A traditional Chinese medicine composition for treating insomnia based on a modification of Zhang Zhongjing's Wumei Pill

Abstract

This invention provides a composition comprising: 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica root, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis root, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of polygonum multiflorum stem, 40-60 parts by weight of monkey head mushroom, 3-8 parts by weight of polygala root, and 5-15 parts by weight of poria cocos (a traditional Chinese medicine composition). Further, the composition comprises: 20-40 parts by weight of hydrolyzed milk protein, 20-40 parts by weight of fish collagen peptide, and 20-40 parts by weight of soybean peptide (a biological product). This invention also provides pharmaceutical preparations (especially pills) comprising the above composition, biological products, and methods for preparing the same. The composition has a significant effect on improving sleep and has broad application prospects.

Description

Technical Field

[0001] This invention relates to the fields of biomedicine and biopharmaceutical manufacturing, specifically to a composition for treating insomnia, its application, and its manufacturing method. Background Technology

[0002] Ume pills are typically yellowish-brown water pills or large, dark brown to black honey pills; they taste bitter and sour (water pills); or slightly sweet, bitter, and sour (large honey pills). Ume pills usually contain dried plum, Sichuan pepper, asarum, aconite, dried ginger, cinnamon twig, ginseng, and angelica.

[0003] The indications for Wumei Pills include ascariasis (a condition caused by ascariasis resulting in acute abdominal pain and cold extremities) and chronic dysentery (recurrent dysentery).

[0004] Insomnia is a common sleep disorder, mainly characterized by difficulty falling asleep, difficulty maintaining sleep, early awakening, and decreased sleep quality. According to global epidemiological survey data, approximately 10% to 30% of adults worldwide suffer from chronic insomnia, with some countries reaching as high as 40%. Women, the elderly, and urban residents are high-risk groups. In China, studies have shown that over 300 million people have varying degrees of sleep disorders, of which about 15% are clinically chronic insomnia. The incidence of insomnia increases significantly with age, with over 50% of people over 65 years of age experiencing sleep problems.

[0005] Insomnia not only reduces quality of life but also causes significant harm to physical and mental health. The harms of insomnia include: cognitive impairment, affecting attention, memory, and decision-making abilities, increasing the risk of accidents; increased risk of psychological disorders, with long-term insomniacs having a 2-3 times higher risk of anxiety and depression; increased burden on the cardiovascular system, increasing the risk of hypertension, coronary heart disease, stroke, and other diseases; decreased immune function, as insomnia is closely related to chronic inflammation and weakened immunity; metabolic disorders and obesity, as long-term insomnia easily leads to insulin resistance and metabolic syndrome; increased cancer risk, with some studies suggesting that chronic sleep disorders may be related to breast cancer, colorectal cancer, etc.; and high social and economic costs, including decreased productivity, increased medical expenses, and higher traffic accident rates, creating a significant social burden.

[0006] Despite the high incidence and wide impact of insomnia, current treatment methods still have many problems, and there is an urgent need for safer, more effective, and more adherent medications.

[0007] Western medicines have issues with dependence and side effects, benzodiazepines Benzodiazepines (such as diazepam and lorazepam) have a rapid onset of action, but are highly addictive, causing drowsiness and memory impairment; non-benzodiazepines... Long-term use of certain drugs (such as zolpidem) can lead to tolerance and complex side effects; the use of antidepressants and antihistamines for insomnia treatment is often "off-label" and lacks specificity. Summary of the Invention

[0008] The inventors improved the types and proportions of raw materials based on Zhang Zhongjing's classic formula, Wumei Wan, to obtain a superior composition (traditional Chinese medicine composition). The formulation design focuses more on nourishing the heart and calming the mind, and harmonizing the internal organs. Unbound by theoretical constraints, Polygonum multiflorum (Ye Jiao Teng) is a key herb for calming the mind; when combined with Polygala tenuifolia (Yuan Zhi), it harmonizes the heart and kidneys, enhancing intervention for anxiety and difficulty falling asleep; Poria cocos (Fu Shen) strengthens the spleen and calms the mind, regulating the central nervous system. This invention does not use processed Aconitum carmichaelii (Pao Fu Zi), thus avoiding its pungent, hot, and drying properties, reducing interference with patients suffering from insomnia due to deficiency and restlessness. The ratio of Hericium erinaceus (Hericium erinaceus) and japonica rice is reasonable: Hericium erinaceus can improve gastrointestinal function and regulate emotions; traditional Chinese medicine believes that an upset stomach leads to restless sleep, and its higher proportion is beneficial for the coordination of the digestive system and sleep rhythm.

[0009] Subsequently, the inventors discovered that further formulation with hydrolyzed milk protein, fish collagen peptides, and soybean peptides (resulting in a biological drug) could further improve sleep. The hypothetical reasons are as follows: peptide nutrients are rich in amino acids that promote neurotransmitter synthesis; hydrolyzed milk protein contains abundant L-tryptophan and GABA-like peptides, which help promote the synthesis of 5-HT and melatonin; fish collagen peptides have a calming effect on the central nervous system and relieve anxiety; soybean peptides contain arginine and tyrosine, which can enhance memory and improve sleep quality; traditional Chinese medicine ingredients are mostly polysaccharides, glycosides, volatile oils, etc., which are absorbed slowly through the digestive tract; small molecule peptides are absorbed rapidly and can enter the bloodstream shortly after ingestion, providing immediate support in terms of onset time and initial sedation, laying the foundation for the slow-acting effect of traditional Chinese medicine. There may be multiple synergistic pathways involved. In traditional Chinese medicine, Polygonum multiflorum, Polygala tenuifolia, and Poria cocos act on the central nervous system, while peptides promote the synthesis of neurotransmitters. Phellodendron amurense and Coptis chinensis regulate hormone rhythms, and peptide nutrition enhances the regulatory basis. Hericium erinaceus and Lilium brownii improve the gastrointestinal environment, and together with peptides, they regulate the flora and improve the conversion and utilization rate of tryptophan in the intestine.

[0010] Therefore, the present invention is obtained.

[0011] In a first aspect of the invention, a composition is provided comprising 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum stem, 40-60 parts by weight of monkey head mushroom, 3-8 parts by weight of polygala tenuifolia, and 5-15 parts by weight of poria cocos.

[0012] In some embodiments of the present invention, the composition comprises: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, and 10 parts by weight of poria cocos.

[0013] In some embodiments of the present invention, the composition comprises the following: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, and 10 parts by weight of poria cocos.

[0014] In some embodiments of the present invention, the preparation method of the composition is as follows: Take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, and 30 parts by weight of poria cocos; wash and pulverize; add 30 parts by weight of bitter wine and 15 parts by weight of honey, mix evenly, and dry to obtain the final product.

[0015] In some embodiments of the present invention, the preparation method of the composition is as follows: Take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, and 30 parts by weight of poria cocos; wash them with clean water, dry them with hot air at 40°C, chop them, mix them evenly, and pulverize them with a pulverizer until the average particle size is 150-180 micrometers; add 30 parts by weight of bitter wine and 15 parts by weight of honey, stir quickly to mix evenly, and let them air dry naturally to obtain the final product.

[0016] In some embodiments of the present invention, the preparation method of the composition is as described in any of Examples 1 of the present invention.

[0017] In some embodiments of the present invention, the composition comprises: 20-40 parts by weight of hydrolyzed milk protein, 20-40 parts by weight of fish collagen peptide, and 20-40 parts by weight of soybean peptide.

[0018] In some embodiments of the present invention, the composition comprises: 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide.

[0019] In some embodiments of the present invention, the plum is a dried, nearly mature fruit.

[0020] In some embodiments of the present invention, the cassia branch is a dried branch.

[0021] In some embodiments of the present invention, the ginseng is a dried stem.

[0022] In some embodiments of the present invention, the Angelica sinensis is the dried root.

[0023] In some embodiments of the present invention, the Asarum is the dried whole herb.

[0024] In some embodiments of the present invention, the dried ginger is a dried rhizome.

[0025] In some embodiments of the present invention, the Sichuan pepper is a dried, mature pericarp.

[0026] In some embodiments of the present invention, the cork tree bark is dried bark.

[0027] In some embodiments of the present invention, the Coptis chinensis (dried rhizome with fibrous roots removed) is used.

[0028] In some embodiments of the present invention, the bitter liquor is sorghum vinegar; further, the sorghum vinegar is Shiquan brand sorghum vinegar.

[0029] In some embodiments of the present invention, the japonica rice is dried japonica rice kernels.

[0030] In some embodiments of the present invention, the lily is a dried bulb.

[0031] In some embodiments of the present invention, the Polygonum multiflorum is a dried stem.

[0032] In some embodiments of the present invention, the Hericium erinaceus is a dried fruiting body.

[0033] In some embodiments of the present invention, the Polygala tenuifolia is dried root bark.

[0034] In some embodiments of the present invention, the Poria cocos is the white part of a dried sclerotium containing pine root.

[0035] In some embodiments of the present invention, the hydrolyzed milk protein is purchased from Dulai Biotechnology, product number CM0034.

[0036] In some embodiments of the present invention, the fish collagen peptides are purchased from Aladdin, catalog number F573426.

[0037] In some embodiments of the present invention, the soybean peptides are purchased from Beptai.

[0038] In a second aspect of the invention, a composition is provided, the composition comprising: 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum stem, 40-60 parts by weight of monkey head mushroom, 3-8 parts by weight of polygala tenuifolia, 5-15 parts by weight of poria cocos, 20-40 parts by weight of hydrolyzed milk protein, 20-40 parts by weight of fish collagen peptide, and 20-40 parts by weight of soybean peptide.

[0039] In some embodiments of the present invention, the composition comprises: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, 10 parts by weight of poria cocos, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide.

[0040] In some embodiments of the present invention, the composition comprises the following: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, 10 parts by weight of poria cocos, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide.

[0041] In some embodiments of the present invention, the preparation method of the composition is as follows: take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, 30 parts by weight of poria cocos, 30 parts by weight of bitter wine, 15 parts by weight of honey, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide; mix evenly to obtain the final product.

[0042] In some embodiments of the present invention, the preparation method of the composition is as follows: Take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, and 30 parts by weight of poria cocos; wash them with clean water, dry them with hot air at 40°C, chop them, mix them evenly, and pulverize them with a pulverizer until the average particle size is 150-180 micrometers; add 30 parts by weight of bitter wine and 15 parts by weight of honey, stir quickly to mix evenly, and let them air dry naturally; add 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide; mix evenly to obtain the final product.

[0043] In some embodiments of the present invention, the plum is a dried, nearly mature fruit.

[0044] In some embodiments of the present invention, the cassia branch is a dried branch.

[0045] In some embodiments of the present invention, the ginseng is a dried stem.

[0046] In some embodiments of the present invention, the Angelica sinensis is the dried root.

[0047] In some embodiments of the present invention, the Asarum is the dried whole herb.

[0048] In some embodiments of the present invention, the dried ginger is a dried rhizome.

[0049] In some embodiments of the present invention, the Sichuan pepper is a dried, mature pericarp.

[0050] In some embodiments of the present invention, the cork tree bark is dried bark.

[0051] In some embodiments of the present invention, the Coptis chinensis (dried rhizome with fibrous roots removed) is used.

[0052] In some embodiments of the present invention, the bitter liquor is sorghum vinegar; further, the sorghum vinegar is Shiquan brand sorghum vinegar.

[0053] In some embodiments of the present invention, the japonica rice is dried japonica rice kernels.

[0054] In some embodiments of the present invention, the lily is a dried bulb.

[0055] In some embodiments of the present invention, the Polygonum multiflorum is a dried stem.

[0056] In some embodiments of the present invention, the Hericium erinaceus is a dried fruiting body.

[0057] In some embodiments of the present invention, the Polygala tenuifolia is dried root bark.

[0058] In some embodiments of the present invention, the Poria cocos is the white part of a dried sclerotium containing pine root.

[0059] In some embodiments of the present invention, the hydrolyzed milk protein is purchased from Dulai Biotechnology, product number CM0034.

[0060] In some embodiments of the present invention, the fish collagen peptides are purchased from Aladdin, catalog number F573426.

[0061] In some embodiments of the present invention, the soybean peptides are purchased from Beptai.

[0062] In some embodiments of the present invention, the preparation method of the composition is as described in any of Examples 1 of the present invention.

[0063] In a third aspect of the invention, a pharmaceutical preparation is provided, the pharmaceutical preparation comprising the composition described herein.

[0064] In some embodiments of the present invention, the pharmaceutical preparations include, but are not limited to: pills, granules, tablets, capsules, decoctions, powders, ointments, honey pills, water pills, concentrated pills, drop pills, medicated wines, tinctures, mixtures, pastes, suppositories, powders, liquid preparations, injections, granules, external washes, enemas, sprays, oral liquids, lozenges, sublingual tablets, sustained-release preparations, transdermal patches, mucosal membranes, and traditional Chinese medicine plasters.

[0065] In some embodiments of the present invention, the pharmaceutical preparation is a pill.

[0066] In some embodiments of the present invention, the pills are selected from: water pills, honey pills, concentrated pills, paste pills, water-honey pills, wax pills, coated pills, drop pills, small pills, large pills, dextrin pills, premixed pills, instant pills, and sustained-release pills.

[0067] In some embodiments of the present invention, the pharmaceutical preparation comprises pharmaceutically acceptable excipients.

[0068] In some embodiments of the present invention, the excipients are selected from: honey, dextrin, starch, gelatin, gum arabic, microcrystalline cellulose, lactose, sucrose, glucose, fructose, soluble starch, sodium carboxymethyl starch, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, povidone, crospovidone, polyvinylpyrrolidone, hydroxypropyl cellulose, ethanol, glycerin, propylene glycol, sorbitol, maltodextrin, aspartame, magnesium stearate, talc, stearic acid, silicon dioxide, anhydrous silicic acid, polyethylene glycol, polyoxyethylene hydrogenated castor oil, glyceryl monostearate, sodium lactate, sodium citrate, dicalcium phosphate, calcium dihydrogen phosphate, calcium sulfate, calcium carbonate, magnesium oxide, titanium dioxide, beeswax, carnauba wax, fatty alcohol polyoxyethylene ether, edible flavor, menthol, vanillin, edible color, caramel color, red yeast rice, and carmine.

[0069] In some embodiments of the present invention, the preparation method of the pills is as follows: the composition of the present invention is mixed with an appropriate amount of water to form a soft wet material, which is then stirred, sieved, rolled into pills, and dried at low temperature to obtain water pills.

[0070] In some embodiments of the present invention, the pills are prepared by mixing the composition of the present invention with an appropriate amount of honey to form plastic pills, which are then formed by hand or machine, air-dried, and dried to obtain honey pills.

[0071] In some embodiments of the present invention, the preparation method of the pills is as follows: the composition of the present invention is prepared into a dry concentrated extract powder, an appropriate amount of excipients are added and mixed evenly, then the mixture is shaped into pills and dried to obtain concentrated pills.

[0072] In some embodiments of the present invention, the preparation method of the pills is as follows: the composition of the present invention is mixed with a dextrin solution to form a moist and uniform soft material, which is then extruded, pelletized, and dried to obtain paste pills.

[0073] In some embodiments of the present invention, the pills are prepared by mixing the composition of the present invention with an appropriate amount of purified water to form water pills, and then rolling them with honey after shaping to form a honey-like coating on their surface, thus obtaining water-honey pills.

[0074] In some embodiments of the present invention, the pills are prepared by making the composition of the present invention into water pills or concentrated pills, and then coating them with a thin film coating or sugar coating to obtain coated pills.

[0075] In some embodiments of the present invention, the pills are prepared by melting or dissolving the composition of the present invention and then dripping it into a condensing medium to form pills.

[0076] In some embodiments of the present invention, the pills are prepared by coating their surface with beeswax or other pharmaceutically acceptable hydrophobic materials after obtaining the water pills or concentrated pills of the present invention, thereby forming a controlled-release structure, thus obtaining wax pills.

[0077] In some embodiments of the present invention, the pills are prepared by mixing the composition of the present invention with palatable excipients such as soluble starch, lactose, and edible flavoring, and preparing small-dose water-honey pills or drop pills by wet granulation, which have the characteristics of good taste and easy swallowing, and are suitable for children.

[0078] In some embodiments of the present invention, the pills are prepared by blending the composition of the present invention with sustained-release excipients such as hydroxypropyl methylcellulose, carnauba wax, beeswax, and fatty alcohol polyoxyethylene ether to prepare a sustained-release pill with a coating structure, which can achieve sustained release of drug efficacy and is suitable for chronic disease patients who need to maintain a constant blood drug concentration.

[0079] In some embodiments of the present invention, the pills are prepared by mixing the composition of the present invention with a disintegration promoter such as crospovidone or sodium carboxymethyl starch, and then forming the mixture into pills. The particle structure is optimized by a special process so that the pills can be rapidly dissolved in water, making them suitable for rapid-acting drug administration or for patients with difficulty swallowing.

[0080] In some embodiments of the present invention, the preparation method of the pills is to premix the powder of the composition of the present invention with excipients and then perform a hot melt drop pelleting process, dropping the mixture into a cooling liquid (such as liquid paraffin) to form the pellets. The resulting pellets have small particle size and are absorbed quickly, making them suitable for emergency treatment scenarios that require rapid onset of action.

[0081] In some embodiments of the present invention, the pills are prepared by mixing the composition of the present invention with a binder and a flavoring agent, and then using a low-temperature slow rolling process to obtain low-hardness pills that are easy to chew or hold in the mouth, and are suitable for children, the elderly and people with swallowing disorders.

[0082] In some embodiments of the present invention, the preparation method of the pills is to mix the composition of the present invention with anti-hygroscopic excipients such as silica, microcrystalline cellulose, anhydrous lactose, etc., and form pills by a low moisture content dry pill-making process or a vacuum drying process. The resulting pills have excellent moisture resistance and are suitable for storage in high temperature and high humidity environments.

[0083] In some embodiments of the present invention, the pills are prepared by mixing the composition of the present invention with sugar-free sweeteners such as sorbitol, mannitol or aspartame, and then using a wet pelleting method or a dripping method to obtain sucrose-free pills, which are suitable for diabetic patients and people who need to control their sugar intake.

[0084] In some embodiments of the present invention, the pill is prepared by coating the composition of the present invention in an acid-resistant coating material, such as acrylic resin, cellulose acetate phthalate, etc., to form an enteric-coated pill, so that the drug is not released in the stomach but is released at a specific point in the small intestine, which is suitable for drugs that are highly irritating to the stomach or need to be absorbed by the intestine.

[0085] In some embodiments of the present invention, the pills are prepared by compressing the composition of the present invention together with wax materials (such as beeswax, carnauba wax), hydroxypropyl methylcellulose, ethylcellulose and other sustained-release matrices into pills, and achieving sustained-release at night through structural controlled-release technology, which is suitable for patients who need to maintain the efficacy of the drug for an entire night (such as insomnia drugs or cardiovascular drugs).

[0086] In some embodiments of the present invention, the preparation method of the pill is to preform the composition of the present invention into a pill core, and use multi-layer coating technology to coat it with a flavor masking layer and a sustained-release layer, which can both mask the taste of the medicine and adjust the release rate, and is suitable for use scenarios where the taste is sensitive or a two-phase release is required.

[0087] In some embodiments of the present invention, the pills are prepared by optimizing the dosage of the components with potentially high liver and kidney metabolic load in the composition of the present invention, and using low-toxicity, highly biocompatible excipients (such as microcrystalline cellulose, polyethylene glycol, sodium carboxymethyl cellulose), followed by wet pill making and low-temperature drying, which is suitable for patients with limited liver or kidney function.

[0088] In some embodiments of the present invention, the preparation method of the pills is as follows: the composition of the present invention is adjusted in terms of dosage according to veterinary drug specifications, and palatable and storable excipients (such as dextrin, maltodextrin, flavorings, etc.) are selected to prepare pills suitable for animal ingestion, which is applicable to the development of oral dosage forms of traditional Chinese veterinary medicine.

[0089] In some embodiments of the present invention, the preparation method of the pills is to mix the composition of the present invention with excipients with low moisture and low migration risk, and to use cold pressing or drip condensation to form pills, supplemented by vacuum drying and moisture-proof coating. The resulting preparation is convenient for long-distance transportation in high-temperature areas and can be carried by hand, and is suitable for field operations or emergency medicine storage scenarios.

[0090] In some embodiments of the present invention, the preparation method of the pills is as follows: the composition of the present invention is subjected to standardized pulverization, sieving, mixing and pill formation operations in accordance with the standards of the Chinese Pharmacopoeia or the pharmacopoeia of the target country of export, and then dried and packaged in a clean environment that meets GMP requirements. The resulting pills have good batch-to-batch consistency and regulatory compliance, and are suitable for international registration and export sales.

[0091] In some embodiments of the present invention, the preparation method of the pills is to prepare oral-absorbable sustained-release microspheres by combining the composition of the present invention with excipients that have the functions of solubilizing, aiding absorption or enhancing transdermal absorption, and to improve their stability by a moisture control process, which is suitable for targeted treatment of patients with chronic diseases or transdermal absorption research scenarios.

[0092] In a preferred embodiment of the present invention, the method for preparing the pills includes the following steps:

[0093] Raw material crushing and sieving: Weigh the raw materials of the traditional Chinese medicine composition of the present invention according to a predetermined ratio, crush them with a crusher until they pass through an 80-mesh sieve, and mix them evenly for later use;

[0094] Mixing and preparing wet material: Add the above-mentioned powder to an appropriate amount of excipients (such as dextrin, honey, purified water, etc.), and slowly add the binder (such as 10% dextrin solution or honey water) to the mixer while stirring until a uniform and moderately moist soft wet material is obtained.

[0095] Pelletizing: After the wet material is extruded and cut into sections, it is rolled into pellets on a pelletizing machine, or pellets are made by hand rolling to obtain uniformly shaped pills.

[0096] Drying: Place the pills in an oven and dry at 40℃~60℃ for 4~8 hours until the moisture content of the pills is less than 10%, and the dried finished pills are obtained.

[0097] Sieving and Coating (if required): After drying, defective pellets are sieved out and can be further coated with film, sugar coating or wax coating to improve appearance and controlled release performance;

[0098] Packaging: The obtained pills shall be packaged according to the prescribed standards and stored in a sealed, light-proof, and dry place.

[0099] In some embodiments of the present invention, the composition comprises 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum, 40-60 parts by weight of monkey head mushroom, 3-8 parts by weight of polygala tenuifolia, and 5-15 parts by weight of poria cocos.

[0100] In some embodiments of the present invention, the composition comprises: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, and 10 parts by weight of poria cocos.

[0101] In some embodiments of the present invention, the pharmaceutical preparation comprises a composition comprising: 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum stem, 40-60 parts by weight of Hericium erinaceus, 3-8 parts by weight of Polygala tenuifolia, 5-15 parts by weight of Poria cocos, 20-40 parts by weight of hydrolyzed milk protein, 20-40 parts by weight of fish collagen peptide, and 20-40 parts by weight of soybean peptide.

[0102] In some embodiments of the present invention, the pharmaceutical preparation comprises a composition comprising: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, 10 parts by weight of poria cocos, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide.

[0103] In some embodiments of the present invention, the preparation method of the composition is as described in any composition of Example 1 of the present invention.

[0104] In some embodiments of the present invention, the preparation method of the pharmaceutical formulation is as described in any of the embodiments of the present invention.

[0105] In a fourth aspect of the invention, the use of the composition of the invention in the preparation of a medicament for improving sleep is provided.

[0106] In some embodiments of the present invention, the use of the composition in the preparation of a medicament for improving sleep is provided, said composition comprising 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum stem, 40-60 parts by weight of monkey head mushroom, 3-8 parts by weight of polygala tenuifolia, and 5-15 parts by weight of poria cocos.

[0107] In some embodiments of the present invention, the use of the composition in the preparation of a medicament for improving sleep is provided, said composition comprising: 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum stem, 40-60 parts by weight of monkey head mushroom, 3-8 parts by weight of polygala tenuifolia, and 5-15 parts by weight of poria cocos.

[0108] In some embodiments of the present invention, the use of the composition in the preparation of a medicament for improving sleep is provided, said composition comprising: 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum stem, 40-60 parts by weight of Hericium erinaceus, 3-8 parts by weight of Polygala tenuifolia, 5-15 parts by weight of Poria cocos, 20-40 parts by weight of hydrolyzed milk protein, 20-40 parts by weight of fish collagen peptide, and 20-40 parts by weight of soybean peptide.

[0109] In some embodiments of the present invention, the use of the composition in the preparation of a medicament for improving sleep is provided, said composition comprising: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, 10 parts by weight of poria cocos, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide.

[0110] In some embodiments of the present invention, the improvement of sleep is to promote sleep onset and / or prolong sleep duration.

[0111] In some embodiments of the present invention, the improvement of sleep is to promote sleep onset.

[0112] In some embodiments of the present invention, improving sleep means prolonging sleep time.

[0113] In some embodiments of the present invention, the improvement of sleep is to increase serum 5-HT levels.

[0114] In a fifth aspect of the invention, a biological medicine is provided, the biological medicine comprising a composition comprising: 5-15 parts by weight of dried plum, 10-20 parts by weight of cinnamon twig, 10-20 parts by weight of ginseng, 3-8 parts by weight of angelica, 5-15 parts by weight of asarum, 10-30 parts by weight of dried ginger, 5-15 parts by weight of Sichuan pepper, 5-15 parts by weight of phellodendron bark, 3-8 parts by weight of coptis, 20-40 parts by weight of bitter wine, 20-30 parts by weight of japonica rice, 10-20 parts by weight of honey, 3-8 parts by weight of lily bulb, 40-60 parts by weight of Polygonum multiflorum stem, 40-60 parts by weight of Hericium erinaceus, 3-8 parts by weight of Polygala tenuifolia, 5-15 parts by weight of Poria cocos, 20-40 parts by weight of hydrolyzed milk protein, 20-40 parts by weight of fish collagen peptide, and 20-40 parts by weight of soybean peptide.

[0115] In some embodiments of the present invention, the biological drug comprises a composition comprising: 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 5 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 10 parts by weight of phellodendron bark, 5 parts by weight of coptis, 30 parts by weight of bitter wine, 25 parts by weight of japonica rice, 15 parts by weight of honey, 5 parts by weight of lily bulb, 50 parts by weight of Polygonum multiflorum, 50 parts by weight of monkey head mushroom, 5 parts by weight of polygala tenuifolia, 10 parts by weight of poria cocos, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide.

[0116] In a sixth aspect of the present invention, a method for manufacturing a biological drug is provided, the method comprising: taking 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, 30 parts by weight of poria cocos, 30 parts by weight of bitter wine, 15 parts by weight of honey, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide; mixing them evenly to obtain the product.

[0117] The technical effects of the present invention are as follows: The composition of the present invention can significantly shorten the sleep latency and prolong the sleep time, which is superior to the prior art and achieves unexpected technical effects. Furthermore, the composition of the present invention is very safe, has few side effects, is simple to prepare, and has low preparation cost. Detailed Implementation

[0118] The raw materials used in the following examples are: dried nearly mature plum, dried cinnamon twigs, dried ginseng stems, dried angelica root, dried asarum root, dried ginger rhizome, dried mature fruit peel of Sichuan pepper, dried phellodendron bark, dried rhizome of coptis root (with fibrous roots removed), and bitter wine (sorghum vinegar). ), japonica rice (dried japonica rice kernels), honey, lily bulbs (dried bulbs), Polygonum multiflorum (dried stems), Hericium erinaceus (dried fruiting bodies), Polygala tenuifolia (dried root bark), Poria cocos (dried sclerotium with the white part containing pine root), hydrolyzed milk protein (Dulai Biotechnology, product number CM0034), fish collagen peptides (Aladdin, product number F573426), soybean peptides (Beputai).

[0119] Example

[0120] Example 1:

[0121] Take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, and 30 parts by weight of poria cocos; wash them separately with clean water, dry them with hot air at 40℃, chop them, mix them evenly, and grind them with a grinder until the average particle size is 150-180 micrometers; add 30 parts by weight of bitter wine and 15 parts by weight of honey, stir quickly to mix evenly, and let them air dry naturally to obtain solid powder composition 1.

[0122] Take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, and 30 parts by weight of poria cocos; wash them separately with clean water, dry them with hot air at 40℃, chop them, mix them evenly, and grind them with a grinder until the average particle size is 150-180 micrometers; add 30 parts by weight of bitter wine and 15 parts by weight of honey, stir quickly to mix evenly, and let them air dry naturally; add 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide; mix evenly to obtain solid powder composition 2.

[0123] Take 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide; mix them evenly to obtain a solid powder composition 3.

[0124] Take 35 parts by weight of dried plum, 3 parts by weight of prepared aconite root, 5 parts by weight of cinnamon twig, 3 parts by weight of ginseng, 3 parts by weight of angelica root, 5 parts by weight of asarum, 6 parts by weight of dried ginger, 4 parts by weight of Sichuan pepper, 3 parts by weight of phellodendron bark, 10 parts by weight of coptis root, 48 parts by weight of japonica rice, 16 parts by weight of lily bulb, 26 parts by weight of Polygonum multiflorum stem, 27 parts by weight of monkey head mushroom, 10 parts by weight of polygala root, and 16 parts by weight of poria cocos. Wash each ingredient with clean water, dry them with hot air at 40°C, chop them, mix them evenly, and grind them with a grinder until the average particle size is 160-180 micrometers. Add 60 parts by weight of bitter wine and 12 parts by weight of honey, stir quickly to mix evenly, and let them air dry naturally to obtain solid powder composition C.

[0125] Example 2: Sleep Improvement Effect Test

[0126] Take appropriate amounts of each of the above compositions and shake them in sterile water for 2 minutes to obtain a 100 mg / mL aqueous suspension.

[0127] Healthy SD rats, weighing 205g-216g, with equal numbers of males and females, were randomly divided into groups of 12 animals each. Each rat was intraperitoneally injected with an equal volume of p-chlorophenylalanine to establish a rat insomnia model, while the control group was intraperitoneally injected with an equal volume of physiological saline. Subsequently, the model rats were administered the following treatments daily: the model group received 2mL of physiological saline by gavage; experimental group 1 received 2mL of aqueous suspension of composition 1 by gavage daily; experimental group 2 received 2mL of aqueous suspension of composition 2 by gavage daily; experimental group 3 received 2mL of aqueous suspension of composition 3 by gavage daily; and experimental group 4 received 2mL of aqueous suspension of composition C by gavage daily. This gavage treatment continued for 10 consecutive days.

[0128] Twelve hours after the last gavage, rats were injected intraperitoneally with sodium pentobarbital at a dose of 28 mg / kg. The righting reflex test synergistic with sodium pentobarbital was then performed to compare the sleep latency and sleep duration of each group of rats.

[0129] The results are shown in Table 1, and the average values ​​of each group are taken. The sleep latency of rats in Experiment 1 and Experiment 2 was significantly shorter than that in the model group, Experiment 3 and Experiment 4, with statistically significant differences (P<0.05); the sleep latency of rats in Experiment 2 was also significantly shorter than that in Experiment 1 (P<0.05).

[0130] In addition, the sleep duration of rats in experimental groups 1 and 2 was significantly greater than that in the model group, experimental group 3 and experimental group 4, with statistically significant differences (P<0.05); the sleep duration of rats in experimental group 2 was also significantly greater than that in experimental group 1 (P<0.05).

[0131] This indicates that compositions 1 and 2 have a significant effect on improving sleep, and are more effective than composition C.

[0132] Table 1. Sleep test results

[0133] Sleep latency (minutes) Sleep duration (minutes) Blank group 7.1 68.7 Model group 20.3 35.5 Experimental Group 1 (Composition 1) 11.6 57.1 Experimental Group 2 (Composition 2) 7.8 70.4 Experimental Group 3 (Composition 3) 18.4 41.2 Experimental Group 4 (Composition C) 16.5 49.8

[0134] Example 3: Formulation Preparation

[0135] Preparation Example 1: Take 1 gram of Composition 1 prepared as described in Example 1, add 10 grams of honey and mix. Knead repeatedly to obtain an ointment-like material with good plasticity. Roll the ointment material into uniform thin strips; cut into segments and roll into 30mg pills. Spread the initially formed pills flat on a clean plate and air dry until the surface is dry and no longer sticky. The pills are then obtained. Check the appearance and hardness of the pills; both are qualified; the moisture content is about 9%. Store in a dry and cool place.

[0136] Formulation Example 2: Take 1 gram of Composition 2 prepared as described in Example 1, add 10 grams of honey and mix. Knead repeatedly to obtain an ointment-like material with good plasticity. Roll the ointment material into uniform thin strips; cut into segments and roll into 30mg pills. Spread the initially formed pills flat on a clean plate and air dry until the surface is dry and no longer sticky. The pills are then obtained. Check the appearance and hardness of the pills; both are qualified; the moisture content is about 9%. Store in a dry and cool place.

[0137] Formulation Example 3: Take 1 gram of composition 1 prepared as described in Example 1, add 5 grams of honey and an appropriate amount of purified water to form a soft and moist lumpy material, and roll it by hand into honey pills with a diameter of about 3 mm. Dry them in an oven at 45°C for 6 hours to obtain the pills described in this invention.

[0138] Formulation Example 4: Take 1 gram of Composition 2 prepared as described in Example 1, add 5 grams of honey and an appropriate amount of purified water to form a soft and moist lumpy material, and roll it by hand into honey pills with a diameter of about 3 mm. Dry them in an oven at 45°C for 6 hours to obtain the pills described in this invention.

[0139] Example 4: Detection of serum 5-HT levels

[0140] Rats (n=12 per group) treated as described in Example 2 were anesthetized the day after the last gavage and blood was collected from the abdominal aorta in 5 mL samples. The blood was allowed to stand for 3 hours and then centrifuged at 2000 rpm for 20 minutes at 4°C. Serum 5-HT levels were detected by ELISA. The results showed that the average serum 5-HT levels in rats treated with either Composition 1 or Composition 2 exceeded 516 pg / mL, significantly higher than those in the model group (average 113 pg / mL) and Composition C group, with statistically significant differences (P<0.001). This suggests that the mechanism of action may involve increasing serum 5-HT levels.

Claims

1. A composition for improving sleep, characterized in that, The preparation method of the composition is as follows: Take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, 30 parts by weight of poria cocos, 30 parts by weight of bitter wine, 15 parts by weight of honey, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide; mix them evenly to obtain the final product.

2. A pharmaceutical preparation for improving sleep, characterized in that, The pharmaceutical preparation comprises the composition as described in claim 1.

3. The pharmaceutical preparation according to claim 2, wherein the pharmaceutical preparation is a pill.

4. The pharmaceutical preparation according to claim 3, wherein the pill is a honey pill.

5. Use of the composition of claim 1 in the preparation of a medicament for improving sleep; wherein improving sleep refers to prolonging sleep time.

6. A method for manufacturing a medicament for improving sleep, the method comprising: Take 10 parts by weight of dried plum, 15 parts by weight of cinnamon twig, 15 parts by weight of ginseng, 15 parts by weight of angelica, 10 parts by weight of asarum, 20 parts by weight of dried ginger, 10 parts by weight of Sichuan pepper, 30 parts by weight of phellodendron bark, 5 parts by weight of coptis, 25 parts by weight of japonica rice, 5 parts by weight of lily bulb, 30 parts by weight of Polygonum multiflorum, 30 parts by weight of monkey head mushroom, 25 parts by weight of polygala tenuifolia, 30 parts by weight of poria cocos, 30 parts by weight of bitter wine, 15 parts by weight of honey, 30 parts by weight of hydrolyzed milk protein, 30 parts by weight of fish collagen peptide, and 30 parts by weight of soybean peptide; mix them evenly to obtain the final product.