CN115715757A - Composite gel containing platelet-rich plasma and etamsylate and preparation method thereof - Google Patents

Abstract

The invention discloses a composite gel containing platelet-rich plasma and etamsylate, which is prepared from the following raw materials of 1-10% of hydroxypropyl chitosan, 3-25% of benzaldehyde-polyethylene glycol, 2-10% of platelet-rich plasma and 1-10% of etamsylate by mass. The composite gel realizes the combined application of the platelet-rich plasma and the etamsylate, delays the release speed of the platelet-rich plasma and the etamsylate, prolongs the drug effect, and further more effectively treats body wounds.

Description

Composite gel containing platelet-rich plasma and etamsylate and preparation method thereof

Technical Field

The invention belongs to the technical field of medical high polymer materials, and particularly relates to a composite gel containing platelet-rich plasma and etamsylate and a preparation method thereof.

Background

Fatal massive hemorrhage is a main cause of death of wounded personnel in traumatic events such as war injury reduction and car accidents, operations and the like. Infection is yet another leading cause of death of the victim following blood loss. Therefore, the hemostatic and antibacterial wound healing device can timely and effectively treat wounds to stop bleeding and prevent bacterial infection, promote wound healing to a certain extent, and has a decisive effect on improving the treatment efficiency and later recovery of wounded persons.

Chitosan (Chitosan) can achieve the aim of hemostasis by promoting the aggregation of red blood cells and platelets, but Chitosan with a single component is almost insoluble in water, so that the development and utilization of Chitosan are limited to a certain extent, and the limitation of Chitosan needs to be broken through by modification treatment.

Polyethylene glycol (PEG) is a non-toxic, non-immunogenic, non-irritating, water-soluble polymer with multiple organic components, is approved by FDA as a polymer material for use in living bodies, and is widely used in the fields of medicines and cosmetics, such as drug release, surface modification of medical polymer materials, and cosmetic moisturizers.

Platelet Rich Plasma (PRP) is a highly concentrated platelet rich plasma, rich in fibrinogen and various growth factors, and commonly used in the fields of surgical hemostasis, burn healing, plastic surgery, sports medicine, and the like. The freeze-dried Platelet-rich plasma (LPRP) prepared by the freeze-drying technology not only can keep the original biological characteristics, but also has low requirement on the storage environment, and can prolong the storage time.

The etamsylate accelerates blood coagulation by enhancing the aggregation and adhesion of blood platelets and promoting the release of blood coagulation substances.

At present, no report exists that platelet-rich plasma and etamsylate are added into the same carrier at the same time, so that the two drugs can simultaneously exert the drug effects.

Disclosure of Invention

In order to realize the combined application of the platelet-rich plasma and the etamsylate, delay the release speed of the platelet-rich plasma and the etamsylate, prolong the drug effect and further more effectively treat the body wound.

In a first aspect, the invention provides a composite gel containing platelet rich plasma and etamsylate, which is prepared from raw materials including hydroxypropyl chitosan, bi-polar benzaldehyde-polyethylene glycol, platelet rich plasma and etamsylate. The mass fraction of the hydroxypropyl chitosan is 1-10%, the mass fraction of the bi-terminal benzaldehyde-polyethylene glycol is 3-25%, the mass fraction of the platelet rich plasma is 2-10%, and the mass fraction of the etamsylate is 1-10%.

Preferably, the hydroxypropyl chitosan has a mass fraction of 1% to 7%, more preferably 1% to 4%, for example: 1%, 1.2%, 1.4%, 1.5%, 1.7%, 2.0%, 2.1%, 2.2%, 2.3%, 2.5%, 2.7%, 3.0%, 3.2%, 3.4%, 3.5%, 3.7%, 4.0%.

Preferably, the mass fraction of the bi-terminal benzaldehyde-polyethylene glycol is 3% -20%, more preferably 4% -20%, for example: 4.0%, 4.2%, 4.5%, 4.7%, 5.0%, 5.2%, 5.5%, 5.7%, 6.0%, 6.3%, 6.6%, 7.0%, 7.3%, 7.7%, 8.0%, 8.4%, 8.8%, 9.1%, 9.5%, 10.0%, 10.5%, 11.0%, 11.6%, 12.0%, 12.4%, 13.0%, 13.5%, 14.0%, 14.6%, 15.0%, 15.5%, 16.0%, 16.6%, 17.1%, 17.7%, 18.2%, 18.7%, 19.3%, 19.6%, 20.0%.

Preferably, the platelet-rich mass fraction is 2% to 6%, more preferably 3.5% to 6%, for example: 3.5%, 3.8%, 4.0%, 4.3%, 4.8%, 5.0%, 5.5%, 6.0%.

Preferably, the mass fraction of the etamsylate is 1.5% to 5%, more preferably 1.5% to 4%, for example: 1.5%, 1.9%, 2.3%, 2.7%, 3.0%, 3.3%, 3.6%, 4.0%.

Preferably, the mass ratio of hydroxypropyl chitosan to both ends and benzaldehyde-polyethylene glycol is 1:1.

Preferably, the mass ratio of hydroxypropyl chitosan to platelet rich plasma is 1:1.

Preferably, the mass ratio of hydroxypropyl chitosan to the etamsylate is 1:1.0, 1.

Preferably, the platelet rich plasma is freeze-dried platelet rich plasma.

In a second aspect, the invention provides a preparation method of the composite gel of the first aspect, wherein the inventor utilizes the principle of schiff base reaction to react hydroxypropyl chitosan and benzaldehyde-polyethylene glycol to obtain a high molecular drug carrier matrix, and then combines platelet-rich plasma and etamsylate with the drug-carrying matrix to obtain the composite gel of the first aspect.

In one embodiment of the present invention, the preparation method specifically comprises the following steps:

preparing hydroxypropyl chitosan solution and bi-terminal benzaldehyde-polyethylene glycol solution;

adding platelet-rich plasma and etamsylate into the bi-terminal benzaldehyde-polyethylene glycol solution respectively, and mixing uniformly to obtain a mixed solution A;

and dropwise adding the mixed solution A into the hydroxypropyl chitosan solution, uniformly stirring, and standing to obtain the composite gel.

Preferably, the hydroxypropyl chitosan solution has a mass fraction of 2% -10%, more preferably 3% -8%, for example: 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%.

Preferably, the solvent of the hydroxypropyl chitosan solution is at least one of Phosphate Buffer Solution (PBS), distilled water and purified water, and further preferably is a PBS solution.

Preferably, the hydroxypropyl chitosan has a molecular weight of 1000Da to 4000 Da, more preferably 1500Da to 3000Da, for example: 1500Da, 1800Da, 2000Da, 2300Da, 2500Da, 2800Da and 3000Da.

Preferably, the weight fraction of the bi-terminal benzaldehyde-polyethylene glycol solution is 5% -50%, more preferably 10% -45% such as: 10%, 12.5%, 15%, 17.5%, 20%, 22.5%, 25%, 27.5%, 30%, 32.5%, 35%, 37.5%, 40%, 42.5%, 45%.

Preferably, the solvent of the double-ended benzaldehyde-polyethylene glycol solution is at least one of Phosphate Buffer Solution (PBS), distilled water and purified water, and further preferably is a PBS solution.

Preferably, in the mixed solution a, the mass fraction of the platelet-rich plasma is 5% to 20%, more preferably 5% to 15%, for example: 5%, 6%, 7%, 8% |, 9%, 10%, 11%, 12%, 13%, 14%, 15%.

Preferably, the platelet rich plasma is lyophilized platelet rich plasma.

Preferably, in the mixed solution a, the mass fraction of the etamsylate is 2% to 10%, and more preferably 3% to 7%, for example: 3.0%, 3.3%, 3.6%, 4.0%, 4.3%, 4.7%, 5.0%, 5.3%, 5.7%, 6.0%, 6.3%, 6.7%, 7.0%.

In a third aspect, the invention provides the use of the method of the second invention for the manufacture of a medical dressing.

Preferably, the medical dressing comprises a spray, drop or patch, such as a liquid wound patch, a conventional wound patch.

In a fourth aspect, the present invention provides a medical dressing, which is prepared from raw materials including the composite gel of the first aspect.

Preferably, the medical dressing comprises a spray, drop or patch, such as a liquid wound patch, a conventional wound patch.

The invention has the beneficial effects that:

hydroxypropyl chitosan and bi-end benzaldehyde-polyethylene glycol are prepared into a drug carrier matrix, and platelet-rich plasma and etamsylate are added, so that the platelet-rich plasma and etamsylate can simultaneously play a drug role, and the repair and healing of body wounds can be effectively promoted; in addition, the drug carrier matrix can control the slow release of the drug, prolong the action time of the drug and improve the drug effect.

Drawings

FIG. 1 is a graph showing the effect of scanning frequency on the modulus of a composite gel in a mechanical test according to the present invention;

FIG. 2 is a graph illustrating the effect of strain on composite gel modulus in the mechanics of the present invention;

FIG. 3 is a dynamic rheology analysis of a composite gel of the present invention;

FIG. 4 shows the scanning result of the composite gel of the present invention by electron microscope;

FIG. 5 is a Fourier infrared spectrum of a composite gel of the present invention;

FIG. 6 illustrates the hemostatic effect of the composite gel of the present invention;

FIG. 7 illustrates the antimicrobial effect of the composite gel of the present invention;

FIG. 8 shows the effect of the composite gel of the present invention in promoting wound healing.

Detailed Description

The invention will be further described with reference to specific embodiments and drawings, the advantages and features of which will become apparent as the description proceeds. These examples are illustrative only and do not limit the scope of the present invention in any way. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention, and that such changes and modifications may be made without departing from the spirit and scope of the invention.

EXAMPLE one preparation of composite gel samples

1. Preparation of composite gel sample 1

1.1 weighing the materials according to the mixture ratio in the table 1.

Table 1: material proportioning

1.2 preparation of composite gel

The specific preparation process of the composite gel sample 1 comprises the following steps:

1) 0.5g of hydroxypropyl chitosan with the molecular weight of 2000Da is weighed and added into 9.5mL of PBS solution, and the mixture is stirred until the hydroxypropyl chitosan is completely dissolved to obtain a 5% hydroxypropyl chitosan solution.

2) Weighing 2g of benzaldehyde-polyethylene glycol at the two ends, adding the weighed materials into 8mL of PBS solution, and stirring the materials until the materials are completely dissolved to obtain a 20% benzaldehyde-polyethylene glycol solution at the two ends.

3) Adding 1.2g of freeze-dried platelet-rich plasma and 0.8g of etamsylate into the 20% double-ended benzaldehyde-polyethylene glycol solution, uniformly mixing, and stirring until the components are completely dissolved to obtain a mixed solution A.

4) Dropwise adding the mixed solution A prepared in the step 3) into the 5% hydroxypropyl chitosan solution prepared in the step 1) under the stirring condition, and standing for 5-10min at room temperature to obtain a composite gel sample 1.

2. Preparation of composite gel sample 2

2.1 weighing the materials according to the mixture ratio in the table 2.

Table 2: material proportioning

2.2 preparation of composite gel

The specific preparation process of the composite gel sample 2 comprises the following steps:

1) Weighing 0.3g of hydroxypropyl chitosan with the molecular weight of 1500Da, adding the hydroxypropyl chitosan into 9.7mL of PBS solution, and stirring the mixture until the hydroxypropyl chitosan is completely dissolved to obtain a 3% hydroxypropyl chitosan solution.

2) Weighing 1g of bi-terminal benzaldehyde-polyethylene glycol, adding the bi-terminal benzaldehyde-polyethylene glycol into 9mL of PBS solution, and stirring until the bi-terminal benzaldehyde-polyethylene glycol is completely dissolved to obtain a 10% bi-terminal benzaldehyde-polyethylene glycol solution.

3) Adding 0.8g of freeze-dried platelet-rich plasma and 0.4g of etamsylate into the 10% double-ended benzaldehyde-polyethylene glycol solution, uniformly mixing, and stirring until the mixture is completely dissolved to obtain a mixed solution A.

4) And (3) dropwise adding the mixed solution A prepared in the step 3) into the hydroxypropyl chitosan solution with the concentration of 3% prepared in the step 1 under the condition of stirring, and standing for 5-10min at room temperature to obtain a composite gel sample 2.

3. Preparation of composite gel sample 3

3.1 weighing the materials according to the mixture ratio in the table 3.

Table 3: material proportioning

3.2 preparation of composite gel

The specific preparation process of the composite gel sample 3 comprises the following steps:

1) Weighing 0.6g of hydroxypropyl chitosan with the molecular weight of 3000Da, adding the hydroxypropyl chitosan into 9.4mL of PBS solution, and stirring the mixture until the hydroxypropyl chitosan is completely dissolved to obtain 6% hydroxypropyl chitosan solution.

2) Weighing 4g of benzaldehyde-polyethylene glycol at the two ends, adding the benzaldehyde-polyethylene glycol at the two ends into 6mL of PBS solution, and stirring the mixture until the benzaldehyde-polyethylene glycol is completely dissolved to obtain a 40% benzaldehyde-polyethylene glycol solution at the two ends.

3) Adding 1.2g of freeze-dried platelet-rich plasma and 0.8g of etamsylate into the 40% double-ended benzaldehyde-polyethylene glycol solution, uniformly mixing, and stirring until the components are completely dissolved to obtain a mixed solution A.

4) Dropwise adding the mixed solution A prepared in the step 3) into the hydroxypropyl chitosan solution with the concentration of 6% prepared in the step 1) under the stirring condition, and standing for 5-10min at room temperature to obtain a composite gel sample 3.

EXAMPLE two preparation of comparative sample of composite gel

1. Preparation of comparative sample 1 of composite gel

The composite gel comparative sample 1 was prepared in the same manner as the composite gel sample 1 except that the compounding list contained no platelet-rich plasma and no platelet-rich plasma was added to the mixed solution a.

2. Preparation of composite gel comparative sample 2

The preparation process of comparative composite gel sample 1 was the same as that of composite gel sample 1 except that the formulation table contained no etamsylate and that etamsylate was not added to the mixed solution a.

EXAMPLE three composite gel sample Performance testing

Taking the composite gel sample 1 as an example, the performance of the prepared composite gel sample is tested, and the specific test process is as follows:

1. mechanical property test of composite gel sample 1

1.1 composite gel sample 1 was tested for elastic (G ') and viscous (G') modulus using a rheometer (AR G2, jig 40 mm) at 37 deg.C under steady state conditions of 1% shear stress, with the results shown in Table 4 and FIG. 1.

TABLE 4 modulus of elasticity and viscous modulus at different frequencies

As can be seen from Table 4 and FIG. 1, as the shear frequency increased, G' floated between 89-115Pa and G "floated between 3.6-6Pa, indicating that composite gel sample 1 had a relatively constant elastic strength while also having a certain viscosity.

1.2 the elastic (G ') and viscous (G') moduli of composite gel sample 1 were measured by rheometer (AR G2, jig 40 mm) at 37 deg.C, steady state conditions of shear frequency of 6rad/s, with varying strain magnitude, and the results are shown in Table 5 and FIG. 2.

TABLE 5 modulus of elasticity and viscous modulus at different strains

As can be seen from Table 5 and FIG. 2, G 'and G' are both relatively constant at strains less than 100%, and G 'is gradually decreased and G' is gradually increased at strains greater than 100%, intersecting at strains approaching 400%. It shows that the composite gel sample 1 has better stability and better elasticity at 100% strain, then the elasticity of the composite gel sample gradually increases along with the increase of the strain rate, and the fluid property of the composite gel sample 1 is changed until the elasticity decreases at 400%.

2. Rheological testing of composite gel samples

The elastic (G ') and viscous (G') moduli of the composite gel samples were measured at 37 deg.C, 6rad/s shear frequency, dynamic rheology with alternating strains of 1% and 700% using a rheometer (AR G2, jig 40 mm) with the results shown in Table 6 and FIG. 3.

TABLE 6 elastic and viscous moduli at 1% and 700% alternating strain

As can be seen from Table 6 and FIG. 3, at low strain (1%), the G 'position of the composite gel sample was around 100Pa, G "floated over a small range of 1-46Pa, and overall G' > G"; when the strain suddenly reaches a high strain (700%), the G 'value rapidly decreases to around 20-40Pa, G' increases to around 30, and G '≈ G' is in a gel state. When several high and low strains occur alternately, the same state appears in G 'and G' of the MF-CP, which indicates that the composite gel sample has the characteristic of self-healing.

3. Transmission electron microscopy testing of composite gel sample structures

The microscopic morphology of the freeze-dried composite gel sample 1 was observed using a VEGA3 transmission electron microscope. The scanning result of the electron microscope is shown in FIG. 4. As can be seen from fig. 4, after the composite gel sample 1 subjected to the freeze-drying treatment is respectively enlarged by 100 times, 200 times, 500 times and 2000 times, the composite gel sample 1 presents a staggered three-dimensional network structure, forming a better spatial structure, thereby enabling the hemostatic drug to be loaded in the network.

4. Fourier transform infrared spectrometer testing of composite gel sample structure

The microscopic topography of the composite gel sample 1 was scanned using a fourier transform infrared spectrometer (siemer fly IS 5). The results of the Fourier transform infrared spectrometer scan are shown in FIG. 5. As can be seen from fig. 5, the composite gel sample 1 exhibited a moderate waveform absorption peak in the 1548.14cm wavelength vibration region, the peak shape was relatively sharp, and the absorption peak was in the infrared light vibration region where schiff base-C = N-appeared. Indicating that schiff base reaction is present in composite gel sample 1.

Example four test of hemostatic Effect of composite gel sample

The same batch of 32 Japanese white rabbits were selected and randomly divided into 4 groups of 8 rabbits each. The four experimental groups were: a common hemostatic gauze control, a composite gel sample 1 group, a composite gel comparative sample 1 group, and a composite gel comparative sample 2 group. The test rabbits were anesthetized and the left ear was unhaired, and a 0.5cm incision perpendicular to the artery was made 1/3 of the auricular artery, and blood was allowed to flow freely. After the blood was freely ejected for 5s, each group of samples was covered on the wound, and a 200g weight was pressurized, immediately timed until bleeding stopped, the hemostasis time was recorded, and the amount of bleeding was calculated. The results are shown in Table 7 and FIG. 6.

TABLE 7 hemostasis time and amount of bleeding in hemostasis test

As can be seen from Table 7 and FIG. 6, the hemostatic time and amount of bleeding were reduced (P < 0.01) for each of the composite gel sample 1, comparative sample 1, and comparative sample 2, compared to the regular gauze control, and the difference was statistically significant. The composite gel sample 1, the comparative sample 1 and the comparative sample 2 respectively have the hemostatic time reduced by 44.7%, 23.6% and 34.6%, and the hemorrhagic amount reduced by 85.7%, 53.4% and 73.0%.

In addition, the bleeding time and the bleeding amount of the composite gel sample 1 are both smaller than those of the composite gel comparative sample 1 and the composite gel comparative sample 2 (P is less than 0.05), and the difference has statistical significance. The bleeding time of the composite gel sample 1 is reduced by 27.6% and 15.4% respectively compared with the composite gel comparative sample 1 and the comparative sample 2, and the bleeding amount is reduced by 69.3% and 47.0% respectively compared with the composite gel comparative sample 1 and the comparative sample 2.

The results in table 7 and fig. 6 show that the composite gel sample 1, the composite gel comparative sample 1 and the composite gel comparative sample 2 all have good hemostatic effects, and can reduce the amount of bleeding and avoid the influence of excessive blood loss on the amount of circulating blood. In addition, the hemostatic effect of the compound gel sample 1 is better than that of a compound gel comparison sample, and the synergistic effect of the platelet-rich plasma and the etamsylate is reflected.

EXAMPLE five experiments on bacteriostasis of composite gel samples

20 mul of staphylococcus aureus suspension is evenly coated on the whole MH agar plate by using a sterile coating rod to prepare a plate containing bacteria. After burning the forceps with an alcohol lamp for sterilization, the blank drug sensitive paper sheet and the tablet prepared from the composite gel sample 1 were respectively stuck to a flat plate. The flat plate is inverted, put into a 35 ℃ bacteria incubator for 20h, taken out for observing the antibacterial condition, and the diameter of the inhibition zone is accurately measured by a ruler, and the result is shown in figure 7.

As can be seen from fig. 7, there is no significant zone of inhibition around the blank tablet; the periphery of the compound gel sample tablet has an obvious inhibition zone, and the diameter of the inhibition zone is (18.9 +/-0.6) mm. The results in FIG. 7 demonstrate that the complex gel sample significantly inhibited Staphylococcus aureus compared to the blank control.

Example six composite gel sample wound healing promotion experiments

The same batch of 8 Japanese white rabbits were selected and randomly divided into 2 groups of 4 rabbits each. One group was the control of ordinary hemostatic gauze, and the other group was the hemostatic gauze group of composite gel sample 1. The rabbit is characterized in that 1cm is arranged along the side of the spine of the back of the rabbit as the center, a round wound mark with the diameter of 2cm at the left side is made, a cross-shaped full-layer skin incision is made at the marked position by using a sterile scalpel, the skin is a skin scratch model, two groups of hemostatic gauze are covered on the scratched position immediately after scratching, and the medicines are changed for 1 time every other day until the 14 th day after the injury. Experimental rabbits were sacrificed at 3, 7 and 14 days post-injury to observe wound appearance and wound tissue was taken for HE staining to examine skin histopathological changes. The results are shown in FIG. 8.

As can be seen from fig. 8, on day 3 after scratching, the wounds of the large white rabbits of the composite gel sample hemostatic gauze group had a part of scabs without significant necrosis, the epidermis outside the wounds had fallen off, and a small part of inflammatory cells infiltrated; the wounds of the white rabbits in the common hemostatic gauze group are exuded, the wounds are not completely scabbed, and part of the wounds are still exposed in the air, the epidermal cells are necrotic, and a large amount of inflammatory cells infiltrate. The wound of the white rabbit of the composite gel sample hemostatic gauze group is almost healed on the 7 th day after scratching, a large amount of epidermal cells migrate, a small amount of hair follicle cells begin to grow, fibroblasts and part of new capillary vessels can be seen, and inflammatory cells are hardly infiltrated; the wounds of the white rabbits in the common hemostatic gauze group have a large amount of necrosis, the flesh and eyes have inflammatory reactions represented by redness and swelling, a large amount of inflammatory cell infiltration is caused, and only a small amount of epidermal cells migrate. On 14 th day after scratching, the wounds of the large white rabbits of the composite gel sample hemostatic gauze group can only see scars, newly generated epidermal cells completely cover the wounds, hair follicle cells grow out, subcutaneous fibrous tissues are greatly proliferated, and the tissue structures are more compact; the wounds of the white rabbits of the common hemostatic gauze group have obvious scars, and part of fibroblasts are generated, but part of inflammatory cells are infiltrated. The results in fig. 8 demonstrate that the composite gel sample of the present invention promotes wound healing better than conventional hemostatic gauze.

Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that modifications may be made to the embodiments described above, or equivalents may be substituted for elements thereof. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. A composite gel containing platelet-rich plasma and etamsylate is prepared from hydroxypropyl chitosan, bi-polar benzaldehyde-polyethylene glycol, platelet-rich plasma and etamsylate, and is characterized in that: the mass fraction of hydroxypropyl chitosan is 1-10%, the mass fraction of benzaldehyde-polyethylene glycol is 3-25%, the mass fraction of platelet-rich plasma is 2-10%, and the mass fraction of etamsylate is 1-10%.

2. The composite gel of claim 1, wherein: the mass ratio of hydroxypropyl chitosan to the double ends and benzaldehyde-polyethylene glycol is (1).

3. The composite gel of claim 1, wherein: the mass ratio of the hydroxypropyl chitosan to the platelet-rich plasma is 1.

4. The composite gel of claim 1, wherein: the mass ratio of the hydroxypropyl chitosan to the etamsylate is 1-4, preferably 1-2.5.

5. The composite gel according to any one of claims 1 to 4, wherein: the platelet rich plasma is freeze-dried platelet rich plasma.

6. A preparation method of a composite gel containing platelet-rich plasma and etamsylate is characterized in that: the preparation method comprises the following steps:

preparing hydroxypropyl chitosan solution and double-end benzaldehyde-polyethylene glycol solution;

respectively adding the freeze-dried platelet-rich plasma and the etamsylate into a double-ended benzaldehyde-polyethylene glycol solution, and uniformly mixing to obtain a mixed solution A;

and dropwise adding the mixed solution A into the hydroxypropyl chitosan solution, uniformly stirring, and standing to obtain the composite gel.

7. The method of claim 6, wherein: the mass fraction of the hydroxypropyl chitosan solution is 2-10%; the mass fraction of the bi-terminal benzaldehyde-polyethylene glycol solution is 5% -50%.

8. The method of claim 6, wherein: in the mixed solution A, the mass fraction of the platelet-rich plasma is 5-20%, and the mass fraction of the etamsylate is 2-10%.

9. Use of the manufacturing method of any one of claims 6 to 8 in the manufacture of a medical dressing.

10. A medical dressing, characterized by: the starting material for a medical dressing comprises the composite gel of any one of claims 1 to 5.

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