An external application dressing of mesenchymal stem cell exosomes, its preparation method and application

Abstract

The present invention discloses an external application dressing of mesenchymal stem cell exosomes, its preparation method and application, which relates to the technical field of medical dressings; in order to improve the wound healing performance, the present invention prepares a polyurethane foam dressing, and introduces castor oil polyol containing guanidine group during the preparation process, thereby improving the biocompatibility and antibacterial performance of the dressing, effectively reducing the risk of the wound being infected by external bacteria, and in order to further promote wound healing, the present invention also adds mesenchymal stem cell exosomes, which can effectively promote cell proliferation, reduce inflammation and promote tissue regeneration, further promoting wound healing and reducing the pain of patients.

Description

Technical Field

[0001] The present invention relates to the technical field of medical dressings, and specifically to an external dressing of mesenchymal stem cell exosomes, a preparation method thereof, and an application thereof. Background Art

[0002] The skin, as the natural barrier that wraps the human body surface, undertakes important protective functions. All kinds of superficial skin injuries suffered in life, such as knee abrasions, finger cuts, etc., the healing of these wounds has a precise repair process: from the initial blood coagulation to seal the wound surface, to the aggregation of immune cells to remove germs, then to the filling of defects by new cells, and finally to complete the reconstruction of tissue structure. The whole process requires the precise cooperation of dozens of bioactive substances (such as coagulation factors released by platelets, antibacterial proteins secreted by white blood cells, and collagen fibers generated by fibroblasts), and also needs to face the invasion of external bacteria after the skin barrier is damaged. In order to accelerate the healing of wounds, people often use band-aids, bandages, etc. to protect the wounds; however, although the commonly used band-aids and bandages in traditional nursing can temporarily isolate external pollution, they will hinder the further healing of the wounds, adhere to the wounds or make the wounds airtight, thereby causing an immersion effect on the wounds; therefore, new dressings with more excellent performance are gradually replacing traditional dressings such as medical bandages. Summary of the Invention

[0003] The purpose of the present invention is to provide an external dressing of mesenchymal stem cell exosomes, a preparation method thereof, and an application thereof, so as to solve the problems proposed in the prior art.

[0004] To achieve the above purpose, the present invention provides the following technical solution: A preparation method of an external dressing of mesenchymal stem cell exosomes, comprising the following steps:

[0005] S1. Prepare modified castor oil polyol;

[0006] S11. Place castor oil in a container, heat it up to 105 - 110 °C and keep it warm for 15 - 30 min, then add ferric chloride and absolute ethanol to it. After stirring and mixing evenly, add sodium azide to it, cool it down to 0 - 5 °C, irradiate it with blue light, stir and react for 12 - 24 h, then rotary evaporate to remove the excess solvent, and wash the reaction product with deionized water 2 - 3 times. Then heat the remaining reaction product to 105 - 110 °C again, keep it warm for 15 - 30 min, and obtain azido castor oil;

[0007] S12. Disperse 1,3 - bis - BOC - 2 - (carboxymethyl)guanidine in DMF, add N,N - dicyclohexylcarbodiimide to it, continue to mix and stir evenly, then drop it into the DMF solution dissolved with butynediol, heat it up to 75 - 80 °C, stir and react for 3 - 6 h, then rotary evaporate to remove the excess solvent, and obtain an alkynol intermediate;

[0008] S13. Dissolve azidized castor oil in DMF, add the alkynol intermediate thereto, maintain the temperature of the reaction system at 20 - 25 °C, stir and react for 12 - 24 h, then rotary evaporate to remove the excess solvent to obtain modified castor oil polyol;

[0009] S2. Prepare a mesenchymal stem cell exosome topical dressing;

[0010] S21. Mix polyethylene glycol and modified castor oil polyol, heat up to 105 - 110 °C, keep warm for 12 - 24 h, then cool down to room temperature, add toluene diisocyanate and glycerol, protect under a nitrogen atmosphere, stir and mix at 45 °C for 5 - 8 min to obtain a mixed solution for standby;

[0011] S22. Add mesenchymal stem cell exosomes to ultrapure water, stir and mix evenly, then add a foaming agent and a foam stabilizer, stir evenly, add the mixed solution, stir and mix at high speed, place it in a foaming mold, keep warm and foam, after foaming is completed, cut to obtain a mesenchymal stem cell exosome topical dressing.

[0012] Further, by weight, in step S11, 10 parts of castor oil, 0.05 - 0.12 part of ferric chloride and 1.1 - 2.1 parts of sodium azide need to be added.

[0013] Further, by weight, in step S12, 10 parts of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine, 0.03 - 0.07 part of N,N - dicyclohexylcarbodiimide and 2.5 - 2.8 parts of butynediol need to be added.

[0014] Further, by weight, in step S13, 10 parts of azidized castor oil and 10 - 11.5 parts of alkynol intermediate need to be added.

[0015] Further, in step S2, the mesenchymal stem cell exosome topical dressing is composed of 24 - 32 parts of polyethylene glycol, 6 - 10 parts of modified castor oil polyol, 28 - 32 parts of toluene diisocyanate, 1.5 - 2.8 parts of glycerol, 2 - 8 parts of ultrapure water, 0.3 - 0.5 part of mesenchymal stem cell exosomes, 0.5 - 0.8 part of foaming agent and 1 - 1.2 parts of foam stabilizer.

[0016] Further, the foaming agent is alkyl polyglycoside; the foam stabilizer is any one of silicone - based surfactants.

[0017] Further, a mesenchymal stem cell exosome topical dressing is prepared by the above - mentioned method.

[0018] Further, the mesenchymal stem cell exosome topical dressing can be used as a wound dressing.

[0019] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0020] In order to improve the wound healing performance, the present invention prepares a polyurethane foam dressing. Compared with traditional bandages, the polyurethane foam dressing has better skin affinity, can effectively absorb wound exudate, avoid adhesion to the wound surface, reduce the risk of skin maceration around the wound, and the porous structure of the foam dressing also has a better stress dispersion effect compared with traditional bandages, which can effectively reduce the friction on the wound, reduce the pain of the patient and facilitate the healing of wounds in movable parts;

[0021] In addition, in order to further improve the biocompatibility of the polyurethane foam dressing and accelerate wound healing, when preparing the dressing, the present invention uses castor oil as a raw material. Castor oil is rich in olefins. When it is mixed with sodium azide and under the irradiation of ferrous ions and blue light, the unactivated olefins will react with sodium azide to form alkyl azide products, thereby introducing azide groups into the castor oil molecules;

[0022] On this basis, the present invention further uses 1,3 - di - BOC - 2 - (carboxymethyl) guanidine containing carboxyl and guanidine groups as a raw material, reacts it with butynediol containing alkynyl groups, thereby generating an alkynol intermediate containing hydroxyl and guanidine groups. The guanidine group therein has broad - spectrum antibacterial activity, can effectively affect the cell membrane activity of bacteria and other microorganisms, thereby inhibiting the bacterial activity and playing an antibacterial role; then the alkynol intermediate is mixed with azide - modified castor oil, and by using the reaction between azide and alkynyl groups, a castor oil polyol containing guanidine groups is generated. Then, as a polyol raw material, it is further mixed with isocyanate for foaming reaction, thereby finally preparing a foam dressing with biocompatibility and antibacterial activity;

[0023] Meanwhile, in order to further accelerate wound healing, the present invention also adds mesenchymal stem cell exosomes during the preparation of the foam dressing. Mesenchymal stem cell exosomes are nanoscale vesicles released by mesenchymal stem cells (MSCs) through paracrine action, which contain various bioactive substances such as proteins and mRNAs, can effectively promote cell proliferation, reduce inflammation and promote tissue regeneration. Adding them to the dressing can effectively promote wound healing. Specific Embodiments

[0024] Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0025] In the examples and comparative examples of the present invention, the polyethylene glycol has a weight - average molecular weight of 2000, and the mesenchymal stem cell exosomes used are human umbilical cord mesenchymal stem cell exosomes of model FRE - 08;

[0026] Example 1. A preparation method of an external dressing of mesenchymal stem cell exosomes, comprising the following steps:

[0027] S1. Prepare modified castor oil polyol;

[0028] S11. By weight, place 10 parts of castor oil in a container, heat it up to 105 °C and keep it warm for 15 min, then add 0.05 part of ferric chloride and absolute ethanol to it. After stirring and mixing evenly, add 1.1 parts of sodium azide to it, cool it down to 0 °C, irradiate it with blue light, stir and react for 12 h, then rotary evaporate to remove the excess solvent, and wash the reaction product 2 times with deionized water. Then heat the remaining reaction product to 105 °C again and keep it warm for 15 min to obtain azido castor oil;

[0029] S12. By weight, disperse 10 parts of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine in DMF, add 0.03 part of N,N - dicyclohexylcarbodiimide to it, continue to mix and stir evenly, then drop it into the DMF solution containing 2.5 parts of butynediol, heat it up to 75 °C, stir and react for 3 h, then rotary evaporate to remove the excess solvent to obtain an alkynol intermediate;

[0030] S13. By weight, dissolve 10 parts of azido castor oil in DMF, add 10 parts of the alkynol intermediate to it, maintain the temperature of the reaction system at 20 °C, stir and react for 12 h, then rotary evaporate to remove the excess solvent to obtain modified castor oil polyol;

[0031] S2. Prepare an external dressing of mesenchymal stem cell exosomes;

[0032] S21. By weight, mix 24 parts of polyethylene glycol and 6 parts of modified castor oil polyol, heat it up to 105 °C, keep it warm for 12 h, then cool it down to room temperature, add 28 parts of toluene diisocyanate and 1.5 parts of glycerol, protect it under a nitrogen atmosphere, stir and mix and react at 45 °C for 5 min to obtain a mixed solution for standby;

[0033] S22. By weight, add 0.3 part of mesenchymal stem cell exosomes to 2 parts of ultrapure water, stir and mix evenly, then add 0.5 part of foaming agent and 1 part of foam stabilizer to it, stir evenly, add the mixed solution, stir and mix at high speed, then place it in a foaming mold, keep it warm and foam. After the foaming is completed, cut it to obtain an external dressing of mesenchymal stem cell exosomes.

[0034] Example 2. A preparation method of an external dressing of mesenchymal stem cell exosomes, comprising the following steps:

[0035] S1. Prepare modified castor oil polyol;

[0036] S11. Weigh 10 parts of castor oil by weight and place it in a container. Heat it up to 110 °C and keep it warm for 30 min. Then add 0.12 part of ferric chloride and absolute ethanol to it. After stirring and mixing until uniform, add 1.1 parts of sodium azide to it. Cool it down to 5 °C, irradiate it with blue light, and stir and react for 24 h. Then rotary evaporate to remove the excess solvent, and wash the reaction product with deionized water 3 times. Then heat the remaining reaction product to 110 °C again and keep it warm for 30 min to obtain azidated castor oil.

[0037] S12. Weigh 10 parts of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine by weight and disperse it in DMF. Add 0.07 part of N,N - dicyclohexylcarbodiimide to it. After continuing to mix and stir evenly, drop it into the DMF solution containing 2.5 parts of butynediol. Heat it up to 80 °C and stir and react for 6 h. Then rotary evaporate to remove the excess solvent to obtain the alkynol intermediate.

[0038] S13. Weigh 10 parts of azidated castor oil and dissolve it in DMF. Add 10 parts of the alkynol intermediate to it. Maintain the temperature of the reaction system at 25 °C and stir and react for 24 h. Then rotary evaporate to remove the excess solvent to obtain the modified castor oil polyol.

[0039] S2. Prepare the mesenchymal stem cell exosome topical dressing.

[0040] S21. Weigh 24 parts of polyethylene glycol and 6 parts of the modified castor oil polyol by weight, heat it up to 110 °C, and keep it warm for 24 h. Then cool it down to room temperature, add 28 parts of toluene diisocyanate and 1.5 parts of glycerol. Under the protection of a nitrogen atmosphere, stir and mix and react at 45 °C for 8 min to obtain a mixed solution for standby.

[0041] S22. Weigh 2 parts of ultrapure water by weight, add 0.3 part of mesenchymal stem cell exosomes to it, stir and mix evenly. Then add 0.5 part of foaming agent and 1 part of foam stabilizer to it, stir evenly, add the mixed solution, stir and mix at high speed, and then place it in a foaming mold, keep it warm and foam. After foaming is completed, cut it to obtain the mesenchymal stem cell exosome topical dressing.

[0042] Example 3. A preparation method of a mesenchymal stem cell exosome topical dressing, comprising the following steps:

[0043] Compared with Example 2, the amount of sodium azide added in step S11 is increased in this example.

[0044] S1. Prepare the modified castor oil polyol.

[0045] S11. Weigh 10 parts of castor oil by weight and place it in a container. Heat it up to 110 °C and keep it warm for 30 min. Then add 0.12 part of ferric chloride and absolute ethanol to it. After stirring and mixing until uniform, add 2.1 parts of sodium azide to it. Cool it down to 5 °C, irradiate it with blue light, and stir and react for 24 h. Then rotary evaporate to remove the excess solvent, and wash the reaction product with deionized water 3 times. Then heat the remaining reaction product to 110 °C again and keep it warm for 30 min to obtain azido castor oil;

[0046] S12. Weigh 10 parts of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine by weight and disperse it in DMF. Add 0.07 part of N,N - dicyclohexylcarbodiimide to it. After continuing to mix and stir evenly, drop it into the DMF solution containing 2.5 parts of butynediol. Heat it up to 80 °C and stir and react for 6 h. Then rotary evaporate to remove the excess solvent to obtain an alkynol intermediate;

[0047] S13. Weigh 10 parts of azido castor oil and dissolve it in DMF. Add 10 parts of the alkynol intermediate to it. Keep the temperature of the reaction system at 25 °C and stir and react for 24 h. Then rotary evaporate to remove the excess solvent to obtain a modified castor oil polyol;

[0048] S2. Prepare a mesenchymal stem cell exosome topical dressing;

[0049] S21. Weigh 24 parts of polyethylene glycol and 6 parts of modified castor oil polyol by weight, heat it up to 110 °C, and keep it warm for 24 h. Then cool it down to room temperature, add 28 parts of toluene diisocyanate and 1.5 parts of glycerol. Under the protection of a nitrogen atmosphere, stir and mix and react at 45 °C for 8 min to obtain a mixed solution for standby;

[0050] S22. Weigh 2 parts of ultrapure water by weight, add 0.3 part of mesenchymal stem cell exosomes to it, stir and mix evenly. Then add 0.5 part of a foaming agent and 1 part of a foam stabilizer, stir evenly, add the mixed solution, stir and mix at high speed, and then place it in a foaming mold, keep it warm and foam. After foaming is completed, cut it to obtain a mesenchymal stem cell exosome topical dressing.

[0051] Example 4. A method for preparing a mesenchymal stem cell exosome topical dressing, comprising the following steps:

[0052] Compared with Example 3, the amount of butynediol added in step S12 is increased in this example, and the other steps remain unchanged;

[0053] S1. Prepare a modified castor oil polyol;

[0054] S11. Place 10 parts by weight of castor oil in a container, heat it up to 110 °C and keep it warm for 30 min. Then add 0.12 part of ferric chloride and absolute ethanol to it. After stirring and mixing until uniform, add 2.1 parts of sodium azide to it, cool it down to 5 °C, irradiate it with blue light, stir and react for 24 h. Then rotary evaporate to remove the excess solvent, and wash the reaction product 3 times with deionized water. Then heat the remaining reaction product to 110 °C again and keep it warm for 30 min to obtain azido castor oil;

[0055] S12. Disperse 10 parts by weight of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine in DMF, add 0.07 part of N,N - dicyclohexylcarbodiimide to it, continue to mix and stir evenly, then drop it into the DMF solution containing 2.8 parts of butynediol, heat it up to 80 °C, stir and react for 6 h. Then rotary evaporate to remove the excess solvent to obtain an alkynol intermediate;

[0056] S13. Dissolve 10 parts by weight of azido castor oil in DMF, add 10 parts of the alkynol intermediate to it, maintain the temperature of the reaction system at 25 °C, stir and react for 24 h. Then rotary evaporate to remove the excess solvent to obtain modified castor oil polyol.

[0057] Example 5. A preparation method of a mesenchymal stem cell exosome topical dressing, comprising the following steps:

[0058] Compared with Example 4, this example increases the addition amount of the alkynol intermediate in step S13, and the other steps remain unchanged;

[0059] S1. Prepare modified castor oil polyol;

[0060] S11. Place 10 parts by weight of castor oil in a container, heat it up to 110 °C and keep it warm for 30 min. Then add 0.12 part of ferric chloride and absolute ethanol to it. After stirring and mixing until uniform, add 2.1 parts of sodium azide to it, cool it down to 5 °C, irradiate it with blue light, stir and react for 24 h. Then rotary evaporate to remove the excess solvent, and wash the reaction product 3 times with deionized water. Then heat the remaining reaction product to 110 °C again and keep it warm for 30 min to obtain azido castor oil;

[0061] S12. Disperse 10 parts by weight of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine in DMF, add 0.07 part of N,N - dicyclohexylcarbodiimide to it, continue to mix and stir evenly, then drop it into the DMF solution containing 2.8 parts of butynediol, heat it up to 80 °C, stir and react for 6 h. Then rotary evaporate to remove the excess solvent to obtain an alkynol intermediate;

[0062] S13. Dissolve 10 parts of azidized castor oil by weight in DMF, add 11.5 parts of alkynol intermediate thereto, maintain the temperature of the reaction system at 25 °C, stir and react for 24 h, then rotary evaporate to remove the excess solvent to obtain modified castor oil polyol.

[0063] Example 6. A preparation method of a mesenchymal stem cell exosome external dressing, comprising the following steps:

[0064] Compared with Example 1, the addition amounts of the raw materials of each component in step S2 are changed in this example;

[0065] S1. Prepare modified castor oil polyol;

[0066] S11. Place 10 parts of castor oil in a container by weight, heat up to 105 °C and keep warm for 15 min, then add 0.05 part of ferric chloride and absolute ethanol thereto, stir and mix evenly, then add 1.1 parts of sodium azide thereto, cool down to 0 °C, irradiate with blue light, stir and react for 12 h, then rotary evaporate to remove the excess solvent, and wash the reaction product 2 times with deionized water, and then heat the remaining reaction product to 105 °C again, keep warm for 15 min to obtain azidized castor oil;

[0067] S12. Disperse 10 parts of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine by weight in DMF, add 0.03 part of N,N - dicyclohexylcarbodiimide thereto, continue to mix and stir evenly, then drop it into the DMF solution containing 2.5 parts of butynediol, heat up to 75 °C, stir and react for 3 h, then rotary evaporate to remove the excess solvent to obtain alkynol intermediate;

[0068] S13. Dissolve 10 parts of azidized castor oil by weight in DMF, add 10 parts of alkynol intermediate thereto, maintain the temperature of the reaction system at 20 °C, stir and react for 12 h, then rotary evaporate to remove the excess solvent to obtain modified castor oil polyol;

[0069] S2. Prepare mesenchymal stem cell exosome external dressing;

[0070] S21. Mix 32 parts of polyethylene glycol and 10 parts of modified castor oil polyol by weight, heat up to 105 °C, keep warm for 12 h, then cool down to room temperature, add 32 parts of toluene diisocyanate and 2.8 parts of glycerol, protect under a nitrogen atmosphere, stir and mix and react at 45 °C for 5 min to obtain a mixed solution for standby;

[0071] S22. Add 0.5 part of mesenchymal stem cell exosomes to 8 parts of ultrapure water by weight. After stirring and mixing evenly, add 0.8 part of foaming agent and 1.2 parts of foam stabilizer thereto. After stirring evenly, add the mixed solution. After high-speed stirring and mixing, place it in a foaming mold, keep it warm for foaming. After the foaming is completed, cut it to obtain the mesenchymal stem cell exosome external dressing.

[0072] Comparative Example 1. A method for preparing a mesenchymal stem cell exosome external dressing, comprising the following steps:

[0073] Compared with Example 2, mesenchymal stem cell exosomes were not added in this comparative example, and the remaining steps remained unchanged;

[0074] S1. Prepare modified castor oil polyol;

[0075] S11. Place 10 parts of castor oil in a container by weight. After heating and raising the temperature to 110 °C and keeping it warm for 30 min, add 0.12 part of ferric chloride and absolute ethanol thereto. After stirring and mixing evenly, add 1.1 parts of sodium azide thereto. Cool down to 5 °C, irradiate with blue light, stir and react for 24 h, then rotary evaporate to remove the excess solvent, and wash the reaction product 3 times with deionized water. Then raise the remaining reaction product to 110 °C again, keep it warm for 30 min to obtain azido castor oil;

[0076] S12. Disperse 10 parts of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine in DMF by weight. Add 0.07 part of N,N - dicyclohexylcarbodiimide thereto, continue to mix and stir evenly, then drop it into the DMF solution containing 2.5 parts of butynediol. Raise the temperature to 80 °C, stir and react for 6 h, then rotary evaporate to remove the excess solvent to obtain an alkynol intermediate;

[0077] S13. Dissolve 10 parts of azido castor oil in DMF by weight. Add 10 parts of alkynol intermediate thereto, maintain the temperature of the reaction system at 25 °C, stir and react for 24 h, then rotary evaporate to remove the excess solvent to obtain modified castor oil polyol;

[0078] S2. Prepare the mesenchymal stem cell exosome external dressing;

[0079] S21. Mix 24 parts of polyethylene glycol and 6 parts of modified castor oil polyol by weight, raise the temperature to 110 °C, keep it warm for 24 h, then cool down to room temperature, add 28 parts of toluene diisocyanate and 1.5 parts of glycerol, protect it under a nitrogen atmosphere, and stir and mix and react at 45 °C for 8 min to obtain a mixed solution for standby;

[0080] S22. Add 0.5 part of foaming agent and 1 part of foam stabilizer to 2 parts of ultrapure water by weight. After stirring evenly, add the mixed solution. After high-speed stirring and mixing, place it in a foaming mold, keep warm and foam. After the foaming is completed, cut it to obtain the mesenchymal stem cell exosome external dressing.

[0081] Comparative Example 2. A preparation method of a mesenchymal stem cell exosome external dressing, comprising the following steps:

[0082] Compared with Example 2, in this comparative example, modified castor oil polyol was not prepared and directly replaced with an equal mass of polyethylene glycol;

[0083] S1. Prepare the mesenchymal stem cell exosome external dressing;

[0084] S11. Heat 30 parts of polyethylene glycol to 110 °C by weight, keep warm for 24 h, then cool down to room temperature, add 28 parts of toluene diisocyanate and 1.5 parts of glycerol. Under the protection of nitrogen atmosphere, stir and mix at 45 °C for 8 min to obtain a mixed solution for standby;

[0085] S12. Add 0.3 part of mesenchymal stem cell exosomes to 2 parts of ultrapure water by weight. After stirring and mixing evenly, add 0.5 part of foaming agent and 1 part of foam stabilizer to it. After stirring evenly, add the mixed solution. After high-speed stirring and mixing, place it in a foaming mold, keep warm and foam. After the foaming is completed, cut it to obtain the mesenchymal stem cell exosome external dressing.

[0086] Detection: Calculate the antibacterial activities of the mesenchymal stem cell exosome external dressings prepared in Examples 1-6 and Comparative Examples 1-2 against Staphylococcus aureus, Escherichia coli, and Candida albicans by the plate counting method;

[0087] Select 100 SPF-grade male SD rats with similar body weights and ages, with an average weight of 250 ± 10 g. After feeding them in the same environment and conditions for 2 weeks, remove the hair on their backs, create a 2×10 mm wound on their backs, and place the mesenchymal stem cell exosome external dressings prepared in Examples 1-6 and Comparative Examples 1-2 on the wound sites of the rats in turn, and observe their hemostasis conditions. Calculate the wound closure degree by comparing the wound areas on the first day and the seventh day. The test results are shown in the following table;

[0088]

[0089] Finally, it should be noted that the above are only preferred embodiments of the present invention and are not used to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or perform equivalent replacements for some of the technical features. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A preparation method of an external application dressing of mesenchymal stem cell exosomes, characterized in that, It includes the following steps: S1. Prepare modified castor oil polyol; S11. Place castor oil in a container, heat it up to 105 - 110 °C and keep it warm for 15 - 30 min. Then add ferric chloride and absolute ethanol to it. After stirring and mixing until uniform, add sodium azide to it. Cool it down to 0 - 5 °C, irradiate it with blue light, stir and react for 12 - 24 h. Then rotary evaporate to remove the excess solvent, and wash the reaction product with deionized water 2 - 3 times. Again, heat the remaining reaction product to 105 - 110 °C and keep it warm for 15 - 30 min to obtain azido castor oil; S12. Disperse 1,3 - di - BOC - 2 - (carboxymethyl)guanidine in DMF, add N,N - dicyclohexylcarbodiimide to it, continue to mix and stir evenly. Then drop it into the DMF solution containing butynediol, heat it up to 75 - 80 °C, stir and react for 3 - 6 h. Then rotary evaporate to remove the excess solvent to obtain an alkynol intermediate; S13. Dissolve azido castor oil in DMF, add the alkynol intermediate to it, maintain the temperature of the reaction system at 20 - 25 °C, stir and react for 12 - 24 h. Then rotary evaporate to remove the excess solvent to obtain modified castor oil polyol; S2. Prepare a mesenchymal stem cell exosome external dressing; S21. Mix polyethylene glycol and modified castor oil polyol, heat it up to 105 - 110 °C and keep it warm for 12 - 24 h. Then cool it down to room temperature, add toluene diisocyanate and glycerol, protect it under a nitrogen atmosphere, and stir and mix at 45 °C for 5 - 8 min to obtain a mixed solution for standby; S22. Add mesenchymal stem cell exosomes to ultrapure water, stir and mix evenly. Then add a foaming agent and a foam stabilizer to it, stir evenly, add the mixed solution, stir and mix at high speed, then place it in a foaming mold, keep it warm and foam. After the foaming is completed, cut it to obtain a mesenchymal stem cell exosome external dressing.

2. The preparation method of an external dressing of mesenchymal stem cell exosomes according to claim 1, characterized in that: By weight, in step S11, 10 parts of castor oil, 0.05 - 0.12 parts of ferric chloride and 1.1 - 2.1 parts of sodium azide need to be added.

3. The preparation method of a mesenchymal stem cell exosome topical dressing according to claim 1, characterized in that: By weight, in step S12, 10 parts of 1,3 - di - BOC - 2 - (carboxymethyl)guanidine, 0.03 - 0.07 parts of N,N - dicyclohexylcarbodiimide and 2.5 - 2.8 parts of butynediol need to be added.

4. The preparation method of a mesenchymal stem cell exosome topical dressing according to claim 1, characterized in that: By weight, in step S13, 10 parts of azido castor oil and 10 - 11.5 parts of alkynol intermediate need to be added.

5. The preparation method of an external dressing with mesenchymal stem cell exosomes according to claim 1, characterized in that: In step S2, the mesenchymal stem cell exosome external dressing is composed of 24 - 32 parts of polyethylene glycol, 6 - 10 parts of modified castor oil polyol, 28 - 32 parts of toluene diisocyanate, 1.5 - 2.8 parts of glycerol, 2 - 8 parts of ultrapure water, 0.3 - 0.5 parts of mesenchymal stem cell exosomes, 0.5 - 0.8 parts of foaming agent and 1 - 1.2 parts of foam stabilizer.

6. The preparation method of an external dressing of mesenchymal stem cell exosomes according to claim 1, characterized in that: The foaming agent is alkyl polyglycoside; the foam stabilizer is any one of silicone - based surfactants.

7. An external application dressing of mesenchymal stem cell exosomes, characterized in that, The mesenchymal stem cell exosome external dressing is prepared by the preparation method described in any one of claims 1 - 6.

8. Use of the mesenchymal stem cell exosome external application dressing as claimed in claim 7 as a wound dressing.

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