Sleep-promoting microcapsule and preparation method thereof

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to a microcapsule for promoting sleep and a preparation method thereof. The hevea brasiliensis seed oil, the panax notoginseng extract, the semen cassiae extract, the lotus leaf extract and the gastrodia elata extract are reasonably combined for the first time, the effects are mutually matched, the gastrointestinal tract can be effectively regulated, absorption and biological utilization of active substances are promoted, and the effect of improving sleep for a long time is achieved; a natural raw material double-layer microcapsule embedding process is adopted, carnosic acid is selected to be introduced into a capsule core system, the stability of the capsule core system is improved, inulin is selected to be introduced into a capsule material system, intestinal tract movement is promoted, meanwhile, the carnosic acid is preferentially utilized by probiotics such as bifidobacterium and lactobacillus, and the actual effect and bioavailability of the microcapsule are improved to a large extent; according to the preparation method, the vitamin E membrane is formed outside the condensation nucleus, so that the performance of the composite wall material is integrally improved, and the prepared microcapsule has strong oxidation resistance, so that the microcapsule can endure the test of gastric acid to be released and proliferated at a fixed point in the intestinal tract, and the bioavailability is improved.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine, and particularly relates to a sleep-promoting microcapsule and a preparation method thereof. Background Art

[0002] Sleep is closely related to human health. Poor sleep often causes low human immunity, mental irritability, tinnitus and forgetfulness, inattention, and may also cause various diseases, seriously affecting people's quality of life.

[0003] Modern medicine believes that the occurrence of sleep disorders is often related to neurotransmitters, immune regulation, gut microbiota, environment, and psychological factors. Clinically, the treatment mode mainly takes drug treatment and supplemented by psychological and behavioral interventions. Currently, the chemical drugs for treating sleep disorders clinically mainly include barbiturates, benzodiazepines, non-benzodiazepines, etc. These drugs have a rapid onset and clear action mechanisms, but long-term use is prone to side effects such as residual effects, amnestic effects, and withdrawal effects. In traditional Chinese medicine practice, natural herbs or compound preparations with daily foods are often used to improve sleep, which has the advantages of not being prone to drug resistance and dependence, and is a sustainable slow conditioning mode, ultimately enabling the human body to sleep normally.

[0004] Hevea seed oil is a woody vegetable oil with a very high degree of unsaturation and rich in essential fatty acids for the human body. The content of unsaturated fatty acids in the oil is about 84%, especially α-linolenic acid, which is essential for the human body but cannot be synthesized. After being ingested by the human body, it is converted into EPA and DHA to play a role, and has high value in health care. In addition to the high content of unsaturated fatty acids, Hevea seed oil also contains single-molecule natural rubber, which has the effect of scraping oil and detoxifying in the large intestine; traditional Chinese medicine is rich in polysaccharides, oligosaccharides, and glycoside components. After polysaccharides are ingested, they can reach the distal intestine and ferment through the action of the intestinal microbiota.

[0005] Microencapsulation technology is one of the high-techs that have developed rapidly and are widely used today. It is a technology that uses natural or synthetic polymer materials to encapsulate dispersed solid, liquid, or even gaseous substances to form tiny particles with semi-permeable or sealed capsule membranes. This technology can protect substances from the environment, improve the stability of substances, and can shield the taste and smell of the embedded substances, isolate and protect active ingredients, and change the form of substances for easy storage, transportation, etc. Summary of the Invention

[0006] In order to overcome the above technical defects, the present invention provides a sleep-promoting microcapsule and a preparation method thereof. By using microencapsulation technology, it isolates and protects active ingredients, improves quality and efficacy, and avoids poor solubility and resulting taste discomfort during the taking process.

[0007] One of the objectives of the present invention is to provide a sleep-promoting microcapsule, which comprises a core and a first encapsulating material and a second encapsulating material that successively wrap the core;

[0008] The core comprises rubber tree seed oil, cassia seed extract, lotus leaf extract, gastrodia extract, and notoginseng extract;

[0009] The first encapsulating material comprises a colloid and a protein;

[0010] The second encapsulating material comprises a colloid and vitamin E.

[0011] Furthermore, the core comprises 1-100 parts by weight of rubber tree seed oil; for example, 5-90 parts by weight, or 10-80 parts by weight, or 15-70 parts by weight, or 20-60 parts by weight, or 25-55 parts by weight; and

[0012] 1-10 parts by weight of carnosic acid, for example, 1-8 parts by weight, or 1-6 parts by weight, or 3-5 parts by weight; and

[0013] 1-50 parts by weight of cassia seed extract, for example, 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight;

[0014] 1-50 parts by weight of lotus leaf extract, for example, 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight;

[0015] 1-50 parts by weight of gastrodia extract, for example, 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight;

[0016] 0.1-20 parts by weight of notoginseng extract, for example, 0.5-15 parts by weight, or 1-12 parts by weight, or 1-10 parts by weight.

[0017] In this specification, "parts by weight" of each Chinese medicinal material represents the dosage ratio relationship between each Chinese medicinal material, rather than an actual mass unit. According to the actual situation, the unit of parts by weight can be any mass, such as 1 part by weight can be 1 g, 500 g, or 1 kg, or even 15 g, 30 g, etc.

[0018] Those skilled in the art can understand that the notoginseng extract is obtained by extracting notoginseng with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, and pentanone.

[0019] Furthermore, the notoginseng extract is a water extract or an alcohol extract of notoginseng.

[0020] The cassia seed extract is obtained by extracting cassia seeds with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, and pentanone.

[0021] Furthermore, the cassia seed extract is a water extract of cassia seeds or an alcohol extract of cassia seeds.

[0022] The lotus leaf extract is obtained by extracting lotus leaves with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, and pentanone.

[0023] Furthermore, the lotus leaf extract is a water extract of lotus leaves or an alcohol extract of lotus leaves.

[0024] The gastrodia elata extract is obtained by extracting gastrodia elata with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, and pentanone.

[0025] Furthermore, the gastrodia elata extract is a water extract of gastrodia elata or an alcohol extract of gastrodia elata.

[0026] Furthermore, the colloid is selected from natural and / or synthetic polymer materials;

[0027] Furthermore, the colloid is selected from one or more of gelatin, gum arabic, alginate, soy protein, starches and maltodextrin, inulin, fructooligosaccharide, polycarbonate, polyamino acid, polylactic acid, polyvinyl alcohol, methyl cellulose, ethyl cellulose, or hydroxypropyl methyl cellulose;

[0028] Furthermore, the colloid is selected from one of inulin, fructooligosaccharide, or xylooligosaccharide.

[0029] Furthermore, the protein is selected from one or more of casein, whey protein, milk fat globule membrane protein, and hydrolyzed protein;

[0030] Furthermore, the protein is selected from casein.

[0031] Furthermore, the addition amount of vitamin E is 0.01 - 10% of the total mass of the microcapsules; for example, 0.01 - 8%, or 0.05 - 5%, or 0.1 - 3%, or 0.1 - 1%.

[0032] Further, the addition amount of the colloid is 10 - 50% of the total mass of the microcapsules; for example, 15 - 50%, or 20 - 45%, or 25 - 45%, or 30 - 40%.

[0033] Further, the addition amount of the protein is 0.1 - 10% of the total mass of the microcapsules; for example, 0.5 - 8%, or 1 - 5%, or 1 - 3%.

[0034] Further, the first wall material and / or the second wall material further comprises other pharmaceutical excipients.

[0035] Further, the pharmaceutical excipients include any one or more of fillers, binders, wetting agents, disintegrants, solubilizing agents, solubilizers, osmotic pressure regulators, surfactants, pH regulators, antioxidants, bacteriostatic agents or buffers.

[0036] In addition, if necessary, colorants, preservatives, fragrances, flavoring agents, sweeteners or other materials can also be added.

[0037] The second object of the present invention is to provide a method for preparing microcapsules, comprising mixing rubber tree seed oil, carnosic acid, cassia seed extract, lotus leaf extract, gastrodia extract and notoginseng extract to obtain a core material; mixing the core material with the first wall material and then spray drying to prepare coagulation nuclei; and mixing the coagulation nuclei with the second wall material and then spray drying to obtain the microcapsules.

[0038] Further, the first wall material comprises a colloid, a protein and pharmaceutically acceptable excipients in the art, and the addition amount of the colloid is 10 - 50% of the total mass of the microcapsules; for example, 15 - 50%, or 20 - 45%, or 25 - 45%, or 30 - 40%;

[0039] Further, the addition amount of the protein is 0.1 - 10% of the total mass of the microcapsules; for example, 0.5 - 8%, or 1 - 5%, or 1 - 3%.

[0040] Further, the second wall material comprises a colloid, vitamin E and pharmaceutically acceptable excipients in the art, and the addition amount of the colloid is 10 - 50% of the total mass of the microcapsules; for example, 15 - 50%, or 20 - 45%, or 25 - 45%, or 30 - 40%;

[0041] The addition amount of vitamin E is 0.01 - 10% of the total mass of the microcapsules; for example, 0.01 - 8%, or 0.05 - 5%, or 0.1 - 3%, or 0.1 - 1%.

[0042] Compared with the prior art, the present invention has the following beneficial effects:

[0043] (1) For the first time, the present invention rationally combines rubber tree seed oil, Panax notoginseng extract, Cassia obtusifolia extract, lotus leaf extract, and Gastrodia elata extract. Their effects cooperate with each other, which can both nourish the liver blood to calm the mind and clear internal heat to remove restlessness, having the effects of nourishing blood and tonifying the liver, calming the mind and tranquilizing the nerves, nourishing yin and moistening the lungs, tonifying the kidney and replenishing essence, clearing heat and removing annoyance, promoting qi movement and relieving depression, and regulating yin and yang, and has the effect of improving sleep.

[0044] (2) The present invention adopts a double-layer microcapsule embedding process for natural raw materials, and uses carnosic acid to introduce into the core system, which not only improves the stability of the core system, but also improves the solubility of the microcapsules in warm water; inulin is selected to introduce into the capsule wall material system. After inulin enters the human body, it is not absorbed by the stomach and small intestine but directly enters the large intestine, promoting intestinal peristalsis and being preferentially utilized by probiotics such as Bifidobacterium and Lactobacillus, which is beneficial to the proliferation of probiotics, and greatly improves the actual effect and bioavailability of the above-mentioned microcapsules; a vitamin E film is formed outside the coagulation nucleus to further improve the antioxidant property, thereby improving the performance of the composite wall material as a whole, enabling the composite wall material to play a better role in protecting the core material activity and significantly improving the stability of the core material, making the prepared microcapsules have strong acid resistance, so that they can withstand the test of gastric acid and release and proliferate at a fixed point in the intestine, improving the bioavailability.

[0045] (3) The microcapsules of the present invention have no side effects, prevent and treat sleep disorders by regulating the intestinal microecology, can be taken for a long time, have small side effects, and have a good taste, and patients have good compliance. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] Figure 1 It is a solubility result diagram of the present invention;

[0047] Among them, 1A is the dissolution result of Comparative Example 1; 1B is the dissolution result of Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0048] To enable those skilled in the art to better understand the technical solutions of the present invention, the present invention will be described in detail below in conjunction with the specific embodiments. The experimental methods without specific conditions noted in the following examples are usually carried out according to conventional conditions or according to the conditions recommended by the manufacturer. Unless otherwise stated, percentages and parts are calculated by weight. Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to the described content can be applied to the present invention. The preferred implementation methods and materials described herein are only for illustrative purposes.

[0049] The endpoints and any values within the ranges disclosed herein are not limited to the exact ranges or values. These ranges or values should be understood to include values close to these ranges or values. For numerical ranges, the endpoint values of each range, between the endpoint values of each range and individual point values, and between individual point values can be combined with each other to obtain one or more new numerical ranges, and these numerical ranges should be considered to be specifically disclosed herein.

[0050] According to the present invention, on the one hand, a sleep-promoting microcapsule is provided, which includes a core and a first encapsulating material and a second encapsulating material sequentially wrapped around the core.

[0051] The core includes Hevea brasiliensis seed oil, carnosic acid, Cassia obtusifolia extract, Nelumbo nucifera extract, Gastrodia elata extract, and Panax notoginseng extract.

[0052] The first encapsulating material includes colloid and protein.

[0053] The second encapsulating material includes colloid and vitamin E.

[0054] Based on the present invention, Hevea brasiliensis seed oil, carnosic acid, Cassia obtusifolia extract, Nelumbo nucifera extract, Gastrodia elata extract, and Panax notoginseng extract are used as the core to adjust the intestinal flora to achieve the regulation of biological rhythm expression and the conditioning of sleep disorders.

[0055] Based on traditional Chinese medicine theory, Hevea brasiliensis seed oil contains essential fatty acids linoleic acid and linolenic acid for the human body, and the content of ω-3 fatty acid (linolenic acid) in Hevea brasiliensis seed oil is 18% - 20%, the content of ω-6 fatty acid (linoleic acid) is 34% - 38%, and the ratio of ω-3 fatty acid (linolenic acid) to ω-6 fatty acid (linoleic acid) is nearly 1:2. ω-3 fatty acid (linolenic acid) has good anti-inflammatory effects, while ω-6 fatty acid (linoleic acid) can help regulate the body's metabolic function and promote immune responses.

[0056] Panax notoginseng is warm in nature, sweet and slightly bitter in taste, and belongs to the liver meridian and stomach meridian. It has the effects of dissipating stasis and stopping bleeding, detumescence and relieving pain. It has the efficacy of removing stasis and stopping bleeding, activating blood circulation and relieving pain. It is mainly used for treating various bleeding syndromes, swelling and pain due to blood stasis, traumatic injuries, etc. belonging to blood stasis blockage; Ginseng is sweet and slightly bitter in taste, slightly warm in nature; it belongs to the lung meridian and heart meridian. It has the efficacy of invigorating the spleen and benefiting the lung, promoting the production of body fluid, and calming the nerves and improving intelligence. It is mainly used for treating collapse of qi due to deficiency, feeble pulse on the verge of collapse, deficiency of the spleen qi, sinking of the middle qi, cough and asthma due to lung deficiency, shortness of breath and fatigue, thirst due to fluid injury, consumptive thirst with deficiency heat, insomnia and forgetfulness, palpitation and anxiety, sallow complexion due to blood deficiency, impotence and cold uterus, etc.

[0057] Cassia obtusifolia is sweet, bitter, and salty in taste, slightly cold in nature; it belongs to the liver and large intestine meridians, and has the effects of clearing heat and improving eyesight, and moistening the intestines and promoting defecation; it is mainly used for treating red and swollen eyes, photophobia with excessive tearing, unclear vision, headache, dizziness, and constipation due to intestinal dryness.

[0058] Lotus leaf is bitter in taste and neutral in nature. It belongs to the liver, spleen, and stomach meridians, and has the effects of clearing heat and relieving summer heat, ascending and generating clear yang, and dispersing stasis and stopping bleeding; it is mainly used for treating summer heat and vexation with thirst, summer dampness and diarrhea, spleen deficiency diarrhea, hematemesis and epistaxis due to blood heat, hematochezia, metrorrhagia and metrostaxis.

[0059] Gastrodia elata is sweet in taste and neutral in nature; it belongs to the liver meridian. It has the effects of calming endogenous wind and stopping convulsions, suppressing liver yang, and dispelling wind and dredging collaterals; it is mainly used for treating endogenous liver wind stirring, epileptic convulsions, dizziness, headache, limb numbness, palsy of hands and feet, and rheumatic arthralgia.

[0060] Carnosic acid is a diterpenoid compound isolated from the Lamiaceae plant Rosmarinus officinalis, and has a variety of biological activities and pharmacological effects. Carnosic acid remains stable at 200 °C and has antioxidant properties to scavenge free radicals and reduce the damage of oxidative stress to cells; it can inhibit inflammatory reactions and help alleviate inflammatory diseases.

[0061] In some specific embodiments, the core of the capsule includes 1-100 parts by weight of rubber tree seed oil; for example, 5-90 parts by weight, or 10-80 parts by weight, or 15-70 parts by weight, or 20-60 parts by weight, or 25-55 parts by weight; and

[0062] 1-10 parts by weight of carnosic acid, for example, 1-8 parts by weight, or 1-6 parts by weight, or 3-5 parts by weight; and

[0063] 1-50 parts by weight of cassia seed extract, for example, 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight;

[0064] 1-50 parts by weight of lotus leaf extract, for example, 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight;

[0065] 1-50 parts by weight of Gastrodia elata extract, for example, 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight;

[0066] 0.1-20 parts by weight of notoginseng extract, for example, 0.5-15 parts by weight, or 1-12 parts by weight, or 1-10 parts by weight.

[0067] In some specific embodiments, the notoginseng extract is obtained by extracting notoginseng with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, pentanone.

[0068] In some specific embodiments, the notoginseng extract is the extract of notoginseng stems and leaves.

[0069] In some specific embodiments, the Panax notoginseng extract is a water extract or an alcohol extract of Panax notoginseng.

[0070] The cassia seed extract is obtained by extracting cassia seeds with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, and pentanone.

[0071] In some specific embodiments, the cassia seed extract is a water extract or an alcohol extract of cassia seeds.

[0072] In some specific embodiments, the lotus leaf extract is obtained by extracting lotus leaves with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, and pentanone.

[0073] In some specific embodiments, the lotus leaf extract is a water extract or an alcohol extract of lotus leaves.

[0074] The gastrodia elata extract is obtained by extracting gastrodia elata with an extraction solvent; the extraction solvent is selected from one or more of water, methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, methyl formate, ethyl formate, methyl acetate, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, acetone, butanone, and pentanone.

[0075] In some specific embodiments, the gastrodia elata extract is a water extract or an alcohol extract of gastrodia elata.

[0076] In some specific embodiments, the colloid is selected from natural and / or synthetic polymer materials;

[0077] In some specific embodiments, the colloid is selected from one or more of gelatin, gum arabic, alginate, soy protein, starches and maltodextrin, inulin, fructooligosaccharide, xylooligosaccharide, polycarbonate, polyamino acid, polylactic acid, polyvinyl alcohol, methyl cellulose, ethyl cellulose, or hydroxypropyl methyl cellulose;

[0078] In some specific embodiments, the colloid is selected from one of inulin, fructooligosaccharide, and xylooligosaccharide.

[0079] In some specific embodiments, the protein is selected from one or more of casein, whey protein, milk fat globule membrane protein, and hydrolyzed protein;

[0080] In some specific embodiments, the protein is selected from casein.

[0081] In some specific embodiments, the addition amount of vitamin E is 0.01-10% of the total mass of the microcapsules; for example, 0.01-8%, or 0.05-5%, or 0.1-3%, or 0.1-1%.

[0082] In some specific embodiments, the addition amount of the colloid is 10-50% of the total mass of the microcapsules; for example, 15-50%, or 20-45%, or 25-45%, or 30-40%.

[0083] In some specific embodiments, the addition amount of the protein is 0.1-10% of the total mass of the microcapsules; for example, 0.5-8%, or 1-5%, or 1-3%.

[0084] In some specific embodiments, the first encapsulating material and / or the second encapsulating material further comprises other pharmaceutical excipients.

[0085] In some specific embodiments, the pharmaceutical excipients include any one or more of fillers, binders, wetting agents, disintegrants, solubilizing agents, solubilizers, osmotic pressure regulators, surfactants, pH regulators, antioxidants, bacteriostatic agents or buffers.

[0086] In addition, if necessary, colorants, preservatives, fragrances, flavoring agents, sweeteners or other materials can also be added.

[0087] In a second aspect, the present invention provides a method for preparing microcapsules, comprising mixing rubber tree seed oil, carnosic acid, cassia seed extract, lotus leaf extract, gastrodia extract, and panax notoginseng extract to obtain a core material; mixing the core material with a first encapsulating material and then spray-drying to prepare nuclei; and mixing the nuclei with a second encapsulating material and then spray-drying to obtain the microcapsules.

[0088] The main absorption sites of panax notoginseng extract, cassia seed extract, lotus leaf extract, and gastrodia extract are all the intestine. The absorption mode of panax notoginseng stem and leaf extract is passive diffusion. By the method of this patent, it can effectively protect panax notoginseng stem and leaf from being decomposed by gastric acid, maintain a high concentration in the intestine, and be more easily absorbed and utilized by panax notoginseng stem and leaf, achieving a better therapeutic effect on calming the nerves and promoting sleep. The main absorption site of gastrodia is also in the intestine, and it also has a good sedative effect. Similarly, cassia seed is absorbed quickly in the intestine, and the polysaccharide substances in cassia seed can stimulate the body to produce immune cells, improving the body's immunity and having a good effect on maintaining intestinal health. Lotus leaf extract has a good anti-inflammatory effect and also has a good effect on maintaining intestinal health. The present invention targets and transports cassia seed extract, lotus leaf extract, gastrodia extract, panax notoginseng extract, and rubber tree seed oil to the intestine through a double-layer microcapsule embedding process, avoiding the destruction of the above substances by gastric acid.

[0089] Further, the first coating material includes a colloid, a protein, and pharmaceutically acceptable excipients in the art. The addition amount of the colloid is 10 - 50% of the total mass of the microcapsules; for example, 15 - 50%, or 20 - 45%, or 25 - 45%, or 30 - 40%.

[0090] Further, the addition amount of the protein is 0.1 - 10% of the total mass of the microcapsules; for example, 0.5 - 8%, or 1 - 5%, or 1 - 3%.

[0091] Further, the second coating material includes a colloid, vitamin E, and pharmaceutically acceptable excipients in the art. The addition amount of the colloid is 10 - 50% of the total mass of the microcapsules; for example, 15 - 50%, or 20 - 45%, or 25 - 45%, or 30 - 40%.

[0092] The addition amount of vitamin E is 0.01 - 10% of the total mass of the microcapsules; for example, 0.01 - 8%, or 0.05 - 5%, or 0.1 - 3%, or 0.1 - 1%.

[0093] Those skilled in the art can understand that the "parts by weight" of each traditional Chinese medicine ingredient represents the dosage ratio relationship between each traditional Chinese medicine ingredient, rather than an actual mass unit. According to the actual situation, a unit part by weight can be any mass, such as 1 part by weight can be 1 g, 500 g, or 1 kg, and even can be 15 g, 30 g, etc.

[0094] Those skilled in the art can understand that the dosage of the pharmaceutical composition of the present invention depends on many factors, such as the gender, age, weight, and individual response of the patient or animal, the administration route, and the number of administrations, etc. The above dosage can be administered in a single dosage form or divided into several, for example, two, three, or four dosage forms. The dosage level must be selected according to the specific administration route, the severity of the condition to be treated, and the condition and medical history of the patient to be treated. However, the practice in the art is to start with a dosage lower than the level required to obtain the desired therapeutic effect and gradually increase the dosage until the desired effect is obtained.

[0095] The dosage of the composition and the drug of the present invention can be 10 mg - 10 g of the active ingredient / kg body weight. For example, 200 mg of the active ingredient / kg body weight, 3 g of the active ingredient / kg body weight, 4 g of the active ingredient / kg body weight, or 10 mg of the active ingredient / kg body weight.

[0096] The embodiments of the present invention will be described in detail below in conjunction with the examples. However, those skilled in the art will understand that the following examples are only used to illustrate the present invention and should not be regarded as limiting the scope of the present invention. Those conditions not specified in the examples are carried out according to the conventional conditions or the conditions recommended by the manufacturer. Those reagents or instruments not specified by the manufacturer can be obtained as conventional products through commercial purchase.

[0097] Example 1 Microcapsule

[0098] The microcapsule includes a core and a first coating material wrapped around the core material and a second coating material wrapped around the first coating material; the core includes the following components: 55 parts of rubber tree seed oil, 2 parts of caffeic acid, 5 parts of cassia seed extract, 5 parts of lotus leaf extract, 1 part of gastrodia extract, 1 part of panax notoginseng stem and leaf extract; the first coating material includes the following components: 20 parts of inulin, 0.55 parts of sodium caseinate, 1.65 parts of casein, 0.5 parts of sodium stearoyl lactate, 1 part of mono- and diglycerol fatty acid esters, 0.03 parts of silicon dioxide; the second coating material includes the following components: 7.24 parts of inulin, 0.03 parts of natural vitamin E.

[0099] Preparation method: Mix 55 parts by mass of rubber tree seed oil, 2 parts of caffeic acid, 5 parts of cassia seed extract, 5 parts of lotus leaf extract, 1 part of gastrodia extract, and 1 part of panax notoginseng stem and leaf extract to obtain a core material; mix the core material with 20 parts by mass of inulin, 0.55 parts of sodium caseinate, 1.65 parts of casein, 0.5 parts of sodium stearoyl lactate, 1 part of mono- and diglycerol fatty acid esters, and 0.03 parts of silicon dioxide, and then spray-dry to form nuclei wrapped with the first coating material; mix the nuclei with 7.24 parts by mass of inulin and 0.03 parts of natural vitamin E, and then spray-dry to obtain the microcapsule wrapped with the second coating material.

[0100] Example 2

[0101] The microcapsule includes a core and a first coating material wrapped around the core material and a second coating material wrapped around the first coating material; the core includes the following components: 20 parts of rubber tree seed oil, 5 parts of caffeic acid, 15 parts of cassia seed extract, 15 parts of lotus leaf extract, 10 parts of gastrodia extract, 10 parts of panax notoginseng stem and leaf extract; the first coating material includes the following components: 15 parts of inulin, 0.55 parts of sodium caseinate, 1.65 parts of casein, 0.5 parts of sodium stearoyl lactate, 1 part of mono- and diglycerol fatty acid esters, 0.03 parts of silicon dioxide; the second coating material includes the following components: 6.24 parts of inulin, 0.03 parts of natural vitamin E.

[0102] Example 3

[0103] The microcapsule includes a core and a first coating material wrapped around the core material and a second coating material wrapped around the first coating material; the core includes the following components: 35 parts of rubber tree seed oil, 1 part of caffeic acid, 3 parts of cassia seed extract, 3 parts of lotus leaf extract, 10 parts of gastrodia extract, 10 parts of panax notoginseng stem and leaf extract; the first coating material includes the following components: 27 parts of inulin, 0.55 parts of sodium caseinate, 1.65 parts of casein, 0.5 parts of sodium stearoyl lactate, 1 part of mono- and diglycerol fatty acid esters, 0.03 parts of silicon dioxide; the second coating material includes the following components: 7.24 parts of inulin, 0.03 parts of natural vitamin E.

[0104] Example 4

[0105] The microcapsules include a core, a first coating material coated outside the core material, and a second coating material coated outside the first coating material; the core includes the following components: 25 parts of rubber tree seed oil, 6 parts of carnosic acid, 9 parts of cassia seed extract, 12.2 parts of lotus leaf extract, 4 parts of gastrodia extract, and 8.6 parts of panax notoginseng stem and leaf extract; the first coating material includes the following components: 18 parts of inulin, 4 parts of sodium caseinate, 5 parts of casein, 1 part of sodium stearoyl lactate, 1 part of mono- and diglycerol fatty acid esters, and 0.4 part of silicon dioxide; the second coating material includes the following components: 4.8 parts of inulin and 1 part of natural vitamin E.

[0106] Example 5

[0107] The microcapsules include a core, a first coating material coated outside the core material, and a second coating material coated outside the first coating material; the core includes the following components: 30 parts of rubber tree seed oil, 4 parts of carnosic acid, 13 parts of cassia seed extract, 9.4 parts of lotus leaf extract, 1.9 parts of gastrodia extract, and 0.5 part of panax notoginseng stem and leaf extract; the first coating material includes the following components: 22 parts of inulin, 2 parts of sodium caseinate, 8 parts of casein, 1 part of sodium stearoyl lactate, 1 part of mono- and diglycerol fatty acid esters, and 0.2 part of silicon dioxide; the second coating material includes the following components: 3 parts of inulin and 4 parts of natural vitamin E.

[0108] Example 6

[0109] The microcapsules include a core, a first coating material coated outside the core material, and a second coating material coated outside the first coating material; the core includes the following components: 35 parts of rubber tree seed oil, 5 parts of carnosic acid, 15 parts of cassia seed extract, 6.5 parts of lotus leaf extract, 3.8 parts of gastrodia extract, and 4 parts of panax notoginseng stem and leaf extract; the first coating material includes the following components: 18.9 parts of inulin, 3 parts of sodium caseinate, 1 part of casein, 1 part of sodium stearoyl lactate, 0.4 part of mono- and diglycerol fatty acid esters, and 0.3 part of silicon dioxide; the second coating material includes the following components: 6 parts of inulin and 0.1 part of natural vitamin E.

[0110] Comparative Example

[0111] Same as Example 1, except that carnosic acid is not added.

[0112] Examine the solubility of the microcapsules of the present invention and observe the phenomena for comparison.

[0113] From Figure 1 It can be seen that the microcapsules prepared by the present invention have better dispersibility in water and can be completely dissolved in warm water with only proper stirring. In contrast, the microcapsules prepared in the comparative example have poor solubility, and there are still some insoluble lumps after stirring for a long time. It can be seen that adding carnosic acid helps to enhance the dispersibility of the microcapsules in water, making them dissolve better in water, convenient to use, and greatly improving the taste.

[0114] Clinical efficacy study of the microcapsules of the present invention: 60 patients who met the diagnostic criteria and inclusion criteria of this study, including 36 males and 24 females, with ages ranging from 20 to 60 years old.

[0115] Inclusion criteria: People who are not satisfied with their sleep quality are screened using the Pittsburgh Sleep Quality Index questionnaire, and eligible volunteers are included in the experimental group; those with onset time exceeding 1 month.

[0116] Exclusion criteria: Those with age < 20 years old or > 60 years old, pregnant or lactating women; those suffering from severe diseases such as cardiovascular and cerebrovascular, liver, kidney, and hematopoietic systems, as well as endocrine diseases and psychiatric patients; those who have taken sleep-improving drugs in the short term.

[0117] Treatment plan: The patients take the microcapsules prepared in Example 2 every day, once a day, 15 g each time, half an hour before going to bed at night. Taking continuously for 3 months is one course of treatment.

[0118] Efficacy evaluation criteria: Refer to the "Guiding Principles for Clinical Research of New Chinese Medicines": Cured: Sleep time is greater than 6 h or basically returns to normal, and the patient feels energetic after waking up and has sufficient deep sleep; Markedly effective: Sleep time is less than 6 h, but can be increased to more than 3 h, and the sleep quality is significantly optimized and the deep sleep time is significantly increased; Effective: The increase in sleep time is less than 3 h, but the patient feels improved; Ineffective: There is no obvious improvement or even aggravation in sleep time and quality.

[0119] The treatment effects are shown in Table 1 below:

[0120] Table 1

[0121] Number of people Ratio Cured 28 18.7％ Markedly effective 43 28.7％ Effective 72 48％ Ineffective 7 4.7％

[0122] It can be seen that the effective rate of the clinical efficacy of the microcapsules of the present invention reaches 95.3%, which can effectively improve the sleep quality of insomnia patients and no adverse reactions have occurred, indicating that the microcapsules provided by the present invention have high safety, are suitable for all groups to use, and have the efficacy of effectively improving insomnia and enhancing sleep quality.

[0123] The following is further illustrated with specific cases:

[0124] Li Mou, female, 38 years old, due to great work pressure, has poor sleep. She basically wakes up at 5 o'clock every morning and can't fall asleep again. After taking this product, her sleep state has been greatly improved and she can sleep until about 6:30 in the morning.

[0125] Zhang, male, 16 years old. Due to high learning pressure, he has many dreams and poor mental state in the early morning, which affects his study throughout the day. After taking the patented product of the present invention, his mental state has been relieved, the sleep quality has been greatly improved, he no longer has many dreams, sleeps until morning, has sufficient energy during the day, and his academic performance has also improved accordingly.

[0126] Ren, female, 65 years old. She has difficulty falling asleep after getting up at night, so she needs to control her water intake at night. After taking this product, the frequency of getting up at night has decreased, and she can fall asleep normally after getting up at night. The quality of life has been greatly improved.

[0127] Finally, it should be noted that the above description is only the preferred embodiment of the present invention. Those skilled in the art can make various similar representations under the inspiration of the present invention without violating the purpose and claims of the present invention. Such transformations all fall within the protection scope of the present invention.

Claims

1. A sleep-promoting microcapsule, characterized in that: It comprises a capsule core and a first capsule material and a second capsule material sequentially wrapped on the capsule core; The capsule core comprises rubber tree seed oil, carnosic acid, cassia seed extract, lotus leaf extract, gastrodia elata extract, and panax notoginseng extract; The first capsule material includes colloid and protein; The second capsule material includes colloid and vitamin E.

2. The microcapsule according to claim 1, characterized in that The capsule core comprises 1-100 parts by weight of rubber tree seed oil; for example, 5-90 parts by weight, or 10-80 parts by weight, or 15-70 parts by weight, or 20-60 parts by weight, or 25-55 parts by weight; as well as 1-10 parts by weight of carnosic acid, for example 1-8 parts by weight, or 1-6 parts by weight, or 3-5 parts by weight; and 1-50 parts by weight of Cassia seed extract, for example 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight; 1-50 parts by weight of lotus leaf extract, for example 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight; 1-50 parts by weight of Gastrodia elata extract, for example 1-40 parts by weight, or 1-30 parts by weight, or 1-20 parts by weight, or 5-20 parts by weight; The notoginseng extract is 0.1-20 parts by weight, for example 0.5-15 parts by weight, or 1-12 parts by weight, or 1-10 parts by weight.

3. The microcapsule according to claim 1, characterized in that The colloid is selected from natural and / or synthetic polymer materials; further, selected from one or more of gelatin, gum arabic, alginate, soy protein, starch and maltodextrin, inulin, oligofructose, oligoxylose, polycarbonate, polyamino acid, polylactic acid, polyvinyl alcohol, methyl cellulose, ethyl cellulose or hydroxypropyl methyl cellulose; further, selected from one of inulin and oligofructose.

4. The microcapsule according to claim 1, characterized in that The protein is selected from one or more of casein, whey protein, milk fat globule membrane protein, and hydrolyzed protein; further, selected from casein.

5. The microcapsule according to claim 1, characterized in that The added amount of vitamin E is 0.01-10% of the total mass of the microcapsule; for example, 0.01-8%, or 0.05-5%, or 0.1-3%, or 0.1-1%.

6. The microcapsule according to claim 1, characterized in that The amount of the colloid added is 10-50% of the total mass of the microcapsule; for example, 15-50%, or 20-45%, or 25-45%, or 30-40%.

7. The microcapsule according to claim 1, characterized in that The added amount of the protein is 0.1-10% of the total mass of the microcapsule; for example, 0.5-8%, or 1-5%, or 1-3%.

8. A method for preparing microcapsules, characterized in that: The rubber tree seed oil, carnosic acid, cassia seed extract and panax notoginseng extract are mixed to obtain a capsule core; the capsule core is mixed with a first capsule material and then spray-dried to obtain a condensation nucleus; the condensation nucleus is mixed with a second capsule material and then spray-dried to obtain the product.

9. The preparation method according to claim 8, characterized in that: The first capsule material includes colloid, protein and pharmaceutical excipients acceptable in the art, wherein the colloid is added in an amount of 10-50% of the total mass of the microcapsule; for example, 15-50%, or 20-45%, or 25-45%, or 30-40%; the protein is added in an amount of 0.1-10% of the total mass of the microcapsule; for example, 0.5-8%, or 1-5%, or 1-3%.

10. The preparation method according to claim 8, characterized in that: The second capsule material includes a colloid, vitamin E and pharmaceutical excipients acceptable in the art. The amount of the colloid added is 10-50% of the total mass of the microcapsule; for example, 15-50%, or 20-45%, or 25-45%, or 30-40%; the amount of vitamin E added is 0.01-10% of the total mass of the microcapsule; for example, 0.01-8%, or 0.05-5%, or 0.1-3%, or 0.1-1%.

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