A kind of exosome-like bionic preparation and its preparation method and application

By using exosome-like bionic preparations composed of bionic phospholipid bimolecular shell and capsule, the existing exosome extraction methods are solved, and efficient and stable preparation of bionic preparations is achieved, with good skin-friendly and sustained release effects of active substances.

CN116327613BActive Publication Date: 2025-03-11XIAN KYUSHU REGENERATIVE MEDICINE GRP CO LTD
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Patent Information

Application Number
CN202310311417.9
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Filing Date
2023-03-28
Publication Date
2025-03-11
Estimated Expiration
2043-03-28

AI Technical Summary

Technical Problem

The existing exosome extraction methods are inefficient and costly, making it difficult to achieve mass production, and the extracted exosome components are easy to destroy, store and transport difficult, and the components are uncertain.

Method used

An exosome-like bionic preparation consisting of bionic phospholipid bimolecular shell and capsule is prepared through high-pressure homogeneity treatment and special processes to form a stable bionic preparation to simulate the structure and function of the exosome.

Benefits of technology

It realizes the efficient preparation of exosome-like bionic preparations, has better skin-friendly and sustained release effects of active substances, has stable structure, is easy to store and transport, and can achieve qualitative and quantitative control components.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention belongs to the field of biomedicine technology, and in particular, relates to a method for preparing an exosome-like bionic preparation and its application. The exosome-like bionic preparation includes a plurality of exosome-like precursors LPO-EXO; the exosome-like precursor LPO-EXO includes: a bionic phospholipid bimolecular shell, the bionic phospholipid bimolecular shell includes a bionic phospholipid bimolecular outer shell and a bionic phospholipid bimolecular inner shell, the bionic phospholipid bimolecular inner shell is on the inside, and the bionic phospholipid bimolecular outer shell is on the outside; capsule content, the capsule content includes a water-soluble active substance and an oil-soluble active substance, the water-soluble active substance is arranged between the bionic phospholipid bimolecular outer shell and the bionic phospholipid bimolecular inner shell, and inside the bionic phospholipid bimolecular inner shell; the oil-soluble active substance is wrapped between the bionic phospholipid bimolecular outer shell and the bionic phospholipid bimolecular inner shell. The structure is more stable, the skin affinity is higher, and the content components can be qualitatively and quantitatively determined.
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Description

Technical Field

[0001] The present invention belongs to the field of biomedicine technology, and in particular relates to a preparation method of an exosome-like bionic preparation and its application. Background Art

[0002] Exosomes are natural nano-scale vesicles secreted by all living cells. They are an important medium for information exchange between cells. The vesicles are rich in nucleic acids, proteins and lipids. Umbilical cord mesenchymal stem cell exosomes are widely used in medicine, cosmetics and medical beauty because of their rich nutrients and targeting.

[0003] Exosomes are difficult to obtain and resources are scarce. Various extraction methods more or less affect the purity and activity of umbilical cord mesenchymal stem cell exosomes. For example, ultracentrifugation is costly, difficult to operate, and takes a long time. High-speed centrifugation will damage the exosomes and affect the purity. Ultrafiltration centrifugation is simple to operate and low in cost, but the purity is average, and some exosomes will lose their biological activity, and there is a problem of insufficient purity. Immunoaffinity capture method has high actual cost and low yield, which is suitable for free cell samples. Cancer heterogeneity will affect immune recognition, and antigenic determinants may be blocked. Microfluidics lacks large-scale clinical sample testing, lacks methodological verification, and is suitable for extraction of small sample quantities. The exosomes obtained by the above four methods are not easy to store at room temperature for a long time, and the exosomes obtained by extraction have complex nutrients and are difficult to qualitatively and quantitatively analyze. Therefore, there is an urgent need for an exosome-like bionic preparation that can replace the existing exosomes extracted from organisms such as the placenta. And then solve the application needs in the fields of medicine, cosmetics and medical beauty. However, there is currently no technology to achieve this. Summary of the invention

[0004] The present invention provides a method for preparing an exosome-like bionic preparation and its application, which solves the technical problems of low efficiency and difficulty in obtaining exosomes, inability to mass produce, and easy destruction of the extracted exosome components.

[0005] In order to achieve the above-mentioned object, the embodiments of the present invention disclose, on the one hand, a bionic exosome-like preparation, wherein the bionic exosome-like preparation comprises a plurality of exosome-like precursors LPO-EXO;

[0006] The exosome-like precursor LPO-EXO comprises:

[0007] A biomimetic phospholipid bimolecular shell, wherein the biomimetic phospholipid bimolecular shell comprises a biomimetic phospholipid bimolecular outer shell and a biomimetic phospholipid bimolecular inner shell, wherein the biomimetic phospholipid bimolecular inner shell is on the inner side and the biomimetic phospholipid bimolecular outer shell is on the outer side;

[0008] The capsule contents include water-soluble active substances and oil-soluble active substances. The water-soluble active substances are arranged in a first space between a bionic phospholipid bimolecular outer shell and a bionic phospholipid bimolecular inner shell, and in a second space inside the bionic phospholipid bimolecular inner shell; the oil-soluble active substances are wrapped in a third space inside the bionic phospholipid bimolecular outer shell and in a fourth space inside the bionic phospholipid bimolecular inner shell.

[0009] Furthermore, the oil-soluble active substance comprises, by weight: 1.8-2.5 parts of hydrogenated lecithin, 0.2-0.3 parts of tocopherol acetate, 0.3-0.5 parts of ceramide and 2-3 parts of squalane.

[0010] Furthermore, the water-soluble active substance includes, by weight, 78.8-89 parts of pure water, 2-5 parts of glycerol, 0.4-0.6 parts of hydroxyacetophenone, 0.5-1.5 parts of tryptophan, 2-3.5 parts of pyrrolidone carboxylic acid, 0.3-1 parts of hydrolyzed sodium hyaluronate, 0.2-0.5 parts of hydrolyzed actin, 0.2-0.5 parts of hydrolyzed collagen, 0.2-0.5 parts of β-nicotinamide mononucleotide, 0.5-1.2 parts of polydeoxyribonucleotide and 0.4-0.6 parts of 1,2-hexanediol.

[0011] Furthermore, the surface of the exosome-like biomimetic preparation is a soft burr structure protruding outward.

[0012] Furthermore, the exosome-like bionic preparation also includes gold powder.

[0013] The present invention also provides a method for preparing an exosome-like biomimetic preparation, comprising the following steps:

[0014] (1) Mix 78.8-89 parts of pure water, 2-5 parts of glycerol, and 0.4-0.6 parts of hydroxyacetophenone to form phase A. Add phase A into a 70°C water phase pot and heat and stir at a speed of 30 r / min until fully dissolved. Keep warm for 15 minutes and then cool to 35°C for use;

[0015] (2) Add 0.5-1.5 parts of tryptophan, 2-3.5 parts of pyrrolidone carboxylic acid, 0.3-1 parts of hydrolyzed sodium hyaluronate, 0.2-0.5 parts of hydrolyzed actin, 0.2-0.5 parts of hydrolyzed collagen, 0.2-0.5 parts of β-nicotinamide mononucleotide, 0.5-1.2 parts of polydeoxyribonucleotide and 0.4-0.6 parts of 1,2-hexanediol to phase A one by one, stir at a speed of 30 r / min for 30 min, and stir evenly to form an aqueous phase mixture for use;

[0016] (3) Mix 1.8-2.5 parts of hydrogenated lecithin, 0.2-0.3 parts of tocopherol acetate, 0.3-0.5 parts of ceramide, and 2-3 parts of squalane to form phase C, add phase C to the above mixture, stir at a speed of 40 r / min, homogenize at 40 Hz, and homogenize for 5 minutes to initially form an emulsified system for use;

[0017] (4) The obtained fluid is then subjected to high-pressure homogenization treatment using a microfluidizer at a pressure of 1000-1200 bar and a temperature of 30-35°C to obtain an exosome-like precursor LPO-EXO;

[0018] (5) Add 0.5-0.8 parts of agarose and 0.5-1 parts of gold powder into an emulsifier, heat to 75-80°C at 45 r / min while stirring, and keep warm for 5 minutes, then cool to 40-45°C and keep warm, add 100 parts of exosome precursor LPO-EXO, and stir at 10 r / min until a uniform aqueous phase mixture is obtained;

[0019] (6) Add 100 parts of coconut oil caprylate / caprate TO, 1.485-2.475 parts of polyamide-8, and 0.015-0.025 parts of pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) into an oil phase pot, mix, heat and dissolve to form an oil phase mixture;

[0020] (7) Transfer the oil phase mixture to a cooling device, control the temperature at 5-10°C, and maintain the oil phase stirring speed at 20-30 r / min;

[0021] (8) The aqueous phase mixture is added to the oil phase mixture through a 0.5-3 mm hydrophobic filter, with a weight ratio of aqueous phase mixture: oil phase mixture = 1:0.5-1:1. The stirring rate of the oil phase is kept unchanged and the temperature is controlled at 5-10 °C. After the particles harden, stirring is continued for 1 hour and then sealed to obtain the exosome-like biomimetic preparation MO-LPO-EXO.

[0022] Furthermore, the method for preparing the exosome-like biomimetic preparation comprises the following steps:

[0023] (1) Mix 83.9 parts of pure water, 3 parts of glycerol, and 0.5 parts of hydroxyacetophenone to form phase A. Add phase A into a 70°C water phase pot and heat and stir at a speed of 30 r / min until fully dissolved. Keep warm for 15 minutes and then cool to 35°C for use.

[0024] (2) Add 1 part of tryptophan, 3 parts of pyrrolidone carboxylic acid, 0.3 parts of hydrolyzed sodium hyaluronate, 0.3 parts of hydrolyzed actin, 0.5 parts of hydrolyzed collagen, 0.3 parts of β-nicotinamide mononucleotide, 1 part of polydeoxyribonucleotide and 0.5 parts of 1,2-hexanediol to phase A one by one, stir at a speed of 30 r / min for 30 min, and stir evenly to form an aqueous phase mixture for use;

[0025] (3) Mix 2 parts of hydrogenated lecithin, 0.2 parts of tocopherol acetate, 0.5 parts of ceramide, and 3 parts of squalane to form phase C, add phase C to the above mixture, stir at a speed of 40 r / min, homogenize at 40 Hz, and homogenize for 5 minutes to initially form an emulsified system for use;

[0026] (4) The obtained fluid is then subjected to high-pressure homogenization treatment using a microfluidizer at a pressure of 1000-1200 bar and a temperature of 30-35°C to obtain an exosome-like precursor LPO-EXO;

[0027] (5) Add 0.7 parts of agarose and 0.8 parts of gold powder into an emulsifier, heat to 75-80°C at 45 r / min while stirring, and keep warm for 5 minutes, then cool to 40-45°C and keep warm, add 100 parts of exosome precursor LPO-EXO TO, and stir at 10 r / min until a uniform aqueous phase mixture is obtained;

[0028] (6) Add 100 parts of coconut oil caprylate / caprate TO, 2.475 parts of polyamide-8, and 0.025 parts of pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) into an oil phase pot, mix, heat and dissolve to form an oil phase mixture;

[0029] (7) The oil phase mixture is transferred to a cooling device, the temperature is controlled at 10°C, and the oil phase stirring speed is maintained at 30 r / min;

[0030] (8) The aqueous phase mixture was added to the oil phase mixture through a 0.5-3 mm hydrophobic filter, with a weight ratio of aqueous phase mixture: oil phase mixture = 1:0.5. The stirring rate of the oil phase was kept unchanged and the temperature was controlled at 8 °C. After the particles hardened, stirring was continued for 1 hour and sealed to obtain the exosome-like biomimetic preparation MO-LPO-EXO.

[0031] Furthermore, the gold powder is used for coloring.

[0032] Furthermore, the exosome-like biomimetic preparation is used in essence.

[0033] Furthermore, exosome-like biomimetic preparations are used in facial creams, facial masks, eye creams, facial cleansers or toners.

[0034] Compared with the prior art, the present invention has the following advantages: through the unique internal phospholipid bilayer structure, it has better skin affinity, and at the same time, the exosome-like bionic preparation has better sustained-release effect of active substances; the structure is more stable and easier to store and transport; the source of ingredients is controllable, and qualitative and quantitative control can be achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 is a schematic diagram of the optical microscope structure of the exosome-like precursor LPO-EXO described in the present application;

[0036] Figure 2 It is a schematic diagram of the structure of a single exosome-like precursor LPO-EXO described in the present application;

[0037] Figure 3 It is a structural representation diagram of the entire exosome-like biomimetic preparation described in the present application;

[0038] Figure 4 It is a structural representation diagram of a monomer of the exosome-like biomimetic preparation described in the present application;

[0039] Figure 5 It is a schematic diagram of the structure of the exosome-like biomimetic preparation described in the present application;

[0040] Figure 6 is a process flow chart of the preparation of the exosome-like precursor LPO-EXO described in the present application;

[0041] Figure 7 It is a process flow chart of curing of the exosome-like biomimetic preparation MO-LPO-EXO described in the present application;

[0042] Figure 8 This is a picture of the patch test results of the exosome biomimetic preparation of this application;

[0043] Fig. 9 SCH change chart of skin stratum corneum water content after using essence;

[0044] Fig.10 , SCH change chart of skin stratum corneum water content after using facial cream;

[0045] Fig.11 , Changes in transepidermal water loss (TEWL) values ​​after using the essence;

[0046] Fig.12 , Changes in transepidermal water loss TEWL value after using facial cream;

[0047] Fig.13 , R0 change chart of skin firmness after using essence;

[0048] Fig.14 , Skin firmness R0 change chart after using facial cream;

[0049] Fig.15 , R2 change chart of skin elasticity after using essence;

[0050] Fig.16 , Changes in skin elasticity R2 after using facial cream.

[0051] Explanation of the accompanying drawings: 1. hydrophilic group; 2. lipophilic group; 3. water-soluble active substance; 4. bionic phospholipid bimolecular outer shell; 5. oil-soluble active substance; 6. bionic phospholipid bimolecular inner shell; 7. third space; 8. first space; 9. fourth space; 10. second space. DETAILED DESCRIPTION

[0052] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0053] The terms "first" and "second" in the description and claims of the embodiments of the present application are used to distinguish different objects rather than to describe a specific order of the objects. For example, the first guide wheel and the second guide wheel are used to distinguish different dielectric layers rather than to describe a specific order of the dielectric layers.

[0054] In the description of the embodiments of the present application, unless otherwise specified, the meaning of "plurality" refers to two or more than two. For example, a plurality of elements refers to two elements or more than two elements.

[0055] In the embodiments of the present application, words such as "exemplary" or "for example" are used to indicate examples, illustrations or descriptions. Any embodiment or design described as "exemplary" or "for example" in the embodiments of the present application should not be interpreted as being more preferred or more advantageous than other embodiments or designs. Specifically, the use of words such as "exemplary" or "for example" is intended to present related concepts in a specific way.

[0056] In the prior art, exosome-like substances are used in medicine and cosmetics, usually by extraction and separation. However, the extracted exosome-like substances are easily damaged and difficult to preserve, and the exosome-like substances are also uncertain. Therefore, obtaining an exosome-like bionic preparation and its preparation method will solve this problem well.

[0057] The embodiment of the present invention discloses an exosome-like bionic preparation, including a plurality of exosome-like precursors LPO-EXO; the exosome-like precursor LPO-EXO includes: a bionic phospholipid bimolecular shell, the bionic phospholipid bimolecular shell includes a bionic phospholipid bimolecular outer shell and a bionic phospholipid bimolecular inner shell, the bionic phospholipid bimolecular inner shell is on the inside, and the bionic phospholipid bimolecular outer shell is on the outside; the capsule content includes a water-soluble active substance and an oil-soluble active substance, the water-soluble active substance is arranged in the first space between the bionic phospholipid bimolecular outer shell and the bionic phospholipid bimolecular inner shell, and in the second space inside the bionic phospholipid bimolecular inner shell; the oil-soluble active substance is wrapped in the third space inside the bionic phospholipid bimolecular outer shell and in the fourth space inside the bionic phospholipid bimolecular inner shell. The bionic phospholipid bimolecular shell with double layers inside and outside is used to imitate the structure of exosomes, so that it has the targeting and skin affinity of exosomes, and has better sustained release of active substances. This effectively solves the technical problems of high cost of obtaining exosomes, low efficiency of batch preparation, difficulty in obtaining, difficulty in storage and transportation, large uncertainty of active ingredients, and inability to achieve qualitative and quantitative control of active substances. At the same time, through artificially synthesized exosome-like bionic preparations, not only can the special properties of exosomes be obtained, but also it is more convenient to transport and store them. Through the control of active substances such as internal water phase and oil phase, the active substances can be clearly defined and quantitatively controlled. In addition, through special processes and external structural adjustments, it has better skin affinity and a more stable structure. This lays a solid foundation for the large-scale application of exosome-like bionic preparations in biology, medicine, medical beauty, etc.

[0058] LPO-EXO: exosome-like precursor.

[0059] MO-LPO-EXO: exosome-like biomimetic preparation.

[0060] Pure water to 100 parts: refers to adding pure water after adding other substances to make the total amount of substances reach 100 parts.

[0061] Coconut oil alcohol-caprylate / caprate TO 100 parts: refers to adding coconut oil alcohol-caprylate / caprate after adding other substances to make the total amount of substances reach 100 parts.

[0062] The embodiments of the present application are further described below in conjunction with the accompanying drawings. Figure 1-Figure 5As shown, an embodiment of the present invention discloses an exosome-like bionic preparation, specifically, the exosome-like bionic preparation includes multiple exosome-like precursors LPO-EXO and capsule contents, the capsule contents include water-soluble active substances 3 and oil-soluble active substances 5; the exosome-like precursor LPO-EXO includes: a bionic phospholipid bimolecular shell, the bionic phospholipid bimolecular shell includes a bionic phospholipid bimolecular outer shell 4 and a bionic phospholipid bimolecular inner shell 6, the inner and outer sides of the bionic phospholipid bimolecular outer shell 4 and the bionic phospholipid bimolecular inner shell 6 are hydrophilic groups 1, and the lipophilic groups 2 are facing the middle. The biomimetic phospholipid bimolecular inner shell 6 is on the inside, and the biomimetic phospholipid bimolecular outer shell 4 is on the outside; the water-soluble active substance 3 is arranged in the first space 8 between the biomimetic phospholipid bimolecular outer shell 4 and the biomimetic phospholipid bimolecular inner shell 6, and in the second space 10 inside the biomimetic phospholipid bimolecular inner shell 6; the oil-soluble active substance 5 is wrapped in the third space 7 inside the biomimetic phospholipid bimolecular outer shell 4 and in the fourth space 9 inside the biomimetic phospholipid bimolecular inner shell 6. Thus, the water-soluble active substance 3 and the oil-soluble active substance 5 are wrapped in double layers in sequence.

[0063] Exemplarily, in order to make the exosome-like biomimetic preparation have better stability, antioxidant properties, and repair and moisturizing effects, the oil-soluble active substance 5 includes, by weight: 1.8 parts of hydrogenated lecithin, 0.2 parts of tocopherol acetate, 0.3 parts of ceramide, and 2 parts of squalane. In order to make the exosome-like biomimetic preparation have better stability, moisturizing properties, and anti-aging properties, the water-soluble active substance 3 includes, by weight, 89 parts of pure water, 2 parts of glycerol, 0.4 parts of hydroxyacetophenone, 0.5 parts of tryptophan, 2 parts of pyrrolidone carboxylic acid, 0.3 parts of hydrolyzed sodium hyaluronate, 0.2 parts of hydrolyzed actin, 0.2 parts of hydrolyzed collagen, 0.2 parts of β-nicotinamide mononucleotide, 0.5 parts of polydeoxyribonucleotide, and 0.4 parts of 1,2-hexanediol.

[0064] Exemplarily, in order to make the exosome-like biomimetic preparation have better stability, antioxidant properties, and repair and moisturizing effects, the oil-soluble active substance 5 includes, by weight: 2 parts of hydrogenated lecithin, 0.2 parts of tocopherol acetate, 0.5 parts of ceramide, and 3 parts of squalane. The water-soluble active substance 3 includes, by weight, 83.7 parts of pure water, 3 parts of glycerol, 0.5 parts of hydroxyacetophenone, 1 part of tryptophan, 3 parts of pyrrolidone carboxylic acid, 0.5 parts of hydrolyzed sodium hyaluronate, 0.3 parts of hydrolyzed actin, 0.5 parts of hydrolyzed collagen, 0.3 parts of β-nicotinamide mononucleotide, 1 part of polydeoxyribonucleotide, and 0.5 parts of 1,2-hexanediol.

[0065] Exemplarily, in order to make the exosome-like bionic preparation have better stability, antioxidant properties, and repair and moisturizing effects, the oil-soluble active substance 5 includes, by weight: 2.5 parts of hydrogenated lecithin, 0.3 parts of tocopherol acetate, 0.5 parts of ceramide, and 3 parts of squalane. In order to make the exosome-like bionic preparation have better stability, moisturizing properties, and anti-aging properties, the water-soluble active substance 3 includes, by weight, 78.8 parts of pure water, 5 parts of glycerol, 0.6 parts of hydroxyacetophenone, 1.5 parts of tryptophan, 3.5 parts of pyrrolidone carboxylic acid, 1 part of hydrolyzed sodium hyaluronate, 0.5 parts of hydrolyzed actin, 0.5 parts of hydrolyzed collagen, 0.5 parts of β-nicotinamide mononucleotide, 1.2 parts of polydeoxyribonucleotides, and 0.6 parts of 1,2 hexanediol.

[0066] The combination of hydroxyacetophenone and 1,2-hexanediol makes the two have a synergistic effect. In the experimental testing of the entire exosome-like bionic preparation, it was found that neither of them alone had a preservative effect, but the combination of the two made the entire exosome-like bionic preparation have a good preservative function. At the same time, the combination is gentle and non-irritating, and does not affect the activity of other substances.

[0067] By combining 0.5-1.5 parts of tryptophan, 2-3.5 parts of pyrrolidone carboxylic acid, 0.3-1 parts of hydrolyzed sodium hyaluronate, 0.2-0.5 parts of hydrolyzed actin, 0.2-0.5 parts of hydrolyzed collagen, 0.2-0.5 parts of β-nicotinamide mononucleotide, 0.5-1.2 parts of polydeoxyribonucleotide, 0.2-0.3 parts of tocopherol acetate, 0.3-0.5 parts of ceramide and 2-3 parts of squalane, and combining the design of a bionic phospholipid bimolecular outer shell and a bionic phospholipid bimolecular inner shell structure, the skin can be better moisturized, repaired, tightened and elastic within a certain range through artificial precise matching of combinations and components.

[0068] Preferably, the surface of the exosome-like bionic preparation is a soft burr structure protruding outward. During the curing modification process, a suitable external cooling environment and appropriate mechanical external force pulling are used to form the soft burr structure protruding outward, so that the structure of the exosome-like bionic preparation is more stable, the skin feel is more layered, the product appearance looks more colorful, and it is softer to use. At the same time, it also further improves the product adhesion and the sustained release effect of the active substance.

[0069] Preferably, the exosome-like bionic preparation further comprises gold powder. The addition of gold powder can effectively improve the UV blocking effect and antioxidant property of the product.

[0070] In one embodiment of the present invention, Figure 6 , Figure 7 As shown, a method for preparing an exosome-like biomimetic preparation is provided, comprising the following steps:

[0071] (1) Mix 83.7 parts of pure water, 3 parts of glycerol, and 0.5 parts of hydroxyacetophenone to form phase A. Add phase A into a 70°C water phase pot and heat and stir at a speed of 30 r / min until fully dissolved. Keep warm for 15 minutes and then cool to 35°C for use.

[0072] (2) Add 1 part of tryptophan, 3 parts of pyrrolidone carboxylic acid, 0.3 parts of hydrolyzed sodium hyaluronate, 0.3 parts of hydrolyzed actin, 0.5 parts of hydrolyzed collagen, 0.3 parts of β-nicotinamide mononucleotide, 1 part of polydeoxyribonucleotide and 0.5 parts of 1,2-hexanediol to phase A one by one, stir at a speed of 30 r / min for 30 min, and stir evenly to form an aqueous phase mixture for use;

[0073] (3) Mix 2 parts of hydrogenated lecithin, 0.2 parts of tocopherol acetate, 0.5 parts of ceramide, and 3 parts of squalane to form phase C, add phase C to the above mixture, stir at a speed of 40 r / min, homogenize at 40 Hz, and homogenize for 5 minutes to initially form an emulsified system for use;

[0074] (4) The obtained fluid is then subjected to high-pressure homogenization treatment using a microfluidizer at a pressure of 1200 bar and a temperature of 30-35°C to obtain an exosome-like precursor LPO-EXO;

[0075] (5) Add 0.7 parts of agarose and 0.8 parts of gold powder to an emulsifier, heat to 75°C while stirring at 45 r / min, and keep warm for 5 minutes, then cool to 40°C and keep warm, add 100 parts of exosome precursor LPO-EXO TO (add exosome precursor LPO-EXO to make the total amount of substance reach 100 parts), and stir at 10 r / min until a uniform aqueous phase mixture is obtained;

[0076] (6) Add 100 parts of coconut oil alcohol-caprylate / caprate TO (the total amount of the substance is 100 parts by adding coconut oil alcohol-caprylate / caprate), 2.475 parts of polyamide-8, and 0.025 parts of pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) into the oil phase pot, mix and heat to dissolve to form an oil phase mixture;

[0077] (7) Transfer the oil phase mixture into the cooling equipment, control the temperature at 10°C, and maintain the oil phase stirring speed at 20-30r / min;

[0078] (8) The aqueous phase mixture was added to the oil phase mixture through a 1.5 mm hydrophobic filter at a weight ratio of 1:0.5. The stirring rate of the oil phase was kept constant and the temperature was controlled at 10 °C. After the particles hardened, stirring was continued for 1 hour and then sealed to obtain the exosome-like biomimetic preparation MO-LPO-EXO.

[0079] Exemplarily, in step (6), 100 parts of coconut oil alcohol-caprylate / caprate TO (the total amount of the substance is made to 100 parts by adding coconut oil alcohol-caprylate / caprate), 1.485 parts of polyamide-8, and 0.015 parts of pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) are added into the oil phase pot, mixed, heated and dissolved to form an oil phase mixture.

[0080] The exosome-like bionic preparation MO-LPO-EXO particles are all formed by the aggregation of multiple exosome-like precursor LPO-EXO microspheres. The unique internal phospholipid bilayer structure is highly skin-friendly and meets the sustained release of active substances. After further strengthening and beautifying the preparation, the composition has better structural stability, clearer skin layering, and more colorful and soft appearance. The exosome-like bionic preparation MO-LPO-EXO particles modified and beautified by this process are all formed by the aggregation of multiple exosome-like precursor LPO-EXO microspheres. The preparation process is simple, the cost is low, and mass production can be achieved. It is also easy to store and transport at room temperature. Through steps 5-8, the exosome-like precursor LPO-EXO is solidified and modified, so that the structure and active substances are more stable. At the same time, the unique surface structure after special modification can increase the adhesion of the preparation to the skin, and it can be better spread after massage to release the active ingredients, which is easy for skin absorption. The agarose in the water phase has a melting point of 62-68°C and a solidification point of 24-29°C, which can effectively protect the activity of the biologically derived water phase functional ingredients and prevent them from denaturing due to high temperature. The addition of gold powder can make the exosome-like bionic preparation have better antioxidant properties and better UV blocking effect; the appropriate consistency of the oil phase can provide a suitable external environment for the water phase, so that the exosome-like bionic preparation can form a fine soft burr structure on the surface through the external force (appropriate stirring rate).

[0081] like Figure 1 , Figure 2 As shown, spherical bilayer structure vesicles are clearly visible, indicating that a microcapsule structure in which the active ingredients are wrapped by a phospholipid bilayer is formed.

[0082] like Figure 3 , Figure 4 As shown, the surface of the exosome-like bionic preparation MO-LPO-EXO has many tiny soft burrs, which can increase its adhesion when applied to the skin, facilitate the rupture of the microcapsule structure, release active substances, and have higher penetration and absorption efficiency.

[0083] Safety evaluation of the exosome-like biomimetic preparation MO-LPO-EXO.

[0084] 1.CAMVA Chicken chorioallantoic membrane vascular test:

[0085] 1.1 Test sample: Grind the exosome biomimetic preparation MO-LPO-EXO into powder and dilute it with water to a 50% solution, and keep it at room temperature for later use;

[0086] 1.2 Test method The chicken embryos were placed in a microcomputer fully automatic incubator for incubation. On the 4th day, a small hole was drilled at the narrow end of the chicken embryo and about 4 mL of egg white was extracted. A window of about 2 cm was opened above the chicken ring and covered with plastic wrap. Then it was placed in a constant temperature and humidity chamber for further incubation. On the 10th day, the chicken embryos were taken out, the eggshells around the window were peeled off, and 20 well-grown chicken embryos were selected and randomly divided into two groups, 10 negative control groups (blank) and 10 test samples, respectively. The chorionic blood vessels were exposed, and Teflon rings were placed in the densely vascular areas. One Teflon ring was placed for each chicken embryo. 40 μL of each group of samples was added to each ring, and then it was placed in a constant temperature and humidity chamber for incubation for 30 minutes. The Teflon ring was removed and rinsed with PBS until there was no obvious residue of the test sample. The area outside the Teflon ring was used as a control, and the vascular damage in the Teflon ring was observed under a stereomicroscope. The vascular stimulation effect was scored according to Table 1.

[0087] Table 1 shows the CAMVA test scoring criteria

[0088]

[0089] Table 2 is the CAMVA test score table

[0090]

[0091] The scoring results show that the preparation is safe and non-irritating.

[0092] 2 Human patch test:

[0093] 2.1 Test sample: Grind the exosome-like biomimetic preparation MO-LPO-EXO and dilute it with water to a 50% solution, and keep it at room temperature for later use;

[0094] 2.2 Test method: The test was conducted in accordance with the method of repeated open smear test: (1) At least 30 participants were selected according to the subject inclusion criteria. (2) The flexor side of the forearm was used as the test site, with an area of ​​3×3 cm². The test site should be kept dry and avoid contact with other topical preparations. (3) About 0.050±0.005g (mL) of the test substance was evenly applied to the test site once a day for 6 consecutive days. The skin reaction was observed at the same time. If a skin reaction of 3 points or more occurred during this process, it should be decided whether to continue the test according to the specific situation. (4) The skin reaction was observed according to the evaluation criteria of the repeated open smear test skin reaction in Table 1, and the results were recorded.

[0095] Table 3 is the standard table for judging skin reactions in the repeated open smear test

[0096]

[0097] 2.3 Test Results Subjects applied the combined preparation at a dose of approximately 0.050 ± 0.005 g (mL) / time, evenly to the test area once a day, and observed the skin reaction results for 6 consecutive days. Figure 8 As shown, all were negative reactions without any adverse reactions.

[0098] Exemplarily, the exosome-like biomimetic preparation is used in an essence.

[0099] The method for preparing the essence is to add the exosome-like biomimetic preparation MO-LPO-EXO into the essence matrix.

[0100] The essence formula includes water TO 100kg, disodium EDTA 0.05kg, xanthan gum 0.25kg, butylene glycol 4kg, sodium acrylate / sodium acryloyldimethyl taurate copolymer 0.1125kg, isohexadecane 0.0675kg, polysorbate-800.0225kg, sorbitan oleate 0.0075kg, water 0.090kg, bis(hydroxymethyl)imidazolidinyl urea 0.0395kg, iodopropynyl butylcarbamate 0.0005kg, propylene glycol 0.06kg and exosome-like biomimetic preparation MO-LPO-EXO 5kg.

[0101] The process is as follows:

[0102] 100 kg of pure water (after adding other substances, add water to 100 kg), 0.05 kg of disodium EDTA and 0.25 kg of xanthan gum powder are dispersed with 4 kg of butanediol and added to the emulsifier. Heat to 75-80 °C at 50 r / min while stirring. Then, homogenize at 50 r / min, 45 Hz for 2 min until the powder is completely dissolved. Finally, keep warm for 15 min. (2) While keeping warm, add 0.1125 kg of sodium acrylate / sodium acryloyldimethyl taurate copolymer, 0.0675 kg of isohexadecane, 0.0225 kg of polysorbate-80, 0.0075 kg of sorbitan oleate and 0.090 kg of water in sequence. Stir at 50 r / min, 45 Hz for 2 min (in principle, the material can be turned over). Then, stir at 50 r / min for 3-5 min. (3) Cool to 35°C, add 0.0395kg of bis(hydroxymethyl)imidazolidinyl urea, 0.0005kg of iodopropynyl butyl carbamate, and 0.06kg of propylene glycol, and stir for 5 minutes to obtain the essence matrix. Take out half of the material as the blank control sample. (4) Then add 5kg of exosome-like biomimetic preparation MO-LPO-EXO and stir for 15 minutes. Prepare to discharge at 38°C. After observing uniformity, the material can be discharged after passing the inspection to obtain the essence.

[0103] Exemplarily, the exosome-like biomimetic preparation is used in a facial cream, a facial mask, an eye cream, a facial cleanser or a toner.

[0104] The method for preparing a facial cream comprises adding the exosome-like biomimetic preparation MO-LPO-EXO into the facial cream matrix.

[0105] The cream formula includes: 100kg water TO, 0.25kg ammonium acryloyldimethyltaurate / VP copolymer, 0.15kg xanthan gum, 0.05kg methylparaben, 0.05kg disodium EDTA, 5.00kg butylene glycol, 1.92kg polyglyceryl-6 distearate, 0.57kg jojoba esters, 0.255kg polyglyceryl-3 beeswax ester, 0.255kg cetyl alcohol, 2kg C10-18 fatty acid triglycerides, 3kg squalane, 2.5kg dipentaerythritol hexacaprylate / hexadecanoate, 2.50kg tridecyl trimellitate, 2.00kg polydimethylsiloxane, 0.0395kg bis(hydroxymethyl)imidazolidinyl urea, 0.0005kg iodopropynyl butylcarbamate, 0.06kg propylene glycol and 5kg exosome-like biomimetic preparation MO-LPO-EXO.

[0106] The process is as follows: (1) 100 kg of water (after adding other substances, add water to 100 kg), 0.25 kg of ammonium acryloyldimethyltaurate / VP copolymer, 0.15 kg of xanthan gum, 0.05 kg of methylparaben, and 0.05 kg of disodium EDTA are dispersed with 5.00 kg of butylene glycol and added to an emulsifier. Heat to 75-80 ° C at 50 r / min while stirring, then stir and homogenize at 50 r / min, 45 Hz for 2 minutes until the powder is completely dissolved. Finally, keep warm for 15 minutes. (2) While keeping warm, add 1.92 kg of polyglycerol-6 distearate, 0.57 kg of jojoba esters, and polyglycerol-3 Beeswax ester 0.255kg, cetyl alcohol 0.255kg, C10-18 fatty acid triglyceride 2kg, squalane 3kg, dipentaerythritol hexacaprylate / hexadecanoate 2.5kg, tridecyl trimellitate 2.50kg and polydimethylsiloxane 2.00kg, 50r / min, 45HZ, homogenize while stirring for 2min (in principle, the material can be turned over), then stir at 50r / min for 3-5 minutes, evacuate until the material is defoamed and keep warm for 10 minutes; (3) cool to 35℃, add bis(hydroxymethyl)imidazolidinyl urea 0.0395kg, iodopropynyl butyl carbamate 0.0005kg and propylene glycol 0.06kg, stir for 5 minutes to obtain the cream base. Half of the material is used as the blank control sample. (4) Then add 5 kg of exosome-like biomimetic preparation MO-LPO-EXO and stir for 15 minutes. Prepare the material for discharge at 38°C. After observing that the material is uniform and passes the inspection, it can be discharged.

[0107] The essence and cream prepared with the exosome-like bionic preparation MO-LPO-EXO were tested for stratum corneum moisture content, transepidermal water loss, and firmness and elasticity, respectively, to evaluate their performance in moisturizing, repairing and anti-aging.

[0108] 1. Experiment on moisture content of stratum corneum

[0109] 1.1 Test sample experimental groups: Experimental group 1: serum containing exosome-like bionic preparation MO-LPO-EXO; Experimental group 2: cream containing exosome-like bionic preparation MO-LPO-EXO.

[0110] Control group: Control group 1 does not contain the essence of the exosome-like bionic preparation MO-LPO-EXO; Control group 2 does not contain the cream of the exosome-like bionic preparation MO-LPO-EXO.

[0111] 1.2 Test Method

[0112] 35 volunteers with similar facial wrinkles were selected, including 32 females and 3 males, aged 18 to 60 years old, with an average age of 35.26 years old, for human efficacy testing. The essence and cream containing the exosome-like bionic agent MO-LPO-EXO were randomly applied to one cheek of the left or right cheek of each volunteer, and they were used as experimental group 1 and experimental group 2; the volunteers used the essence and cream without the exosome-like bionic agent MO-LPO-EXO on the other cheek as control group 1 and control group 2. Volunteers applied the experimental group and control products once in the morning and evening every day, with a usage cycle of 28 days. No other cosmetics were allowed during the test period. Note: The test interval between the essence and cream samples was one month;

[0113] Use the skin moisture tester Corneometer CM825 to collect the SCH data of the stratum corneum water content on the 0th day before product use (0day), 7 days after product use (7day), 14 days after product use (14day), and 28 days after product use (28day). The test site is the cheek. During the measurement, the probe repeats the measurement 3 times in the same test area and takes the average value;

[0114] The test parameter SCH indicates the water content of the skin stratum corneum. The higher the value, the higher the water content of the skin stratum corneum.

[0115] Average change value on day N , where: N is the test time;

[0116] Average rate of change: , where: SCH is the water content of the stratum corneum; is the average change rate of stratum corneum water content SCH on day N, where N is the test time.

[0117] like Fig. 9 Table 4 below shows the test results of the serum.

[0118]

[0119] From the above test results, it can be seen that after 28 days of using the essence containing the exosome-like bionic preparation MO-LPO-EXO, the water content of the skin stratum corneum can be effectively increased, and the change rate is more significant than that of the control group, indicating that the exosome-like bionic preparation MO-LPO-EXO of the present invention has a good moisturizing effect. In addition, it can be seen that the change rate is most obvious in the first week of use, indicating that the essence containing the exosome-like bionic preparation MO-LPO-EXO will have a significant improvement in the moisturizing effect of the skin after one week of use, and the skin moisturizing property is continuously improved within a skin metabolism cycle (28 days).

[0120] like Fig.10 The following table 5 is the test results of the cream

[0121]

[0122] From the above test results, it can be seen that after using the cream containing the exosome-like bionic preparation MO-LPO-EXO for 28 days, the water content of the skin stratum corneum can be effectively increased, and the change rate is more significant than that of the control group, indicating that the exosome-like bionic preparation MO-LPO-EXO of the present invention has a good moisturizing effect. In addition, it can be seen that the change rate is most obvious in the first week of use, indicating that the cream containing the preparation will have a significant improvement in the moisturizing effect of the skin after one week of use, and the skin moisturizing performance continues to improve within a skin metabolism cycle (28 days).

[0123] After two groups of experiments, it was further fully proved that the exosome biomimetic preparation of the present application can effectively increase the water content of the skin stratum corneum and has a good moisturizing effect.

[0124] 2. Transepidermal water loss test

[0125] 2.1 Test sample experimental groups: Experimental group 3 contains the essence of the exosome biomimetic preparation MO-LPO-EXO of Example 1; Experimental group 4 contains the cream of the exosome biomimetic preparation MO-LPO-EXO of Example 1;

[0126] Test sample experimental groups: Control group 3: essence without the exosome biomimetic preparation MO-LPO-EXO of Example 1; Control group 4: cream without the exosome biomimetic preparation MO-LPO-EXO of Example 1;

[0127] 35 volunteers with similar facial wrinkles were selected, including 32 females and 3 males, aged 18 to 60 years old, with an average age of 35.26 years old, for human efficacy testing. The serum / cream containing the exosome-like bionic agent MO-LPO-EXO was randomly applied to one cheek of each volunteer's left or right cheek, and used as experimental group 3 and experimental group 4; the volunteers used the serum / cream without the exosome-like bionic agent MO-LPO-EXO on the other cheek as control group 3 and 4. Volunteers applied the experimental group and control group products once in the morning and evening every day, and the use cycle was 28 days. No other cosmetics were allowed during the test period. Note: The test interval between the serum and cream samples was one month;

[0128] The transepidermal water loss (TEWL) data of the skin were collected using a Vapometer on the 0th day before product use (0day), 7 days after product use (7day), 14 days after product use (14day), and 28 days after product use (28day). The test site was the cheek. The probe was measured 3 times in the same test area and the average value was taken.

[0129] Average change value on day N: , where: N is the test time;

[0130] Average rate of change: ,in: is the average change rate of transepidermal water loss TEWL on day N, where N is the test time.

[0131] like Fig.11 Table 6 below shows the results of transepidermal water loss testing after using the essence.

[0132]

[0133] From the above test results, it can be seen that after using the essence containing the exosome-like bionic preparation MO-LPO-EXO for 28 days, the transepidermal water loss can be effectively reduced, and the change rate is more significant than that of the control group, indicating that the exosome-like bionic preparation MO-LPO-EXO of the present invention has a good effect of repairing the stratum corneum barrier. The change rate is most obvious in the first week of use, indicating that the essence containing the exosome-like bionic preparation MO-LPO-EXO has a significant effect of repairing the stratum corneum of the skin after one week of use, and the repair effect of the stratum corneum of the skin continues to improve within a skin metabolism cycle (28 days).

[0134] like Fig.12 Table 7 below shows the results of transepidermal water loss testing after using the cream.

[0135]

[0136] From the above test results, it can be seen that after using the cream containing the exosome-like bionic preparation MO-LPO-EXO for 28 days, the transepidermal water loss can be effectively reduced, and the change rate is more significant than that of the control group, indicating that the exosome-like bionic preparation MO-LPO-EXO of the present invention has a good effect of repairing the stratum corneum barrier. At the same time, the change rate is most obvious in the first week of use, indicating that the cream containing the exosome-like bionic preparation MO-LPO-EXO has a significant effect of repairing the stratum corneum of the skin after one week of use, and the repair effect of the stratum corneum of the skin continues to improve within a skin metabolism cycle (28 days).

[0137] Through the above-mentioned experiments on essences and creams containing the exosome-like bionic preparation MO-LPO-EXO, it can be seen that after adding the exosome-like bionic preparation MO-LPO-EXO, the essence and cream have a significant effect on reducing transepidermal water loss and have a good effect on repairing the keratin barrier.

[0138] 3. Firmness and elasticity test;

[0139] 3.1 Anti-aging effect evaluation test

[0140] 3.1.1 Test samples

[0141] Experimental group 5: essence containing the exosome biomimetic preparation MO-LPO-EXO of Example 1; Experimental group 6: facial cream containing the exosome biomimetic preparation MO-LPO-EXO of Example 1; Control group 5: essence without the exosome biomimetic preparation MO-LPO-EXO of Example 1; Control group 6: facial cream without the exosome biomimetic preparation MO-LPO-EXO of Example 1;

[0142] 3.1.2 Test Method

[0143] 35 volunteers with similar facial wrinkles were selected, including 32 females and 3 males, aged 18 to 60 years old, with an average age of 35.26 years old, for human efficacy testing. The serum / cream containing the exosome-like bionic agent MO-LPO-EXO was randomly applied to one cheek of each volunteer's left or right cheek, and used as experimental group 5 and experimental group 6; the other cheek of the volunteer who used the serum / cream without the exosome-like bionic agent MO-LPO-EXO was used as control group 5 and control group 6. Volunteers applied the experimental group and control group products once in the morning and evening every day, with a usage period of 28 days. No other cosmetics were allowed during the test period. Note: The tests of the serum and cream samples were separated by one month;

[0144] Then, the skin elasticity meter Cutometer dual MPA580 was used to collect skin firmness R0 and skin elasticity R2 data on the 0th day before product use (0day), 7 days after product use (7day), 14 days after product use (14day), and 28 days after product use (28day). The test site was the cheek, and the probe repeated the measurement 3 times in the same test area, and the average value was taken.

[0145] The test parameter R0 indicates the skin firmness (the depth of the skin sucked into the probe is measured by a non-contact optical test system, and the ratio of light is proportional to the depth of light sucked into the skin). The further R0 is from 1, the better the skin firmness.

[0146] Average change value on day N: , where: N is the test time;

[0147] Average rate of change: ,in: is the average rate of change of firmness R0 on day N, where N is the test time.

[0148] The test parameter R2 represents skin elasticity (the ratio of the skin's rebound amount Ua when there is no negative pressure to the maximum stretch amount Uf when there is negative pressure). The closer R2 is to 1, the better the skin's elasticity.

[0149] Average change value on day N: , where: N is the test time;

[0150] Average rate of change ,in: is the average rate of change of elasticity R2 on the Nth day, where N is the test time.

[0151] like Fig.13 Table 8 below shows the test results of the skin firmness R0 of the serum.

[0152]

[0153] like Fig.14 Table 9 below shows the results of the serum skin elasticity R2 test.

[0154]

[0155] From the above experimental results, it can be seen that after using the essence containing the exosome-like bionic preparation MO-LPO-EXO for 28 days, the skin firmness and elasticity can be effectively improved, and the effect is significant compared with the comparative ratio, indicating that the exosome-like bionic preparation MO-LPO-EXO of the present invention has a good synergistic effect of each component, which can better improve skin wrinkles, delay skin aging, and achieve the effect of firming skin and anti-aging. In the first two weeks of use, the skin elasticity and firmness continued to increase, and the change rate reached the maximum on the 7th to 14th day, indicating that the use of the essence containing the exosome-like bionic preparation MO-LPO-EXO within two weeks will significantly improve the skin firmness and elasticity within two weeks of use, and the preparation has a good anti-aging effect.

[0156] like Fig.15 The following table 10 is the test results of the skin firmness R0 of the cream

[0157]

[0158] like Fig.16 The following table 11 is the test results of skin elasticity R2 of facial cream

[0159]

[0160] From the above experimental results, it can be seen that after using the cream matrix containing the exosome-like bionic preparation MO-LPO-EXO for 28 days, the skin firmness and elasticity can be effectively improved, and the effect is more significant than that of the control group, indicating that the components of the composition of the present invention have a good synergistic effect within a reasonable addition range, which can better improve skin wrinkles, delay skin aging, and achieve the effect of firming skin and anti-aging. At the same time, from the change rate, it can be seen that the skin elasticity and firmness continue to increase in the first two weeks, and the change rate reaches the maximum on the 7th to 14th day, indicating that the use of cosmetics containing the exosome-like bionic preparation MO-LPO-EXO within two weeks will significantly improve the skin firmness and elasticity, and the preparation has a good anti-aging effect.

[0161] In summary, the combined preparation MO-LPO-EXO has good moisturizing, repairing and anti-aging effects, and can be used in skin care products such as lotions and creams.

Claims

1. A method for preparing an exosome-like biomimetic preparation, characterized in that: The following steps are included: (1) Mix 78.8-89 parts of pure water, 2-5 parts of glycerol, and 0.4-0.6 parts of hydroxyacetophenone to form phase A. Add phase A into a 70°C water phase pot and heat and stir at a speed of 30 r / min until fully dissolved. Keep warm for 15 minutes and then cool to 35°C for use; (2) Add 0.5-1.5 parts of tryptophan, 2-3.5 parts of pyrrolidone carboxylic acid, 0.3-1 parts of hydrolyzed sodium hyaluronate, 0.2-0.5 parts of hydrolyzed actin, 0.2-0.5 parts of hydrolyzed collagen, 0.2-0.5 parts of β-nicotinamide mononucleotide, 0.5-1.2 parts of polydeoxyribonucleotide and 0.4-0.6 parts of 1,2-hexanediol to phase A one by one, stir at a speed of 30 r / min for 30 min, and stir evenly to form an aqueous phase mixture for use; (3) Mix 1.8-2.5 parts of hydrogenated lecithin, 0.2-0.3 parts of tocopherol acetate, 0.3-0.5 parts of ceramide, and 2-3 parts of squalane to form phase C, add phase C to the above mixture, stir at a speed of 40 r / min, homogenize at 40 Hz, and homogenize for 5 minutes to initially form an emulsified system for use; (4) The obtained fluid is then subjected to high-pressure homogenization treatment using a microfluidizer at a pressure of 1000-1200 bar and a temperature of 30-35°C to obtain an exosome-like precursor LPO-EXO; (5) Add 0.5-0.8 parts of agarose and 0.5-1 parts of gold powder into an emulsifier, heat to 75-80°C at 45 r / min while stirring, and keep warm for 5 minutes, then cool to 40-45°C and keep warm, add 100 parts of exosome precursor LPO-EXO, and stir at 10 r / min until a uniform aqueous phase mixture is obtained; (6) Add 100 parts of coconut oil caprylate / caprate, 1.485-2.475 parts of polyamide-8, and 0.015-0.025 parts of pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) into an oil phase pot, mix, heat and dissolve to form an oil phase mixture; (7) Transfer the oil phase mixture to a cooling device, control the temperature at 5-10°C, and maintain the oil phase stirring speed at 20-30 r / min; (8) The aqueous phase mixture is added to the oil phase mixture through a 0.5-3 mm hydrophobic filter, with a weight ratio of aqueous phase mixture: oil phase mixture = 1:0.5-1:

1. The stirring rate of the oil phase is kept unchanged and the temperature is controlled at 5-10 °C. After the particles harden, stirring is continued for 1 hour and then sealed to obtain the exosome-like biomimetic preparation MO-LPO-EXO.

2. The method for preparing an exosome-like biomimetic preparation according to claim 1, characterized in that: The following steps are included: (1) Mix 83.9 parts of pure water, 3 parts of glycerol, and 0.5 parts of hydroxyacetophenone to form phase A. Add phase A into a 70°C water phase pot and heat and stir at a speed of 30 r / min until fully dissolved. Keep warm for 15 minutes and then cool to 35°C for use. (2) Add 1 part of tryptophan, 3 parts of pyrrolidone carboxylic acid, 0.3 parts of hydrolyzed sodium hyaluronate, 0.3 parts of hydrolyzed actin, 0.5 parts of hydrolyzed collagen, 0.3 parts of β-nicotinamide mononucleotide, 1 part of polydeoxyribonucleotide and 0.5 parts of 1,2-hexanediol to phase A one by one, stir at a speed of 30 r / min for 30 min, and stir evenly to form an aqueous phase mixture for use; (3) Mix 2 parts of hydrogenated lecithin, 0.2 parts of tocopherol acetate, 0.5 parts of ceramide, and 3 parts of squalane to form phase C, add phase C to the above mixture, stir at a speed of 40 r / min, homogenize at 40 Hz, and homogenize for 5 minutes to initially form an emulsified system for use; (4) The obtained fluid is then subjected to high-pressure homogenization treatment using a microfluidizer at a pressure of 1000-1200 bar and a temperature of 30-35°C to obtain an exosome-like precursor LPO-EXO; (5) Add 0.7 parts of agarose and 0.8 parts of gold powder to an emulsifier, heat to 75-80°C at 45 r / min while stirring, and keep warm for 5 minutes, then cool to 40-45°C and keep warm, add 100 parts of exosome precursor LPO-EXO, and stir at 10 r / min until a uniform aqueous phase mixture is obtained; (6) Add 100 parts of coconut oil caprylate / caprate, 2.475 parts of polyamide-8, and 0.025 parts of pentaerythritol tetra(di-tert-butyl hydroxyhydrocinnamate) into an oil phase pot, mix and heat to dissolve to form an oil phase mixture; (7) The oil phase mixture is transferred to a cooling device, the temperature is controlled at 10°C, and the oil phase stirring speed is maintained at 30 r / min; (8) The aqueous phase mixture was added to the oil phase mixture through a 0.5-3 mm hydrophobic filter, with a weight ratio of aqueous phase mixture: oil phase mixture = 1:0.

5. The stirring rate of the oil phase was kept unchanged and the temperature was controlled at 8 °C. After the particles hardened, stirring was continued for 1 hour and sealed to obtain the exosome-like biomimetic preparation MO-LPO-EXO.

3. The exosome-like bionic preparation prepared by the method for preparing an exosome-like bionic preparation according to claim 1, characterized in that: The oil-soluble active substance comprises, by weight, 1.8-2.5 parts of hydrogenated lecithin, 0.2-0.3 parts of tocopherol acetate, 0.3-0.5 parts of ceramide and 2-3 parts of squalane.

4. The exosome-like bionic preparation prepared by the method for preparing an exosome-like bionic preparation according to claim 1, characterized in that: The water-soluble active substance includes, by weight, 78.8-89 parts of pure water, 2-5 parts of glycerol, 0.4-0.6 parts of hydroxyacetophenone, 0.5-1.5 parts of tryptophan, 2-3.5 parts of pyrrolidone carboxylic acid, 0.3-1 parts of hydrolyzed sodium hyaluronate, 0.2-0.5 parts of hydrolyzed actin, 0.2-0.5 parts of hydrolyzed collagen, 0.2-0.5 parts of β-nicotinamide mononucleotide, 0.5-1.2 parts of polydeoxyribonucleotide and 0.4-0.6 parts of 1,2-hexanediol.

Citation Information

Patent Citations

  • Methods of producing membrane vesicles

    AU2006201173A1

  • Preparation method of pigment nano vesicle biomimetic gas sensor

    CN107228885A