Qi-tonifying, restlessness-relieving and nerve-calming paste as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine compound preparations, and particularly relates to a qi-tonifying, restlessness-relieving and nerve-calming paste, a preparation method thereof and application of the paste in preparation of a medicine for treating depressive disorder related insomnia. The paste is prepared from the following raw materials in parts by weight: 9-30 parts of spina date seeds, 9-15 parts of rhizoma anemarrhenae, 15-30 parts of Huai wheat, 9-15 parts of honey-fried licorice roots, 12-30 parts of lily bulbs, 15-30 parts of lotus seeds, 10-20 parts of sesame seeds, 10-20 parts of crystal sugar and 3-5 parts of maltose. By reinforcing qi and nourishing yin to consolidate the root, clearing heat and relieving restlessness to calm the symptom and calming the heart and tranquilizing the mind, the three methods are combined to achieve the purposes of tonifying without dryness, clearing without injury, recovering qi and yin, relieving deficiency-heat and calming the mind.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine compound preparation technology, specifically relating to a Qi-invigorating, anxiety-relieving, and calming ointment, its preparation method, and its application in the preparation of drugs for treating depression insomnia-related (DRI). Background Technology

[0002] Insomnia refers to a subjective experience where sleep quality and / or duration are insufficient to meet the body's normal needs, thereby affecting daytime social functioning. Symptoms include difficulty falling asleep, frequent awakenings, early awakenings, and difficulty falling back asleep. WHO research indicates that nearly 30% of the global population suffers from insomnia, making it one of the world's recognized public health problems that has not received sufficient attention and effective solutions. Epidemiological studies show that the incidence of insomnia in my country has reached as high as 10%–20%.

[0003] Depressive disorders are common mental illnesses, and insomnia is one of the main somatic symptoms of depressive disorders. 60%–90% of depressed patients experience sleep problems, with 80% of these manifesting as insomnia. Somatic symptoms can even be more prominent than the core symptoms of depressive disorders, appearing earlier or even masking them. Clinically, approximately 80% of depressed patients present with severe insomnia. Depression-related insomnia (DRI) is characterized by sleep disturbances in depressed patients with mood and / or affective disorders. In severe cases, insomnia can mask depressive symptoms, and the severity of insomnia is positively correlated with the severity of mood and / or affective disturbances. Characteristic manifestations of DRI include difficulty falling asleep, frequent nighttime awakenings, early awakening, unrecovered sleep, reduced total sleep volume, and vivid dreams or nightmares. Compared to general insomnia, insomnia or poor sleep quality is the most common complaint, with patients experiencing more severe subjective insomnia and more pronounced negative emotions. Patients experience a decline in mental activity efficiency, severely impacting their social functioning and leading to systemic dysfunction, thus increasing the risk of a range of physical illnesses. The risk of relapse is significantly increased in depressed patients with insomnia compared to those without, and a significantly increased risk of suicide is another serious consequence of insomnia in depressed patients. Due to the unique characteristics of insomnia associated with depressive disorders, its diagnosis and treatment are particularly important.

[0004] Currently, Western medicine primarily treats DRIs with antidepressants and sedative-hypnotic drugs. While these can improve some symptoms, long-term use leads to severe withdrawal symptoms and numerous adverse reactions. Tricyclic antidepressants (TCAs) are traditional antidepressants, but these drugs typically have long half-lives, causing daytime sleepiness and exhibiting anticholinergic activity, resulting in significant adverse reactions; their clinical use has decreased considerably. Selective serotonin reuptake inhibitors (SSRIs) are currently the most widely used antidepressants, showing significant efficacy in relieving depression and anxiety, but they can induce or worsen insomnia. Reports indicate that the incidence of insomnia during SSRI treatment is 12%–20%, and patients with persistent insomnia during treatment may retain it even after depression is relieved. Serotonin and norepinephrine (NE) reuptake inhibitors (SNRIs) are dose-dependent and affect the continuity of sleep in patients with depression. Clinically, the most commonly used sedative-hypnotic drugs fall into two main categories: benzodiazepines (BZDs), such as diazepam and clonazepam, which have adverse effects including amnesia and addiction; and newer non-benzodiazepines (nBZDs), such as zolpidem and eszopiclone, which have strong sedative-hypnotic effects but lack significant antidepressant and anti-anxiety effects. Regarding the treatment of depressive disorders, international guidelines suggest that combining sedative-hypnotic drugs with antidepressants in the initial stages of antidepressant treatment can help improve symptoms and alleviate the adverse effects of antidepressants, but long-term use is not recommended. Therefore, there is an urgent clinical need for an intervention that addresses both DRI-induced insomnia and depressive symptoms, is highly safe, and can be taken long-term.

[0005] Traditional Chinese medicine categorizes insomnia related to depression under the terms "depression syndrome," "insomnia," "excessive dreaming," and "visceral agitation." Modern TCM scholars generally believe that the disease is located in the heart and brain, involving the liver, spleen, and kidneys, with the liver being the most crucial organ. The pathogenesis is rooted in liver dysfunction and stagnation of Qi, with phlegm, heat, and blood stasis acting as secondary symptoms, ultimately leading to malnourishment of the heart and spirit, and the soul not returning to its resting place. Hence, symptoms include low mood, difficulty falling asleep, excessive dreaming and easy awakening, and fatigue upon waking. Common syndrome differentiation types include: ① Liver Qi stagnation and restlessness, represented by Chaihu Shugan San with the addition of Ziziphus jujuba seed and Polygonum multiflorum stem to soothe the liver, relieve depression, nourish blood, and calm the mind; ② Phlegm-heat disturbing the heart and stomach disharmony, represented by Huanglian Wendan Tang with the addition of Arisaema cum Bile and Gardenia to clear heat, resolve phlegm, harmonize the middle jiao, and calm the mind; ③ Deficiency of both heart and spleen and blood failing to nourish the heart, represented by Guipi Tang with the addition of Longan pulp and Platycladus orientalis seed to invigorate Qi, strengthen the spleen, nourish blood, and calm the mind; ④ Kidney deficiency and liver hyperactivity and Yin-Yang imbalance, represented by Tianwang Buxin Dan combined with Liuwei Dihuang Wan with modifications to nourish Yin, reduce fire, and harmonize the heart and kidneys; ⑤ Blood stasis obstructing the collaterals and mental disturbance, represented by Xuefu Zhuyu Tang with the addition of Salvia miltiorrhiza and Amber to invigorate blood, remove blood stasis, open the orifices, and calm the mind. Although some studies have suggested that traditional Chinese medicine has a certain effect on improving insomnia related to depressive disorders, the following significant shortcomings still exist: (1) It focuses on a single symptom of insomnia or depression, and lacks a treatment framework that addresses the overall Qi-emotion-sleep linkage of "depression-insomnia comorbidity". (2) The syndrome differentiation is chaotic and lacks a unified diagnostic standard based on the core pathogenesis of "depressive disorder-related insomnia", which leads to arbitrary selection of prescriptions and drugs and large differences in efficacy. (3) Current treatment methods often adhere to the conventional approach of "soothing the liver and relieving depression, clearing heat and resolving phlegm", and often use large doses of bitter and cold, heavy and sedative drugs, which can easily lead to "overuse of cold and cooling drugs, which can suppress the Qi mechanism" and "excessive heavy sedative drugs, which can suppress the Yang spirit", resulting in side effects such as epigastric fullness and loss of appetite, morning drowsiness, and worsening of low mood. (4) The intervention method is still mainly decoction, which has a poor taste and is inconvenient to decoct. Patients with depression already have low compliance, making it even more difficult to persist. Commercial Chinese patent medicines such as jujube seed capsules and antidepressant and calming granules have fixed prescriptions, which are difficult to take into account the severity and urgency of depression and insomnia and the accompanying symptoms. The long-term efficacy and relapse control are still not ideal.

[0006] In summary, current technology lacks a safe, convenient, and controllable traditional Chinese medicine preparation for treating insomnia associated with depression. Summary of the Invention

[0007] To address the lack of safe, convenient, and process-controllable traditional Chinese medicine preparations for treating depression-related insomnia in existing technologies, this invention proposes a "Qi-Boosting, Anti-irritability, and Mind-Calming Paste," which uses the principles of boosting Qi and nourishing Yin, clearing heat and relieving irritability, and calming the mind and soothing the nerves. It is prepared into a paste using modern pharmaceutical technology, aiming to solve at least one of the following technical problems: (1) Provides a traditional Chinese medicine compound formula for the core pathogenesis of depression combined with insomnia; (2) Establish a standardized preparation process suitable for this compound ointment; (3) To achieve controllable formulation quality, convenient administration, and high long-term compliance, thereby overcoming the shortcomings of existing technologies.

[0008] In a first aspect, the present invention provides a Qi-boosting, irritability-relieving, and calming ointment, which is made from the following raw materials in parts by weight: 9-30 parts of jujube seed, 9-15 parts of anemarrhena rhizome, 15-30 parts of wheat, 9-15 parts of prepared licorice root, 12-30 parts of lily bulb, 15-30 parts of lotus seed, 10-20 parts of sesame seed, 10-20 parts of rock sugar, and 3-5 parts of maltose.

[0009] Preferably, it is made from the following raw materials in parts by weight: 9-15 parts of jujube seed, 9-12 parts of anemarrhena rhizome, 15-20 parts of wheat, 9-12 parts of roasted licorice root, 12-20 parts of lily bulb, 15-25 parts of lotus seed, 10-15 parts of sesame seed, 10-15 parts of rock sugar, and 3-5 parts of maltose.

[0010] More preferably, it is made from the following ingredients in parts by weight: 9 parts jujube seed, 9 parts anemarrhena rhizome, 15 parts wheat, 9 parts prepared licorice root, 12 parts lily bulb, 15 parts lotus seed, 15 parts sesame seed, 15 parts rock sugar, and 3 parts maltose. Among them, black sesame seeds are preferred.

[0011] Secondly, the present invention provides a method for preparing the Qi-boosting, anxiety-relieving, and tranquilizing ointment, comprising the following steps: (S1) Soaking the medicinal materials: Soak the six medicinal materials, namely, jujube seed, anemarrhena rhizome, wheat, roasted licorice root, lily bulb, and lotus seed, in water. (S2) Decoction: The fully soaked medicinal materials are decocted to obtain a decoction; (S3) Concentrate and concentrate the decoction. After filtering and concentrating, add rock sugar and maltose and stir continuously until the decoction becomes thick. When it becomes semi-solid, add sesame seeds and stir quickly to obtain a semi-solid ointment. (S4) Cooling in the mold: While still hot, fill the mold with the semi-solid ointment, press it to release the air, and cool it until it is completely solidified to obtain a solid ointment block.

[0012] In some embodiments, one of the following conditions is also met: (1) In step S1, the amount of water used for soaking is 7-9 times the volume of the medicinal materials. (2) In step S1, the soaking time is 8-24 hours; (3) In step S2, the simmering time is 1-3 hours; (4) In step S3, the decoction is filtered and concentrated three times. Specifically, the decoction is filtered for the first time through a 100-mesh sieve. The resulting liquid is concentrated at a low temperature of 60°C and allowed to stand for sedimentation for more than 2 hours. After sedimentation, the supernatant liquid is filtered for the second time through a 100-mesh sieve and then transferred to a copper pot for concentration. The liquid is concentrated over high heat and then over low heat. During this concentration process, rock sugar and maltose are added and stirred continuously. Before the liquid is concentrated to a semi-solid state, it is filtered for the third time while it is still hot through a 120-150 mesh silk cloth. After filtration, when the liquid is concentrated to a semi-solid state, sesame seeds are added and stirred quickly to obtain a semi-solid ointment. (5) In step S4, the cooling place is a cooling cream room at a temperature below 20°C.

[0013] In some embodiments, the method further includes a cutting and packaging step, in which the solidified paste is removed from the mold, cut into uniform and neat blocks using a professional cutting tool, and then vacuum-sealed and packaged.

[0014] The preparation method of the Qi-boosting, irritability-relieving, and mind-calming paste of the present invention includes soaking medicinal materials, decocting, primary filtration, low-temperature concentration and precipitation, secondary filtration, concentration, adding rock sugar and maltose and heating and micro-refining, tertiary filtration, adding black sesame seeds to form a paste, pressing and cooling in a mold, and cutting and packaging.

[0015] Preferably, during the soaking stage, a thorough and comprehensive inspection of the prepared medicinal materials is conducted to ensure that each ingredient is accurate. The materials are then placed in a clean, appropriately sized container. Approximately eight times the volume of the materials is added in water, ensuring the materials are completely submerged to allow for full water absorption and expansion. Depending on the specific water absorption capacity of the materials and seasonal variations, the water volume can be increased appropriately, ensuring the water level is about 10 cm above the surface of the materials to guarantee adequate soaking. The materials should be soaked under these conditions for at least eight hours to ensure the full extraction of active ingredients.

[0016] Preferably, during the decoction stage, the fully soaked medicinal materials are transferred to a decoction machine and decocted for approximately 1.5 hours. After decoction, the liquid is drained and filtered for the first time using a 100-mesh sieve to remove impurities. The filtered liquid then undergoes a low-temperature concentration process at 60°C and is allowed to settle for at least two hours to further remove precipitates and ensure the purity of the liquid.

[0017] As a preferred method, during the concentration stage, the precipitated medicinal liquid is filtered a second time through a 100-mesh sieve to ensure its fineness. Then, the filtered liquid is poured into a copper pot for concentration. Initially, high heat is used to accelerate water evaporation, and any foam that rises to the surface is skimmed off promptly to prevent impurities from entering. As the water content decreases and the liquid thickens, rock sugar and maltose should be added to adjust the taste and efficacy, and the heat should be reduced to low to continue concentration. Because the liquid is prone to sticking to the bottom and burning at this stage, constant stirring is necessary to ensure even heating and prevent scorching.

[0018] As a preferred method, during the final stage of paste preparation, the concentrated medicinal liquid undergoes a third fine filtration to ensure no impurities remain. It is then poured into a copper pot for further processing. The liquid is continuously stirred using a bamboo spatula until it becomes extremely viscous, reaching a semi-solid state. A measured amount of black sesame seeds is then added and stirred thoroughly until evenly distributed throughout the paste. Finally, the paste is poured into specially designed molds using a spatula and compacted using a special tool to ensure no air pockets remain, guaranteeing the uniformity and integrity of each piece.

[0019] Preferably, during the cooling stage, the mold containing the ointment is placed in a cooling room where the temperature is strictly controlled below 20°C. The surface of the mold is covered with clean gauze to prevent contamination by dust and impurities. The mixture is allowed to cool for approximately six hours until it completely solidifies, ensuring a dense texture for easier subsequent cutting and storage.

[0020] As a preferred method, during the cutting and packaging stage, the solidified herbal paste is removed from the mold and cut into uniform and neat pieces using professional cutting tools. This ensures accurate dosage for each piece, making it easy for patients to take. The cut paste pieces are then vacuum-sealed to prevent air and moisture intrusion, ensuring the paste's shelf life and efficacy.

[0021] Thirdly, the present invention also provides the application of the aforementioned Qi-invigorating and anxiety-relieving ointment in the preparation of a medicament for treating depression-related insomnia.

[0022] In some embodiments, the Qi-Boosting, Anxiety-Relieving, and Mind-Calming Paste is cut into uniform doses; the Qi-Boosting, Anxiety-Relieving, and Mind-Calming Paste is the sole raw material or sole active ingredient of the drug.

[0023] In some embodiments, the drug is a combination formulation comprising at least two active ingredients, and the Qi-invigorating and calming ointment is one of the active ingredients.

[0024] The active ingredient refers to the component that has therapeutic effects on depression-related insomnia.

[0025] In Traditional Chinese Medicine (TCM), insomnia related to depressive disorders falls under the categories of "depression syndrome," "insomnia," "excessive dreaming," and "visceral agitation," with its pathogenesis generally exhibiting a pattern of "deficiency of the root and excess of the branch, with heat within the deficiency." Prolonged unresolved depression depletes the heart and spleen; excessive thinking weakens the spleen's function, leading to insufficient production of qi and blood, resulting in malnourishment of the heart and loss of mental control, manifesting as low mood, difficulty falling asleep, and frequent awakenings due to excessive dreaming. Spleen deficiency also leads to malnourishment of the muscles, causing fatigue and heaviness in the limbs upon waking. Spleen deficiency and impaired function cause dampness to accumulate and transform into phlegm, which in turn generates heat. This internal heat disturbs the flow of qi, further agitating the mind, resulting in symptoms such as five-center heat (heat in the palms, soles, and chest), chest discomfort, and restlessness. Damage to both qi and yin leads to internal heat, with phlegm and heat obstructing the flow, disturbing the heart and liver; insufficient heart blood and liver yin also deplete, causing the soul to lose its abode, resulting in confused dreams, restless sleep, and difficulty falling back asleep after waking. Therefore, the root cause lies in the deficiency of both heart, spleen, and yin, while the manifestation lies in the internal disturbance of deficiency heat, which manifests as restlessness and a lack of mental focus.

[0026] Therefore, this invention takes "deficiency of both Qi and Yin, internal disturbance of deficiency heat, and restlessness of mind" as its core principle, and formulates a Qi-tonifying, irritability-relieving, and mind-calming ointment. It employs three methods simultaneously, with the ointment formula working gradually: tonifying Qi and nourishing Yin to strengthen the root cause—tonifying spleen Qi and nourishing heart Yin, ensuring a source for the generation of Qi and blood, restoring Yin fluids, and nourishing the mind; clearing heat and relieving irritability to calm the symptoms—clearing deficiency heat and eliminating vexation, ensuring that heat does not disturb the heart and irritability does not disturb the mind; and calming the mind to stabilize the will—nourishing heart blood, calming the mind, and stabilizing the spirit, ensuring orderly sleep and restful rest at night. The three methods combined are nourishing without causing dryness and clearing without harming, so that "Qi and Yin are restored, deficiency heat is completely relieved, and the mind is at peace."

[0027] The Qi-Boosting, Anti-Irritability, and Anshen Ointment targets the core pathogenesis of depression-insomnia comorbidity: "Qi and Yin deficiency, internal disturbance of deficiency heat, and restlessness of mind." It breaks through the three major bottlenecks of existing treatments, which often focus on "treating the liver," using bitter and cold herbs for heavy sedation, and using decoctions for short-term effects. The pathogenesis target is shifted from "liver" to "heart and spleen." It uses wheat, prepared licorice root, and lotus seeds to boost Qi, while anemarrhena, lily bulb, and jujube seed nourish Yin and clear deficiency heat. In terms of treatment method, it changes from "heavy sedation and suppression" to "boosting Qi and nourishing Yin, clearing heat and eliminating irritability, and calming the mind and spirit" in parallel. The whole formula is nourishing without being drying and clearing without being harmful. It not only addresses the symptoms of "internal disturbance of deficiency heat" but also avoids the drawbacks of excessive sedation, so that Qi and Yin are restored, deficiency heat is calmed, and the mind is at peace. The dosage form has been upgraded from "bitter and cold decoction" to "sweet and mild paste". Sesame, rock sugar and maltose moisturize dryness and strengthen the spleen, prolong the efficacy of the medicine and reshape the sleep-wake rhythm. It has a sweet taste and is easy to take, which significantly improves the long-term compliance of people with low compliance in a depressed state, meeting the needs of "safe, convenient and long-term intervention" for depression-related insomnia.

[0028] The Qi-Boosting, Anti-irritability, and Anshen Ointment uses jujube seed as the principal ingredient, entering the heart and liver meridians. It nourishes blood and liver, calms the mind and soothes the nerves, and is used in large quantities to directly calm the mind and spirit, targeting the key symptom of "insomnia due to deficiency and irritability." Wheat, prepared licorice root, and anemarrhena rhizome are used as assistant ingredients: Wheat, sweet and cool, enters the heart meridian, boosting qi, relieving irritability, nourishing the heart, and reducing sweating, assisting the principal ingredient in replenishing heart qi and blood supply; Prepared licorice root, sweet and neutral, enters the spleen meridian, tonifying the heart and spleen, relieving spasms, and harmonizing the middle jiao. It assists wheat in "boosting spleen qi to replenish the source of transformation" and also mitigates the coldness of anemarrhena rhizome, ensuring it is clearing without harm; Anemarrhena rhizome, bitter, sweet, and cold, clears deficiency heat, nourishes yin, and reduces fire, addressing the symptoms of "internal disturbance of deficiency heat," and, together with prepared licorice root, balances cold and warm properties, ensuring "clearing without excess." These three herbs work together as assistant ingredients, one tonifying, one clearing, and one harmonizing, supporting the deficiency of the heart and spleen, suppressing the momentum of deficiency heat, and restoring qi and yin. Lily bulb and lotus seed are used as adjuvant herbs: Lily bulb is sweet and slightly cold, nourishing yin and moistening the lungs, clearing the heart and calming the mind, assisting anemarrhena in clearing deficiency heat, and also assisting jujube seed in calming the mind and relieving vexation; Lotus seed is sweet, astringent, and neutral, tonifying the spleen and kidneys, nourishing the heart and calming the mind, combined with wheat and roasted licorice root to rebuild the digestive system and eliminate the source of dampness and phlegm. Sesame is used as the guiding herb, sweet and neutral in nature, tonifying the liver and kidneys, replenishing essence and blood, moistening the intestines and promoting bowel movements, and also moistening dryness to prevent the paste from being too greasy and hindering the spleen, and the oil slowly releases the other herbs, allowing the medicinal effects to continue day and night, and steadily regulating the sleep-wake rhythm. Rock sugar and maltose are used as auxiliary ingredients, sweet and mild to harmonize the middle, correct the taste and reduce bitterness, guide the medicine to the spleen, and facilitate long-term use. The combined use of these herbs is nourishing without being drying, clearing without being harmful, and moistening without being greasy. The preparation of the paste aims for "slow and long-lasting effects, sweet and easy to take," and is especially suitable for long-term intervention in insomnia related to depression.

[0029] The beneficial effects of this invention are as follows: (1) The fundamental difference in TCM legislation: The applicant proposed that the core pathogenesis of depression-related insomnia is "deficiency of both Qi and Yin, internal disturbance of deficiency heat, and restlessness of mind and spirit". He pioneered the treatment principle of "tonifying Qi and nourishing Yin, clearing heat and relieving irritability, and calming mind and spirit" to break through the old framework of "treating from the perspective of the liver" and realize the shift from "liver" to "heart and spleen", combining tonification and clearing, and regulating both the root cause and the symptoms.

[0030] (2) Different drug formulations: Ziziphus jujuba seed is used as the monarch drug and is emphasized for calming the mind and soothing the nerves; the common wheat, roasted licorice root, and Anemarrhena rhizome are used as the minister drugs, which can replenish qi, remove vexation, clear away deficiency-heat without damaging healthy qi; Lily and lotus seeds are used as assistant drugs, nourishing yin and strengthening the spleen, cutting off the source of phlegm production; Sesame seeds, rock sugar, and maltose are used as envoy drugs, moistening dryness, releasing slowly, and having a sweet and moistening flavor to correct the taste. The whole formula is tonifying without being dry, clearing without being damaging, and moistening without being greasy.

[0031] (3) Dosage form innovation: Adopting the modern paste formula technology of "decocting three times, filtering three times, and concentrating three times", cold soaking for eight hours, concentrating at 60°C at low temperature, and cutting after cooling below 20°C, to make solid paste blocks with vacuum packaging; having a sweet taste, accurate dosage, stable absorption, no need for decocting, convenient to carry and store, significantly improving the long-term compliance of the low-compliance population with depression, and achieving the "safe, convenient, and long-lasting" intervention.

[0032] In summary, the traditional Chinese medicine paste preparation - Yiqi Chufan Anshen Paste prepared from Chinese herbal medicines in the present invention targets the core pathogenesis of insomnia related to depressive disorder - "qi and yin deficiency, internal disturbance of deficiency-heat, and restlessness of the mind", that is, taking deficiency as the root, heat as the branch, disturbance as the change, and the mind not staying in place as the application. By tonifying qi and nourishing yin to strengthen the root, clearing away heat and removing vexation to calm the branch, and calming the mind and soothing the nerves to stabilize the will, the three methods are used together to achieve the purpose of tonifying without being dry, clearing without being damaging, enabling qi and yin to recover, deficiency-heat to be completely cleared, and the mind to be at peace, solving the problems in the prior art such as large toxic and side effects of drugs for treating insomnia related to depressive disorder, poor taste of traditional Chinese medicine decoctions, low compliance, limited curative effect, and easy recurrence and prolongation, and realizing the long-term intervention requirements of taking into account both mood disorders and sleep disorders, high safety, convenient administration, and quality control. Brief Description of the Drawings

[0033] Figure 1 It is the preparation process flow of the Yiqi Chufan Anshen Paste of the present invention. Detailed Embodiments

[0034] The following will give a detailed description of the specific embodiments provided by the present invention in conjunction with the drawings. The following examples are implemented on the premise of the technical solution of the present invention, and detailed implementation manners are given, but the protection scope of the present invention is not limited to the following examples. The following reagents are all commercially available unless otherwise specified.

[0035] The Yiqi Chufan Anshen Paste for treating insomnia related to depressive disorder in the present invention is made from the following raw materials in parts by weight: 9 - 30 parts of Ziziphus jujuba seed, 9 - 15 parts of Anemarrhena rhizome, 15 - 30 parts of common wheat, 9 - 15 parts of roasted licorice root, 12 - 30 parts of Lily, 15 - 30 parts of lotus seeds, 10 - 20 parts of sesame seeds, 10 - 20 parts of rock sugar, and 3 - 5 parts of maltose.

[0036] The preferred weight ratio range for preparing the Qi-invigorating, irritability-relieving, and calming ointment for treating depression-related insomnia of the present invention is as follows: 9-15 parts of jujube seed, 9-12 parts of anemarrhena rhizome, 15-20 parts of wheat, 9-12 parts of prepared licorice root, 12-20 parts of lily bulb, 15-25 parts of lotus seed, 10-15 parts of sesame seed, 10-15 parts of rock sugar, and 3-5 parts of maltose.

[0037] The optimal weight ratio range for preparing the Qi-invigorating and calming ointment for treating depression-related insomnia of the present invention is as follows: 9 parts of jujube seed, 9 parts of anemarrhena rhizome, 15 parts of wheat, 9 parts of prepared licorice root, 12 parts of lily bulb, 15 parts of lotus seed, 15 parts of sesame seed, 15 parts of rock sugar, and 3 parts of maltose.

[0038] Among them, black sesame seeds are preferred.

[0039] The present invention discloses a method for preparing a Qi-tonifying, irritability-relieving, and mind-calming herbal paste for treating depression-related insomnia, comprising the following steps: Taking nine herbs in total, including jujube seed, anemarrhena rhizome, wheat, prepared licorice root, lily bulb, lotus seed, black sesame seed, rock sugar, and maltose. Except for black sesame seed, rock sugar, and maltose, the remaining six herbs are placed in a clean container, and eight times their volume of water is added (the water level is approximately 10 cm above the herbs), and soaked for at least 8 hours. After soaking, the herbs are placed in a decoction machine and decocted for 1.5 hours. The decoction is then filtered for the first time through a 100-mesh sieve. The liquid is concentrated at 60℃ and allowed to settle for more than 2 hours. After settling, it is filtered twice through a 100-mesh sieve. The mixture is then transferred to a copper pot and concentrated over high heat followed by low heat. Rock sugar and maltose are added as needed while stirring constantly. Before the mixture reaches a semi-solid state, it is filtered a third time. The mixture is then returned to the pot to collect the paste and a measured amount of black sesame seeds are added and stirred well. While still hot, the paste is poured into a mold, pressed to remove air. The mold is immediately moved to a cooling room below 20℃, covered with gauze, and allowed to cool for 6 hours until completely solidified. Finally, the solid paste is cut into uniform portions and vacuum-sealed for packaging.

[0040] The embodiments of the present invention will be described in detail below: Example 1: This example discloses a Qi-invigorating and calming ointment for treating depression-related insomnia, made from the following ingredients in parts by weight: 9 parts of jujube seed, 9 parts of anemarrhena rhizome, 15 parts of wheat, 9 parts of prepared licorice root, 12 parts of lily bulb, 15 parts of lotus seed, 15 parts of sesame seed, 15 parts of rock sugar, and 3 parts of maltose.

[0041] Example 2: This example discloses a preparation method for the Qi-boosting, anxiety-relieving, and calming ointment used in Example 1, such as... Figure 1 As shown, the preparation method includes the following steps: S1. Soaking medicinal herbs Place the following six medicinal herbs in a clean container: jujube seed, anemarrhena rhizome, wheat, prepared licorice root, lily bulb, and lotus seed. Add 8 times the volume of water (the water level should be about 10 cm above the herbs) and soak for at least 8 hours. S2. Initial decoction and low-temperature concentration The soaked medicinal materials and the soaking liquid are put into a decoction machine and decocted for 1.5 hours. The decoction is filtered for the first time through a 100-mesh sieve to obtain filtrate I. The obtained decoction is concentrated at a low temperature of 60℃ and allowed to stand and settle for more than 2 hours to allow fine impurities to settle fully. S3. Secondary filtration and sugar boiling to thicken the syrup After sedimentation, the supernatant liquid was filtered again through a 100-mesh sieve to obtain filtrate II. The filtrate was then transferred to a copper pot and concentrated over high heat followed by low heat. Rock sugar and maltose were added as needed, and the mixture was stirred continuously. S4. Three-stage filtration and addition of sesame seeds Before concentrating to a semi-solid state, perform a third fine filtration using a 120-150 mesh silk cloth while the mixture is still hot. Then, return the mixture to the pan to collect the paste. Pre-fry a measured amount of black sesame seeds until fragrant, cool them, and pour them into the paste. Stir quickly for ≤30 seconds to prevent localized overheating.

[0042] S5. Molding, Cooling, Cutting, and Packaging While still hot, pour the paste into the mold, press it to remove air, and immediately move the mold to a cooling room below 20°C. Cover with gauze and let it cool for 6 hours until completely solidified. Finally, cut the solid paste into uniform portions and vacuum seal it for packaging.

[0043] Comparative Example 1: This comparative example discloses a herbal paste for treating depression-related insomnia, which is made from the following components in parts by weight: Bupleurum chinense 9 parts, Cyperus rotundus 9 parts, Dragon bone 15 parts, Ziziphus jujuba var. spinosa 9 parts, Lilium brownii 12 parts, Nelumbo nucifera 15 parts, Sesame 15 parts, Rock sugar 15 parts, and Maltose 3 parts.

[0044] The preparation method of the above-mentioned herbal paste for treating insomnia related to depression is as follows: Take six herbs—Bupleurum, Cyperus, Dragon Bone, Ziziphus Jujuba Seed, Lily Bulb, and Lotus Seed—and place them in a clean container. Add eight times the volume of water (the water level should be about 10 cm above the herbs) and soak for at least eight hours. After soaking, decoct the herbs in a decoction machine for 1.5 hours. Filter the decoction through a 100-mesh sieve, then transfer it to a copper pot and concentrate it over high heat followed by low heat. At the same time, add sesame seeds, rock sugar, and maltose while stirring constantly. Concentrate until it reaches a semi-solid state, then return it to the pot to thicken the paste. While still hot, pack it into a mold, press it firmly to remove air, and immediately transfer the mold to a cooling room below 20°C. Cover it with gauze and let it cool for six hours until completely solidified. Finally, cut the solid paste into uniform portions and vacuum seal them for packaging.

[0045] clinical trials

[0046] Clinical trials were conducted using the plasters obtained in Example 1 and Comparative Example 1, as detailed below: Study participants: This trial employed a randomized, double-blind, placebo-controlled parallel-group method, following the Declaration of Helsinki and the Consolidated Standards of Reporting Trials (CONSORT). A total of 96 participants with depression-related insomnia were selected from those who visited the outpatient or inpatient department of the Department of Neurology at Longhua Hospital affiliated with Shanghai University of Traditional Chinese Medicine between January 2022 and December 2024 and were willing to follow the treatment methods.

[0047] Western medicine diagnostic criteria: The primary complaint is insomnia (if the symptoms meet criteria ①-⑦ of the diagnosis of insomnia in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, DSM-V, then insomnia symptoms are present), and the symptoms also meet the diagnostic criteria for depressive episode in the ICD-10 Classification of Mental and Behavioral Disorders.

[0048] Diagnosis of insomnia in DSM-V: ① The chief complaint is dissatisfaction with the quantity or quality of sleep, accompanied by one or more of the following related symptoms: a. difficulty falling asleep; b. difficulty maintaining sleep, characterized by frequent awakenings or difficulty falling back asleep after waking; c. early awakening and inability to fall back asleep; ② Sleep disorders cause clinically significant distress or impair social, occupational, educational, academic, behavioral, or other important functions; ③ Difficulty sleeping at least 3 nights a week; ④ Sleep difficulties have persisted for at least 3 months; ⑤Despite having ample opportunities to sleep, sleep difficulties still occur; ⑥ Insomnia cannot be better explained by another sleep-wake disorder, nor does it only occur in the course of another sleep-wake disorder (e.g., narcolepsy, breathing-related sleep disorders, circadian rhythm sleep-wake disorders, sleep paralysis). ⑦ Insomnia cannot be attributed to the physiological effects of a substance (e.g., abused drugs). ⑧ Coexisting mental disorders and physical conditions cannot fully explain the chief complaint of insomnia.

[0049] Diagnosis of depressive episode in CCMD-10: ① Diagnostic criteria: Depressive episodes are characterized primarily by depressed mood, disproportionate to the situation, ranging from mild sadness to profound grief, and even stupor. Severe cases may present with hallucinations, delusions, and other psychomotor symptoms. Anxiety and agitation are prominent in some cases. ②Symptom criteria: Primarily characterized by depressed mood, and at least 4 of the following criteria must be met: a. Loss of interest and lack of pleasure; b. Feelings of decreased energy or fatigue; c. Psychomotor retardation or agitation; d. Low self-esteem, self-blame, or feelings of guilt; E-association difficulties or a decline in conscious thinking ability; f. Repeated thoughts of dying or suicidal / self-harming behavior; Sleep disorders, such as insomnia, early awakening, or excessive sleep; h. Decreased appetite or significant weight loss; Decreased libido; ③ Severe standard: Impaired social functioning, causing suffering or adverse consequences to the individual; ④ Course of Illness Criteria: a. Symptoms and severity criteria must be met for at least 2 weeks. b. Some schizophrenic symptoms may be present, but not meeting the diagnostic criteria for schizophrenia. If the symptom criteria for schizophrenia are also met, the criteria for a depressive episode must be met for at least 2 weeks after the schizophrenic symptoms have subsided.

[0050] ⑤ Exclusion criteria: Exclude organic mental disorders or depression caused by psychoactive substances or non-addictive substances.

[0051] Traditional Chinese Medicine Diagnostic Criteria: ① Traditional Chinese Medicine diagnostic criteria for insomnia (refer to the "Guidelines for Diagnosis and Treatment of Common Internal Diseases in Traditional Chinese Medicine - TCM Diseases and Syndromes" ZYYXH / T4~49-2008, published by the China Association of Traditional Chinese Medicine and China Press in 2008): Difficulty falling asleep, or waking up easily and being unable to fall back asleep, or in severe cases, complete sleeplessness for more than 4 consecutive weeks; often accompanied by symptoms such as excessive dreaming, irritability, dizziness, headache, palpitations, forgetfulness, and fatigue; without other organic lesions or triggers that interfere with sleep.

[0052] ② Diagnostic criteria for depressive disorders (Yu Bing) in Traditional Chinese Medicine (refer to the "Guidelines for the Diagnosis and Treatment of Common Internal Medicine Diseases in Traditional Chinese Medicine (ZYYXH / T4~49-2008)" published by the China Association of Traditional Chinese Medicine and China Press in 2008): The main clinical symptoms are melancholy, emotional instability, chest and rib distension and pain, or easy crying and anger, mood swings, or a feeling of obstruction in the throat. Patients often have a history of emotional distress such as sorrow, anxiety, grief, fear, and anger, and the recurrence of the condition is often related to emotional changes caused by various factors. Examinations of all systems and physical and chemical examinations are normal, ruling out organic diseases.

[0053] Inclusion criteria: (1) Age 18-65 years old, gender not limited; (2) The chief complaint is insomnia, which meets the criteria ①-⑦ of the DSM-V diagnosis of insomnia; (3) Meets the diagnostic criteria for mild to moderate depression in the International Classification of Diseases (ICD-10), with a Hamilton Depression Rating Scale (17-item version) score of ≥7 and ≤24.

[0054] (4) Meets the TCM diagnostic criteria for insomnia and depression, and meets the diagnostic criteria for heart and gallbladder qi deficiency syndrome; (5) The cumulative score of the seven factors of the Pittsburgh Sleep Quality Index (PSQI) is >7; (6) Participation is voluntary and informed consent is signed.

[0055] Exclusion criteria: (1) Does not meet the above diagnostic and inclusion criteria; (2) Patients with severe depression, whose baseline Hamilton Depression Rating Scale score is >24, or who have attempted suicide or are currently at high risk of suicide; (3) Secondary insomnia, environmental sleep disorders, sleep apnea syndrome, depression caused by other mental or physical illnesses; (4) Patients with serious primary heart, liver, lung, kidney, blood or other serious diseases that affect their survival, mental illness or serious suicidal tendencies.

[0056] (5) Individuals with alcohol dependence or drug abuse history within the previous year will be screened; (6) Pregnant and lactating women; (7) Subjects who participated in or are currently participating in other drug clinical trials within 3 months prior to enrollment; (8) Patients who do not meet the screening criteria according to the researchers.

[0057] Treatment plan: This trial employs a randomized, double-blind, parallel-controlled clinical trial design, randomly assigning subjects to either the experimental or control group at a 1:1 ratio.

[0058] The treatment group was given the Qi-boosting and calming ointment obtained in Example 1, one piece twice a day for 8 weeks.

[0059] The control group received the herbal paste obtained in control group 1, twice a day, one piece each time, for 8 weeks.

[0060] Observation indicators: (1) Primary efficacy indicators: Changes in REM sleep indicators (REM sleep latency, REM sleep volume, REM sleep density) in polysomnography records before and after treatment. (2) Secondary efficacy indicators: Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD17), sleep latency (SL), total sleep time (TST), sleep efficiency (SE), percentage of non-rapid eye movement (NREM) sleep stage 1 in total sleep time (N1%), percentage of NREM sleep stage 2 in total sleep time (N2%), and percentage of NREM sleep stage 3 in total sleep time (N3%).

[0061] Research findings: Table 1. Comparison of therapeutic effects between Example 1 and Comparative Example 1

[0062] As shown in Table 1, the Qi-invigorating and calming ointment of the present invention is superior to the ointment obtained in Comparative Example 1 in improving PSQI and HAMD17 scores, increasing sleep efficiency, prolonging total sleep time, shortening sleep latency, and improving REM density in depression-related insomnia. It can safely and effectively treat depression-related insomnia.

Claims

1. A qi-boosting, irritability-relieving, and calming ointment, characterized in that, It is made from the following ingredients in parts by weight: 9-30 parts of jujube seed, 9-15 parts of anemarrhena rhizome, 15-30 parts of wheat, 9-15 parts of roasted licorice root, 12-30 parts of lily bulb, 15-30 parts of lotus seed, 10-20 parts of sesame seed, 10-20 parts of rock sugar, and 3-5 parts of maltose.

2. The Qi-boosting, anxiety-relieving, and tranquilizing ointment according to claim 1, characterized in that, It is made from the following ingredients in parts by weight: 9-15 parts of jujube seed, 9-12 parts of anemarrhena rhizome, 15-20 parts of wheat, 9-12 parts of prepared licorice root, 12-20 parts of lily bulb, 15-25 parts of lotus seed, 10-15 parts of sesame seed, 10-15 parts of rock sugar, and 3-5 parts of maltose.

3. The Qi-boosting, anxiety-relieving, and tranquilizing ointment according to claim 1, characterized in that, It is made from the following ingredients in parts by weight: 9 parts jujube seed, 9 parts anemarrhena rhizome, 15 parts wheat, 9 parts roasted licorice root, 12 parts lily bulb, 15 parts lotus seed, 15 parts sesame seed, 15 parts rock sugar, and 3 parts maltose.

4. The Qi-boosting, anxiety-relieving, and tranquilizing ointment according to any one of claims 1-3, characterized in that, Its preparation method includes the following steps: (S1) Soaking the medicinal materials: Soak the six medicinal materials, namely, jujube seed, anemarrhena rhizome, wheat, roasted licorice root, lily bulb, and lotus seed, in water. (S2) Decoction: The fully soaked medicinal materials are decocted to obtain a decoction; (S3) Concentrate and concentrate the decoction. After filtering and concentrating, add rock sugar and maltose and stir continuously until the decoction becomes thick. When it becomes semi-solid, add sesame seeds and stir quickly to obtain a semi-solid ointment. (S4) Cooling in the mold: While still hot, fill the mold with the semi-solid ointment, press it to release the air, and cool it until it is completely solidified to obtain a solid ointment block.

5. A method for preparing the Qi-boosting, anxiety-relieving, and calming ointment according to any one of claims 1-4, characterized in that, Includes the following steps: (S1) Soaking the medicinal materials: Soak the six medicinal materials, namely, jujube seed, anemarrhena rhizome, wheat, roasted licorice root, lily bulb, and lotus seed, in water. (S2) Decoction: The fully soaked medicinal materials are decocted to obtain a decoction; (S3) Concentrate and concentrate the decoction. After filtering and concentrating, add rock sugar and maltose and stir continuously until the decoction becomes thick. When it becomes semi-solid, add sesame seeds and stir quickly to obtain a semi-solid ointment. (S4) Cooling in the mold: While still hot, fill the mold with the semi-solid ointment, press it to release the air, and cool it until it is completely solidified to obtain a solid ointment block.

6. The preparation method according to claim 5, characterized in that, At least one of the following conditions must be met: (1) In step S1, the amount of water used for soaking is 7-9 times the volume of the medicinal materials. (2) In step S1, the soaking time is 8-24 hours; (3) In step S2, the simmering time is 1-3 hours; (4) In step S3, the decoction is filtered and concentrated three times. Specifically, the decoction is filtered for the first time through a 100-mesh sieve. The resulting liquid is concentrated at a low temperature of 60°C and allowed to stand for sedimentation for more than 2 hours. After sedimentation, the supernatant liquid is filtered for the second time through a 100-mesh sieve and then transferred to a copper pot for concentration. The liquid is concentrated over high heat and then over low heat. During this concentration process, rock sugar and maltose are added and stirred continuously. Before the liquid is concentrated to a semi-solid state, it is filtered for the third time while it is still hot through a 120-150 mesh silk cloth. After filtration, when the liquid is concentrated to a semi-solid state, sesame seeds are added and stirred quickly to obtain a semi-solid ointment. (5) In step S4, the cooling place is a cooling cream room at a temperature below 20°C.

7. The use of the Qi-invigorating and calming ointment according to any one of claims 1-4 in the preparation of a medicament for treating depression-related insomnia.

8. The application according to claim 7, characterized in that, The Qi-Boosting, Anxiety-Relieving, and Mind-Calming Paste is cut into uniform doses; the Qi-Boosting, Anxiety-Relieving, and Mind-Calming Paste is the sole raw material or sole active ingredient of the drug.

9. The application according to claim 7, characterized in that, The drug is a combination prescription comprising at least two active ingredients, and the Qi-boosting and Anxiety-relieving ointment is one of the active ingredients.

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