Glutathione liposome microcapsule granules

Abstract

The utility model provides a kind of glutathione liposome microcapsule granule, it is related to liposome microcapsule field.The utility model is wrapped in three layers of protective layer in glutathione, these three layers of protective layer are in turn lipid bilayer, dense antioxidant layer and film coating layer from inside to outside, wherein lipid bilayer can protect glutathione before entering digestive system its function is not affected, help glutathione enter cell membrane, and then improve its bioavailability;The nano-micellar structure of dense oxidation layer makes it have durable antioxidant property;Film coating layer can improve the fluidity of glutathione liposome microcapsule granule, and can resist gastric acid destruction, further improve the bioavailability of glutathione.By the above structure can make the absorption rate of glutathione preparation significantly improve, so the glutathione liposome microcapsule granule of the utility model has significant potential in liver protection, antioxidant therapy field.

Description

Technical Field

[0001] This utility model relates to the field of liposome microcapsule technology, and more specifically, to a glutathione liposome microcapsule particle. Background Technology

[0002] Glutathione is a natural tripeptide (γ-glutamylcysteine) composed of glutamic acid, cysteine, and glycine. Glutathione exists primarily in two forms: oxidized (GSSG) and reduced (GSH). It is an indispensable antioxidant and detoxifier in the human body, playing a central role in maintaining cellular health, immune function, liver function, and overall health.

[0003] Direct supplementation of glutathione (especially orally) to the human body does present several significant obstacles. For example, the vast majority of orally ingested glutathione is broken down into its constituent amino acids (glutamic acid, cysteine, glycine) or dipeptides (such as cysteylglycine) before reaching the intestinal absorption site, rather than remaining as intact glutathione molecules. Even if a small amount of intact glutathione is not completely broken down, its absorption efficiency through intestinal epithelial cells is extremely low. Even if trace amounts of intact glutathione are absorbed into the portal vein bloodstream, they will first pass through the liver before reaching systemic circulation. The liver is the primary organ for glutathione metabolism and utilization, taking up and utilizing or breaking down this portion of the absorbed glutathione, further reducing the amount of intact glutathione that can enter systemic circulation. Furthermore, glutathione primarily functions within cells, but intact glutathione is difficult to directly cross the cell membrane into the cell.

[0004] For the reasons mentioned above, the bioavailability of conventional glutathione formulations is very low. Therefore, designing a product that helps improve the bioavailability of glutathione is of considerable value. Utility Model Content

[0005] The purpose of this invention is to provide a glutathione liposome microcapsule, the structure of which can improve the bioavailability of glutathione.

[0006] The embodiments of this utility model can be implemented as follows: A glutathione liposome microcapsule includes: a core, and three protective layers surrounding the core; wherein the protective layers, from the inside out, are a lipid bilayer, a dense antioxidant layer, and a thin film coating layer.

[0007] In some embodiments, the lipid bilayer is selected from any one of lecithin, phosphatidylcholine, phosphatidylcholine derivatives, phosphatidylinositol, phosphatidylserine, or cholesterol.

[0008] In some embodiments, the dense antioxidant layer is a nanomicelle structure.

[0009] In some embodiments, the antioxidants in the dense antioxidant layer are hyaluronic acid and sodium ascorbate.

[0010] In some embodiments, the mass ratio of hyaluronic acid to sodium ascorbate in the dense antioxidant layer is 1:0.1~0.4.

[0011] In some embodiments, the film coating layer has a three-dimensional spatial porous structure.

[0012] In some embodiments, the film material of the film coating layer is hydroxypropyl methylcellulose and modified starch.

[0013] In some embodiments, the mass ratio of hydroxypropyl methylcellulose to modified starch in the film coating layer is 0.01 to 0.1:1.

[0014] In some embodiments, the particle size of glutathione liposome microcapsules is less than 200 nm.

[0015] The beneficial effects of the glutathione liposome microcapsule particles provided in this embodiment of the invention include: This invention encapsulates glutathione within three protective layers: a lipid bilayer, a dense antioxidant layer, and a thin-film coating layer, from the inside out. The lipid bilayer protects glutathione from functional impairment before it enters the digestive system and facilitates its entry into cell membranes, thereby improving its bioavailability. The nanomicelle structure of the dense antioxidant layer provides long-lasting antioxidant properties. The thin-film coating layer enhances the fluidity of the glutathione liposome microcapsules and resists gastric acid degradation, further improving glutathione bioavailability. This structure significantly improves the absorption rate of glutathione preparations, thus the glutathione liposome microcapsules of this invention have significant potential in the fields of liver protection and antioxidant therapy. Attached Figure Description

[0016] To more clearly illustrate the technical solutions of the embodiments of this utility model, the drawings used in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of this utility model and should not be regarded as a limitation on the scope. For those skilled in the art, other related drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 This is a schematic diagram of the structure of the glutathione liposome microcapsule particles provided in this embodiment.

[0018] Icons: 1-Core; 2-Lipid bilayer; 3-Dense antioxidant layer; 4-Thin film coating layer. Detailed Implementation

[0019] The main obstacle to the bioavailability of orally administered glutathione is its breakdown by the digestive system. The presence of intestinal peptidase / protease and gamma-glutamyl transferase in the intestines breaks down intact glutathione into amino acids or dipeptides. Additionally, intestinal cells do not readily take up intact glutathione, the liver exhibits a first-pass effect, and intact glutathione has difficulty directly crossing cell membranes into the cell. These factors result in very low bioavailability of orally administered conventional glutathione preparations. This means that only a very small portion of ingested glutathione (usually considered less than 10%, and many studies show even lower) enters the bloodstream intact and is utilized.

[0020] To address the aforementioned issues, this invention provides a novel glutathione liposome microcapsule, which, through a triple mechanism of physical protection, enhanced absorption, and lymphatic delivery, increases the concentration of ordinary oral glutathione from less than 10% to approximately 60%, and effectively increases intracellular glutathione concentration. Glutathione liposome microcapsule can serve as a key technology for overcoming the bottleneck of glutathione production and has significant potential in the fields of liver protection and antioxidant therapy.

[0021] To make the objectives, technical solutions, and advantages of the embodiments of this utility model clearer, the technical solutions of the embodiments of this utility model will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this utility model, and not all embodiments. The components of the embodiments of this utility model described and shown in the accompanying drawings can generally be arranged and designed in various different configurations.

[0022] Therefore, the following detailed description of the embodiments of the present invention provided in the accompanying drawings is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments of the invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

[0023] It should be noted that similar labels and letters in the following figures indicate similar items. Therefore, once an item is defined in one figure, it does not need to be further defined and explained in subsequent figures.

[0024] In the description of this utility model, it should be noted that if terms such as "upper," "lower," "inner," or "outer" are used to indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings, or the orientation or positional relationship in which the utility model product is usually placed during use, they are only for the convenience of describing this utility model and simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation, and therefore should not be construed as a limitation of this utility model.

[0025] Furthermore, the terms "first" and "second" are used only to distinguish descriptions and should not be interpreted as indicating or implying relative importance.

[0026] It should be noted that, where there is no conflict, the features in the embodiments of this utility model can be combined with each other.

[0027] The following detailed description of the overall structure, working principle, and technical effects of the glutathione liposome microcapsules provided by this invention, through examples and in conjunction with the accompanying drawings, is a practical illustration.

[0028] Please refer to Figure 1 The glutathione liposome microcapsule particles provided by this utility model are applied in the field of glutathione oral preparation preparation.

[0029] The glutathione liposome microcapsule particles of this invention include: a core 1, and three protective layers surrounding the core 1; wherein the protective layers, from the inside out, are a lipid bilayer 2, a dense antioxidant layer 3, and a thin film coating layer 4; the dense antioxidant layer 3 has a nanomicelle structure, and the thin film coating layer 4 has a three-dimensional porous structure.

[0030] By setting up three protective layers, the function of glutathione can be protected from being affected before entering the digestive system, help glutathione enter the cell membrane, provide antioxidant properties, and resist gastric acid damage, thereby improving the bioavailability of glutathione.

[0031] The lipid bilayer 2 is selected from any one of lecithin, phosphatidylcholine, phosphatidylcholine derivatives, phosphatidylinositol, phosphatidylserine or cholesterol.

[0032] In some alternative schemes, the lipid bilayer 2 can be lecithin, phosphatidylcholine, phosphatidylcholine derivatives, phosphatidylinositol, phosphatidylserine, or cholesterol.

[0033] The aforementioned lipid bilayers, with their unique amphiphilic structure and self-assembly capabilities, construct the boundaries and gateways of cellular life. They are not only dynamic physical barriers but also core mediators for cellular material exchange, energy conversion, and information transmission. Their fluidity and the functional diversity of embedded proteins make the cell membrane one of the most intricate and indispensable structures in life activities. Drug carriers containing lipid bilayer structures can improve the bioavailability of target drugs in drug delivery systems.

[0034] In this invention, glutathione is encapsulated in a lipid bilayer 2, which effectively protects glutathione from affecting its function before it enters the digestive system of the organism, allowing it to reach the small intestine smoothly for absorption and digestion. The lipid bilayer 2 has mechanisms of action at the tissue and cellular levels, including adsorption, exchange, endocytosis, and fusion. Encapsulating glutathione in a lipid bilayer 2 can improve its bioavailability.

[0035] In this invention, the thickness of the lipid bilayer 2 can be adjusted according to the actual application scenario and preparation process, as long as it can completely encapsulate glutathione and allow it to reach the small intestine smoothly. This invention does not limit this aspect.

[0036] The dense antioxidant layer 3 in the protective layer has a nanomicelle structure. The antioxidants used are hyaluronic acid and sodium ascorbate.

[0037] Preferably, the mass ratio of hyaluronic acid to sodium ascorbate in the dense antioxidant layer 3 is 1:0.1~0.4. The dense antioxidant layer 3 prepared under this ratio has better antioxidant effect.

[0038] Antioxidants play a crucial role in pharmaceutics, primarily aiming to prevent or delay the oxidative degradation of drug active ingredients, thereby ensuring the safety, efficacy, and stability of pharmaceuticals. Drug oxidation is one of the main causes of drug inactivation, the generation of toxic impurities, color changes, off-odors, and even alterations in physicochemical properties. Antioxidants act as "invisible guardians" of drug stability; through precise selection (water-soluble / oil-soluble / chelating agents), rational formulation, and process control, oxidative degradation pathways can be effectively blocked.

[0039] This invention prepares the above-mentioned antioxidants into a dense antioxidant layer 3, which can protect the glutathione in the core 1 from oxidation and extend its shelf life. During preparation, hyaluronic acid and sodium ascorbate are obtained by probe ultrasound and biomembrane dialysis to obtain a micelle structure of hyaluronic acid and sodium ascorbate. This micelle structure has a more durable antioxidant effect than ordinary antioxidants, thereby ensuring that the glutathione in the core 1 is not oxidized.

[0040] In this invention, the thickness of the dense antioxidant layer 3 can be adjusted according to the actual application scenario and preparation process, as long as glutathione is not oxidized. This invention does not limit this aspect.

[0041] The thin film coating layer 4 in the protective layer has a three-dimensional spatial porous structure, and the film material used is hydroxypropyl methylcellulose and modified starch. The three-dimensional spatial porous structure in this invention mainly adopts a coating process, which uses multiple coatings in small amounts to achieve a three-dimensional spatial porous structure. Moreover, because it is a multiple coating process, the pores in the obtained structure are very small.

[0042] Preferably, the mass ratio of hydroxypropyl methylcellulose to modified starch in the film coating layer 4 is 0.01~0.1:1. The dense antioxidant layer 3 prepared at this ratio provides better protection.

[0043] The film coating layer 4 has many advantages and functions in formulations, such as improving drug stability, masking taste, improving appearance, and enhancing safety. In this invention, the use of a film material to encapsulate glutathione, which already has a lipid bilayer 2 and a dense antioxidant layer 3, is mainly for moisture protection, oxygen isolation, prevention of drug component decomposition, improvement of liposome flowability, and extension of drug shelf life.

[0044] By setting a thin film coating layer 4 on the outermost layer of glutathione liposomes, the fluidity of glutathione liposome microcapsules can be improved, increasing their application pathways. Moreover, the thin film coating layer 4 is acid-resistant, which can protect glutathione from being destroyed by gastric acid, allowing it to smoothly enter the small intestine for digestion and absorption, thereby improving the bioavailability of glutathione liposome microcapsules.

[0045] In this invention, the thickness of the film coating layer 4 can be adjusted according to the actual application scenario and preparation process, as long as the film coating layer 4 can completely wrap the glutathione coated by the dense antioxidant layer 3 and improve the fluidity of liposomes and prevent the decomposition of glutathione. This invention does not limit this aspect.

[0046] like Figure 1 As shown, the glutathione liposome microcapsules of this invention are spherical particles, with a core 1 of glutathione, and are sequentially coated from the inside out with a lipid bilayer 2, a dense antioxidant layer 3, and a thin film coating layer 4. The glutathione liposome microcapsules formed by this structure have a particle size of less than 200 nm. This particle size is designed to meet the requirements of oral and injectable formulations. Liposomes of this size have good effects in terms of mucus penetration, cellular uptake, and production stability.

[0047] The above description is only a specific embodiment of this utility model, but the protection scope of this utility model is not limited thereto. Any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in this utility model should be included within the protection scope of this utility model.

Claims

1. A glutathione liposome microcapsule, characterized in that, Includes: a core, and three protective layers surrounding the core; The protective layer consists of a lipid bilayer, a dense antioxidant layer, and a thin film coating layer from the inside out. The lipid bilayer is selected from any one of lecithin, phosphatidylcholine, phosphatidylcholine derivatives, phosphatidylinositol, phosphatidylserine, or cholesterol. The dense antioxidant layer formed by hyaluronic acid and sodium ascorbate has a nanomicelle structure, and the film coating layer formed by hydroxypropyl methylcellulose and modified starch has a three-dimensional porous structure.

2. The glutathione liposome microcapsule particles according to claim 1, characterized in that, The particle size of the glutathione liposome microcapsules is less than 200 nm.

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