Vaseline ointment prepared from exosome and preparation method thereof

Abstract

The invention relates to the technical field of biological medicine preparations, and discloses a vaseline ointment prepared from exosomes and a preparation method of the vaseline ointment, and the vaseline ointment comprises the following components in percentage by weight: 0.01%-5.0% of phospholipid coated-freeze-dried exosome microspheres, 85%-99.89% of a composite network vaseline matrix and 0.1%-2.0% of a physiological body fluid guiding agent. The preparation method comprises the following steps: carrying out phospholipid coating on the exosome, and freeze-drying to prepare microspheres; heating and melting the medical vaseline and the matrix crystal network control agent to prepare an oil phase matrix; and dispersing the microspheres and the physiological body fluid guiding agent in an oil phase matrix under a vacuum low-temperature condition, and controlling cooling and curing. The exosome is prepared into stable solid microspheres, and the control agent capable of forming a three-dimensional microcrystal network in vaseline is introduced, so that the technical problem that the exosome is unstable in storage in an oil phase matrix is solved, the physical stability of the product and the uniformity of active matter distribution are ensured, the biological activity of the exosome is effectively protected, and the bioavailability of the exosome is improved. The finished product has the characteristics of stability and controllable release.

Description

Technical Field

[0001] The present invention relates to the technical field of biopharmaceutical preparations, and specifically to a vaseline ointment prepared using exosomes and a preparation method thereof. Background Art

[0002] Exosomes are nanoscale extracellular vesicles secreted by cells, encapsulating a variety of bioactive molecules such as proteins and nucleic acids. They can transmit signals between cells and participate in various physiological processes such as tissue repair and immune regulation. Due to their excellent biocompatibility and potential as natural drug delivery vehicles, exosomes show broad application prospects in the fields of regenerative medicine and dermatology, especially in promoting wound healing and improving skin condition.

[0003] In the field of topical skin preparations, petrolatum (white petrolatum) is a classic and widely used ointment base. It is chemically stable, has low skin irritation, and possesses excellent occlusive properties. It forms a hydrophobic film on the skin surface, effectively reducing moisture evaporation and creating an ideal moist environment for damaged skin to repair itself.

[0004] However, stably and effectively incorporating water-soluble bioactive components like exosomes into a pure oil-phase matrix like petrolatum presents inherent technical challenges. Exosomes possess a relatively fragile vesicle membrane structure. During conventional preparation and processing, exposure to heat, shear forces, or contact with incompatible chemicals can lead to structural damage and loss of activity. Directly mixing an aqueous suspension containing exosomes with molten petrolatum quickly leads to stratification and aggregation of active ingredients due to the immiscibility of oil and water, preventing the formation of a uniform, stable product.

[0005] Even if exosomes are pre-formed into a dry powder and then dispersed, conventional processes struggle to address their aggregation within a hydrophobic matrix. Furthermore, the strong hydrophobicity and occlusive properties of petrolatum act as a barrier, physically "locking" the exosomes within the matrix. This makes it difficult for them to be effectively released and reach target cells after application to the skin, thus limiting their intended biological functions. Therefore, existing technologies lack a solution that simultaneously addresses the three core issues of long-term stability, uniform distribution, and effective release of exosomes within an oil-based matrix. Summary of the Invention

[0006] The present invention aims to address several issues existing in the prior art. First, exosomes, as bioactive substances, have poor stability in aqueous environments or conventional emulsion systems. Their vesicle structure and bioactivity are easily affected by factors such as pH, temperature, osmotic pressure, and emulsifiers, which can impair their structure. Second, the direct and stable addition of water-soluble exosomes to a pure oil-phase matrix (such as petrolatum) presents technical difficulties due to the inherent incompatibility between the two, which can lead to system stratification, aggregation of active substances, and loss of efficacy.

[0007] Therefore, there is an urgent need in the art to provide an ointment product that can stably store exosomes in a vaseline matrix, and to provide a preparation method that can achieve such stable binding, so as to ensure the long-term stability of the exosomes and their effective release at the application site while utilizing the excellent physical sealing properties of vaseline.

[0008] In order to solve the above technical problems, the present invention provides the following technical solutions: The first aspect of the present invention provides a vaseline ointment prepared using exosomes, the ointment comprising the following components by weight percentage: Phospholipid-coated freeze-dried exosome microspheres: 0.01%-5.0%; Composite network vaseline matrix: 85%-99.89%; Physiological fluid guide agent: 0.1%-2.0%.

[0009] In the above technical solution, the composite network petrolatum matrix is ​​composed of medical-grade white petrolatum and a matrix crystallization network controller. This structure enables the solid phospholipid-coated freeze-dried exosome microspheres to be evenly and stably suspended in the oil phase matrix.

[0010] Preferably, the phospholipid-coated freeze-dried exosome microspheres are prepared by coating exosomes with phospholipids and freeze-drying them. The phospholipids may be soy lecithin or egg yolk lecithin, and exist as a protective layer formed on the surface of the exosome vesicles.

[0011] Preferably, the matrix crystal network controller is one or more substances selected from C16-C22 long-chain fatty alcohols, carnauba wax or candelilla wax. This component forms a three-dimensional microcrystalline network structure when the vaseline matrix cools and solidifies.

[0012] Preferably, the physiological fluid guiding agent is one or more inert porous powders selected from pharmaceutical grade porous silicon dioxide or pharmaceutical grade microcrystalline cellulose, which are uniformly dispersed in the vaseline matrix to form physical microscopic channels.

[0013] Preferably, the complex network vaseline base can further comprise an antioxidant and / or a transdermal absorption and soothing agent. The antioxidant can be vitamin E, and the transdermal absorption and soothing agent can be menthol.

[0014] The second aspect of the present application provides a method for preparing the aforementioned vaseline ointment. The method comprises the following steps: Step one: provide an exosome suspension, add a phospholipid solution to the exosome suspension for mixing and coating treatment, and then freeze-dry the mixture to obtain powder-like phospholipid-coated freeze-dried exosome microspheres; Step two: mix medical-grade white vaseline with a matrix crystalline network control agent, heat and stir until completely melted to prepare a uniform oil phase matrix; Step three: under preset vacuum and low temperature conditions, add the phospholipid-coated freeze-dried exosome microspheres obtained in step one and a physiological body fluid guide agent to the molten oil phase matrix prepared in step two, and stir and disperse; Step four: cool the mixture obtained in step three at a preset control rate to solidify it into a paste-like form.

[0015] Preferably, in step one, the temperature condition for coating treatment is 4-25℃, and the stirring rate condition is 50-200rpm.

[0016] Preferably, in step three, the vacuum condition ranges from -0.08MPa to -0.095MPa, and the low temperature condition ranges from 45-55℃.

[0017] Preferably, in step four, the control rate cooling is performed at a cooling rate of 1.0-3.0℃ / min. During this cooling process, the matrix crystalline network control agent is precipitated in the vaseline to form a three-dimensional microcrystalline lattice network structure.

[0018] Preferably, in step two, an antioxidant and / or a transdermal absorption and soothing agent can be further added to the oil phase matrix and stirred to dissolve.

[0019] The present application provides a vaseline ointment prepared using exosomes and a preparation method thereof. The ointment has the following beneficial effects: 1. The present application realizes double physical protection of bioactive substances by coating exosomes with phospholipids and freeze-drying them into solid microspheres, and then dispersing them in anhydrous vaseline base. The phospholipid layer provides structural support and interface compatibility at the micro level, and the macro vaseline base isolates water vapor and oxygen from the outside. This solid-oil suspension system significantly improves the stability of exosomes during preparation, storage, and use, effectively maintaining their biological activity.

[0020] 2. This invention incorporates a matrix crystal network controller into the oil-phase matrix. During the ointment cooling and forming process, this component forms an internal three-dimensional microcrystalline network structure, either prior to or in conjunction with the petrolatum matrix. This network physically secures and separates the exosome microspheres suspended within it, fundamentally preventing the sedimentation or aggregation of solid particles due to gravity or temperature fluctuations during the product's shelf life, thereby ensuring the long-term physical stability of the ointment product and the uniform distribution of its contents.

[0021] 3. The preparation method of the present invention restricts powder dispersion to vacuum and mild low-temperature conditions. The vacuum environment eliminates potential oxidation or hydrolysis damage to the active ingredients by air and moisture; the low-temperature and low-shear mixing method prevents thermal stress and mechanical damage to the delicate structure of the phospholipid-coated, freeze-dried exosome microspheres. This combination of process conditions ensures that the integrity and activity of the exosomes are maximized throughout the entire preparation process.

[0022] 4. The present invention provides a multifunctional, synergistic ointment composition. The petrolatum base itself provides excellent skin occlusive and moisturizing properties, creating an optimal moist healing environment for damaged skin. Furthermore, the stably loaded exosomes can be released on demand to provide cell regeneration signals, while an optional soothing agent (such as menthol) provides local comfort. Each component has distinct functions and works synergistically, forming a skin preparation that combines physical protection, active repair, and user comfort. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic flow chart of the preparation method of the present invention. DETAILED DESCRIPTION

[0024] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the drawings in the specification of the present invention. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0025] In order to better understand the present invention, the above contents are described in detail below in conjunction with specific embodiments.

[0026] The sources and specifications of the main raw materials and reagents used in the following examples and comparative examples are as follows. Reagents not specifically specified are all commercially available products of analytical grade or higher.

[0027] Exosomes: Exosomes provided by designated laboratories, purified by ultracentrifugation, and stored in PBS buffer.

[0028] White Petrolatum: medical grade, CAS number: 8009-03-8.

[0029] Soybean Lecithin: Injection grade, phosphatidylcholine content not less than 90%, CAS number: 8002-43-5.

[0030] Cetostearyl Alcohol: pharmaceutical grade, CAS number: 67762-27-0.

[0031] Carnauba Wax: pharmaceutical grade, CAS No.: 8015-86-9.

[0032] Tocopherol (Vitamin E, DL-α-Tocopherol): pharmaceutical grade, CAS number: 10191-41-0.

[0033] L-Menthol: pharmaceutical grade, CAS number: 2216-51-5.

[0034] Porous Silica: Pharmaceutical excipient grade, average particle size 20-45µm, CAS No.: 7631-86-9.

[0035] Microcrystalline Cellulose: pharmaceutical excipient grade, model PH-102, CAS number: 9004-34-6.

[0036] Phosphate buffered saline (PBS): pH 7.4, sterile.

[0037] Example Example 1 (1) Ointment formula This embodiment provides an exosome vaseline ointment, and the weight percentages of its components are as follows: (2) Preparation method (2.1) Preparation of phospholipid-coated freeze-dried exosome microspheres (EPLM) First, the protein concentration of the exosome concentrated suspension was determined to be 5.0 mg / mL. The suspension was placed in a constant temperature reactor at 20°C. Another 2.0% of the total protein mass of soy lecithin was dissolved in PBS buffer (pH 7.4). The soy lecithin solution was added to the exosome suspension at a stirring rate of 150 rpm for 20 minutes, and the reaction was continued for 45 minutes after the addition was completed. The resulting mixed suspension was pre-frozen at -80°C for 3 hours, and then freeze-dried: first drying was performed at -20°C and 10 Pa for 36 hours, and then second drying was performed at 25°C and a vacuum degree of less than 5 Pa for 8 hours, to obtain EPLM powder.

[0038] (2.2) Preparation of the final ointment The formula amount of white petrolatum and cetylstearyl alcohol was added to a homogenizing emulsifier, heated to 60°C and stirred to completely melt. The temperature was lowered to 50°C, and tocopherol and L-menthol were added and stirred to completely dissolve. The vacuum system was opened to -0.09 MPa, and the EPLM powder prepared in step (2.1) and the formula amount of porous silicon dioxide were sucked into the kettle at a stirring rate of 40 rpm, and dispersed for 30 minutes. The mixture was cooled to room temperature at a rate of 2.0°C / min under vacuum and stirring, and the final product was obtained.

[0039] Example 2 (1) Ointment formula The weight percentage of each component of the exosome petrolatum ointment provided in this example is as follows: (2) Preparation method The preparation method of this example is exactly the same as that of Example 1.

[0040] Example 3 (1) Ointment formula The ointment formula of this example is exactly the same as that of Example 1.

[0041] (2) Preparation method The preparation method of this example is basically the same as that of Example 1, except that the cooling rate is controlled at 1.0°C / min during the final cooling and solidification step of step (2.2).

[0042] Comparative Example Comparative Example 1: The difference compared with Example 1 is that no phospholipid coating and freeze-drying treatment is performed. The original exosome suspension with the same amount of exosome solid content as Example 1 is directly mixed with the molten oil phase matrix in step (2.2), and high-speed homogenizing stirring is performed.

[0043] Comparative Example 2: Compared with Example 1, the difference is that in step (2.1), the exosome suspension is not subjected to phospholipid coating treatment, and is directly freeze-dried to obtain exosome dry powder. The rest are the same.

[0044] Comparative Example 3: Compared with Example 1, the difference is that: in the preparation of the oil phase matrix in step (2.2), cetearyl alcohol is not added, and its weight is replaced by white vaseline, and the rest are the same.

[0045] Comparative Example 4: Compared with Example 1, the difference is that in the powder dispersion step (2.2), porous silica is not added, and its weight is replaced by white vaseline, and the rest are the same.

[0046] Test Case Test Example 1: Product physical stability test (1) Experimental purpose: This test case aims to evaluate the physical stability of ointments prepared with different formulas and processes under accelerated conditions (40°C), and to evaluate the physical stability through two dimensions: macroscopic appearance observation and microscopic active ingredient distribution uniformity.

[0047] (2) Experimental objects: Example 1, Example 2, Comparative Example 2, Comparative Example 3.

[0048] (3) Experimental steps Sample preparation: The samples of Example 1, Example 2, Comparative Example 2 and Comparative Example 3 were respectively packed into 50 g sealed glass jars and sealed with lids.

[0049] Accelerated storage: Place all samples in a constant temperature and humidity chamber with the set temperature at 40℃±2℃ and relative humidity at 75%±5% for a 30-day accelerated stability study.

[0050] Regular sampling and observation: Samples were taken on day 0, day 15, and day 30 of the experiment. They were first allowed to equilibrate at room temperature for 2 hours before macroscopic and microscopic examinations were performed.

[0051] Macroscopic appearance evaluation: Observe the paste morphology of the sample with the naked eye and record whether there is any color change, delamination, oil separation (oil phase seeping out of the paste) or hardening.

[0052] Evaluation of active ingredient distribution uniformity: Use a clean sampling spoon to accurately weigh approximately 50 mg of sample from three different locations of each sample container: the top (about 1 cm from the liquid surface), the middle, and the bottom (about 1 cm from the bottom of the bottle).

[0053] Each weighed sample is diluted with an appropriate amount of solvent (such as hexane) and vortexed to disperse the oil phase, and then the solid phase precipitate is separated by centrifugation or extraction and resuspended with PBS buffer to extract the protein therein.

[0054] The protein concentration in the sample suspensions extracted from the upper, middle and lower positions was determined using a BCA protein concentration assay kit.

[0055] For each sample bottle, the relative standard deviation (RSD) was calculated based on the protein concentration data at the upper, middle, and lower points. The calculation formula was: RSD (%) = (standard deviation / average value) × 100%.

[0056] (4) Experimental results The results of the accelerated stability testing for each sample are reported in Table 1 below.

[0057] Table 1: Accelerated stability test results (5) Results analysis Test results showed that the samples from Examples 1 and 2 maintained a uniform, smooth, creamy appearance, without oil separation or delamination, even after 30 days of accelerated storage at 40°C. The relative standard deviation (RSD) of the protein concentration distribution increased only slightly over time and remained at a low level, demonstrating the uniform distribution and high stability of the active microsphere components. This stability stems from the synergistic effect of the technical solution: the phospholipid coating improves the interfacial compatibility between the solid microspheres and the oil matrix, while the matrix crystal network controller (cetearyl alcohol or carnauba wax) forms an internal three-dimensional microcrystalline network within the petrolatum, physically fixing and spatially segmenting the microspheres, effectively preventing their migration and aggregation.

[0058] Compared to the examples, Comparative Example 3 exhibited significant oil separation and a significantly increased RSD value during accelerated storage. This is due to the lack of a matrix crystallization network controller in its formulation, which prevented the formation of an effective internal support structure upon cooling. Consequently, despite initial uniform dispersion, the denser exosome microspheres, driven by thermodynamics, underwent gravitational sedimentation, resulting in uneven vertical distribution of the active ingredient. Macroscopically, this manifested as oil phase precipitation and paste delamination, leading to poor physical stability of the product.

[0059] The test results of Comparative Example 2 reveal another dimension of instability. Although no significant oil precipitation occurred, the paste showed particle aggregation and hardening, and the RSD value increased significantly over time. The reason for this phenomenon is that the exosomes were only directly freeze-dried without phospholipid coating. The surface of the uncoated microspheres is highly hydrophilic, and the interfacial energy with the highly hydrophobic vaseline matrix is ​​high, resulting in poor compatibility. Under thermal acceleration conditions, these microspheres tend to contact each other through Brownian motion and agglomerate to reduce the total surface energy of the system, resulting in a decrease in the uniformity of active ingredient distribution and deterioration of product texture.

[0060] Test Example 2: In vitro release behavior test (1) Experimental purpose: This test example aims to evaluate the ability of the ointment of the present invention to release its active ingredient (exosomes) from the oil phase matrix under conditions simulating contact with physiological fluids.

[0061] (2) Experimental objects: Example 1 and Comparative Example 4.

[0062] (3) Experimental steps Experimental equipment: A vertical Franz diffusion cell system was used with an effective diffusion area of ​​1.77 cm 2 , the volume of the receiving chamber is 12.0 mL.

[0063] Membrane treatment and installation: A polyethersulfone (PES) microporous filter membrane with a pore size of 0.45 μm was selected and soaked in the receiving medium for 1 hour before being installed between the supply chamber and the receiving chamber of the diffusion cell.

[0064] Sample application: Accurately weigh 200 mg of the sample (Example 1 or Comparative Example 4) and evenly apply it on one side of the supply chamber of the microporous filter membrane.

[0065] Experimental conditions: The receiving chamber was filled with phosphate-buffered saline (PBS, pH 7.4) and maintained at 37°C ± 0.5°C using a circulating water bath. The receiving medium was continuously stirred at 300 rpm using a magnetic stir bar.

[0066] Sampling and analysis: At 1, 2, 4, 8, 12, and 24 hours after the start of the experiment, 1.0 mL of receiving solution was drawn from the sampling arm of the receiving chamber and immediately supplemented with 1.0 mL of fresh PBS medium preheated to 37°C.

[0067] Concentration determination: The protein concentration in samples from all sampling points was determined using the BCA protein concentration determination kit.

[0068] Data processing: Based on the measured concentration and sampling volume, the cumulative release of exosomes at each time point was calculated and converted into the cumulative release rate (%).

[0069] (4) Experimental results The results of the in vitro release experiments for the two groups of samples are recorded in Table 2 below.

[0070] Table 2: In vitro release test results (5) Results analysis Experimental data showed that throughout the 24-hour test period, the cumulative release rate of Example 1 was significantly higher than that of Comparative Example 4 at all sampling time points. This result demonstrates that the two formulations exhibit fundamentally different release kinetics of the active ingredient when exposed to aqueous media. The formulation structure of Example 1 facilitates more efficient release of the active ingredient from the hydrophobic matrix.

[0071] The structural basis for this difference lies in the presence of a physiological fluid-directing agent in Example 1 but absent in Comparative Example 4. In the system of Example 1, porous silica particles, acting as a physiological fluid-directing agent, are uniformly dispersed within the petrolatum matrix, forming a microscopic porous network throughout the paste. When the paste surface comes into contact with an aqueous receiving medium, the medium is preferentially drawn in through capillary action and conducted along the channels formed by these porous particles, enabling it to quickly reach and wet the exosome microspheres encapsulated within the deeper matrix, triggering their release.

[0072] In contrast, the formulation of Comparative Example 4 does not include such a guide agent. Its active ingredient release process relies entirely on the slow, disordered diffusion of the aqueous medium through the dense, continuous hydrophobic petrolatum oil phase. This process presents significant mass transfer resistance, making it difficult for the aqueous medium to effectively penetrate the paste and come into contact with the exosome microspheres. Consequently, its release rate is very slow, and the cumulative release amount is far lower than that of Example 1. These test results confirm the ability of physiological fluid guide agents to regulate the on-demand release of active ingredients from a pure oil phase matrix.

[0073] Test Example 3: Exosome Bioactivity Maintenance Test (1) Experimental purpose: This test case aims to evaluate the effects of different preparation processes on the biological activity of exosomes and to characterize the maintenance level of their activity through their ability to promote the proliferation of human skin fibroblasts.

[0074] (2) Experimental subjects Ointment prepared in Example 1 Ointment prepared in Comparative Example 2 Original exosome suspension without any treatment (as 100% activity control) (3) Experimental steps Preparation of sample release solution: In vitro release experiments were conducted on the ointments of Example 1 and Comparative Example 2, respectively, with the same specific steps as in Test Example 2. All receiving solutions from 0 to 24 hours were collected and combined to obtain a sample release solution containing the released product.

[0075] The protein concentrations in the two released solutions and the original exosome suspension were determined by the BCA assay.

[0076] Cell culture and treatment: Human dermal fibroblasts (HDFs) were cultured at a rate of 5 × 10 3 The cells were seeded at a density of 1000 / well in a 96-well culture plate and cultured in DMEM medium containing 10% fetal bovine serum for 24 hours to allow them to adhere to the wall.

[0077] The old culture medium was discarded, and the cells were synchronized with serum-free DMEM medium for 12 hours.

[0078] Discard the synchronization medium and set up the following experimental groups, with 6 replicate wells in each group: Blank control group: add 100 μL serum-free DMEM medium.

[0079] Raw exosome group: Raw exosome suspension diluted with serum-free DMEM was added to make the final exosome protein concentration 50 μg / mL.

[0080] Example 1 Group: The sample release solution diluted with serum-free DMEM was added to make the final exosome protein concentration 50 μg / mL.

[0081] Comparative Example 2: The sample release solution diluted with serum-free DMEM was added to make the final exosome protein concentration 50 μg / mL.

[0082] Cell proliferation assay: The culture plate was placed in a 37°C, 5% CO2 incubator and cultured for 48 hours.

[0083] Add 20 μL of MTT solution (5 mg / mL) to each well and continue incubation for 4 hours.

[0084] Terminate the culture, carefully aspirate and discard the supernatant in the wells, add 150µL of dimethyl sulfoxide (DMSO) to each well, and shake at low speed on a shaker for 10 minutes to completely dissolve the formazan crystals.

[0085] The optical density (OD) of each well was measured using a microplate reader at a wavelength of 570 nm.

[0086] (4) Experimental results The OD values ​​of cells in each group after 48 hours of culture were 570 The results are recorded in Table 3 below.

[0087] Table 3: Exosome bioactivity test results (5) Result analysis The experimental results show that the exosomes prepared and released by the process of Example 1 have a significantly higher ability to promote cell proliferation (characterized by OD value) than Comparative Example 2, and are close to the level of the original exosome group without treatment. The OD value of the blank control group is the lowest, which is as expected. This data indicates that the technical solution adopted in Example 1 can effectively protect the biological activity of exosomes, so that they can maintain their function of promoting cell proliferation after going through the complex preparation, storage and release process.

[0088] The effective maintenance of exosome biological activity by Example 1 is attributed to its unique preparation process. The phospholipid coating step performed before freeze-drying provides an additional flexible protective layer for each exosome vesicle, which can buffer the mechanical stress generated by ice crystal formation during freezing and the osmotic pressure impact during dehydration, thereby protecting the integrity of the exosome's own membrane structure. The subsequent mixed dispersion process under low temperature and vacuum conditions avoids the destruction of active proteins by heat degradation and oxidation. This series of mild physical treatment methods collectively ensure that the conformation and activity of key functional molecules of exosomes are not destroyed.

[0089] In contrast, the process of Comparative Example 2 lacks the pre-protective step of phospholipid coating, and the exosomes are directly exposed to the extreme physical environment of freeze-drying. This can cause irreversible damage to the lipid bilayer membrane structure, such as vesicle rupture, surface protein denaturation or aggregation. Although a plaster is finally prepared, the exosomes contained therein have largely lost the ability to interact with target cells and deliver biological signals, so their effect on promoting cell proliferation is much lower than that of Example 1, only slightly higher than the blank control, proving that the process is insufficient to protect biological activity.

[0090] Although embodiments of the present application have been shown and described, it is to be understood that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the present application, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A vaseline ointment prepared using exosomes, characterized in that: The ointment contains the following components by weight: Phospholipid-coated freeze-dried exosome microspheres: 0.01%-5.0%; Composite network vaseline matrix: 85%-99.89%; Physiological fluid guiding agent: 0.1%-2.0%; wherein the composite network vaseline matrix comprises medical grade white vaseline and a matrix crystallization network controller.

2. The ointment according to claim 1, characterized in that The phospholipid-coated freeze-dried exosome microspheres are prepared from exosomes and phospholipids, wherein the phospholipids are soybean lecithin or egg yolk lecithin.

3. The ointment according to claim 1, characterized in that The matrix crystal network control agent is one or more substances selected from C16-C22 long-chain fatty alcohols, carnauba wax or candelilla wax.

4. The ointment according to claim 1, characterized in that The physiological fluid guiding agent is one or more inert porous powders selected from pharmaceutical grade porous silicon dioxide or pharmaceutical grade microcrystalline cellulose.

5. The ointment according to claim 1, characterized in that The composite network vaseline matrix further comprises an antioxidant and / or a transdermal absorption and soothing agent, wherein the antioxidant is vitamin E and the transdermal absorption and soothing agent is menthol.

6. A method for preparing the vaseline ointment according to any one of claims 1 to 5, characterized in that: The following steps are involved: Step 1: The exosome suspension is mixed with a phospholipid solution for coating, and then freeze-dried to obtain phospholipid-coated freeze-dried exosome microspheres; Step 2: heating and melting medical-grade white vaseline and a matrix crystal network control agent to prepare an oil phase matrix; Step 3: Under vacuum and low temperature conditions, the phospholipid-coated, freeze-dried exosome microspheres and the physiological fluid guiding agent obtained in step 1 are dispersed in the molten oil phase matrix prepared in step 2; Step 4: Cooling and solidifying the mixture obtained in step 3 at a controlled rate to form the ointment.

7. The method according to claim 6, characterized in that The coating treatment in step 1 is carried out at a temperature of 4-25° C. and a stirring rate of 50-200 rpm.

8. The method according to claim 6, characterized in that The vacuum condition in step 3 is -0.08 MPa to -0.095 MPa, and the low temperature condition is 45-55°C.

9. The method according to claim 6, characterized in that The controlled rate cooling in step 4 is performed at a rate of 1.0-3.0°C / min. During this process, the matrix crystallization network control agent forms a three-dimensional microcrystalline network structure in the vaseline.

10. The method according to claim 6, characterized in that In step 2, after heating and melting and before adding the microspheres, an antioxidant and / or a transdermal absorption and soothing agent are added to the oil phase matrix.

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