrosion test table 2 of the "Safety Technical Specifications for Cosmetics" (2015 edition).

[0091] Average score per animal per day = (∑ erythema and edema score / number of animals tested) / 14

[0092] The results of multiple skin irritation tests of the Chinese medicine microneedle patch on New Zealand rabbits are shown in Table 1, and the results are non-irritating.

[0093] Table 1 Results of multiple skin irritation tests of Chinese medicine microneedle patches on New Zealand rabbits

[0094]

[0095]

[0096] (2) Multiple skin irritation tests

[0097] A control group of 30 people and a subject of 30 people were selected. Among the subjects, there were 3 males and 27 females, aged 22 to 58 years old, with an average age of 47.70±7.90 years old, which met the voluntary selection criteria of the subjects. Multiple skin irritation tests were conducted with reference to the "Safety Technical Specifications for Cosmetics" (2015 edition).

[0098] Patch test method: Select qualified patch test equipment, use the closed patch test method, place about 0.020g~0.025g (solid) or 0.020mL~0.025mL (liquid) of Chinese medicine microneedle patch in the patch tester, apply it to the back of the subject with hypoallergenic tape, remove the test object after 24 hours, observe the skin reaction at 0.5, 24, and 48 hours after removal, and record the results according to the skin reaction grading standard in the current effective technical specifications, as shown in Table 2. The results showed that the skin reactions of 30 subjects were all negative.

[0099] Table 2 Summary of human skin patch test results

[0100]

[0101] (3) Multiple use safety test

[0102] 32 subjects were included, with an age range of 21-44 years old, including 16 males and 16 females, with an average age of 30.41±4.60 years old. The subjects used a Chinese medicine microneedle patch every night, 0-1 hour before going to bed, on the Yintang acupoint or Anmian acupoint, fell asleep naturally, and tore it off after waking up, and used it continuously for 28 days.

[0103] After 32 subjects used the sleep patch for 28 days, the subjective recognition evaluation results showed that after 28 days of use, 100% of the subjects agreed that the sample was mild and non-irritating. The safety assessment results showed that the 32 subjects used the sleep patch for 28 days and no adverse reactions occurred on their skin.

[0104] 8. Verification of the sleep-aiding effect of Chinese medicine microneedle patches

[0105] According to the principles of traditional Chinese medicine, the basic pathogenesis of insomnia is restlessness and imbalance of yin and yang. Therefore, treatment should focus on the Du channel, Shaoyin meridian of hand and Taiyin meridian of foot. In view of the fact that the acupoints on the forehead are more conducive to sleep and it is best if there is no hair blocking the acupoints, Yintang and Anmian were finally selected as the main acupoints to help sleep.

[0106] Five subjects with mild insomnia were selected to participate in the experimental test. All subjects received verbal and written descriptions of the experiment before the test, signed informed consent, and obtained approval from the Institutional Review Board (reference number: GDUTXS2024017). The inclusion criteria for subjects included healthy adults over 18 years old. Exclusion criteria included people with serious illnesses or who had difficulty completing long-term tests. For each subject, one microneedle patch was applied to the Yintang acupoint and two microneedle patches were applied to the Anmian acupoint before going to bed every day. These microneedle patches that help sleep will dissolve and be absorbed within 1 hour. The sleep-aiding experiment lasted for 21 days. The sleep quality of the five subjects was scored according to the Pittsburgh Sleep Scale scoring method before and after the experiment. The lower the score, the better the sleep quality. The results are shown in Table 3.

[0107] Table 3 Sleep quality of subjects before and after the sleep aid experiment

[0108]

[0109] As can be seen from Table 1, the sleep quality of the 5 subjects with mild insomnia improved after using the sleep-aiding microneedle patch for 21 consecutive days, which proves that the sleep-aiding microneedle patch of the present invention has a good sleep-improving effect.

[0110] The embodiments described above are only descriptions of the preferred modes of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solutions of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A Chinese medicine sleep-aiding microneedle patch, characterized in that: It comprises a microneedle array prepared from a sleep-aiding drug and hyaluronic acid; the mass ratio of the sleep-aiding drug to the hyaluronic acid is 1:9; and the molecular weight of the hyaluronic acid is 200-500 kDa.

2. The Chinese medicine microneedle sleep-aiding patch according to claim 1, characterized in that: The microneedle array is composed of a plurality of microneedles arranged in an array, and the gap between the microneedles is 750-850 μm.

3. The Chinese medicine microneedle sleep-aiding patch according to claim 2, characterized in that: The height of the microneedle is 270-300 μm.

4. The Chinese medicine microneedle sleep-aiding patch according to claim 2, characterized in that: The bottom diameter of the microneedle is 130-150 μm.

5. The Chinese medicine microneedle sleep-aiding patch according to claim 2, characterized in that: The tip radius of the microneedle is 7.5-10 μm.

6. The Chinese medicine microneedle sleep-aiding patch according to claim 1, characterized in that: The ingredients of the sleep-aiding medicine include a sleep-aiding Chinese medicine composition, and the sleep-aiding Chinese medicine composition includes the following components in parts by weight: 6-11 parts of Coptis chinensis, 5-10 parts of lotus seed core, 15-20 parts of Poria cocos, 20-25 parts of stir-fried Ziziphus jujuba seeds, 10-15 parts of Albizzia julibrissin flowers, 20-25 parts of Polygala tenuifolia, and 9-14 parts of processed Polygala tenuifolia.

7. The Chinese medicine microneedle sleep-aiding patch according to claim 6, characterized in that: The sleep-aiding Chinese medicine composition comprises the following components in parts by weight: 6 parts of Coptis chinensis, 10 parts of lotus seed core, 15 parts of Poria cocos, 25 parts of stir-fried Ziziphus jujuba seeds, 10 parts of Flos Albizia Julibrissin, 25 parts of Caulis Polygoni Multiflori, and 9 parts of processed Polygala tenuifolia.

8. A method for preparing the Chinese medicine sleep-aiding microneedle patch according to any one of claims 1 to 7, characterized in that: The following steps are involved: Extracting the active ingredient of the sleep-aiding drug, mixing and dissolving the active ingredient with hyaluronic acid at a mass ratio of 1:9 to obtain a basic solution; The basic solution is defoamed, atomized and dried under high pressure to prepare a microneedle array, which is then adhered to the patch to prepare the traditional Chinese medicine sleep-aiding microneedle patch.

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