Liposome coating containing hydrogen molecules and active substances and preparation method thereof

Abstract

The invention relates to the technical field of medicine and functional food delivery, in particular to a high-stability lipidosome coating containing hydrogen molecules and active substances and a preparation method of the lipidosome coating. The core of the coating is lipidosome loaded with nano-bubble hydrogen-rich water and active substances, and the outer layer of the coating is formed by coating an edible high-barrier material. Generally, in the coating and the method, a physical barrier is constructed by utilizing the primary protection of the lipidosome on the active substance and the extremely high barrier property of the beewax or the hard candy film on the active substance, especially gas, so that the rapid dissipation of hydrogen molecules in the inner core lipidosome is effectively prevented, and the problem of stable storage of the hydrogen molecules in the wrapping substance is solved. The stability of the active ingredients is jointly improved. The liposome has targeting property, can realize intestinal targeted release and slow release effects of active substances and hydrogen molecules, and improves bioavailability. And finally, the product can be prepared into various forms such as microspheres, sugar capsules or wrappers and the like, and can be conveniently delivered and eaten as functional foods, health-care products or medicines and the like.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of drug and functional food delivery, in particular to a liposome coating with high stability containing hydrogen molecules and active substances and a preparation method thereof. Specifically, the core of the coating is a liposome loaded with nanobubble hydrogen-rich water and active substances, and the outer layer is coated with edible high-barrier material (beeswax or sugar block). BACKGROUND

[0002] Hydrogen molecules (H2) have selective antioxidant, anti-inflammatory and cell protection effects, but their small molecular size and strong diffusion make them difficult to store and transport under normal conditions, severely limiting their application.

[0003] Liposomes, as an excellent nanodelivery system, can encapsulate both hydrophilic and lipophilic active substances, but the phospholipid bilayer is still insufficient in blocking hydrogen molecules, which will quickly escape.

[0004] In the prior art, such as a soft capsule pill press, soft capsules directly encapsulating free hydrogen gas cannot be achieved due to the high permeability of the gelatin shell. Therefore, developing a system that can stably coexist with hydrogen molecules and active substances for a long time and achieve targeted delivery has become a technical challenge in the field, and the present application attempts to provide a solution. SUMMARY

[0005] The present application aims to overcome the shortcomings of the prior art and provide a liposome coating containing hydrogen molecules and active substances and a preparation method thereof. The double-layer structure of the coating, which is primary encapsulated by liposomes and secondarily coated with beeswax or sugar block, cooperatively solves the storage problem of hydrogen molecules and achieves the protection and controlled release of hydrogen molecules and active substances.

[0006] To achieve the above-mentioned purpose, the present application adopts the following technical solutions:

[0007] In a first aspect, the present application provides a liposome coating containing hydrogen molecules and active substances, characterized in that it comprises: a core composed of liposomes containing hydrogen molecules, and active substances embedded in the phospholipid bilayer of the liposomes or encapsulated in the internal water phase; and an outer layer of edible high-barrier film material coated on the core.

[0008] Preferably, the edible high-barrier film material is a crystalline food material or a wax.

[0009] Further, the active substance includes one or more combinations of traditional Chinese medicine preparations, traditional Chinese medicine active extracts (such as flavonoids, saponins, and polysaccharides), vitamins (such as vitamin C and vitamin E), polyphenols, or protein peptides.

[0010] On the other hand, the present invention also provides a method for preparing liposome coatings containing hydrogen molecules and active substances. The liposomes are prepared in a closed, oxygen-free, and low-temperature environment. By utilizing the characteristics of liposome precursors, active substances and hydrogen molecules are simultaneously encapsulated in their respective suitable positions and then encapsulated and shaped at the moment of liposome formation.

[0011] The technical solution of this preparation method is as follows:

[0012] A method for preparing a liposome-coated compound containing hydrogen molecules and active substances, comprising the following:

[0013] (a) Preparation of liposomes: Hydrogen-rich water, active substances, and liposome precursors are dissolved to prepare liposomes; or hydrogen molecules, active substances, liposome precursors, and solvents are dissolved to prepare liposomes.

[0014] (II) Preparation of outer layer precursor: Crystalline food includes a crystalline food stock solution formed by heating a mixture of sugar alcohols and binders; wax includes a wax stock solution formed by melting wax and anti-caking agent; or the crystalline food stock solution and the wax stock solution are cooled and spread out separately to form a crystalline food film and a wax film.

[0015] (III) Outer Layer Forming: A wax film or crystalline food ingredient film is laid on a surface with a grooved mold in a soft state at a suitable temperature. The formed liposomes are injected into the grooved mold on which the wax film or crystalline food ingredient film is laid. Finally, another wax film or crystalline food ingredient film is laid on the grooved mold containing the injected liposomes. Then, the periphery of the double-layered wax film or crystalline food ingredient film formed on the grooved mold is pressed, sealed, and shaped, and cut along the edge of the grooved mold, thereby detaching the wax film or crystalline food ingredient film encapsulating the liposomes from the grooved mold, thus forming this coating; or,

[0016] The crystalline food ingredient solution or waxy food ingredient solution is placed in a reactor and heated until it is completely melted into a liquid. Under high-speed stirring (homogenization), the preheated liposome is slowly added to the completely melted liquid in the form of droplets or sprays. The center of the droplet is the liposome, and the outer layer is a molten waxy coating layer or a crystalline food ingredient coating layer. Then, it is cooled and solidified to form the coating.

[0017] Preferably, the weight ratio of the raw materials for preparing liposomes to those for preparing the outer layer precursor is (1-10) to (0.5-3). Further, the solvent is one or more of water, hydrogen-rich water, anhydrous ethanol, methanol, and diethyl ether.

[0018] Preferably, the hydrogen-rich water is nanobubble hydrogen-rich water, and the hydrogen molecule concentration in the nanobubble hydrogen-rich water is not less than 1.0 ppm.

[0019] Preferably, the steps for preparing liposomes include: using water as the solvent, first mixing hydrogen molecules with water in a high-pressure sealed container under continuous high-speed rotational shearing at a pressure of 2-5 MPa, a temperature of 2-6°C, and a time of 4-6 hours. Then, the active substance, liposome precursor, and the mixture are dissolved in the high-pressure sealed container under continuous high-speed rotational shearing to form liposomes.

[0020] Here, high-purity hydrogen is introduced into water and mixed by continuous high-speed rotation and shearing in a high-pressure, sealed container.

[0021] Under high pressure, the solubility of hydrogen increases. The enormous energy generated by high-speed rotational shearing breaks the hydrogen into extremely tiny bubbles (i.e., nanobubbles), forming hydrogen-rich water with stable physical properties and high hydrogen concentration. The high-pressure, sealed environment prevents hydrogen escape. The active substance and liposome precursor are then mixed and introduced into the hydrogen-rich water undergoing continuous high-speed rotational shearing. Due to the high shear energy, the active substance, liposome precursor, and hydrogen-rich water mix rapidly and intensely. When injected into the aqueous phase, it spontaneously self-assembles into liposomes due to changes in solubility. During this process, hydrogen molecules and dissolved active substances in the hydrogen-rich water are simultaneously encapsulated within the forming liposomes.

[0022] Preferably, the step of preparing liposomes includes:

[0023] 1) Preparation of liposome membranes: Liposome precursors and cholesterol are dissolved in anhydrous ethanol and then rotary evaporated to form liposome membranes.

[0024] 2) Hydration and Loading: The lipid film was hydrated with phosphate-buffered saline (PBS) to obtain blank liposomes. Active substances were added, and drug-loaded liposome suspensions were prepared by ultrasonic extrusion.

[0025] 3) Hydrogen loading: The liposome suspension containing oil-loaded active substances is placed in a high-pressure hydrogen reaction device and subjected to a pressure of 2-5 MPa, 2-6℃, and a time of 4-6 hours to saturate hydrogen molecules onto the lipid bilayer.

[0026] 4) Purification and formulation: The nano-formulation with a particle size distribution of 80-120nm was obtained by ultrafiltration and centrifugation purification, and then dispensed into containers pre-filled with protective hydrogen and stored at 4°C in the dark.

[0027] Preferably, the steps for preparing liposomes include: using water and ethanol as solvents, hydrogen-rich water (formed by hydrogen molecules and water solvent) is dissolved with water-soluble active substances in the active material to form a water-soluble solution; the liposome precursor and the solvent ethanol are dissolved, and then the lipid-soluble active substances in the active material are added to form a lipid-soluble organic phase; the lipid-soluble organic phase is introduced into a high-pressure sealed container containing the water-soluble solution and subjected to high-speed shear dissolution to form liposomes. Further, the lipid-soluble organic phase is introduced into a high-pressure sealed container containing the water-soluble solution and subjected to high-speed shear dissolution, followed by evaporation of the solvent ethanol to form liposomes.

[0028] Here, hydrogen molecules are dissolved in water under high pressure to create hydrogen-rich water. Water-soluble active substances are then dissolved in the hydrogen-rich water. The aim is to ensure that both hydrogen molecules and water-soluble active substances are present in the internal aqueous phase of the final liposomes. Using hydrogen-rich water is fundamental to achieving high-concentration hydrogen loading. The high-pressure, closed environment prevents premature hydrogen escape.

[0029] The liposome precursor is first dissolved in ethanol, and then the liposoluble active substance is added and dissolved. This ensures that the phospholipids and the liposoluble active substance are uniformly mixed at the molecular level in the ethanol solvent. Pre-binding the liposoluble active substance to the phospholipid ensures that it can naturally embed into the final lipid bilayer during liposome formation.

[0030] Liposome precursors dissolved in ethanol are injected into a high-pressure, closed container subjected to high-speed shearing. Since phospholipids are soluble in ethanol but insoluble in a large aqueous phase, the solubility of phospholipids decreases instantaneously when the ethanol phase is injected into the aqueous phase. To allow their hydrophobic tails to avoid the water molecule environment, they spontaneously self-assemble to form liposomes.

[0031] The effect of high-speed shearing: ultimate mixing: high-speed shearing ensures that the ethanol phase can be instantly and uniformly dispersed into the entire aqueous phase in an extremely fine stream, avoiding the formation of large agglomerates due to excessively high local concentrations.

[0032] Particle size control: The powerful shear force can directly break down and reshape the formed liposomes into smaller, more uniform particles (typically in the 50-200 nm range). This step replaces or reduces subsequent extrusion or sonication steps.

[0033] Simultaneous encapsulation: At the moment of liposome formation, water-soluble components and hydrogen molecules in the aqueous phase are encapsulated into the core, while lipid-soluble components in the organic phase are embedded in the membrane.

[0034] After the solvent ethanol is evaporated and liposomes are formed by high-speed shearing, the ethanol in the system is removed by evaporation in the same high-pressure vessel or in a subsequent process by means of depressurization, heating or introduction of inert gas.

[0035] Improved liposome stability: Residual ethanol increases the fluidity of the lipid bilayer, making it more porous and prone to leakage of contents. Removing ethanol results in a denser and more rigid lipid membrane, significantly improving long-term stability and reducing leakage of active ingredients and hydrogen molecules. Reduced toxicity.

[0036] Preferably, the steps for preparing liposomes include:

[0037] 1) Raw material preparation and phase classification and separation

[0038] Liposome precursors, whose components include phospholipids and cholesterol;

[0039] Active substances, including fat-soluble active substances and water-soluble active substances;

[0040] Hydrogen-rich water is formed by water and hydrogen molecules;

[0041] In this process, both fat-soluble and non-fat-soluble active substances dissolve together with phospholipids and cholesterol in the solvent to form a fat-soluble organic phase.

[0042] Water-soluble active substances can be mixed with hydrogen-rich water to form a water-soluble solution.

[0043] 2) Film formation and hydration film formation: The prepared lipid-soluble organic phase is subjected to a rotary evaporator to remove the solvent, forming a uniform lipid film containing lipid-soluble active substances on the glass bottle wall.

[0044] Hydration: The prepared water-soluble solution (containing water-soluble active substances and hydrogen molecules) is added to the bottle containing the lipid film and stirred gently at a limited temperature (e.g., 0-50℃).

[0045] Fusion process:

[0046] When a water-soluble solution comes into contact with a lipid membrane, the phospholipids hydrate, swell, and self-coil to form liposomes.

[0047] Water-soluble active substances in the water-soluble solution are spontaneously encapsulated into the internal aqueous phase of the forming liposomes.

[0048] Hydrogen molecules in water-soluble solutions, due to their small size and slight lipophilicity, partially diffuse and embed themselves in the hydrophobic region of the phospholipid bilayer, while the other part is encapsulated in the internal aqueous phase in the form of bubbles.

[0049] Lipid-soluble active substances, pre-dissolved in a lipid-soluble organic phase, become part of the lipid bilayer.

[0050] 3) Post-processing and refinement

[0051] The liposomes of varying sizes obtained after hydration are extruded at least once through a polycarbonate membrane with a specific pore size to obtain liposomes with uniform particle size and stable structure.

[0052] Here, among the active substances, fat-soluble active substances include flavonoids, terpenes, and volatile oils, while water-soluble active substances include saponins, polysaccharides, and alkaloids.

[0053] Here, the prepared fat-soluble organic phase is solvent-removed in a rotary evaporator. Removing the solvent before contacting the water-soluble solution in this step reduces the escape of hydrogen molecules and increases the coating rate.

[0054] Optionally, the amount of fat-soluble active substances in the active material can be zero.

[0055] Preferably, the active substance comprises a traditional Chinese medicine preparation made from the following raw materials in the indicated weight ratios: Astragalus membranaceus 20-30 parts, Angelica sinensis 10-15 parts, Ligusticum chuanxiong 9-12 parts, Rehmannia glutinosa 15-20 parts, Salvia miltiorrhiza 10-15 parts, Acorus tatarinowii 9-12 parts, Buthus martensii 3-5 parts, and Scolopendra subspinipes 1-2 parts.

[0056] In the preparation of liposomes,

[0057] a) Preparation of Chinese herbal extracts: Weigh the medicinal materials according to the ratio, decoct and extract, concentrate and refine to obtain standardized extract powder.

[0058] b) Preparation of liposome membranes: Liposome precursors and cholesterol are dissolved in a solvent and rotary evaporated to form a liposome membrane.

[0059] c) Hydration and drug loading: The above lipid film was hydrated to obtain blank liposomes, and dry powder of traditional Chinese medicine extract was added. Drug-loaded liposome suspension was prepared by ultrasonic-extrusion method.

[0060] d) Hydrogen loading: The drug-loaded liposome suspension is placed in a high-pressure hydrogen reaction vessel, and the conditions are set as follows: pressure 2-5 MPa, temperature 2-6 °C, time 4-6 hours, so that hydrogen molecules are saturated and loaded in the lipid bilayer.

[0061] e) Purification and Formulation: The nano-formulation with a particle size distribution of 80-120 nm was obtained by ultrafiltration and centrifugation purification, and then dispensed into containers pre-filled with protective hydrogen and stored at 4°C in the dark.

[0062] Here, a preferred example is that this traditional Chinese medicine preparation creates a long-term favorable internal environment for neuronal survival and repair through multi-target regulation, such as astragalus polysaccharide regulating immunity, tanshinone improving microcirculation, and acorus tatarinowii volatile oil regulating neurotransmitters.

[0063] On the other hand, in the preparation of liposomes, the active substance is zero, that is, the preparation of liposomes does not include the active substance. That is, hydrogen-rich water and liposome precursors are dissolved to form liposomes; or hydrogen molecules, liposome precursors and solvents are dissolved to form liposomes, thereby preparing a liposome coating containing hydrogen molecules.

[0064] Preferably, the steps for preparing the outer layer precursor include:

[0065] Raw material mixing:

[0066] Formula (1): Food-grade beeswax (80-90%) + plasticizer (10-22%) + stabilizer (1-2%). Or formula (2): Sugar powder (70-80%) + film-forming agent (6-10%) + anti-caking agent (1-2%) + water (10-15%).

[0067] Raw material mixing: Weigh the basic formula raw materials according to the proportions and add them to the container.

[0068] Melt degassing: Heat to 60-120℃ and stir until completely melted (stirring speed 300r / min), vacuum degassing: 15-20min (vacuum degree 0.08MPa).

[0069] Keep warm for later use: Maintain the outer precursor temperature at 30-90℃ (below the melting temperature but in a softened liquid state), and control the viscosity at 90-1000 mPa·s.

[0070] Film forming: Pour the heat-insulated and prepared outer layer precursor into a roller film forming machine (roller temperature 30-80℃) to form a continuous film with a thickness of 0.2-3.0mm.

[0071] Thin film pretreatment: The thin film is cut into the appropriate width to form a waxy film or a crystalline food film.

[0072] Here, plasticizers include vegetable oils and triglycerides, stabilizers include lecithin, sugar powders include crystalline maltose and isomaltulose, film-forming agents include hydroxypropyl methylcellulose (HPMC), and anti-caking agents include silica.

[0073] Preferably, the outer layer forming step includes:

[0074] (1) Pressing with a relatively rotating grooved mold roller of an existing shot press machine, wherein the grooved mold (capacity 5-30g), the temperature of the grooved mold roller is 40-45℃, and the relative rotation biting pressure of the grooved mold roller is 0.15-0.5MPa.

[0075] (2) The formed waxy film or crystalline food film is conveyed to the groove mold via guide rollers, and the pump injects liposomes between the two films through quantitative feeding.

[0076] (3) When the relative rotating grooved mold roller presses and engages, the coating molding, liposome sealing and edge cutting are completed simultaneously. The formed coating falls off as the grooved mold roller continues to rotate downward, thus forming the coating.

[0077] Preferably, the outer layer forming step includes:

[0078] (1) Using the existing dropper equipment with double-layer dropper head (outer layer beeswax capsule material, inner layer contents), the dropper head orifice diameter is Φ3-6mm, and the inner and outer layer channel diameter ratio is 1:2.5.

[0079] (2) Outer beeswax capsule material feeding rate: 10-15 mL / min, contents feeding rate: 5-8 mL / min (ensuring capsule shell thickness of 0.2-0.3 mm)

[0080] Coolant: Food-grade liquid paraffin (temperature 20-25℃, density lower than the molten capsule material, facilitating capsule sinking)

[0081] Drop height: 15-20cm (to ensure the sphericity of the capsule)

[0082] Molding and curing: The molten capsule material and contents are extruded simultaneously, and after the coolant is dripped in, it solidifies rapidly in 3-5 seconds. It is then soaked in the coolant for 1-2 hours for further curing.

[0083] In the preparation of liposomes, the active substance is zero, that is, the preparation of liposomes does not include the active substance; and a liposome coating containing hydrogen molecules prepared by the method.

[0084] Here, hard candy, rock candy, and highly crystalline sugars are preferred as crystalline ingredients. Because when sugar is highly crystalline or in a glassy state, the molecules are arranged very tightly and orderly, with almost no free volume for hydrogen molecules to diffuse, thus providing excellent barrier properties against hydrogen molecules.

[0085] Here, cocoa butter, beeswax, and food-grade paraffin are preferred waxes because their long-chain, highly saturated, and neatly arranged crystal structure forms a dense barrier. Although hydrogen is fat-soluble, its diffusion rate is greatly reduced in highly ordered solid waxes, especially beeswax, whose main component is long-chain fatty acid esters. At room temperature, beeswax is a dense solid lipid film with no obvious pores, belonging to a purely fat-soluble, dense structure.

[0086] Here, the core of outer layer molding preparation is to encapsulate oily or fat-soluble contents in a coating made of a high-barrier material to form a sealed single-dose unit.

[0087] It should be noted that different liposome phases can be encapsulated using molding methods (such as sugar cube embedding) or dripping methods (such as beeswax balls) to more effectively store hydrogen molecules and active substances within the liposomes, such as:

[0088]

[0089] The table lists only preferred examples and is not limited to the above-mentioned contents. For example, waxy materials can also be embedded by membrane pressing.

[0090] For example: 1. Molding method, which uses a rotary shot blasting machine for continuous production.

[0091] A shot blasting machine has two main components:

[0092] Two conveyors: one for conveying strip film.

[0093] Two molding rollers: The surface has a large number of matching hemispherical pits (molds), the size and shape of which determine the final size and appearance of the capsule material (such as oval, elliptical, etc.).

[0094] process:

[0095] 1) The insulating adhesive is conveyed and cooled on a drum at a low temperature (about 20°C) to form two continuous, soft strip films.

[0096] 2) The two strips of film are fed at a constant speed between two rotating die rollers.

[0097] 3) Before the die rollers engage, a metering pump precisely injects the contents into the designated position on the lower die roller.

[0098] 4) The left and right mold rollers close under precise pressure, and the tape is pressed into the grooves of the mold rollers, wrapping the contents inside. At the same time, it is cut and shaped to form sealed packages.

[0099] The pressed soft capsules have a high water content (about 40%) on the outer layer, are soft, and are easily deformed.

[0100] It is placed into a shaping and drying drum and slowly rolled for several hours under temperature and humidity conditions (such as 20-24℃, 20-30% relative humidity) to initially shape it and make its shape stable.

[0101] After shaping, the package is transferred to a drying tunnel for further drying under low temperature (approximately 25-30°C) and low humidity conditions, reducing the moisture content of the outer layer of the package to the required level for the finished product (typically 12-15%). This is a slow process that can last 24-48 hours and is designed to prevent the package from deforming or forming a crust on the surface.

[0102] For example: 2. Droplet method, which utilizes the principle of droplet formation to complete the generation of the outer layer and the encapsulation of liposomes in one step.

[0103] Process flow:

[0104] 1. Place the prepared outer liquid and liposomes into their respective storage tanks.

[0105] 2. The liquid is extruded simultaneously through a double-layer nozzle, with the outer layer channel discharging the outer liquid and the inner layer channel discharging the liposomes.

[0106] 3. At the nozzle outlet, the liposomes are encapsulated by the outer liquid, forming concentric droplets.

[0107] 4. The droplets are regularly dropped into a coolant (such as liquid paraffin or vegetable oil).

[0108] 5. Due to surface tension and cooling, the droplets rapidly solidify into spherical soft capsules.

[0109] 6. Collect the capsules and then perform drying and packaging steps similar to those of the molding method.

[0110] The beneficial effects of this invention are:

[0111] Loading hydrogen molecules into liposomes perfectly compensates for the shortcomings of both hydrogen molecules and liposomes, while amplifying their respective advantages and creating a synergistic effect.

[0112] (I) Enabling hydrogen molecules with liposomes (solving the shortcomings of H2)

[0113] 1. The "hydrogen storage reservoir" effect solves the problems of storage and retention:

[0114] The aqueous phase inside liposomes can dissolve a large number of hydrogen molecules from nanobubbles, and their phospholipid bilayer, due to its slight lipophilicity, can also dissolve a considerable concentration of H2. This is equivalent to creating a miniature "hydrogen storage unit," significantly increasing the hydrogen molecule loading capacity.

[0115] The encapsulation of liposomes significantly slows down the escape rate of hydrogen molecules. Although H2 still diffuses slowly, its circulation time and stability in vivo are improved by orders of magnitude compared to its free state.

[0116] 2. The "navigation vehicle" effect enables targeted delivery:

[0117] The nanoscale size and EPR effect of liposomes can actively "deliver" hydrogen molecules to specific lesion sites (such as inflamed tissues and tumor microenvironments), achieving targeted therapy of hydrogen molecules, increasing the effective local concentration, and reducing the systemic dose requirement.

[0118] 3. "Slow-release pump" effect, prolonging the duration of action:

[0119] Liposomes gradually degrade in the body, slowly releasing the encapsulated hydrogen molecules, thus providing a continuous and long-lasting hydrogen source and avoiding the drawback of free hydrogen molecules "fleeting".

[0120] (II) The feedback effect of hydrogen molecules on liposomes (addressing the shortcomings of liposomes)

[0121] 1. "Antioxidant guardian" effect, enhancing liposome stability:

[0122] During storage and circulation in vivo, phospholipids in liposomes are easily oxidized (lipid peroxidation), leading to changes in membrane fluidity, rupture, and leakage of contents.

[0123] The exceptional selective antioxidant capacity of hydrogen molecules can efficiently scavenge free radicals and protect phospholipid molecules from oxidative damage, thereby significantly improving the physical stability and shelf life of liposomes. This is one of the most crucial synergistic effects.

[0124] 2. The "synergistic treatment" effect enhances the overall therapeutic effect:

[0125] Synergistic antioxidant / anti-inflammatory effects: When liposomes encapsulate other active substances (such as anti-inflammatory components of traditional Chinese medicine, vitamin C / E), hydrogen molecules can work synergistically with these components to exert antioxidant and anti-inflammatory effects, targeting different pathways and multiplying the effects.

[0126] Protecting active ingredients: Hydrogen molecules indirectly protect the encapsulated, easily degradable active substances (such as certain vitamins and polyphenols) inside the liposome membrane by maintaining its integrity, ensuring that they can reach the site of action intact.

[0127] (III) Active substances are the core functional source for exerting preventive or therapeutic effects. Liposomes and hydrogen molecules together constitute an "intelligent delivery system" and a "functional enhancement system", while active substances are the "core contents" to be delivered.

[0128] Overall, in this coating and method,

[0129] By utilizing the extremely high gas barrier properties of beeswax or hard candy membranes, a physical barrier is constructed, effectively preventing the rapid escape of hydrogen molecules from the core liposomes and solving the problem of hydrogen molecule stability and storage within the encapsulation material. Dual protection and synergistic effects: Liposomes provide initial protection for active substances (such as traditional Chinese medicine extracts and vitamins), while the outer beeswax or sugar membrane provides secondary protection, jointly improving the stability of the active ingredients. Hydrogen molecules and active substances can achieve synergistic antioxidant, anti-inflammatory, and other biological effects.

[0130] Targeted and sustained-release effects: Liposomes themselves have a certain degree of targeting, and the outer beeswax membrane slowly dissolves in the intestinal environment, which can achieve the targeted release and sustained release of active substances and hydrogen molecules in the intestine, thereby improving bioavailability.

[0131] Safe to eat and available in various forms: All ingredients are edible materials, ensuring high safety. The final product can be made into microspheres, granules, sugar cubes, and other forms, making it convenient to consume as a functional food or health supplement.

[0132] The following will further explain the concept, specific methods, and technical effects of the present invention in conjunction with the accompanying drawings, so as to fully understand the purpose, features, and effects of the present invention. Attached Figure Description

[0133] Figure 1 This is a step example diagram of one of the preferred embodiments of the method for preparing liposome coatings containing hydrogen molecules and active substances in this invention.

[0134] Figure 2 This is a step example diagram of one of the preferred embodiments of the method for preparing liposome coatings containing hydrogen molecules and active substances in this invention.

[0135] Figure 3 This is a schematic diagram illustrating a structural example of a liposome with an outer layer encapsulating the core in this invention.

[0136] exist Figure 3 In the middle: 1 is the grooved mold roller in the pellet press, 2 is the crystalline food film and wax film, 3 is the core liposome, 4 is the liposome extrusion head or wedge injector, and 5 is the formed soft capsule or coating. Detailed Implementation

[0137] The embodiments of the present invention will be described in detail below with reference to the accompanying drawings, but the present invention can be implemented in many different ways as defined and covered by the claims.

[0138] Example 1:

[0139] A method for preparing a liposome-coated compound containing hydrogen molecules and active substances, comprising the following:

[0140] (I) Preparation of liposomes: Hydrogen-rich water, active substances, liposome precursors and ethanol are dissolved and mixed to prepare liposomes.

[0141] (II) Preparation of outer layer precursor: The wax includes wax stock solution formed by melting wax and anti-caking agent; the wax stock solution is cooled and spread into a wax film.

[0142] (III) Outer layer forming: The wax film is laid on the surface of the grooved mold in a soft state at an appropriate temperature. The formed liposomes are injected into the grooved mold on the surface where the wax film is laid. Finally, another wax film is laid on the grooved mold where the liposomes are injected. Then, the periphery of the double-layered wax film formed on the grooved mold is pressed, sealed and shaped, and cut along the edge of the grooved mold, thereby removing the wax film encapsulating the liposomes from the grooved mold, thus forming this coating.

[0143] Here are the detailed steps:

[0144] The solvents are hydrogen-rich water and ethanol, and the active substance is a traditional Chinese medicine liquid.

[0145] The specific detailed steps are as follows Figure 1 , Figure 3 As shown: Here, the ratio of raw materials for preparing liposomes to preparing the outer layer precursor is 2:1. In the preparation of liposomes: liposome precursor (30%-70%), active substance (10%-30%), hydrogen-rich water (10%-30%), and anhydrous ethanol (10%-20%).

[0146] 1) Raw material preparation and phase classification and separation

[0147] The liposome precursor consists of 9.8 kg of phospholipids and 0.2 kg of cholesterol, with a ratio of phospholipids (9.0%-9.8%) to cholesterol (0.2%-1.0%).

[0148] 3 kg of active substances, including fat-soluble and water-soluble active substances. In this embodiment, the traditional Chinese medicine liquid is Astragalus membranaceus liquid. The traditional Chinese medicine liquid or concentrated traditional Chinese medicine liquid is obtained by decoction and filtration of Astragalus membranaceus and then used as water-soluble active substances.

[0149] 4kg of hydrogen-rich water; it is nano-bubble hydrogen-rich water with a hydrogen molecule content of 2.0ppm.

[0150] 3kg of anhydrous ethanol:

[0151] Among them, the fat-soluble active substances are all dissolved together with phospholipids and cholesterol in the solvent ethanol to form a fat-soluble organic phase;

[0152] Water-soluble active substances can be mixed with hydrogen-rich water to form a water-soluble solution.

[0153] 2) Film formation and hydration film formation: The prepared lipid-soluble organic phase is subjected to a rotary evaporator to remove the solvent, forming a uniform lipid film containing lipid-soluble active substances on the glass bottle wall.

[0154] Hydration: The prepared water-soluble solution (containing water-soluble active substances and hydrogen molecules) is added to the bottle containing the lipid film and stirred gently at a limited temperature of 30°C or under a limited temperature of 30°C and sealed high pressure to prevent hydrogen molecules from escaping.

[0155] Fusion process:

[0156] When a water-soluble solution comes into contact with a lipid membrane, the phospholipids hydrate, swell, and self-coil to form liposomes.

[0157] Water-soluble active substances in the water-soluble solution are spontaneously encapsulated into the internal aqueous phase of the forming liposomes.

[0158] Hydrogen molecules in water-soluble solutions, due to their small size and slight lipophilicity, partially diffuse and embed themselves in the hydrophobic region of the phospholipid bilayer, while the other part is encapsulated in the internal aqueous phase in the form of bubbles.

[0159] Lipid-soluble active substances, pre-dissolved in a lipid-soluble organic phase, become part of the lipid bilayer.

[0160] 3) Post-processing and refinement

[0161] The liposomes of varying sizes obtained after hydration are extruded at least once through a polycarbonate membrane with a specific pore size to obtain liposomes with uniform particle size and stable structure.

[0162] (a) Preparation of outer layer precursor:

[0163] In this embodiment, since the weight ratio of the raw materials for preparing liposomes to those for preparing the outer layer precursor is 2:1, the mixing ratio of these raw materials is: 8.5 kg of food-grade beeswax + 1.3 kg of plasticizer + 0.2 kg of stabilizer. Here, the plasticizer is triglyceride, and the stabilizer is lecithin.

[0164] Raw material mixing: Weigh the basic formula raw materials according to the proportions and add them to the container.

[0165] Melt degassing: Heat to 100℃ and stir until completely melted (stirring speed 300r / min), vacuum degassing: 15-20min (vacuum degree 0.08MPa).

[0166] Keep warm for later use: Maintain the outer precursor temperature at 40℃ (below the melting temperature but in a softened liquid state), and control the viscosity at 100mPa·s.

[0167] Film forming: The outer layer precursor guide roller film forming machine (roller temperature 50℃) is used to form a continuous film with a thickness of 2.0mm.

[0168] Thin film pretreatment: Cut the two irregular edges of the film to the corresponding width to form a wax film.

[0169] Add 0.1-0.3% preservative (such as methylparaben) to the prepared liposomes or not, and keep them at 35-40℃ for later use.

[0170] (b) Outer layer molding:

[0171] (1) Pressing is performed by the relative rotation grooved mold roller of the existing capsule pressing machine, wherein the grooved mold capacity is 10g, the grooved mold roller temperature is 40-45℃, and the relative rotation biting pressure of the grooved mold roller is 0.15-0.5MPa.

[0172] (2) The formed wax film is conveyed to the top of the groove mold by the guide roller, and the liposomes are injected between the two films by quantitative feeding.

[0173] (3) When the relative rotating grooved mold roller presses and engages, the coating molding, liposome sealing and edge cutting are completed simultaneously. The formed coating falls off as the grooved mold roller continues to rotate downward, thus forming the coating.

[0174] (c) Post-processing of the coating

[0175] Drying and stabilization: Place the capsule in a drying room at 30-35℃ and 40-50% relative humidity, and allow it to dry statically for 6-8 hours (surface curing).

[0176] Anti-sticking treatment: After drying, spray a small amount of silica powder (≤0.5%) onto the surface of the capsule, and gently rub to remove excess powder. Check for leakage of contents. No leakage or deformity.

[0177] Example 2:

[0178] (i) Preparation of liposomes: Hydrogen molecules, active substances, liposome precursors and solvents are dissolved and mixed to prepare liposomes; in this embodiment, the active substance is ginseng Chinese medicine liquid, which is obtained by decoction and filtration of Chinese medicine liquid or Chinese medicine concentrate.

[0179] (II) Preparation of outer layer precursor: Crystallized food ingredients include sugar alcohols and binders mixed and heated to form a crystalline food ingredient stock solution; the crystalline food ingredient stock solution is cooled and spread out to form a crystalline food ingredient film.

[0180] (III) Outer Layer Forming: The crystalline food film is laid on the surface of a grooved mold under suitable temperature and soft conditions. The formed liposomes are injected into the grooved mold on which the crystalline food film is laid. Finally, the water-soluble contents of the crystalline food are laid on the grooved mold containing the injected liposomes. The solid content needs to be concentrated to 40-50% (to reduce the moisture content and prevent the capsule shell from absorbing moisture and deforming). 0.1-0.3% preservative (such as methylparaben) is added, and the mixture is stirred evenly and kept at 35-40℃ for later use. Then, the periphery of the double-layered crystalline food film formed on the grooved mold is pressed and sealed to shape it, and then cut along the edge of the grooved mold, thereby detaching the crystalline food film encapsulating the liposomes from the grooved mold, thus forming this coating.

[0181] Here are the detailed steps:

[0182] The ratio of raw materials for liposome preparation to that for outer layer preparation is 2.5:1, and the solvent is water. In the preparation of liposomes: liposome precursor (30%-70%), active substance (10%-30%), water (10%-30%), and anhydrous ethanol (10%-20%).

[0183] The liposome precursor consists of 12.25 kg of phospholipids and 0.25 kg of cholesterol, with a ratio of phospholipids (9.0%-9.8%) to cholesterol (0.2%-1.0%).

[0184] The active ingredient comprises 2.5 kg of water, 6 kg of anhydrous ethanol, and at least 12 mg or 147 mL of hydrogen gas (hydrogen molecules), preferably 12 mg to 1000 mg, or 147 mL to 10000 mL. In this embodiment, the amount of hydrogen gas (hydrogen molecules) is 900 mL.

[0185] First, hydrogen molecules and water are continuously mixed at high speed in a high-pressure sealed container under pressure controlled at at least 1 MPa. Then, active substances and liposome precursors are introduced into the high-pressure sealed container under continuous high-speed rotation and shearing to dissolve and form liposomes.

[0186] Here, high-purity hydrogen is introduced into water and mixed by continuous high-speed rotation and shearing in a high-pressure, sealed container.

[0187] Under high pressure or high-pressure injection, the solubility of hydrogen increases. The enormous energy generated by high-speed rotational shearing breaks the hydrogen into extremely tiny bubbles (nanobubbles), forming hydrogen-rich water with stable physical properties and high hydrogen concentration. The high-pressure, sealed environment prevents hydrogen escape. The active substance and liposome precursor are then mixed and introduced into the hydrogen-rich water undergoing continuous high-speed rotational shearing. Due to the high shear energy, the active substance, liposome precursor, and hydrogen-rich water mix rapidly and intensely. When injected into the aqueous phase, they spontaneously self-assemble into liposomes due to changes in solubility. During this process, hydrogen molecules and dissolved active substances in the hydrogen-rich water are simultaneously encapsulated within the forming liposomes.

[0188] The effect of high-speed shearing: ultimate mixing: high-speed shearing ensures that the ethanol phase can be instantly and uniformly dispersed into the entire aqueous phase in an extremely fine stream, avoiding the formation of large agglomerates due to excessively high local concentrations. The material is impacted by high-speed shearing, and the particles are further refined through turbulence and cavitation effects, allowing hydrogen molecules to enter the cavities.

[0189] Particle size control: The powerful shear force can directly break down and reshape the formed liposomes into smaller, more uniform particles (typically in the 50-200 nm range). This step replaces or reduces subsequent extrusion or sonication steps.

[0190] Simultaneous encapsulation: At the moment of liposome formation, water-soluble components and hydrogen molecules in the aqueous phase are encapsulated into the core, while lipid-soluble components in the organic phase are embedded in the membrane.

[0191] (a) Preparation of outer layer precursor

[0192] Material ratio of the outer layer precursor: 60%-80% granulated sugar powder, 0.5%-1.0% hydroxypropyl methylcellulose (HPMC), 0.1%-0.5% silica, and 1.0%-3.0% deionized water. Weigh 7.8 kg of granulated sugar powder, 0.3 kg of hydroxypropyl methylcellulose (HPMC), and 0.1 kg of silica according to the above ratio, add 1.8 kg of deionized water, heat to 70-150℃, and stir until completely dissolved (stirring speed 500 r / min) to form a sugar block solution, or adjust the sugar block solution to a concentrated solids content of 40-50% (reduce the moisture content to prevent the outer layer from absorbing moisture and deforming), add 0.1-0.3% preservative (such as methylparaben), stir evenly, and keep warm for later use.

[0193] Film Forming: Pour the sugar solution into a roller film forming machine (roller temperature 50-55℃) to form a continuous film with a thickness of 1mm. The film must be free of bubbles and have a smooth surface (it should be flexible after cooling to room temperature and fold without cracking). Film Pretreatment: Cut the film to a width matching the mold (e.g., 10-15cm) and place it in an environment with a relative humidity of 50-60% for equilibration for 1-2 hours (to prevent drying and cracking or moisture absorption and sticking).

[0194] (b) Compression molding

[0195] Using an existing rotary soft capsule press, select a mold roller with an elliptical groove (capacity 6g), and adjust the mold temperature to 40-45℃ and the biting pressure to 0.15-0.2MPa.

[0196] Suppression process:

[0197] The sugar block film is conveyed to the surface of the mold rollers by the guide rollers of the press, and the feed pump injects the prepared liposomes into the elliptical grooves of the two mold rollers through the metering nozzle (the metering accuracy error is ≤ ±3%).

[0198] When the two mold rollers rotate and mesh in opposite directions, the shell is formed, the contents are sealed and the edges are cut simultaneously. The formed capsule falls off with the mold, thus forming the package.

[0199] (c) Post-processing

[0200] Drying and stabilization: Place the capsule in a drying room at 30-35℃ and 40-50% relative humidity, and allow it to dry statically for 6-8 hours (surface curing).

[0201] Anti-sticking treatment: After drying, spray a small amount of silica powder (≤0.5%) onto the surface of the capsule, and gently rub to remove excess powder. After checking for leakage, proceed with packaging.

[0202] Example 3

[0203] A method for preparing a liposome-coated compound containing hydrogen molecules and active substances, such as...Figure 2 As shown, it includes: (i) preparation of liposomes: hydrogen molecules, active substances, liposome precursors and solvents are dissolved and mixed to prepare liposomes;

[0204] (II) Preparation of outer layer precursor: wax includes wax stock solution formed by melting wax and anti-caking agent. (III) Outer layer forming: heat the wax stock solution to completely melt it into a homogeneous liquid, and slowly drop the preheated liposome into the corresponding wax stock solution homogeneous liquid in the form of droplets. The center of the droplet is the liposome, and the outer layer is covered by a molten wax coating layer or a crystalline food coating layer. Then, it is cooled and solidified to form this coating.

[0205] In this embodiment,

[0206] The ratio of raw materials for liposome preparation to those for outer layer preparation is 1:1.

[0207] The solvents are water and anhydrous ethanol.

[0208] The active substances include fat-soluble active substances and water-soluble active substances. The fat-soluble active substance is Angelica sinensis volatile oil, and the water-soluble active substance is Panax notoginseng saponins.

[0209] In the preparation of liposomes: liposome precursor (30%-70%), active substance (10%-30%), water (10%-30%), and anhydrous ethanol (10%-20%).

[0210] The liposome precursor consists of 5.25 kg of phospholipids and 0.25 kg of cholesterol, with a ratio of 9.0%-9.8% phospholipids to 0.2%-1.0% cholesterol.

[0211] The active ingredient is 1 kg, including 0.3 kg of Angelica sinensis volatile oil and 0.7 kg of Panax notoginseng saponins.

[0212] 2 kg of water, 1.5 kg of anhydrous ethanol, and at least 2 mg or 25 mL of hydrogen gas (hydrogen molecules), preferably 2 mg-300 mg or 25 mL-1000 mL. In this embodiment, the amount of hydrogen gas (hydrogen molecules) is 500 mL.

[0213] The detailed steps are as follows:

[0214] The steps for preparing liposomes include: using water and ethanol as solvents, hydrogen molecules and the solvent water form hydrogen-rich water, which dissolves with the water-soluble active substance in the active material to form a water-soluble solution. After the liposome precursor and the solvent ethanol are dissolved, the lipid-soluble active substance in the active material is added to form a lipid-soluble organic phase. The lipid-soluble organic phase is then introduced into a high-pressure sealed container containing the water-soluble solution and undergoes high-speed shear dissolution to form liposomes. Further, the lipid-soluble organic phase is introduced into a high-pressure sealed container containing the water-soluble solution and undergoes high-speed shear dissolution, followed by evaporation of the solvent ethanol to form liposomes.

[0215] Here, hydrogen molecules are dissolved in water under high pressure to create hydrogen-rich water. Water-soluble active substances are then dissolved in the hydrogen-rich water. The aim is to ensure that both hydrogen molecules and water-soluble active substances are present in the internal aqueous phase of the final liposomes. Using hydrogen-rich water is fundamental to achieving high-concentration hydrogen loading. The high-pressure, closed environment prevents premature hydrogen escape.

[0216] Secondly, the liposome precursor is dissolved in ethanol before the liposoluble active substance is added and dissolved. This ensures that the phospholipids and the liposoluble active substance are uniformly mixed at the molecular level in the ethanol solvent. Pre-binding the liposoluble active substance to the phospholipid ensures that it can naturally embed into the final lipid bilayer during liposome formation.

[0217] Liposome precursors dissolved in ethanol are injected into a high-pressure, closed container subjected to high-speed shearing. Since phospholipids are soluble in ethanol but insoluble in a large aqueous phase, the solubility of phospholipids decreases instantaneously when the ethanol phase is injected into the aqueous phase. To allow their hydrophobic tails to avoid the water molecule environment, they spontaneously self-assemble to form liposomes.

[0218] The effect of high-speed shearing: ultimate mixing: high-speed shearing ensures that the ethanol phase can be instantly and uniformly dispersed into the entire aqueous phase in an extremely fine stream, avoiding the formation of large agglomerates due to excessively high local concentrations.

[0219] Particle size control: The powerful shear force can directly break down and reshape the formed liposomes into smaller, more uniform particles (typically in the 50-200 nm range). This step replaces or reduces subsequent extrusion or sonication steps.

[0220] Simultaneous encapsulation: At the moment of liposome formation, water-soluble components and hydrogen molecules in the aqueous phase are encapsulated into the core, while lipid-soluble components in the organic phase are embedded in the membrane.

[0221] After the solvent ethanol is evaporated and liposomes are formed by high-speed shearing, the ethanol in the system is either evaporated and removed by heating in the same high-pressure container or in a subsequent process, or the solvent ethanol is retained without evaporation. In this embodiment, evaporation is not performed.

[0222] Improved liposome stability: Residual ethanol increases the fluidity of the lipid bilayer, making it more porous and prone to leakage of contents. Removing ethanol results in a denser and more rigid lipid membrane, significantly improving long-term stability and reducing leakage of active ingredients and hydrogen molecules. Reduced toxicity.

[0223] (a) Preparation of capsule material

[0224] Raw material mixing: Weigh 8.5 kg of food-grade beeswax, 1.4 kg of sunflower seed oil (plasticizer), and 0.1 kg of soybean lecithin according to the proportions, and add them to the wax melting tank.

[0225] Melting and degassing: Heat to 70-75℃ (5-10℃ above the melting point of beeswax), stir until completely melted (stirring speed 300r / min), and degas under vacuum for 15-20min (vacuum degree 0.08MPa) to remove air bubbles and avoid pitting on the shell.

[0226] Insulation and standby: Maintain the temperature of the capsule material at 65-70℃ (below the melting temperature but in a liquid state), and control the viscosity at 500-1000 mPa·s.

[0227] (b) Droplet forming

[0228] Equipment debugging: Utilize the existing double-layer dripping device with publication number CN209237881U, i.e., the outer layer is beeswax capsule material and the inner layer is liposome, the dripping pore diameter is Φ3-6mm, and the inner and outer layer channel diameter ratio is 1:2.5.

[0229] Parameter settings:

[0230] Capsule material feeding rate: 10-15 mL / min; Contents feeding rate: 5-8 mL / min (ensuring capsule shell thickness of 0.2-0.3 mm).

[0231] Coolant: Food-grade liquid paraffin (temperature 20-25℃, density lower than the molten capsule material, facilitating capsule sinking)

[0232] Drop height: 15-20cm (to ensure the sphericity of the capsule)

[0233] Molding and curing: The molten capsule material and contents are extruded simultaneously, and after the coolant is dripped in, it solidifies rapidly in 3-5 seconds. It is then soaked in the coolant for 1-2 hours for further curing.

[0234] (c) Post-processing

[0235] Cleaning and drying: Remove the capsule, wipe off any residual liquid paraffin on the surface with anhydrous ethanol, and air dry at 35-40℃ for 30 minutes (to remove ethanol residue). There should be no leakage or deformity.

[0236] Example 4

[0237] In this embodiment, the difference from Embodiment 1 is that the active substance is zero in the preparation of liposomes, that is, the preparation of liposomes does not include active substances, which is a method for preparing liposome coatings containing hydrogen molecules.

[0238] Here, the ratio of raw materials for liposome preparation to those for outer layer preparation is 1:1.

[0239] Liposome precursor (30%-70%), hydrogen-rich water (10%-30%), anhydrous ethanol (10%-20%).

[0240] 1. Raw material preparation and phase classification and separation

[0241] The liposome precursor consists of 5.25 kg of phospholipids and 0.25 kg of cholesterol, with a ratio ranging from 9.0% to 9.8% phospholipids to 0.2% to 1.0% cholesterol.

[0242] 2.5kg of hydrogen-rich water; it is nano-bubble hydrogen-rich water with a hydrogen molecule content of 2.0ppm.

[0243] 1.5 kg of anhydrous ethanol.

[0244] Example 5

[0245] In this embodiment, the difference from Embodiment 3 is that, in the preparation of liposomes, the active ingredients are prepared according to the following proportions: Astragalus membranaceus 25 parts, Angelica sinensis 12 parts, Ligusticum chuanxiong 10 parts, Rehmannia glutinosa 18 parts, Salvia miltiorrhiza 12 parts, Acorus tatarinowii 10 parts, Buthus martensii 4 parts, and Scolopendra subspinipes 1.5 parts. After supercritical carbon dioxide extraction, 1 kg of refined extract is obtained. Phospholipids 5.25 kg and cholesterol 0.25 kg are added, with a ratio of phospholipids (9.0%-9.8%) to cholesterol (0.2%-1.0%). 2 kg of water and 1.5 kg of anhydrous ethanol are used to dissolve the phospholipids and cholesterol in ethanol, followed by rotary evaporation to form a membrane. The membrane is hydrated with hydrogen-rich water to obtain liposomes. The above-mentioned refined herbal extract powder is added, and the mixture is extruded through ultrasound and a microporous membrane to obtain drug-loaded liposomes with a particle size of approximately 100 nm.

[0246] The drug-loaded liposome suspension was placed in a high-pressure reactor, hydrogen molecules were introduced to a pressure of 3.5 MPa, and the reaction was carried out at 4°C with shaking for 5 hours to prepare hydrogen-rich drug-loaded liposomes.

[0247] In summary, the coordination among liposomes, active substances, and hydrogen molecules can be summarized as follows:

[0248] 1) Liposomes → Hydrogen molecules / active substances: Provide protection and targeted delivery: Encapsulate both to prevent damage from the external environment and target to the lesion site through the EPR effect. Prolong the half-life of hydrogen molecules: The phospholipid layer greatly slows down the escape rate of hydrogen molecules.

[0249] 2) Hydrogen molecules → Liposomes / Active substances: Protecting the liposome membrane: The selective antioxidant effect of hydrogen molecules can scavenge free radicals, prevent phospholipid oxidation, and maintain the integrity of the liposome structure. Protecting active substances: Through antioxidant action, it reduces the degradation of active substances (especially easily oxidized components) during storage and delivery.

[0250] 3) Active substances → synergistic effect: They may produce synergistic or additive effects with hydrogen molecules in anti-inflammatory, antioxidant and other pathways, enhancing the final effect.

[0251] Therefore, the preferred embodiments of the present invention have been described in detail above. It should be understood that those skilled in the art can make numerous modifications and variations based on the concept of the present invention without creative effort. Therefore, all technical solutions that can be obtained by those skilled in the art based on the concept of the present invention through logical analysis, reasoning, or limited experimentation on the basis of existing technology should be within the scope of protection defined by the claims.

Claims

1. A liposome-coated compound containing hydrogen molecules and active substances, characterized in that, include: The core, composed of liposomes containing hydrogen molecules, has active substances embedded in or encapsulated in the aqueous phase within the phospholipid bilayer of the liposomes; and... The outer layer is an edible, high-barrier membrane material that covers the core.

2. The coating according to claim 1, characterized in that, The active substances include one or more combinations of traditional Chinese medicine preparations, active extracts of traditional Chinese medicine, vitamins, polyphenols, or protein peptides; the active substances are fat-soluble and water-soluble active substances, the fat-soluble active substances include flavonoids, terpenes, and volatile oils, and the water-soluble active substances include saponins, polysaccharides, and alkaloids; the edible high-barrier membrane material is a crystalline food or a wax.

3. A method for preparing a liposome-coated compound containing hydrogen molecules and active substances, characterized in that, Including the following: (a) Preparation of liposomes: Liposomes are prepared by dissolving hydrogen-rich water, active substances, and liposome precursors; or liposomes are prepared by dissolving hydrogen molecules, active substances, liposome precursors, and solvents. (II) Preparation of outer layer precursor: Crystalline food includes a crystalline food stock solution formed by heating a mixture of sugar alcohols and binders; wax includes a wax stock solution formed by melting wax and anti-caking agent; or the crystalline food stock solution and the wax stock solution are cooled and spread out separately to form a crystalline food film and a wax film; (III) Outer Layer Forming: A wax film or crystalline food ingredient film is laid on a surface with a grooved mold in a soft state at a suitable temperature. The formed liposomes are injected into the grooved mold on which the wax film or crystalline food ingredient film is laid. Finally, the wax film or crystalline food ingredient film is laid on the grooved mold containing the injected liposomes. At the same time, the periphery of the double-layered wax film or crystalline food ingredient film formed on the grooved mold is pressed, sealed, and shaped, and then cut along the edge of the grooved mold, thereby detaching the wax film or crystalline food ingredient film encapsulating the liposomes from the grooved mold, thus forming this coating; or, The crystalline food ingredient liquid or waxy food ingredient liquid is heated to completely melt it into a homogeneous liquid. The preheated liposome is slowly dripped into the corresponding homogeneous liquid in the form of droplets. The center of the droplet is the liposome, and the outer layer is a molten waxy coating layer or a crystalline food ingredient coating layer. Then it is cooled and solidified to form the coating.

4. The method according to claim 3, characterized in that, The solvent is one or more of water, anhydrous ethanol, methanol, and diethyl ether.

5. The method according to claim 3, characterized in that, The steps for preparing liposomes include: the solvent is water; hydrogen molecules and water are first continuously mixed at high speed in a high-pressure sealed container; the active substance and liposome precursor are then introduced into the high-pressure sealed container for continuous high-speed rotation and shearing to form liposomes. Alternatively, the step of preparing liposomes may include: 1) Preparation of liposome membranes: Liposome precursors and cholesterol are dissolved in anhydrous ethanol and then rotary evaporated to form liposome membranes; 2) Hydration and loading: The above lipid film was hydrated with phosphate-buffered saline (PBS) to obtain blank liposomes. Active substances were added, and drug-loaded liposome suspensions were prepared by ultrasonic-extrusion method. 3) Hydrogen loading: The liposome suspension of oil-loaded active substances is placed in a high-pressure hydrogen reaction device and subjected to a pressure of 2-5 MPa, 2-6℃ and a time of 4-6 hours to saturate hydrogen molecules in the lipid bilayer. 4) Purification and formulation: The liposomes were purified by ultrafiltration to obtain nano-formulations with a particle size distribution of 80-120 nm. They were then dispensed into containers pre-filled with protective hydrogen and stored at 4°C in the dark.

6. The method according to claim 3, characterized in that, The steps for preparing liposomes include: the solvent is water and ethanol; the hydrogen molecules and the solvent water form hydrogen-rich water, which is dissolved with the water-soluble active substance in the active substance to form a water-soluble solution; the liposome precursor and the solvent ethanol are dissolved, and then the lipid-soluble active substance in the active substance is dissolved to form a lipid-soluble organic phase; the lipid-soluble organic phase is introduced into a high-pressure sealed container containing the water-soluble solution and dissolved under high speed to form liposomes.

7. The method according to claim 3, characterized in that, The steps for preparing liposomes include: 1) Raw material preparation and phase classification and separation The liposome precursor comprises phospholipids and cholesterol; active substances, including lipid-soluble and water-soluble active substances; and hydrogen-rich water formed by water and hydrogen molecules. The lipid-soluble or non-lipin-soluble active substances are dissolved together with phospholipids and cholesterol in a solvent to form a lipid-soluble organic phase; the water-soluble active substances are miscible with the hydrogen-rich water to form a water-soluble solution. 2) Film formation and hydration Film formation: The prepared lipid-soluble organic phase is subjected to a rotary evaporator to remove the solvent, forming a uniform lipid film containing lipid-soluble active substances on the glass bottle wall; Hydration: The prepared water-soluble solution (containing water-soluble active substances and hydrogen molecules) is added to the bottle containing the lipid film and stirred gently at a limited temperature (e.g., 0-50℃). Fusion process: When the water-soluble solution comes into contact with the lipid membrane, the phospholipids hydrate, swell, and self-coil to form liposomes; the water-soluble active substances in the water-soluble solution are spontaneously encapsulated into the internal aqueous phase of the forming liposomes; due to their small molecular size and mild lipophilicity, some hydrogen molecules in the water-soluble solution diffuse and embed into the hydrophobic region of the phospholipid bilayer, while others are encapsulated in the internal aqueous phase in the form of bubbles; the lipophilic active substances pre-dissolved in the lipophilic organic phase become part of the lipid bilayer; 3) Post-processing and refinement The liposomes of varying sizes obtained after hydration are squeezed through the pores of a polycarbonate membrane at least once to obtain liposomes with uniform particle size and stable structure.

8. The method according to claim 3, characterized in that, The active substance comprises a traditional Chinese medicine preparation made from the following raw materials in the indicated weight ratios: Astragalus membranaceus 20-30 parts, Angelica sinensis 10-15 parts, Ligusticum chuanxiong 9-12 parts, Rehmannia glutinosa 15-20 parts, Salvia miltiorrhiza 10-15 parts, Acorus tatarinowii 9-12 parts, Buthus martensii 3-5 parts, and Scolopendra subspinipes 1-2 parts. In the preparation of liposomes, a) Preparation of Chinese herbal extracts: Weigh the medicinal materials according to the ratio, decoct and extract, concentrate and refine to obtain standardized extract powder; b) Preparation of liposome membranes: Liposome precursors and cholesterol are dissolved in a solvent and rotary evaporated to form liposome membranes; c) Hydration and drug loading: The above lipid film was hydrated to obtain blank liposomes, and dry powder of traditional Chinese medicine extract was added. Drug-loaded liposome suspension was prepared by ultrasonic-extrusion method. d) Hydrogen loading: The drug-loaded liposome suspension is placed in a high-pressure hydrogen reaction vessel, and the conditions are set as follows: pressure 2-5 MPa, temperature 2-6℃, time 4-6 hours, so that hydrogen molecules are saturated and loaded in the lipid bilayer. e) Purification and Formulation: Nanoparticles with a particle size distribution of 80-120 nm were obtained by ultrafiltration purification and dispensed into containers pre-filled with protective hydrogen gas and stored at 4°C in the dark.

9. The method according to claim 3, characterized in that, The steps for preparing the outer layer precursor include: raw material mixing ratio (1): food-grade beeswax (80-90%) + plasticizer (10-22%) + stabilizer (1-2%); Or the formula (2): sugar powder (70-80%) + film-forming agent (6-10%) + anti-caking agent (1-2%) + water (10-15%); Raw material mixing: Weigh the basic formula raw materials according to the proportion and add them to the container; Melt degassing: Heat to 60-120℃ and stir until completely melted (stirring speed 300r / min), vacuum degassing: 15-20min (vacuum degree 0.08MPa); Keep warm and ready for use: Maintain the outer precursor temperature at 30-90℃ (below the melting temperature but in a softened liquid state), and control the viscosity at 90-1000 mPa·s; Film forming: Pour the heat-insulated and prepared outer layer precursor into a roller film forming machine (roller temperature 30-80℃) to form a continuous film with a thickness of 0.2-3.0mm; Thin film pretreatment: Cut the thin film into appropriate widths to form a waxy film or a crystalline food film; The outer layer forming steps include: (1) Pressed by a relatively rotating grooved die roller, wherein the temperature of the grooved die roller is 40-45℃ and the relative rotational engagement pressure of the grooved die roller is 0.15-0.5MPa; (2) The formed waxy film or crystalline food film is conveyed to the groove mold via guide rollers, and the pump injects liposomes between the two films through quantitative feeding. (3) When the relative rotating grooved mold roller presses and interlocks, the coating molding, liposome sealing and edge cutting are completed simultaneously. The formed coating falls off as the grooved mold roller continues to rotate downward, thus forming this coating. Alternatively, the outer layer forming step may include: (1) The dripper is made of double-layered material (outer layer beeswax capsule, inner layer contents), with a dripper orifice diameter of Φ3-6mm and an inner-outer channel diameter ratio of 1:2.

5. (2) Outer beeswax capsule material feeding rate: 10-15 mL / min, contents feeding rate: 5-8 mL / min (ensuring capsule shell thickness of 0.2-0.3 mm); cooling through food-grade liquid paraffin (temperature 20-25℃, density lower than the molten capsule material, facilitating capsule sinking); drip height: 15-20 cm (ensuring capsule sphericity); Molding and curing: The molten capsule material and contents are extruded simultaneously, and after the coolant is dripped in, it solidifies rapidly in 3-5 seconds. It is then soaked in the coolant for 1-2 hours for further curing.

10. The method according to claim 3, characterized in that, In the preparation of liposomes, the active substance is zero, that is, the preparation of liposomes does not include the active substance; and a liposome coating containing hydrogen molecules prepared by the method.

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