CN117224473A - Preparation method and application of A-PRF-loaded injectable temperature-sensitive hydrogel - Google Patents
Preparation method and application of A-PRF-loaded injectable temperature-sensitive hydrogel Download PDFInfo
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- CN117224473A CN117224473A CN202311525264.4A CN202311525264A CN117224473A CN 117224473 A CN117224473 A CN 117224473A CN 202311525264 A CN202311525264 A CN 202311525264A CN 117224473 A CN117224473 A CN 117224473A
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 44
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 229920001661 Chitosan Polymers 0.000 claims abstract description 51
- 229960002901 sodium glycerophosphate Drugs 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 239000000843 powder Substances 0.000 claims abstract description 18
- 206010052428 Wound Diseases 0.000 claims abstract description 17
- 208000027418 Wounds and injury Diseases 0.000 claims abstract description 17
- 238000000227 grinding Methods 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 12
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 11
- 239000000499 gel Substances 0.000 claims abstract description 9
- 210000004369 blood Anatomy 0.000 claims abstract description 8
- 239000008280 blood Substances 0.000 claims abstract description 8
- 238000001816 cooling Methods 0.000 claims abstract description 7
- 230000003187 abdominal effect Effects 0.000 claims abstract description 6
- 229960000583 acetic acid Drugs 0.000 claims abstract description 6
- 239000008367 deionised water Substances 0.000 claims abstract description 6
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 6
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 6
- 238000004108 freeze drying Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 53
- AVPCPPOOQICIRJ-UHFFFAOYSA-L sodium glycerol 2-phosphate Chemical compound [Na+].[Na+].OCC(CO)OP([O-])([O-])=O AVPCPPOOQICIRJ-UHFFFAOYSA-L 0.000 claims description 20
- 241000700159 Rattus Species 0.000 claims description 15
- 238000003756 stirring Methods 0.000 claims description 12
- 238000002156 mixing Methods 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 210000000702 aorta abdominal Anatomy 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 239000008176 lyophilized powder Substances 0.000 claims 1
- 230000035876 healing Effects 0.000 abstract description 9
- 239000003814 drug Substances 0.000 abstract description 8
- 230000000694 effects Effects 0.000 abstract description 6
- 230000001788 irregular Effects 0.000 abstract description 6
- 230000001737 promoting effect Effects 0.000 abstract description 3
- 208000008960 Diabetic foot Diseases 0.000 description 6
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 5
- 102000009123 Fibrin Human genes 0.000 description 4
- 108010073385 Fibrin Proteins 0.000 description 4
- 229950003499 fibrin Drugs 0.000 description 4
- 230000037314 wound repair Effects 0.000 description 4
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 239000003634 thrombocyte concentrate Substances 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 238000001266 bandaging Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000001804 debridement Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 229940099259 vaseline Drugs 0.000 description 1
Classifications
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Medicinal Preparation (AREA)
Abstract
The invention relates to the technical field of biological medicine, and discloses a preparation method and application of an A-PRF-loaded injectable temperature-sensitive hydrogel, wherein the preparation method comprises the following steps of S1: extracting and centrifuging abdominal aortic blood of a healthy SD rat to obtain an intermediate gel layer which is A-PRF, and freeze-drying and grinding the prepared A-PRF to obtain A-PRF powder for later use, wherein S2: dissolving chitosan powder in 0.1M glacial acetic acid for 24 hours to prepare a 2% chitosan solution, dissolving beta-sodium glycerophosphate in deionized water to obtain a beta-sodium glycerophosphate solution, and then cooling the beta-sodium glycerophosphate solution and the chitosan solution, wherein S3: the method can promote the healing of diabetic wounds and fill irregular diabetic wounds, and achieves better effect than clinical common healing promoting medicaments under the condition of using the A-PRF more economically.
Description
Technical Field
The invention relates to the technical field of biological medicine, in particular to a preparation method and application of an injectable thermosensitive hydrogel loaded with A-PRF.
Background
The diabetic foot refers to skin and deep tissue damage caused by distal nerve lesions and/or vascular lesions of lower limbs of a diabetic patient due to diabetes, is often infected by a combination, affects muscle and bone tissues, is one of the most serious chronic complications of diabetes, has the characteristics of high morbidity and high mortality, has large treatment difficulty, long period and high cost, and brings heavy burden to the patient, family and society.
At present, the local wound surface of the diabetic foot is mostly covered by gauze or some functional dressing after debridement, the treatment has the problems of low cure rate, long treatment time and high cost, and for the chronic wound surface of the diabetic foot, the healing is a slow process, so that a biological material with lasting effect is required to slowly act to promote the healing of the wound surface, and the leukocyte-rich platelet fibrin (Leucocyte and Platelet Rich Fibrin, L-PRF) is a second-generation platelet gel product, so that the healing of the diabetic foot ulcer can be promoted to a certain extent, but the treatment effect is required to be improved, and therefore, a medicament with good treatment effect and high safety is needed urgently.
The application of the improved platelet-rich fibrin in the prior patent (publication number: CN 114209806B) in preparing the medicine for treating diabetic foot ulcers adopts the improved platelet-rich fibrin to have loose reticular fibrin structure, can be rich in more platelets and white blood cells, can release more growth factors and cytokines more continuously, is more beneficial to tissue regeneration and wound repair, and can shorten the healing time of the diabetic foot ulcers, improve the healing rate, have good treatment effect and also have higher safety.
Aiming at the problems, the prior patent provides a solution, but in the practical use process, the preparation amount of the A-PRF in the A-PRF film is not huge, so that a patient with an irregular wound surface needing to be treated is difficult to fully fill and attach the prepared A-PRF film to the irregular wound surface, certain limitation exists, the tissue regeneration and wound repair of the patient are influenced, and the improvement is needed.
Therefore, a preparation method and application of the injectable thermosensitive hydrogel loaded with the A-PRF are provided.
Disclosure of Invention
The invention aims to solve the technical problem of providing a preparation method and application of injectable temperature-sensitive hydrogel which combines freeze-dried A-PRF with temperature-sensitive hydrogel (chitosan-beta-sodium glycerophosphate) and fills and adheres irregular wound surfaces while promoting vascularization of the wound surfaces.
In order to achieve the above purpose, the present invention adopts the following technical scheme: a preparation method of a load A-PRF injectable temperature-sensitive hydrogel comprises the following steps:
s1: extracting abdominal aortic blood of healthy SD rats, centrifuging to obtain an intermediate gel layer A-PRF, freeze-drying the A-PRF, and grinding to obtain A-PRF powder for later use;
s2: dissolving chitosan powder in 0.1M glacial acetic acid for 24h to prepare a 2% chitosan solution, dissolving beta-sodium glycerophosphate in deionized water (56% w/v) to obtain a beta-sodium glycerophosphate solution, and then cooling the beta-sodium glycerophosphate solution and the chitosan solution;
s3: and (3) slightly stirring the beta-sodium glycerophosphate solution in an ice bath, dropwise adding the solution into the chitosan solution, then placing the solution on ice to mix for 30min to obtain injectable temperature-sensitive hydrogel, adding A-PRF into the chitosan temperature-sensitive hydrogel on ice, and stirring for 10min to obtain the injectable temperature-sensitive hydrogel loaded with the A-PRF.
Preferably, in said S1, after the blood of the abdominal aorta of the rat is drawn and put into a centrifuge for centrifugation at 1500r/min for 14min within 1 min.
Preferably, in the step S1, the A-PRF is frozen at-80 ℃ for 24 hours in a refrigerator, and then freeze-dried for 12 hours in a freeze dryer, and ground into powder by using a grinding rod and a grinding dish.
Preferably, in the step S2, the beta-sodium glycerophosphate solution and the chitosan solution are respectively stored in a refrigerator at 4 ℃ for cooling.
Preferably, in the step S3, the mixing time of the beta-sodium glycerophosphate solution and the chitosan solution is 30min.
Preferably, in the S2-S3, the injectable temperature-sensitive hydrogel is a mixed solution of a medium molecular weight chitosan solution with a mass concentration of 1-5% and a beta-sodium glycerophosphate aqueous solution with a mass concentration of 50-60%, wherein the volume ratio of the medium molecular weight chitosan solution to the beta-sodium glycerophosphate aqueous solution is 0.5-4: 6 to 9.5, wherein the molecular weight of the chitosan with medium molecular weight is 300000 ～ 500000Da.
Preferably, in the step S3, the stirring and mixing time of the A-PRF freeze-dried powder and the injectable temperature-sensitive hydrogel is 10min.
Preferably, in the S1-S3, the A-PRF is used at a concentration of 1% -20%, the chitosan is used at a concentration of 1% -3%, the beta-sodium glycerophosphate is used at a concentration of 56%, and the chitosan: the proportion of the beta-sodium glycerophosphate is 3:1-9:1.
An application of a load A-PRF injectable temperature-sensitive hydrogel is provided, wherein the load A-PRF injectable temperature-sensitive hydrogel is applied to the field of diabetic wound repair.
In summary, compared with the prior art, the invention has the following beneficial effects:
1. the freeze-dried A-PRF is combined with the temperature-sensitive hydrogel (chitosan-beta-sodium glycerophosphate) for the first time, so that the composite temperature-sensitive hydrogel which can not only fully fill irregular wound surfaces, but also slowly release growth factors is prepared more simply, wherein the preparation and the selection of the freeze-dried A-PRF can reduce the adverse effect that the first generation of platelet concentrate PRP needs to use an anticoagulant, the process is more physiological than the second generation of platelet concentrate PRF, the dosage of the A-PRF is reduced, the storage is long, and the use is convenient;
2. the material has been proved in animal experiments that it can promote the healing of diabetic rat wound surface and fill irregular diabetic wound, and can achieve better effect than clinical common healing promoting medicine (external human granulocyte macrophage stimulating factor gel) under the condition of saving A-PRF.
Drawings
FIG. 1 is a flow chart of the method of the present invention;
FIG. 2 is a plot of the HE staining of rat skin on day seven according to the invention;
FIG. 3 is a graph showing a fourteenth day rat wound repair control according to the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
As shown in fig. 1-3, embodiment one:
extracting rat abdominal aortic blood, centrifuging at 1500r/min for 14min, separating to obtain an intermediate gel layer as A-PRF, freezing the obtained A-PRF in a refrigerator at-80deg.C for 24 hr, lyophilizing with a lyophilizer for 12 hr, and grinding with a grinding rod and a grinding dish to obtain A-PRF powder; dissolving chitosan powder in 0.1M glacial acetic acid for 24 hours to prepare a 2% chitosan solution, dissolving sodium beta-glycerophosphate in deionized water to obtain a (56% w/v) sodium beta-glycerophosphate solution, respectively storing the sodium beta-glycerophosphate solution and the chitosan solution in a refrigerator at 4 ℃ for cooling, slightly stirring the sodium beta-glycerophosphate solution in an ice bath and dropwise adding the sodium beta-glycerophosphate solution into the chitosan solution, then placing the sodium beta-glycerophosphate solution on ice for 30 minutes to obtain an injectable chitosan temperature-sensitive hydrogel, adding the A-PRF freeze-dried powder into the injectable chitosan temperature-sensitive hydrogel on ice, and fully stirring and mixing the mixture for 10 minutes to obtain the temperature-sensitive hydrogel loaded with freeze-dried A-PRF.
In this embodiment: the A-PRF is used at a concentration of 1%, the chitosan is used at a concentration of 1%, the beta-sodium glycerophosphate is used at a concentration of 56%, and the chitosan: the ratio of the beta-sodium glycerophosphate is 3:1.
Example two
Extracting rat abdominal aortic blood, centrifuging at 1500r/min for 14min, separating to obtain an intermediate gel layer as A-PRF, freezing the obtained A-PRF in a refrigerator at-80deg.C for 24 hr, lyophilizing with a lyophilizer for 12 hr, and grinding with a grinding rod and a grinding dish to obtain A-PRF powder; dissolving chitosan powder in 0.1M glacial acetic acid for 24 hours to prepare a 2% chitosan solution, dissolving sodium beta-glycerophosphate in deionized water to obtain a (56% w/v) sodium beta-glycerophosphate solution, respectively storing the sodium beta-glycerophosphate solution and the chitosan solution in a refrigerator at 4 ℃ for cooling, slightly stirring the sodium beta-glycerophosphate solution in an ice bath and dropwise adding the sodium beta-glycerophosphate solution into the chitosan solution, then placing the sodium beta-glycerophosphate solution on ice for 30 minutes to obtain an injectable chitosan temperature-sensitive hydrogel, adding the A-PRF freeze-dried powder into the injectable chitosan temperature-sensitive hydrogel on ice, and fully stirring and mixing the mixture for 10 minutes to obtain the temperature-sensitive hydrogel loaded with freeze-dried A-PRF.
In this embodiment: the A-PRF is used at a concentration of 10%, the chitosan is used at a concentration of 2%, the sodium beta-glycerophosphate is used at a concentration of 56%, and the chitosan: the ratio of the beta-sodium glycerophosphate is 6:1.
Example III
Extracting rat abdominal aortic blood, centrifuging at 1500r/min for 14min, separating to obtain an intermediate gel layer as A-PRF, freezing the prepared A-PRF in a refrigerator at-80deg.C for 24h, lyophilizing with a lyophilizing machine for 24h, and grinding to obtain A-PRF powder; dissolving chitosan powder in 0.1M glacial acetic acid for 24 hours to prepare a 2% chitosan solution, dissolving sodium beta-glycerophosphate in deionized water to obtain a (56% w/v) sodium beta-glycerophosphate solution, respectively storing the sodium beta-glycerophosphate solution and the chitosan solution in a refrigerator at 4 ℃ for cooling, slightly stirring the sodium beta-glycerophosphate solution in an ice bath and dropwise adding the sodium beta-glycerophosphate solution into the chitosan solution, then placing the sodium beta-glycerophosphate solution on ice for 30 minutes to obtain an injectable chitosan temperature-sensitive hydrogel, adding the A-PRF freeze-dried powder into the injectable chitosan temperature-sensitive hydrogel on ice, and fully stirring and mixing the mixture for 10 minutes to obtain the temperature-sensitive hydrogel loaded with freeze-dried A-PRF.
In this embodiment: the A-PRF is used at a concentration of 20%, the chitosan is used at a concentration of 3%, the beta-sodium glycerophosphate is used at a concentration of 56%, and the chitosan: the ratio of the beta-sodium glycerophosphate is 9:1.
The temperature sensitive hydrogel loaded with freeze-dried A-PRF prepared in the three embodiments is subjected to diabetes rat experiments, a male SD rat with the age of 8-10 weeks is induced into a diabetes rat model by a streptozotocin intraperitoneal injection method, a full-layer skin defect wound surface with the diameter of 10mm is manufactured on the back of each rat, the rats are divided into a blank control group (without other treatment), a positive control group (with external human granulocyte macrophage stimulating factor gel) and a temperature sensitive hydrogel loaded with A-PRF treatment group by adopting a random digital meter method, the medicine is changed once every three days, the wound is covered by using Vaseline gauze after the medicine change, general sterile gauze and elastic bandaging are used for recording the general HE staining of the skin of the seventh day rat and the fourteen days wound surface, and the detection results are shown in figures 2-3: the HE staining of the visible hydrogel group resulted in more new blood vessels than the other two groups and a smaller general wound surface than the other two groups.
The foregoing is only a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art, who is within the scope of the present invention, should make equivalent substitutions or modifications according to the technical scheme of the present invention and the inventive concept thereof, and should be covered by the scope of the present invention.
Claims (9)
1. The preparation method of the A-PRF loaded injectable temperature-sensitive hydrogel is characterized by comprising the following steps of:
s1: extracting abdominal aortic blood of healthy SD rats, centrifuging to obtain an intermediate gel layer A-PRF, freeze-drying the A-PRF, and grinding to obtain A-PRF powder for later use;
s2: dissolving chitosan powder in 0.1M glacial acetic acid for 24h to prepare a 2% chitosan solution, dissolving beta-sodium glycerophosphate in deionized water (56% w/v) to obtain a beta-sodium glycerophosphate solution, and then cooling the beta-sodium glycerophosphate solution and the chitosan solution;
s3: and (3) slightly stirring the beta-sodium glycerophosphate solution in an ice bath, dropwise adding the solution into the chitosan solution, then placing the solution on ice to mix for 30min to obtain injectable temperature-sensitive hydrogel, adding A-PRF into the chitosan temperature-sensitive hydrogel on ice, and stirring for 10min to obtain the injectable temperature-sensitive hydrogel loaded with the A-PRF.
2. The method for preparing an injectable thermosensitive hydrogel loaded with a-PRF according to claim 1, wherein in S1, after the blood of the abdominal aorta of the rat is drawn and put into a centrifuge for centrifugation at 1500r/min for 14min within 1 min.
3. The method for preparing a temperature-sensitive injectable hydrogel loaded with a-PRF according to claim 1, wherein in S1, a-PRF is frozen at-80 ℃ for 24 hours in a refrigerator, and then lyophilized for 12 hours in a freeze dryer, and ground into powder using a grinding rod and a grinding dish.
4. The method for preparing a temperature-sensitive injectable hydrogel loaded with a-PRF according to claim 1, wherein in S2, the sodium beta-glycerophosphate solution and the chitosan solution are stored in a refrigerator at 4 ℃ and cooled respectively.
5. The method for preparing a temperature-sensitive injectable hydrogel loaded with a-PRF according to claim 1, wherein in S3, the time for the beta-sodium glycerophosphate solution to mix with the chitosan solution is 30min.
6. The method for preparing the injectable thermosensitive hydrogel loaded with A-PRF according to claim 1, wherein in S2-S3, the injectable thermosensitive hydrogel is a mixed solution of a medium molecular weight chitosan solution with a mass concentration of 1-5% and a beta-sodium glycerophosphate aqueous solution with a mass concentration of 50-60%, wherein the volume ratio of the medium molecular weight chitosan solution to the beta-sodium glycerophosphate aqueous solution is 0.5-4: 6 to 9.5, wherein the molecular weight of the chitosan with medium molecular weight is 300000 ～ 500000Da.
7. The method for preparing an injectable thermosensitive hydrogel loaded with a-PRF according to claim 1, wherein in S3, the stirring and mixing time of the lyophilized powder of a-PRF and the injectable thermosensitive hydrogel is 10min.
8. The method for preparing the injectable thermosensitive hydrogel loaded with the A-PRF according to claim 1, wherein in the S1-S3, the use concentration of the A-PRF is 1% -20%, the use concentration of the chitosan is 1% -3%, the use concentration of the beta-sodium glycerophosphate is 56%, and the chitosan: the proportion of the beta-sodium glycerophosphate is 3:1-9:1.
9. The application of the A-PRF-loaded injectable thermosensitive hydrogel is characterized in that the A-PRF-loaded injectable thermosensitive hydrogel is applied to repairing of diabetic wounds.
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| CN102399378A (en) * | 2010-09-07 | 2012-04-04 | 中国人民解放军总医院 | Temperature sensitive chitosan hydrogel and its preparation method |
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| CN111420117A (en) * | 2020-03-31 | 2020-07-17 | 陕西朗泰生物科技有限公司 | Preparation method of gel containing stem cell exosomes for skin wound repair |
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| CN114209806B (en) * | 2021-12-27 | 2022-08-30 | 中国人民解放军空军特色医学中心 | Application of improved platelet-rich fibrin in preparing medicine for treating diabetic foot ulcer |
-
2023
- 2023-11-16 CN CN202311525264.4A patent/CN117224473A/en active Pending
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102399378A (en) * | 2010-09-07 | 2012-04-04 | 中国人民解放军总医院 | Temperature sensitive chitosan hydrogel and its preparation method |
| US20130158082A1 (en) * | 2010-09-27 | 2013-06-20 | Emory University | Methods of managing blood sugar levels and compositions related thereto |
| US20160074553A1 (en) * | 2012-11-13 | 2016-03-17 | Consejo Superior De Investigaciones Cientificas (Csic) | Dressing for compromised wound healing |
| CN109106977A (en) * | 2018-08-27 | 2019-01-01 | 温州医科大学附属第二医院、温州医科大学附属育英儿童医院 | A kind of self-healing injection aquagel dressing and the preparation method and application thereof for Tissue of Diabetic Wound reparation |
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