External application agent for treating insomnia and preparation method thereof

Abstract

The invention belongs to the technical field of external application agents, and particularly relates to an external application agent for treating insomnia and a preparation method thereof. The external coating agent is prepared from the following raw materials: carbomer, a prepared rehmannia root extract, a poria with hostwood extract, a codonopsis pilosula extract, a spina date seed extract, an angelica sinensis extract, a longan pulp extract, a jujube extract, a cynanchum atratum extract, alginate, a medical stone extracting solution, glycerol, a magnetite extract and water. The external application agent creatively integrates the magnetic therapy principle and the traditional Chinese medicine effect, the neurotransmitter metabolism and the sleep awakening period are adjusted through a constant low-intensity magnetic field generated by the magnet extract, the multiple traditional Chinese medicine extracts are matched for nourishing and soothing the nerves, and the dual effects of physical adjustment and pharmacological nourishing are achieved. Clinical verifications show that the external application coating agent is high in effective rate, the dependence risk and adverse reaction of oral medicines are avoided through the external application mode, and the external application coating agent is high in safety and has important clinical application value.

Description

Technical Field

[0001] This invention belongs to the field of topical application technology, specifically relating to a topical application for treating insomnia and its preparation method. Background Technology

[0002] Insomnia, a common and prevalent clinical condition, causes symptoms such as fatigue and dizziness, which can interfere with people's daily work and life to varying degrees, reducing their quality of life. In recent years, with the continuous acceleration of the pace of social work and the ongoing aging of my country's population, the incidence of insomnia has been rising year by year, bringing a dual impact on individual patients' health and the social medical burden. Therefore, the clinical demand for safe and effective insomnia intervention methods is becoming increasingly urgent.

[0003] Currently, benzodiazepines are commonly used to treat insomnia in clinical practice. While these drugs can relieve insomnia symptoms in the short term, insomnia is prone to recurrence, often requiring long-term medication. Long-term use of benzodiazepines can easily lead to various adverse reactions, including drug dependence, memory loss, endocrine disorders, and liver damage. These adverse reactions further increase the burden on the patient's body and may even create a vicious cycle of "medication-dependence-adverse reactions-recurrence," making it difficult to achieve fundamental improvement and treatment of insomnia, thus exhibiting significant limitations in clinical treatment.

[0004] Therefore, there is an urgent need to provide a new intervention method that is safe, non-drug-dependent, and has both regulatory and curative effects to fill the gaps in existing treatments and meet the health needs of the vast number of insomnia patients. Summary of the Invention

[0005] Based on the above technical background, the main objective of this invention is to provide a topical ointment for treating insomnia and its preparation method, so as to overcome the shortcomings of the prior art.

[0006] To achieve the aforementioned objectives, the technical solution adopted by this invention includes:

[0007] The first aspect of this invention is to provide a topical ointment for treating insomnia, which, based on the total weight of raw materials (100%), is prepared from the following raw materials in weight percentages: carbomer 0.5-1.5%, Rehmannia glutinosa extract 4-6%, Poria cocos extract 3-5%, Codonopsis pilosula extract 0.5-1.5%, Ziziphus jujuba var. spinosa extract 3-5%, Angelica sinensis extract 1-3%, Longan aril extract 2-4%, Jujube extract 3-5%, Cynanchum atratum extract 0.5-0.6%, alginate 0.5-1.5%, Maifan stone extract 1-3%, glycerin 1-3%, magnetite extract 20-27%, and the remainder being water.

[0008] Preferably, based on the total weight of the raw materials (100%), the topical application agent is prepared from the following raw materials in weight percentages: carbomer 0.8–1.2%, Rehmannia glutinosa extract 4.5–5.5%, Poria cocos extract 3.5–4.5%, Codonopsis pilosula extract 0.7–1.2%, Ziziphus jujuba seed extract 3.5–4.5%, Angelica sinensis extract 1.5–2.5%, longan pulp extract 2.5–3.5%, jujube extract 3.5–4.5%, Cynanchum atratum extract 0.52–0.57%, alginate 0.8–1.2%, maifanite extract 1.5–2.5%, glycerin 1.5–2.5%, magnetite extract 23–26%, and the remainder is water.

[0009] More preferably, based on the total weight of the raw materials as 100%, the topical application agent is prepared from the following raw materials in weight percentages: 1.0% carbomer, 5% Rehmannia glutinosa extract, 4% Poria cocos extract, 1.0% Codonopsis pilosula extract, 4% Ziziphus jujuba var. spinosa extract, 2% Angelica sinensis extract, 3% longan pulp extract, 4% jujube extract, 0.55% Cynanchum atratum extract, 1.0% alginate, 2% maifanite extract, 2% glycerin, 25% magnetite extract, and the remainder is water.

[0010] The raw materials used in this invention have the following effects: Carbomer: It has anti-allergic, antiemetic, anti-anxiety, anticholinergic, and anti-tremor effects.

[0011] Rehmannia glutinosa (processed): It is sweet in taste and slightly warm in nature. It belongs to the liver and kidney meridians and is mainly used to nourish blood and yin, and replenish essence and marrow.

[0012] Poria cocos: It has a sweet and bland taste, and is neutral in nature. It enters the heart and spleen meridians and has a calming effect. It can be used to treat restlessness, melancholy, palpitations due to heart deficiency, forgetfulness, and other ailments.

[0013] Codonopsis pilosula: It has a sweet taste and neutral properties. It enters the spleen and lung meridians and has the effects of tonifying the middle energizer and replenishing qi, strengthening the spleen and benefiting the lungs, and promoting the production of body fluids.

[0014] Sour jujube seed: It tastes sweet and sour, is neutral in nature, and enters the liver, gallbladder, and heart meridians. It has the effect of nourishing the heart and calming the mind, and is often used for symptoms such as restlessness and insomnia, palpitations and excessive dreaming, and heart palpitations.

[0015] Angelica sinensis: sweet, pungent, and warm. It enters the liver, heart, and spleen meridians. It has the functions of promoting blood circulation and nourishing blood, regulating menstruation and relieving pain, and moistening the intestines and promoting bowel movements.

[0016] Longan pulp: It is sweet, neutral, and warm in nature, and enters the heart, spleen, and stomach meridians. It has the effects of nourishing the heart and spleen, replenishing qi and blood, and strengthening the spleen and stomach.

[0017] Jujube: Sweet in taste and warm in nature; it enters the spleen, stomach, and heart meridians. It has the effects of tonifying the middle energizer and replenishing qi, nourishing blood and calming the mind. It is mainly used to treat spleen deficiency syndrome, visceral agitation, and insomnia.

[0018] Baiwei (Radix Cynanchi Atrati): Bitter and salty in taste, and cold in nature. It enters the stomach, liver, and kidney meridians. It has the effects of clearing heat and cooling blood, promoting diuresis, and relieving strangury.

[0019] Alginate: A natural polysaccharide polymer extracted from seaweed, which has the effects of lowering cholesterol and blood lipids, anti-inflammation, regulating immunity, promoting intestinal health, anti-oxidation and anti-tumor.

[0020] Maifan stone: It has a sweet taste and warm properties; it enters the liver, stomach, and kidney meridians, and has the effects of detoxifying and dispersing nodules, removing putrefaction and promoting tissue regeneration, dispelling cold and dampness, benefiting the liver and stomach, promoting blood circulation and removing blood stasis, promoting diuresis and dissolving stones, and prolonging life.

[0021] Glycerin: It has the effects of replenishing the body's water, improving constipation, maintaining skin elasticity, lubricating the intestines and promoting bowel movements, and lowering blood lipids.

[0022] Magnetic powder: It is the ore powder of magnetite, an oxide mineral, and has the effects of calming the nerves, improving hearing and vision, soothing the liver and benefiting yang, regulating qi and relieving asthma.

[0023] The working principle of the topical application is as follows: Based on the concept of "treating internal diseases externally" in magnetotherapy, this topical application starts with physical therapy. It uses a constant weak magnetic field from magnetic powder to stimulate acupoints on the head, combined with the effects of traditional Chinese medicine. The constant weak magnetic field generated by the magnetic extract regulates neurotransmitter metabolism and the sleep-wake cycle. Combined with various Chinese herbal extracts for nourishment and calming the mind, this method treats insomnia through physical regulation and pharmacological nourishment. This invention is based on the principle of biological magnetic effects. It utilizes the induced magnetic stimulation effect generated by the magnetic substances in the "magnetic therapy coating" to affect the local current distribution in the brain, the movement of charged particles, the permeability of membrane systems, and the magnetic moment orientation of biological macromolecules. This affects the synthesis and secretion of melatonin (MT) in the pineal gland (PG), regulates the concentrations of serotonin (5-HT), norepinephrine (NA), and acetylcholine (ACh), and can also regulate the nervous system's calcium... 2+ It affects the activity, neuronal excitability, and neurotransmitter metabolism, thereby influencing local brain metabolic function and neurotransmitter levels, improving and treating local brain microcirculation, and, combined with the synergistic effects of various Chinese herbal extracts, regulating the body's normal sleep-wake cycle.

[0024] Furthermore, the synergistic effect of various Chinese herbal extracts such as Rehmannia glutinosa, Poria cocos, Ziziphus jujuba var. spinosa, Angelica sinensis, longan pulp, jujube, and Cynanchum paniculatum in this invention can exert the effects of nourishing blood and yin, calming the mind and soothing the nerves, and replenishing qi. This allows the external application agent described in this invention to improve insomnia from both physical regulation and pharmacological nourishment.

[0025] The external application agent described in the present invention has passed a comprehensive inspection by the Henan Institute for Medical Device Inspection, and the quality of all indicators is stable, fully meeting the requirements of the standard of 《YZB / Yu 0109-2011》. At the same time, approved by the Henan Provincial Drug Administration, this product has entered the clinical verification stage, focusing on carrying out systematic verification of the effectiveness and safety in the treatment of insomnia, aiming to provide a new intervention method that is safe, drug-free, and has both regulatory and radical treatment effects for clinical insomnia treatment, filling the short board of existing treatment methods and meeting the health needs of the vast number of insomnia patients.

[0026] When in use, the external application agent is innovatively filled in a disposable plastic pusher, sealed with an OPP composite film, and supported by the core technologies of biomagnetics and quantum mechanics theories. Based on the physical regulation principle of autonomous energy exchange with the body through the dynamic double electric layer on the body surface, it can specifically improve the insomnia sub-healthy state caused by uneven electron cloud distribution, electron transport chain blockage, and energy imbalance in the human body. Through the dynamic magnetic double electric layer energy regulation, the human body function is restored to the normal natural state, helping patients absorb the energy they need, achieving a harmonious and appropriate regulation of the human body, and achieving the effect of improving insomnia with both root and branch treatment.

[0027] The second aspect of the present invention lies in providing a preparation method for the external application agent for treating insomnia described in the first aspect of the present invention, as Figure 1 shown, the preparation method includes the following steps: Step 1: Heat glycerol to melt it to obtain an oil phase. Heat the extracts of Rehmannia glutinosa, Poria cocos, Ziziphus jujuba var. spinosa, Codonopsis pilosula, Angelica sinensis, longan aril, Chinese date, Cynanchum atratum, magnetite, and extract of Chinese medicinal stone first at low temperature and then continue to heat to obtain a water-soluble polymer solution. Heat alginate and carbomer to obtain a water phase; Step 2: Stir the oil phase, water phase, and water-soluble polymer solution, heat for pre-emulsification, and then carry out homogenization emulsification to obtain an intermediate product; Step 3: Stir and cool the intermediate product, and then age it to obtain the external application agent for treating insomnia.

[0028] The above steps are specifically described below.

[0029] In Step 1, heat glycerol to 60-80 °C to melt it to obtain an oil phase.

[0030] Preferably, heat glycerol to 70 °C to melt it to obtain an oil phase.

[0031] The extracts of Rehmannia glutinosa, Poria cocos, Ziziphus jujuba var. spinosa, Codonopsis pilosula, Angelica sinensis, Longan aril, Jujube, Cynanchum paniculatum, Magnetite, and Maifan stone were first heated at a low temperature to 60-80°C, then heated to 90-110°C and continued to be heated for 3-7 minutes to obtain a water-soluble polymer solution.

[0032] Preferably, the extracts of Rehmannia glutinosa, Poria cocos, Ziziphus jujuba var. spinosa, Codonopsis pilosula, Angelica sinensis, Longan aril, Jujube, Cynanchum paniculatum, Magnetite, and Maifan stone are first heated at a low temperature to 70°C, then heated to 100°C and heated for another 5 minutes to obtain a water-soluble polymer solution.

[0033] Alginate and carbomer were heated to 60–80 °C to obtain an aqueous phase.

[0034] Preferably, alginate and carbomer are heated to 70°C to obtain an aqueous phase.

[0035] In step 2, the pre-emulsification conditions are: heating to 70-75°C and pre-emulsifying for 3-7 minutes.

[0036] Preferably, the pre-emulsification conditions are: heating to 75°C and pre-emulsifying for 5 minutes.

[0037] The conditions for homogenization emulsification are: heating to 65-75°C and homogenizing for 3-7 minutes.

[0038] Preferably, the conditions for homogenization emulsification are: heating to 70°C and homogenizing emulsification for 5 minutes.

[0039] In step 3, the intermediate product is stirred and cooled to 35-45°C.

[0040] Preferably, the intermediate product is stirred and cooled to 40°C.

[0041] The aging conditions are: standing at 35-45℃ for 24-48 hours.

[0042] Preferably, the aging conditions are: standing at 40°C for 36 hours.

[0043] The beneficial effects of this invention are as follows: (1) The topical ointment of the present invention combines the principle of magnetic therapy with traditional Chinese medicine extracts, and by limiting the specific ratio of raw materials, the raw materials work synergistically to effectively improve and treat the insomnia symptoms of insomnia patients.

[0044] (2) The clinical verification results of the topical ointment described in this invention show that the SPIEGEL scale score of the verification group was significantly lower than that of the control group after treatment (P=0.000), and the effective rate was as high as 96.6%, which is far better than the 16.7% of the control group. The topical ointment can significantly shorten the time for insomnia patients to fall asleep, prolong the total sleep time, reduce the number of times they wake up at night, deepen the sleep depth, and improve the feeling after waking up, so as to achieve the effect of treating both the symptoms and the root cause from symptom relief to functional regulation. It can effectively deal with mild, moderate and severe insomnia.

[0045] (3) Compared with traditional benzodiazepine sedative-hypnotic drugs, the topical application of the present invention is applied topically, eliminating the need for oral administration and avoiding adverse reactions such as dependence, memory loss, endocrine disorders, and liver damage caused by drug entry into the body. It also prevents the vicious cycle of "drug use-dependence-adverse reactions-recurring symptoms" caused by long-term medication. During the clinical trial, only one mild adverse reaction (increased sleep) occurred, and no serious adverse events occurred. The safety rating is high, and it requires no power source and poses no risk of electric shock, thus avoiding the possibility of infection. This topical application meets the requirements for safe clinical medication.

[0046] (4) The topical ointment creatively integrates modern magnetic therapy technology with traditional Chinese medicine theory. On the one hand, it affects the local current distribution, neurotransmitter metabolism and melatonin secretion of the pineal gland through the constant weak magnetic field generated by the magnet extract, thereby regulating the concentration of key substances such as serotonin and norepinephrine and restoring the normal sleep-wake cycle. On the other hand, through the synergistic effect of various Chinese medicine extracts such as Rehmannia glutinosa, Poria cocos, and Ziziphus jujuba var. spinosa, it exerts the effects of nourishing blood and yin, calming the mind and soothing the nerves, and replenishing qi. It improves insomnia from the dual dimensions of physical regulation and pharmacological nourishment. The mechanism of action is comprehensive and scientific, making up for the limitations of single treatment methods.

[0047] (5) The topical ointment is a topical ointment formulation. When using it, simply apply it to the skin behind both ears, the front and back earlobes, and the forehead 2-3 hours before bedtime each night, and allow it to air dry. Wash off any residue after waking up. The procedure is simple and easy, requiring no professional medical guidance. Differentiated dosage regimens have been designed for patients with insomnia of varying severity (1 / 2 ampoule for mild, 1 ampoule for moderate, and 2 ampoules for severe), catering to the individual needs of various insomnia populations. Furthermore, no special storage conditions are required, making it convenient for daily home use and improving patient medication adherence. Attached Figure Description

[0048] Figure 1 The flowchart illustrates the preparation method of the topical ointment for treating insomnia according to the present invention. Detailed Implementation

[0049] The present invention will now be described in detail, and its features and advantages will become clearer and more apparent from these descriptions.

[0050] Example The present invention is further illustrated below with specific examples. These embodiments are merely illustrative and not intended to limit the scope of the invention. All raw materials used in the embodiments of the present invention are commercially available.

[0051] Example 1 A topical ointment for treating insomnia, based on the total weight of raw materials (100%), is prepared from the following raw materials in weight percentages: carbomer 1.0%, Rehmannia glutinosa extract 5%, Poria cocos extract 4%, Codonopsis pilosula extract 1.0%, Ziziphus jujuba var. spinosa extract 4%, Angelica sinensis extract 2%, Longan aril extract 3%, Jujube extract 4%, Cynanchum atratum extract 0.55%, alginate 1.0%, Maifan stone extract 2%, glycerin 2%, magnetite extract 25%, and the remainder is water.

[0052] The preparation method of the topical ointment for treating insomnia includes the following steps: Glycerin was heated to 70°C to melt, yielding the oil phase. Extracts of Rehmannia glutinosa, Poria cocos, Ziziphus jujuba var. spinosa, Codonopsis pilosula, Angelica sinensis, Longan arillus, Ziziphus jujuba var. spinosa, Cynanchum atratum, magnetite, and maifanite were first heated at a low temperature to 70°C, then increased to 100°C and heated for another 5 minutes to obtain a water-soluble polymer solution. Alginate and carbomer were heated to 70°C to obtain the aqueous phase.

[0053] The oil phase, aqueous phase, and water-soluble polymer solution were stirred and heated to 75°C for 5 min of pre-emulsification. Then, the temperature was raised to 70°C and homogenized for 5 min to obtain the intermediate product.

[0054] The intermediate product was stirred and cooled to 40°C, and then aged at 40°C for 36 hours to obtain a topical ointment for treating insomnia.

[0055] Example 2 A topical ointment for treating insomnia, based on the total weight of raw materials (100%), is prepared from the following raw materials in weight percentages: carbomer 0.8%, Rehmannia glutinosa extract 4.5%, Poria cocos extract 3.5%, Codonopsis pilosula extract 0.7%, Ziziphus jujuba var. spinosa extract 3.5%, Angelica sinensis extract 1.5%, Longan aril extract 2.5%, Jujube extract 3.5%, Cynanchum atratum extract 0.52%, alginate 0.8%, Maifan stone extract 1.5%, glycerin 1.5%, magnetite extract 23%, and the remainder is water.

[0056] The preparation method of the topical ointment for treating insomnia includes the following steps: Glycerin was heated to 60°C to melt, yielding the oil phase. Extracts of Rehmannia glutinosa, Poria cocos, Ziziphus jujuba var. spinosa, Codonopsis pilosula, Angelica sinensis, Longan arillus, Ziziphus jujuba, Cynanchum atratum, magnetite, and maifanite were first heated at a low temperature to 60°C, then increased to 90°C and heated for 7 minutes to obtain a water-soluble polymer solution. Alginate and carbomer were heated to 60°C to obtain the aqueous phase.

[0057] The oil phase, aqueous phase, and water-soluble polymer solution were stirred and heated to 70°C for pre-emulsification for 3 min. Then, the temperature was raised to 65°C and homogenized for 7 min to obtain the intermediate product.

[0058] The intermediate product was stirred and cooled to 35°C, and then aged at 35°C for 48 hours to obtain a topical ointment for treating insomnia.

[0059] Example 3 A topical ointment for treating insomnia, based on the total weight of raw materials (100%), is prepared from the following raw materials in weight percentages: carbomer 1.2%, Rehmannia glutinosa extract 5.5%, Poria cocos extract 4.5%, Codonopsis pilosula extract 1.2%, Ziziphus jujuba var. spinosa extract 4.5%, Angelica sinensis extract 2.5%, Longan aril extract 3.5%, Jujube extract 4.5%, Cynanchum atratum extract 0.57%, alginate 1.2%, Maifan stone extract 2.5%, glycerin 2.5%, magnetite extract 26%, and the remainder is water.

[0060] The preparation method of the topical ointment for treating insomnia includes the following steps: Glycerin was melted at 80°C to obtain the oil phase. Extracts of Rehmannia glutinosa, Poria cocos, Ziziphus jujuba var. spinosa, Codonopsis pilosula, Angelica sinensis, Longan arillus, Ziziphus jujuba, Cynanchum atratum, magnetite, and maifanite were first heated at a low temperature to 80°C, then increased to 110°C and heated for another 3 minutes to obtain a water-soluble polymer solution. Alginate and carbomer were heated to 80°C to obtain the aqueous phase.

[0061] The oil phase, aqueous phase, and water-soluble polymer solution were stirred and heated to 70°C for pre-emulsification for 7 min. Then, the temperature was increased to 75°C and homogenized for emulsification for 3 min to obtain the intermediate product.

[0062] The intermediate product was stirred and cooled to 45°C, and then aged at 45°C for 24 hours to obtain a topical ointment for treating insomnia.

[0063] Comparative Example Comparative Example 1 The topical ointment was prepared in a manner similar to that in Example 1, except that Rehmannia glutinosa extract, Ziziphus jujuba var. spinosa extract, Poria cocos extract, Jujube extract, Magnetite extract and Maifan stone extract were not added during the preparation process.

[0064] Experimental Example Experiment Example 1: Test of the effect of improving and treating insomnia I. Sixty patients with a clear diagnosis of insomnia were selected. 29 patients were completed in the validation group and 1 patient was lost to follow-up. 30 patients were completed in the control group.

[0065] 1.1 The gender distribution of the validation group and the control group is shown in Table 1.

[0066] Table 1. Gender Comparison

[0067] Note: Both groups of genders were X-rayed. 2 Test, X 2 =0.000P=1.000, indicating that there was no statistically significant difference between the two groups in terms of gender.

[0068] 1.2 Comparison of age distribution between the two groups is shown in Table 2. Table 2 Comparison of age distribution between the two groups (unit: years)

[0069] Note: The t-test between the two age distribution groups showed t=0.722 and P=0.473, indicating that there was no statistically significant difference between the two age distribution groups.

[0070] 1.3 Comparison of height between the two groups is shown in Table 3. Table 3 Comparison of height between the two groups (unit: cm)

[0071] Note: The height distribution of the two groups was analyzed by a t-test, and the results showed t=0.278 and P=0.782, indicating that there was no statistically significant difference in height between the two groups.

[0072] 1.4 Comparison of body weight between the two groups is shown in Table 4. Table 4 Comparison of body weight between the two groups (unit: kg)

[0073] Note: The weight distribution of the two groups was analyzed by a t-test, and the results showed t=1.630 and P=0.109, indicating that there was no statistically significant difference in weight between the two groups.

[0074] 1.5 Comparison of the disease course between the two groups is shown in Table 5. Table 5 Comparison of disease course between the two groups (unit: days)

[0075] Note: The rank-sum test showed that the difference in disease duration between the two groups was -0.200 and P=0.841, indicating that there was no statistically significant difference in disease duration between the two groups.

[0076] 2. Comparison of SPIEGEL (sleep quality) scale scores between the two groups before treatment is shown in Table 6. Table 6 Comparison of SPIEGEL scale scores between the two groups before treatment.

[0077] Note: The t-test of the SPIEGEL scale scores before treatment in the two groups showed t=0.442 and P=0.660, indicating that there was no statistically significant difference in the SPIEGEL scale scores between the two groups before treatment.

[0078] II. Clinical Validation Methods 1. Design Methodology The study employed a randomized, double-blind, placebo-controlled, parallel-controlled, superiority trial design.

[0079] 2. Dosing regimen (1) Verification group: The topical coating prepared according to the preparation method described in Example 1.

[0080] (2) Control group: The topical coating prepared according to the preparation method described in Comparative Example 1.

[0081] Administration method: Clean the application area 2-3 hours before bedtime each night and let it dry. Apply the topical dressing to the skin behind both ears, the front and back earlobes, and the forehead. Let it air dry naturally. Wash off any remaining dressing after waking up. Apply again 2-3 hours before bedtime each night.

[0082] Dosage varies depending on the situation: (1) Mild insomnia: For those who experience short-term insomnia due to occasional mood or other reasons (lasting less than one week), and who have never taken oral tranquilizers, take 1 / 2 vial each night, with each vial containing 0.3 mL.

[0083] (2) Moderate insomnia: Insomnia lasting one week to one month, occasionally taking tranquilizers, one vial per night.

[0084] (3) Severe insomnia: those who have suffered from insomnia for more than a month or for several years, need to take tranquilizers every night, cannot fall asleep without them, or have tried many different kinds of drugs without significant effect, and take 2 doses every night.

[0085] A course of treatment lasts seven days. Note: During the treatment period, both groups are prohibited from using tranquilizers or corresponding physical therapy methods that may affect the assessment of the efficacy of the treatment.

[0086] 3. Verify start and end times The clinical trials ran from July 26 to September 20.

[0087] 4. Ethical principles The clinical validation protocol and informed consent form were approved by the ethics committee prior to the clinical validation. Participants were invited to participate in the clinical validation on a voluntary basis. Before the clinical validation began, the purpose, process, and duration of the clinical validation were explained to the participants in detail, along with the role of the validation device in the clinical setting, potential risks, and corresponding measures. The clinical validation was conducted after obtaining the participants' consent and obtaining their signatures on the informed consent form.

[0088] III. Evaluation Criteria and Statistical Methods The evaluation primarily focuses on the safety and efficacy of topical ointments used in clinical applications. The evaluation criteria are as follows: 1. Safety evaluation Any adverse reactions occurring during the trial should be recorded in the "Adverse Event Form," and followed up with detailed records of the treatment process and results until laboratory tests return to normal and symptoms and signs disappear. Under normal use conditions, the occurrence of adverse reactions should be determined through clinical application by the subjects, and the safety of clinical application should be evaluated and graded based on the records of adverse reactions, categorized as follows: Level 1: Safe, with no adverse reactions; no abnormalities were found in safety indicators.

[0089] Level 2: Relatively safe, with mild adverse reactions. No treatment is required and treatment can continue. Safety indicators show no abnormalities.

[0090] Level 3: There are safety issues, moderate adverse reactions, or mild abnormalities in safety indicators. Treatment can continue after intervention.

[0091] Level 4: Trial discontinued due to severe adverse reactions, or significant abnormalities in safety indicators.

[0092] Upon discovery of adverse reactions, treatment measures will be determined based on the patient's condition, and a decision will be made regarding whether to discontinue observation. In the event of a serious adverse event, necessary measures must be taken immediately to protect the safety of the subject. Simultaneously, the matter will be reported to the ethics committee of the designated research unit and the SFDA, and other branch centers will be notified promptly.

[0093] 2. Efficacy evaluation methods and efficacy indicators are shown in Table 7.

[0094] Table 7 SPIEGEL Scale

[0095] Note: Test scores: ≥9 points, <12 points indicate insomnia; ≥12 points indicate insomnia syndrome. Insomnia syndrome severity: ①≥12 points indicate mild insomnia; ②≥18 points, <24 points indicate moderate insomnia; ③≥24 points indicate severe insomnia.

[0096] 3. Statistical methods 3.1 Methods for evaluating therapeutic effects The efficacy evaluation criteria are shown in Table 7: SPIEGEL scale.

[0097] 3.2 Statistical Processing Methods ① Descriptive statistics: Quantitative data were analyzed using mean, standard deviation, median, maximum, and minimum values; qualitative data were analyzed using actual frequency and relative values. ② Homogeneity analysis: Statistical analysis was performed on indicators such as age between the two groups of subjects, using chi-square and t-tests. ③ Validity analysis: For validity indicators, Wilcoxon rank-sum test or chi-square test was selected based on the characteristics of the data. ④ All hypothesis tests were performed using two-tailed tests, and the test statistics and corresponding p-values ​​were provided. A p-value less than or equal to 0.05 was considered statistically significant. Statistical analysis was performed using SPSS 19.0 statistical software.

[0098] IV. Clinical Evaluation Criteria Evaluation criteria for the efficacy of sleep improvement treatment: ① Cured: Normal sleep with disappearance of symptoms, sleep onset time <30min, total 24-hour sleep time >8h; ② Significantly effective: Prolonged sleep time with significant improvement of symptoms, sleep onset time <30min, total 24-hour sleep time >6h; ③ Effective: Prolonged sleep time with improvement of symptoms, sleep time <30min, total 24-hour sleep time >4h; ④ Ineffective: No change in symptoms, sleep onset time >30min, total 24-hour sleep time <4h.

[0099] V. Clinical Validation Results 1.1 The comparison of SPIEGEL scale scores between the two groups of patients after treatment is shown in Table 8.

[0100] Table 8 Comparison of SPIEGEL scale scores between the two groups after treatment

[0101] Note: The SPIEGEL scale scores of the two groups after treatment were compared by a t-test, with t=6.871 and P=0.000, indicating that the difference in SPIEGEL scale scores between the two groups after treatment was statistically significant.

[0102] 1.2 The comparison of the efficacy evaluation results of the two groups is shown in Table 9.

[0103] Table 9 Comparison of efficacy assessment between the two groups

[0104] VI. Verification Results Analysis The clinical validation was conducted strictly in accordance with the protocol. Sixty cases were enrolled, with 30 in the validation group and 30 in the control group. 59 cases actually completed the validation, with 1 case dropping out. All participants in the clinical validation were admitted voluntarily. They provided informed consent and signed informed consent forms after understanding the purpose, process, and duration of the validation, the clinical effects and benefits of using the validation device, the potential risks of device use, and the corresponding measures.

[0105] Table 9 shows the results of the study, indicating a statistically significant difference in SPIEGEL scale scores between the two groups after treatment. This demonstrates that the topical application described in this invention is significantly superior to the control group in treating insomnia. Disease efficacy analysis showed that the effective rate (cured + significantly + effectively) in the validation group reached 96.6%, while the effective rate (cured + significantly + effectively) in the control group was 16.7%. The difference between the two groups was statistically significant, indicating that the topical application group (validation group) was significantly better than the control group, demonstrating that the topical application has a significant therapeutic effect on insomnia patients.

[0106] VII. Adverse events and side effects discovered during clinical trials and their management 1.1 The list of adverse reactions is shown in Table 10.

[0107] Table 10. Occurrence of adverse reactions in the two groups

[0108] VIII. Clinical Verification Conclusions Clinical trials showed that the topical ointment of this invention was significantly more effective than the control group in treating insomnia. Safety evaluation revealed no serious adverse reactions during the entire trial. This indicates that the topical ointment of this invention is highly effective and safe for treating insomnia.

[0109] The present invention has been described in detail above with reference to specific embodiments and exemplary examples; however, these descriptions should not be construed as limiting the present invention. Those skilled in the art will understand that various equivalent substitutions, modifications, or improvements can be made to the technical solutions and embodiments of the present invention without departing from the spirit and scope of the invention, and all such modifications and improvements fall within the scope of the present invention. The scope of protection of the present invention is defined by the appended claims.

Claims

1. A topical ointment for treating insomnia, characterized in that, The external application agent is prepared from the following raw materials in the weight percentage of 100% of the total weight of the raw materials: carbomer 0.5-1.5%, Radix Rehmanniae preparata extract 4-6%, poria cocos extract 3-5%, radix codonopsis extract 0.5-1.5%, spina date seed extract 3-5%, angelica sinensis extract 1-3%, longan arillus extract 2-4%, jujube extract 3-5%, radix clematidis extract 0.5-0.6%, alginate 0.5-1.5%, medical stone extract 1-3%, glycerol 1-3%, magnetite extract 20-27%, and the rest is water.

2. The external application agent for treating insomnia according to claim 1, wherein The external application agent is prepared from the following raw materials in the weight percentage of 100% of the total weight of the raw materials: carbomer 0.8-1.2%, Radix Rehmanniae preparata extract 4.5-5.5%, poria cocos extract 3.5-4.5%, radix codonopsis extract 0.7-1.2%, spina date seed extract 3.5-4.5%, angelica sinensis extract 1.5-2.5%, longan arillus extract 2.5-3.5%, jujube extract 3.5-4.5%, radix clematidis extract 0.52-0.57%, alginate 0.8-1.2%, medical stone extract 1.5-2.5%, glycerol 1.5-2.5%, magnetite extract 23-26%, and the rest is water.

3. The external application agent for treating insomnia according to claim 2, wherein The external application agent is prepared from the following raw materials in the weight percentage of 100% of the total weight of the raw materials: carbomer 1.0%, Radix Rehmanniae preparata extract 5%, poria cocos extract 4%, radix codonopsis extract 1.0%, spina date seed extract 4%, angelica sinensis extract 2%, longan arillus extract 3%, jujube extract 4%, radix clematidis extract 0.55%, alginate 1.0%, medical stone extract 2%, glycerol 2%, magnetite extract 25%, and the rest is water.

4. A method of producing the external application agent for treating insomnia according to any one of claims 1 to 3, characterized by, The preparation method comprises the following steps: Step 1, glycerol is heated and melted to obtain an oil phase, and Radix Rehmanniae preparata extract, poria cocos extract, spina date seed extract, radix codonopsis extract, angelica sinensis extract, longan arillus extract, jujube extract, radix clematidis extract, magnetite extract and medical stone extract are first heated at low temperature and then heated at high temperature to obtain a water-soluble polymer solution, and alginate and carbomer are heated to obtain an aqueous phase; Step 2, the oil phase, the aqueous phase and the water-soluble polymer solution are stirred and pre-emulsified by heating, and then homogenized to obtain an intermediate product; Step 3, the intermediate product is stirred and cooled, and then aged to obtain the external application agent for treating insomnia.

5. The preparation method according to claim 4, characterized in that, In step 1, The glycerol is heated to 60-80℃ and melted to obtain an oil phase.

6. The preparation method according to claim 4, characterized in that, In step 1, The Radix Rehmanniae preparata extract, poria cocos extract, spina date seed extract, radix codonopsis extract, angelica sinensis extract, longan arillus extract, jujube extract, radix clematidis extract, magnetite extract and medical stone extract are first heated at low temperature to 60-80℃, and then heated at high temperature to 90-110℃ for 3-7 min to obtain a water-soluble polymer solution.

7. The preparation method according to claim 4, characterized in that, In step 1, The alginate and carbomer are heated to 60-80℃ to obtain an aqueous phase.

8. The preparation method according to claim 4, characterized in that, In step 2, The pre-emulsification is performed at 70-75℃ for 3-7 min.

9. The preparation method according to claim 4, characterized in that, In step 2, The homogenizing emulsification is carried out at 65-75℃ for 3-7 min.

10. The method of claim 4, wherein, In step 3, The aging is carried out at 35-45℃ for 24-48 h.

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