Qi-regulating, phlegm-reducing and nerve-soothing 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-regulating, phlegm-reducing and nerve-calming paste, a preparation method thereof and application of the paste in preparation of a medicine for treating Parkinson's disease combined with rapid eye movement sleep behavior disorder. The paste is prepared from the following raw materials in parts by weight: 9-30 parts of semen ziziphi spinosae, 15-30 parts of Chinese yam, 10-15 parts of poria with hostwood, 9-30 parts of semen coicis, 3-10 parts of pericarpium citri reticulatae, 3-10 parts of fingered citron, 10-20 parts of sesame, 10-20 parts of rock candy and 3-5 parts of maltose. By nourishing the heart and strengthening the spleen to consolidate the root, regulating qi and reducing phlegm to relieve stagnation and tranquilizing and sedating the physique to return to the soul, the three methods are combined to achieve the purposes of tonifying without stagnation, eliminating without injury, recovering the heart and the spleen, smoothing phlegm and qi and self-hiding the soul.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine compound preparation technology, specifically relating to a qi-regulating, phlegm-resolving, and calming ointment, its preparation method, and its application in the preparation of drugs for treating Parkinson's disease (PD) combined with rapid eye movement sleep behavior disorder (RBD). Background Technology

[0002] Parkinson's disease (PD) is a common progressive neurodegenerative disease characterized by resting tremor, rigidity, bradykinesia, and postural instability as its core motor symptoms. It is also accompanied by various non-motor symptoms, among which sleep disturbances are particularly prominent. Rapid eye movement (REM) sleep behavior disorder (RBD) manifests as dystonia during REM sleep, accompanied by dream enactment behavior, which can lead to self-injury by the patient or injury to their bed partner. Epidemiological studies show that approximately 30%–60% of PD patients also have RBD, and RBD can appear several years earlier than motor symptoms, considered an important biological marker of alpha-synucleinopathy progression. Patients with PD-RBD comorbidity experience faster cognitive decline, poorer quality of life, and a significantly increased risk of falls and fractures, placing a heavy burden on families and society.

[0003] Currently, Western medicine's intervention strategies for PD-RBD mainly include: (1) Adjusting dopaminergic drugs: such as reducing the dose of dopamine receptor agonists at night, which may alleviate nighttime behavioral abnormalities, but often leads to worsening of daytime motor symptoms; (2) Clonazepam: the first-line drug for RBD, but PD patients often have cognitive impairment and decreased balance function, benzodiazepines (3) Melatonin: Although it can partially improve RBD symptoms, its efficacy on the motor and non-motor symptoms of PD itself is limited; (4) Other symptomatic treatments: such as antidepressants, sedative-hypnotics, etc., have large side effects and poor long-term compliance. Therefore, there is an urgent clinical need for an intervention that takes into account both PD motor disorders and RBD sleep abnormalities, is highly safe, and can be taken for a long time.

[0004] Traditional Chinese medicine classifies PD under the categories of "tremor syndrome" and "tremor," while sleep behavior abnormalities of RBD are mostly classified as "nightmare," "insomnia," and "excessive dreaming." Modern TCM scholars generally believe that the pathogenesis of PD-RBD is located in the brain, rooted in the liver and kidneys, and related to the spleen and heart; the etiology and pathogenesis are rooted in liver and kidney deficiency and yin-yang imbalance; phlegm, blood stasis, internal wind, and deficiency fire are the manifestations; prolonged illness affects the collaterals, phlegm and blood stasis intertwine, and the soul does not return to its abode, hence the excessive dreaming, shouting, and limb movement at night. The syndrome differentiation includes: Liver and Kidney Yin Deficiency with Internal Liver Wind, treated with modified Tianma Gouteng Decoction and Zhengan Xifeng Decoction to nourish the kidneys, soften the liver, extinguish wind, and calm the mind; Phlegm-Heat Disturbing the Mind with Unsettled Spirit, treated with modified Huanglian Wendan Decoction to clear heat, resolve phlegm, harmonize the middle jiao, and calm the mind; Qi and Blood Deficiency with Heart-Mind Malnourishment, treated with modified Guipi Decoction to tonify Qi, nourish blood, strengthen the spleen, and calm the mind; and Blood Stasis Obstructing the Collaterals with Phlegm and Blood Stasis, treated with Xuefu Zhuyu Decoction combined with Daotan Decoction to invigorate blood, remove blood stasis, resolve phlegm, and unblock the collaterals. Although some studies have suggested that traditional Chinese medicine has a certain improving effect on PD-RBD, the following significant shortcomings still exist:

[0005] (1) It focuses on a single symptom (such as insomnia or tremor) and lacks a holistic approach to the treatment of PD-RBD comorbidity;

[0006] (2) The syndrome differentiation is not uniform and there is a lack of specific diagnostic criteria for "PD-RBD comorbidity", which leads to a large degree of randomness and poor reproducibility in the selection of prescriptions and drugs;

[0007] (3) Current TCM treatments for Parkinson's disease complicated with RBD are mostly confined to the conventional approach of "internal liver wind and phlegm-heat disturbing the mind". They focus on calming the liver and extinguishing wind, clearing heat and resolving phlegm. Although they can temporarily relieve tremors and agitation, they are prone to the drawbacks of "excessive use of cold and cooling herbs, which will only damage the spleen and stomach" and "excessive use of strong sedatives, which will further damage the vital spirit". Firstly, bitter and cold mineral herbs damage the middle yang, making the spleen weaker and phlegm more generated. Secondly, strong sedatives are more effective at calming the soul than nourishing the heart. Once the medication is stopped, the symptoms will return and nocturnal agitation and nightmares will recur and be difficult to control.

[0008] (4) Current intervention methods are mostly based on decoctions, which have poor taste, are inconvenient to carry, and have low long-term patient compliance; existing traditional Chinese medicines such as jujube seed capsules and Tianwang Buxin pills are convenient to take, but the prescriptions are fixed and it is difficult to take into account the diverse symptoms of Parkinson's disease combined with RBD.

[0009] In summary, the existing technology lacks a traditional Chinese medicine preparation that is safe, convenient to take, and has a controllable process for treating PD-RBD comorbidity. Summary of the Invention

[0010] To address the lack of safe, convenient, and process-controllable traditional Chinese medicine preparations for treating PD-RBD comorbidity, this invention proposes a "Qi-regulating, phlegm-resolving, and mind-calming ointment." Based on the principles of nourishing the heart and spleen, regulating qi and resolving phlegm, and calming the mind and spirit, this ointment is prepared using modern pharmaceutical technology, aiming to solve at least one of the following technical problems:

[0011] (1) Provides a traditional Chinese medicine compound formula targeting the core pathogenesis of PD combined with RBD comorbidity;

[0012] (2) Establish a standardized preparation process suitable for this compound ointment;

[0013] (3) To achieve controllable formulation quality, convenient administration, and high long-term compliance, thereby overcoming the shortcomings of existing technologies.

[0014] In a first aspect, the present invention provides a qi-regulating, phlegm-resolving, and nerve-calming ointment, which is made from the following raw materials in parts by weight: 9-30 parts of jujube seed, 15-30 parts of yam, 10-15 parts of poria cocos, 9-30 parts of coix seed, 3-10 parts of dried tangerine peel, 3-10 parts of bergamot, 10-20 parts of sesame, 10-20 parts of rock sugar, and 3-5 parts of maltose.

[0015] Preferably, it is made from the following raw materials in parts by weight: 10-20 parts of jujube seed, 15-25 parts of yam, 10-15 parts of poria cocos, 15-30 parts of coix seed, 5-10 parts of dried tangerine peel, 5-10 parts of bergamot, 10-20 parts of sesame, 10-20 parts of rock sugar, and 3-5 parts of maltose.

[0016] More preferably, it is made from the following ingredients in parts by weight: 15 parts jujube seed, 20 parts yam, 15 parts poria cocos, 15 parts coix seed, 9 parts dried tangerine peel, 9 parts citron, 15 parts sesame, 15 parts rock sugar, and 3 parts maltose.

[0017] Secondly, the present invention provides a method for preparing the Qi-regulating, phlegm-resolving, and tranquilizing ointment, comprising the following steps:

[0018] (S1) Soaking the medicinal materials: Soak the six medicinal materials, namely, jujube seed, yam, poria cocos, coix seed, tangerine peel and citron, in water;

[0019] (S2) Decoction: The fully soaked medicinal materials are decocted to obtain a decoction.

[0020] (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.

[0021] (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.

[0022] In some embodiments, one of the following conditions is also met:

[0023] (1) In step S1, the amount of water used for soaking is 7-9 times the volume of the six medicinal materials;

[0024] (2) In step S1, the soaking time is 8-24 hours;

[0025] (3) In step S2, the simmering time is 1-3 hours;

[0026] (4) In step S3, the decoction is filtered and concentrated three times. Specifically, the decoction is first filtered through a 100-mesh sieve, and 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 through a 100-mesh sieve for the second time, and then transferred to a copper pot for concentration. 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 hot using 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.

[0027] (5) In step S4, the cooling location is a cooling room with a temperature below 20°C.

[0028] 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.

[0029] The preparation method of the Qi-regulating, phlegm-resolving, and mind-calming ointment 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 an ointment, pressing and cooling in a mold, and cutting and packaging.

[0030] 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.

[0031] 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.

[0032] 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.

[0033] 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.

[0034] 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.

[0035] 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.

[0036] Thirdly, the present invention also provides the use of the aforementioned Qi-regulating, phlegm-resolving, and tranquilizing ointment in the preparation of a medicament for treating Parkinson's disease complicated with rapid eye movement sleep behavior disorder.

[0037] In some embodiments, the Qi-regulating, phlegm-resolving, and tranquilizing plaster is cut into uniform doses; the Qi-regulating, phlegm-resolving, and tranquilizing plaster is the sole raw material or sole active ingredient of the drug.

[0038] In some embodiments, the drug is a combination formulation comprising at least two active ingredients, and the Qi-regulating, phlegm-resolving, and calming plaster is one of the active ingredients.

[0039] The active ingredient refers to the component that has therapeutic effects on Parkinson's disease complicated with rapid eye movement sleep behavior disorder.

[0040] In Traditional Chinese Medicine (TCM), PD-RBD falls under the categories of "tremor syndrome," "dreamwalking," and "dream terrors," with its pathogenesis generally exhibiting a pattern of "deficiency in the root and excess in the branch, with both deficiency and excess present." Prolonged tremors deplete the patient's essence and blood; or, due to old age and physical weakness, the spleen loses its ability to function properly, leading to insufficient production of qi and blood, resulting in malnourishment of the heart and loss of mental control, manifesting as forgetfulness, excessive dreaming, and nighttime shouting. Spleen deficiency further deprives muscles of nourishment, exacerbating tremors and stiffness. Spleen deficiency also leads to the accumulation of dampness and phlegm, which obstructs the middle jiao (middle burner), disrupting the ascending and descending of qi, causing it to rise upwards and disturb the liver spirit and heart spirit, resulting in nighttime limb flailing, shouting, and even falling out of bed. The obstruction of phlegm and qi disturbs the heart and liver; insufficient heart blood leads to the soul losing its abode, resulting in confused dreams and restless sleep.

[0041] Therefore, this invention takes "deficiency of both heart and spleen, phlegm obstruction and qi stagnation, and restlessness of spirit and soul" as its core principle, and formulates a qi-regulating, phlegm-resolving, and mind-calming ointment. It pioneers a new approach of "three methods working together, with the ointment formula applied gradually": Nourishing the heart and strengthening the spleen to consolidate the foundation—tonifying spleen qi and nourishing heart blood, ensuring a source of biochemical processes, nourishing the spirit, and replenishing muscles; Regulating qi and resolving phlegm to clear stagnation—regulating the qi mechanism of the middle jiao, descending rebellious qi and resolving phlegm, preventing phlegm from disturbing the mind and qi from rising; Calming the mind and stabilizing the spirit to restore the soul—nourishing heart blood, calming the liver spirit, and soothing the mind, ensuring orderly sleep and restful nights. The three methods combined nourish without causing stagnation and eliminate without harming, so that "the heart and spleen are restored, phlegm and qi are completely eliminated, and the spirit and soul are naturally restored."

[0042] The Qi-regulating, phlegm-resolving, and mind-calming ointment breaks through the three major bottlenecks of current treatments: "emphasizing the liver over the spleen," "emphasizing sedation over nourishment," and "short-lived relapses." It shifts from "relieving wind and clearing heat" to "nourishing the heart and strengthening the spleen," moving the treatment target from the "liver" to the "heart and spleen." Through the sweet and warm nourishment of coix seed, yam, and maltose, it rebuilds the body's digestive system, cuts off the source of phlegm, and reverses the predicament of "curing the disease only leads to deficiency." It changes from "heavy sedation" to "regulating Qi and resolving phlegm + calming the mind and stabilizing the spirit" in parallel. With tangerine peel and Buddha's hand, it gently regulates the Qi mechanism, allowing phlegm to dissipate with the Qi, thus relieving the symptoms of "phlegm obstruction and Qi reversal" while avoiding the drawbacks of excessive use of heavy sedative drugs that deplete the body's vital energy. It upgrades from "bitter and cold decoctions" to "sweet and mild ointment." Sesame, rock sugar, and maltose moisturize dryness and nourish the spleen, while also prolonging the efficacy of the medicine, allowing the medicinal properties to continue day and night, and steadily regulating the sleep-wake rhythm. This solves the problems of "rebound after discontinuation of medication and poor compliance," meeting the needs of long-term intervention, safety, and convenience in PD-RBD.

[0043] The Qi-regulating, Phlegm-resolving, and Mind-calming Paste 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 its heavy use directly calms the mind and spirit. Dioscorea opposita and Poria cocos are the assistant ingredients, sweet and neutral in nature, tonifying Qi and Yin, strengthening the spleen and consolidating essence, aiding in the generation of vital energy, and supporting the root cause of "heart and spleen deficiency." Poria cocos strengthens the spleen, eliminates dampness, calms the mind and soothes the nerves, assisting yam in strengthening the spleen and synergizing with jujube seed in calming the nerves, while also resolving phlegm. Coix seed, tangerine peel, and Buddha's hand are the adjuvant ingredients. Coix seed strengthens the spleen, eliminates dampness, clears heat and expels phlegm, assisting Poria cocos in removing dampness to eliminate the source of phlegm; it also benefits the joints and has an auxiliary effect on Parkinson's disease-related limb stiffness. Tangerine peel, bitter, pungent, and warm, regulates Qi, dries dampness, resolves phlegm, and descends rebellious Qi, ensuring that tonification is not stagnant, and phlegm is transformed with Qi. Buddha's hand citron soothes the liver and stomach, regulates qi and resolves phlegm. When combined with dried tangerine peel, it regulates qi, harmonizes the stomach, and reduces nighttime symptoms such as shouting and waving due to qi stagnation. Sesame is used as an adjuvant; its sweet and neutral properties nourish the liver and kidneys, replenish essence and blood, and moisten the intestines to relieve constipation. It also moistens dryness and helps prevent the paste from becoming too greasy and hindering spleen function. Rock sugar and maltose are used as auxiliary ingredients, their sweet and mild properties harmonize the body, correcting the taste for long-term use and also "soothing liver tension and benefiting spleen qi," aligning with the principle of "sweetness to soothe the urgent." The combined effects of these herbs are nourishing without causing stagnation and eliminating without harming the body. The paste is designed for "slow and long-lasting effects, sweet and easy to take," facilitating long-term use while reducing toxicity and correcting the taste, which is suitable for Parkinson's patients who require long-term medication and have fragile gastrointestinal systems.

[0044] The beneficial effects of this invention are as follows:

[0045] (1) The fundamental difference in TCM legislation: The applicant believes that the core pathogenesis of Parkinson's disease combined with rapid eye movement sleep behavior disorder (PD-RBD) is "deficiency of both heart and spleen, phlegm obstruction and qi reversal, and restlessness of spirit and soul". He pioneered the treatment principle of "nourishing the heart and strengthening the spleen, regulating qi and resolving phlegm, and calming the mind and stabilizing the spirit", breaking through the old framework that focuses on calming the liver and extinguishing wind.

[0046] (2) Different drug formulations: This invention uses "sour jujube seed-yam-poria cocos" as the core principal and assistant ingredients, and tangerine peel, Buddha's hand, coix seed, sesame, rock sugar and maltose as adjuvants. The overall formulation nourishes the heart and strengthens the spleen to consolidate the foundation, regulates qi and resolves phlegm to clear stagnation, and calms the mind and stabilizes the spirit to restore the soul. The combined use of these drugs is to nourish without causing stagnation and eliminate without causing harm.

[0047] (3) Dosage form innovation: The present invention adopts the ointment dosage form, which is a solid ointment block made by soaking Chinese medicinal herbs for eight hours, "three decoctions, three filters and three concentrations", collecting the paste, shaping with black sesame seeds, and cooling and cutting at below 20°C. It has the advantages of sweet and moist taste, small dosage, stable absorption, no need for decoction, convenient to carry, and easy to preserve by vacuum packaging.

[0048] In summary, the herbal paste preparation of this invention, formulated from traditional Chinese medicine, targets the core pathogenesis of Parkinson's disease combined with rapid eye movement sleep behavior disorder (PD-RBD) – "deficiency of both heart and spleen, phlegm obstruction and qi stagnation, and restlessness of the spirit and soul." Specifically, it addresses the deficiency as the root cause, phlegm as the manifestation, qi stagnation as the manifestation, and the loss of spirit and soul as the treatment. Through nourishing the heart and strengthening the spleen to consolidate the root, regulating qi and resolving phlegm to clear stagnation, and calming the mind and stabilizing the spirit to restore the soul, the combined approach achieves the goal of replenishing without stagnation and eliminating without harm, thus restoring the heart and spleen, eliminating phlegm and qi stagnation, and restoring the spirit and soul. This solves the problems of existing drugs for treating PD-RBD comorbidities, such as significant side effects, poor taste, low compliance, limited efficacy, and easy relapse and protracted illness. It fulfills the long-term intervention needs of addressing both motor disorders and sleep abnormalities, with high safety, convenient administration, and controllable quality. Attached Figure Description

[0049] Figure 1 The preparation process of the Qi-regulating, phlegm-resolving, and calming ointment of the present invention is as follows. Detailed Implementation

[0050] The specific embodiments of the present invention are described in detail below with reference to the accompanying drawings. The following examples are implemented based on the technical solution of the present invention, and detailed implementation methods are given. However, the scope of protection of the present invention is not limited to the following examples. Unless otherwise specified, all reagents listed below are commercially available.

[0051] The Qi-regulating, phlegm-resolving, and calming ointment for treating Parkinson's disease complicated with RBD of this invention is made from the following raw materials in parts by weight: 9-30 parts of jujube seed, 15-30 parts of yam, 10-15 parts of Poria cocos, 9-30 parts of coix seed, 3-10 parts of dried tangerine peel, 3-10 parts of Buddha's hand, 10-20 parts of sesame, 10-20 parts of rock sugar, and 3-5 parts of maltose.

[0052] The preferred weight ratio range for preparing the Qi-regulating, phlegm-resolving, and calming ointment for treating Parkinson's disease complicated with RBD according to the present invention is as follows: 10-20 parts of jujube seed, 15-25 parts of yam, 10-15 parts of Poria cocos, 15-30 parts of coix seed, 5-10 parts of dried tangerine peel, 5-10 parts of Buddha's hand, 10-20 parts of sesame, 10-20 parts of rock sugar, and 3-5 parts of maltose.

[0053] The optimal weight ratio range for preparing the Qi-regulating, phlegm-resolving, and calming ointment for treating Parkinson's disease complicated with RBD according to the present invention is: 15 parts of jujube seed, 20 parts of yam, 15 parts of poria cocos, 15 parts of coix seed, 9 parts of dried tangerine peel, 9 parts of citron, 15 parts of sesame, 15 parts of rock sugar, and 3 parts of maltose.

[0054] This invention discloses a method for preparing a qi-regulating, phlegm-resolving, and mind-calming herbal paste for treating Parkinson's disease complicated with RBD, comprising the following steps: Take nine herbs: jujube seed, yam, poria cocos, coix seed, tangerine peel, bergamot, sesame, rock sugar, and maltose. Except for sesame, rock sugar, and maltose, place the remaining six herbs in a clean container, add eight times their volume of water (the water level should be approximately 10 cm above the herbs), and soak for at least 8 hours. After soaking, place the container in a decoction machine and decoct for 1.5 hours. Filter the decoction through a 100-mesh sieve for the first time. The resulting liquid... Concentrate at 60℃ and let stand for sedimentation for more than 2 hours; after sedimentation, filter again through a 100-mesh sieve, transfer to a copper pot and concentrate over high heat first, then low heat, adding rock sugar and maltose as needed while stirring constantly; before concentrating to a semi-solid state, perform a third fine filtration, then return to the pot to collect the paste and add a measured amount of black sesame seeds and stir well, while hot, pour into a mold, press to remove air; immediately transfer the mold to a cooling room below 20℃, cover with gauze and let stand to cool for 6 hours until completely solidified; finally, cut the solid paste into uniform portions and vacuum seal for packaging.

[0055] The embodiments of the present invention will be described in detail below:

[0056] Example 1: This example discloses a Qi-regulating, phlegm-resolving, and calming ointment for treating Parkinson's disease complicated with RBD, which is made from the following raw materials in parts by weight: 15 parts of jujube seed, 20 parts of yam, 15 parts of poria cocos, 15 parts of coix seed, 9 parts of dried tangerine peel, 9 parts of citron, 15 parts of sesame, 15 parts of rock sugar, and 3 parts of maltose.

[0057] Example 2: This example discloses a method for preparing the Qi-regulating, phlegm-resolving, and calming plaster used in Example 1, such as... Figure 1 As shown, the preparation method includes the following steps:

[0058] S1. Soaking medicinal herbs

[0059] Place the following six medicinal herbs in a clean container: jujube seed, yam, poria cocos, coix seed, dried tangerine peel, and citron. 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.

[0060] S2. Initial decoction and low-temperature concentration

[0061] 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.

[0062] S3. Secondary filtration and sugar boiling to thicken the paste

[0063] 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.

[0064] S4. Three-stage filtration and addition of sesame seeds

[0065] 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.

[0066] S5. Molding, Cooling, Cutting, and Packaging

[0067] 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.

[0068] Comparative Example 1:

[0069] This comparative example discloses a medicinal paste for treating Parkinson's disease complicated with RBD, which is made from the following components in parts by weight: 12 parts Rehmannia glutinosa, 9 parts Gastrodia elata, 10 parts Paeonia lactiflora, 10 parts Lycium barbarum, 15 parts Coix lacryma-jobi, 9 parts Citrus reticulata peel, 9 parts Citrus medica, 15 parts Sesame seeds, 15 parts Rock sugar, and 3 parts Maltose.

[0070] The preparation method of the above-mentioned herbal paste for treating Parkinson's disease complicated with RBD is as follows:

[0071] Take seven herbs—Rehmannia glutinosa, Gastrodia elata, Paeonia lactiflora, Lycium barbarum, Coix lacryma-jobi, Citrus reticulata peel, and Citrus medica—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.

[0072] Clinical trials were conducted using the plasters obtained in Example 1 and Comparative Example 1, as detailed below:

[0073] 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 180 participants with Parkinson's disease and RBD 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 September 2022 and December 2024 and were willing to follow the treatment plan.

[0074] Western medicine diagnostic criteria:

[0075] The Western medical diagnosis of Parkinson's disease refers to the 2015 MDS diagnostic criteria, which are: Parkinson's syndrome + no absolute exclusion criteria + ≥2 supporting criteria + no warning signs (Red Flegs) .

[0076] Diagnostic criteria for RBD: The diagnostic criteria for RBD in the International Classification of Sleep Disorders 3rd edition (ICSD-3) must meet the following four criteria: (1) recurrent complex motor behaviors related to sleep; (2) these behaviors are recorded by an overnight polysomnography recorder and confirmed to occur during REM sleep, or there is a history of dream-related behaviors assumed to occur during REM sleep; (3) polysomnography shows REM sleep without atonia (RWA); (4) other sleep disorders, mental disorders, neurodegenerative diseases or drug abuse cannot be explained.

[0077] Traditional Chinese Medicine Diagnostic Criteria:

[0078] Referring to the "Standards for Diagnosis and Efficacy Evaluation of Tremor in the Elderly in Traditional Chinese Medicine" formulated at the Third National Symposium on Geriatric Encephalopathy of the Chinese Association of Traditional Chinese Medicine in November 1991:

[0079] 1) The main symptoms are tremors or minimal movement of the head or limbs, limb spasms, and stiffness of the neck and back.

[0080] 2) Concurrent symptoms include a blank expression, forward head posture, slurred speech, incoordination of the upper limbs, sebum overflow, drooling, intellectual decline or mental disorder, and decreased ability to take care of oneself.

[0081] 3) The disease occurs in middle-aged and elderly people.

[0082] 4) Triggers: There may be obvious triggers, such as exposure to external pathogens, poisoning, or brain lesions, or there may be no triggers.

[0083] 5) Chronic onset or progressive worsening. A diagnosis of senile tremor can be made if two or more main symptoms are present, the onset is chronic or progressively worsening, and factors such as age and triggering events are considered.

[0084] Inclusion criteria:

[0085] 1) Age 30-80, gender not limited;

[0086] 2) Meets the diagnostic criteria for primary Parkinson's disease as revised by the Movement Disorder Society (MDS) in 2015;

[0087] 3) Hoehn Yahr's staging period is ≤3 stages;

[0088] 4) A score of ≥17 on the Rapid Eye Movement Sleep Behavior Disorder Scale (RBDQ-HK) of the Chinese University of Hong Kong, and confirmed by polysomnography (PSG) to meet the diagnostic criteria for RBD.

[0089] 5) For subjects who have already received anti-Parkinson's disease treatment (levodopa preparations, dopamine receptor agonists, monoamine oxidase inhibitors, catechol-O-methyltransferase inhibitors, anticholinergic drugs, etc.), the dosage of the anti-Parkinson's disease drug must have been relatively stable for at least 3 months prior to this clinical trial, and there must be no clear plan to change the existing treatment regimen in the next 3 months.

[0090] 6) Participation is voluntary, and informed consent must be signed.

[0091] Exclusion criteria:

[0092] 1) Patients with Parkinson's disease syndrome or Parkinson's disease plus syndrome;

[0093] 2) Active depression or psychosis and / or treatment with antidepressants or antipsychotics;

[0094] 3) Severe sequelae of stroke and diseases of other systems such as the heart, lungs, liver, and kidneys;

[0095] 4) History of drug abuse or alcoholism;

[0096] 5) Patients who are currently participating in other clinical studies or who have participated in other clinical studies within the past 30 days.

[0097] Treatment plan:

[0098] 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.

[0099] The treatment group received the Qi-regulating, phlegm-resolving, and calming ointment obtained in Example 1, twice daily, one ointment each time, for 12 weeks.

[0100] The control group received the herbal paste obtained in control group 1, twice a day, one piece each time, for 12 weeks.

[0101] Observation indicators: Polysomnography, Rapid Eye Movement Sleep Behavior Disorder Scale of the Chinese University of Hong Kong (RBDQ-HK), Parkinson's Disease Sleep Scale (PDSS), Pittsburgh Sleep Quality Index (PSQI), Unified Parkinson's Disease Rating Scale (UPDRS), and Autonomic Nervous System Function Scale (SCOPA-AUT).

[0102] Research findings:

[0103] Comparison of therapeutic effects between Example 1 and Comparative Example 1

[0104] As shown in Table 1, the Qi-regulating, phlegm-resolving, and calming ointment of the present invention improves the RBDHK, PDSS, PSQI, UPDRS, and SCOPA-AUT scores of Parkinson's disease complicated with RBD, increases sleep efficiency and deep sleep time, reduces sleep fragmentation, and improves REM intensity and density, which is superior to the ointment obtained in Comparative Example 1. It can safely and effectively treat Parkinson's disease complicated with RBD.

[0105] Experimental Example 1: Efficacy Test

[0106] The efficacy of the traditional Chinese medicine composition of the Qi-regulating, phlegm-resolving, and calming ointment of this invention on mice with Parkinson's disease and circadian rhythm disorder:

[0107] Grouping and Modeling:

[0108] Fifty SPF-grade male C57BL / 6 mice were randomly divided into four groups: a control group, a Parkinson's disease model group (PD group), a Parkinson's disease circadian rhythm disorder group (CRSD+PD group), a positive drug intervention group (L-Dopa group), and a group receiving a combination of Qi-regulating, phlegm-resolving, and calming plaster and positive drug intervention (LQHTP group), with five mice in each group. Mice in each group were placed in a spontaneous activity box with a timer-controlled switch to regulate the circadian rhythm. The control and PD groups were placed in a 12hL / 12hD environment (photocycle 7:00-19:00, dark cycle 19:00-7:00, illuminance ≈100 lux). The CRSD+PD group, L-Dopa group, and LQHTP group were placed in a 24h dark environment for 50 days to simulate the circadian rhythm disorder in the prodromal phase of Parkinson's disease. The disappearance of the nocturnal circadian rhythm fluctuation in mice indicated successful modeling. On day 51, the PD group, CRSD+PD group, L-Dopa group, and LQHTP group were intraperitoneally injected with MPTP (8 mg / kg) once daily for 28 consecutive days to establish a Parkinson's disease model. The control group received the same dose of solvent as a control. On day 77, the mouse pole climbing test and rotarod test were performed. When the mouse swayed or paused during pole climbing, and the time spent on the rotarod decreased, it indicated that the model was successfully established.

[0109] Intervention method: Prophylactic administration was used. On day 1 of MPTP modeling, the LQHTP group was given a Qi-regulating, phlegm-resolving, and calming formula by gavage at 10:00 a.m. On day 78, after successful PD modeling, both the LQHTP group and the L-Dopa group were given L-Dopa (10 mg / kg) by intraperitoneal injection at 10:00 a.m. for 18 consecutive days.

[0110] Long-term spontaneous activity experiment: Spontaneous activity boxes were placed inside standard soundproof enclosures. A day-night cycle was implemented using a timer switch. A suitable amount of bedding material was placed inside the standard soundproof enclosures. To simulate the social behavior of mice, five mice were placed in each activity box, with free access to food and water. An industrial infrared camera was used to record the mice's activities for 24 hours, and EthoVision XT software was used to calculate the mice's activity distance and trajectory based on the collected data.

[0111] Pole climbing test: Place the mouse head-up at the top of a pole. A normal mouse will naturally orient itself downwards and descend the pole continuously to the ground, returning to its cage. Record the latency of the animal's spontaneous turning (Tturn) and the total time required to descend to the bottom of the pole (Ttotal).

[0112] Rotary bar experiment: Mice were placed one by one on a rotundus bar, facing away from the direction of rotation. The rotundus was started, and after adaptation at 4 rpm, the speed was increased from 4 rpm to 30 rpm within 6 minutes. The mice's movement was observed, including the balance time on the bar and the adaptive rotational speed.

[0113] Research findings:

[0114] In rotundus and pole climbing behavioral tests, the CRSD+PD model group mice showed a significant decrease in dwell time on the rotundus and maximum tolerated rotation speed, and a significant increase in the latency of automatic turning and the total time taken in the pole climbing experiment. After LQHTP intervention, the above motor impairment indicators were significantly reversed, and the improvement was better than that of the L-DOPA group alone, suggesting that LQHTP can more effectively alleviate motor dysfunction in mice with Parkinson's disease and circadian rhythm disorder.

[0115] Long-term spontaneous activity monitoring showed that after modeling, the total activity distance of mice decreased sharply and their circadian rhythm was disrupted, mainly manifested as a sharp decrease in dark-periodic activity and a reversal in photoperiodic activity. Cosine curve analysis indicated the disappearance of the diurnal rhythm. LQHTP combined with L-DOPA treatment not only simultaneously increased both photoperiodic and dark-periodic activity, but also significantly restored nighttime activity and normalized rhythm parameters, while L-DOPA alone was almost ineffective. The results indicate that LQHTP not only improves motor symptoms of PD, but also reshapes the natural diurnal rhythm, showing superior efficacy compared to traditional L-DOPA.

Claims

1. A qi-regulating, phlegm-resolving, and tranquilizing plaster, characterized in that, It is made from the following ingredients in parts by weight: 9-30 parts of jujube seed, 15-30 parts of yam, 10-15 parts of poria cocos, 9-30 parts of coix seed, 3-10 parts of dried tangerine peel, 3-10 parts of bergamot, 10-20 parts of sesame seeds, 10-20 parts of rock sugar, and 3-5 parts of maltose.

2. The Qi-regulating, phlegm-resolving, and tranquilizing plaster according to claim 1, characterized in that, It is made from the following ingredients in parts by weight: 10-20 parts of jujube seed, 15-25 parts of yam, 10-15 parts of poria cocos, 15-30 parts of coix seed, 5-10 parts of dried tangerine peel, 5-10 parts of bergamot, 10-20 parts of sesame seeds, 10-20 parts of rock sugar, and 3-5 parts of maltose.

3. The Qi-regulating, phlegm-resolving, and tranquilizing plaster according to claim 1, characterized in that, It is made from the following ingredients in parts by weight: 15 parts jujube seed, 20 parts yam, 15 parts poria cocos, 15 parts coix seed, 9 parts dried tangerine peel, 9 parts bergamot, 15 parts sesame seeds, 15 parts rock sugar, and 3 parts maltose.

4. The Qi-regulating, phlegm-resolving, and tranquilizing plaster 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, yam, poria cocos, coix seed, tangerine peel and citron, 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 is thick. When it is concentrated to a semi-solid state, 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-regulating, phlegm-resolving, and tranquilizing plaster 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, yam, poria cocos, coix seed, tangerine peel and citron, 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 is thick. When it is concentrated to a semi-solid state, 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 six 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 first filtered through a 100-mesh sieve, and 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 through a 100-mesh sieve for the second time, and then transferred to a copper pot for concentration. 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 hot using 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 location is a cooling room with a temperature below 20°C.

7. The use of the Qi-regulating, phlegm-resolving, and tranquilizing ointment according to any one of claims 1-4 in the preparation of a medicament for treating Parkinson's disease complicated with REM sleep behavior disorder.

8. The application according to claim 7, characterized in that, The Qi-regulating, phlegm-resolving, and tranquilizing plaster is cut into uniform portions; the Qi-regulating, phlegm-resolving, and tranquilizing plaster 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-regulating, phlegm-resolving, and calming plaster is one of the active ingredients.

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