Hemostatic gel nano biomedical dressing

Abstract

The invention relates to the technical field of preparation of auxiliary materials, and particularly discloses a hemostatic gel nano biomedical dressing which comprises the following components in parts by mass: 0.5-4.0 parts of composite nano-particles, 1.5-4.0 parts of chitosan, 0.5-4.0 parts of chitosan, 0.5-4.0 parts of sodium alginate, 0.5-4.0 parts of sodium alginate and the balance of water. The preparation method comprises the following steps: preparing the following components in parts by weight: 0 to 0.8 part of a chitosan-dopamine graft, 4.0 to 10.0 parts of poly (N-isopropylacrylamide), 0.5 to 2.5 parts of tannin, 0 to 0.10 part of a cross-linking agent, 0 to 0.20 part of glutaraldehyde, 0 to 1.0 part of polysorbate 80, 0 to 0.2 part of silver ions and 80 to 95 parts of a PBS (Phosphate Buffer Solution); by constructing a ternary composite gel network, the temperature-sensitive polymer, the cationic chitosan and the polyphenol (tannin) are synergistically cross-linked, the on-site rapid prototyping, the wet adhesive force and the mechanical stability are considered, and the wound surface attaching property and the initial hemostasis durability are remarkably improved. Active ingredients of traditional Chinese medicines are loaded on nano-hydroxyapatite and are dispersed in the gel in situ, so that local slow release on a wound surface and drug-carrier synergistic coagulation promotion, anti-inflammatory and healing promotion effects are realized, and the risk of drug loss and agglomeration is reduced.

Description

Technical Field

[0001] This invention belongs to the field of dressing preparation technology, specifically relating to a hemostatic gel nanobiomedical dressing. Background Technology

[0002] Hemostatic dressings are commonly used medical supplies in wound care and surgery. There are various types of hemostatic materials available, including traditional gauze / cotton pads, biopolymer hemostatic materials such as chitosan, gelatin, and oxidized regenerated cellulose, biological adhesives such as gelatin / fibrin, and more recently, hydrogels, nanomaterial carriers, and drug-device composite dressings.

[0003] Although these technologies have their own clinical applications, they still have some limitations in terms of actual wound control, wound healing, and large-scale manufacturability.

[0004] Many synthetic or natural materials adhere well in the dry state, but their adhesion decreases significantly when soaked in blood or exudate, causing dressings to fail to reliably adhere to moist wounds, affecting hemostasis efficiency and infection control. The hemostatic mechanisms of a single substance (such as physical absorption and protein precipitation) are unlikely to simultaneously provide pharmacological support for antibacterial, anti-inflammatory, and healing-promoting effects.

[0005] In response to this, this application proposes a hemostatic gel nanobiomedical dressing to solve the above-mentioned problems. Summary of the Invention

[0006] The purpose of this invention is to provide a hemostatic gel nanobiomedical dressing to solve the problems mentioned in the background art.

[0007] To achieve the above objectives, the present invention provides the following technical solution:

[0008] A hemostatic gel nanobiomedical dressing, comprising, by weight parts:

[0009] Composite nanoparticles (nHAP-PNS-VES) 0.5–4.0 parts, chitosan (CS) 1.5–4.0 parts, chitosan-dopamine graft (CS-DA) 0–0.8 parts, poly(N-isopropylacrylamide) (PNIPAM) 4.0–10.0 parts, tannin 0.5–2.5 parts, crosslinking agent (genipin or transglutaminase TGase (enzyme activity expressed: 2–6 U / 100 parts) 0–0.10 parts, glutaraldehyde (GA) 0–0.20 parts, surfactant (polysorbate 80) 0–1.0 parts, silver ions 0–0.2 parts, PBS buffer 80–95 parts.

[0010] Preferably, the composite nanoparticles are composed of: 60%–75% nano hydroxyapatite (nHAP), 25%–35% ginseng and Panax notoginseng saponins (PNS), and 8%–12% vitamin E succinate (VES).

[0011] Preferably, the method for preparing the dressing includes the following steps:

[0012] S1. Nano-hydroxyapatite is mixed with the effective components of traditional Chinese medicine, ginseng and Panax notoginseng saponins and vitamin E succinate, and then subjected to ultrasonic dispersion and adsorption treatment to combine the effective components of traditional Chinese medicine with the surface of nano-hydroxyapatite to obtain composite nanoparticles.

[0013] S2. Chitosan is dissolved in an acidic buffer solution and chitosan-dopamine graft is added to prepare a cationic polymer solution with wet adhesion.

[0014] S3. Dissolve poly-N-isopropylacrylamide in a buffer solution and mix it with the cationic polymer solution. At the same time, add polyphenolic tannins to construct a pregel system containing thermosensitive components and polyphenol interactions to obtain a pregel body.

[0015] S4. The composite nanoparticles are dispersed in situ into the pregel and homogenized by ultrasonication or high shear to ensure uniform dispersion of the nanoparticles in the pregel, thereby obtaining a uniform dispersion.

[0016] S5. Add a crosslinking agent to the dispersion and induce a thermosensitive phase transition and chemical crosslinking under conditions close to human body temperature to enable the pregel to form rapidly and complete the secondary crosslinking, thereby obtaining a semi-cured gel.

[0017] S6. The semi-cured gel is washed, its moisture content is adjusted, and it is sterilized to remove free small molecules and obtain a final hemostatic gel nano-biomedical dressing with target moisture content and biocompatibility.

[0018] Preferably, the chitosan has a mass fraction of 1.0%–4.0% (w / w), the dopamine grafting rate is 0.5–3.0 mol%, and the cationic polymer solution is prepared by EDC / NHS.

[0019] Preferably, the mass fraction of the poly(N-isopropylacrylamide) (PNIPAM) is 4.0%–8.0% (w / w), the amount of tannin added is 0.5%–2.0% (w / w), and the pregel is mixed at a temperature below the critical solution temperature of poly(N-isopropylacrylamide) (PNIPAM) to maintain good flowability.

[0020] Preferably, the in-situ dispersion is performed using ultrasonic-assisted or high-shear homogenization to obtain a dispersion with a nanoparticle mass fraction of 0.5%–3.0% (w / w) and uniform particle size distribution, and the pH of the dispersion is adjusted to 6.8–7.2.

[0021] Preferably, the crosslinking agent is Genipin or transglutaminase (TGase), and the induction conditions are to keep the dispersion at 34–39°C to trigger PNIPAM phase separation and complete initial coagulation and subsequent chemical crosslinking within 15–60 min, thereby obtaining a semi-cured gel.

[0022] Preferably, the transglutaminase has an enzyme activity of 2–6 U / 100 parts.

[0023] Preferably, the washing includes rinsing 2–4 times with physiological saline or PBS to remove free crosslinking agents, the moisture content is adjusted to 55%–75% (w / w), and the aseptic treatment is preferably performed by gamma irradiation or ethylene oxide sterilization.

[0024] Compared with the prior art, the beneficial effects of the present invention are:

[0025] This invention constructs a ternary composite gel network, synergistically crosslinking thermosensitive polymers, cationic chitosan, and polyphenols (tannins), balancing rapid on-site molding, wet adhesion, and mechanical stability, significantly improving wound adhesion and initial hemostasis durability. The active ingredients of traditional Chinese medicine are loaded onto nano-hydroxyapatite and dispersed in situ within the gel, achieving local sustained release at the wound site and synergistic drug-carrier effects to promote coagulation, anti-inflammation, and healing, while reducing the risk of drug loss and aggregation. The use of natural / enzymatic or trace amounts of low-toxicity crosslinking agents combined with physical phase change crosslinking balances biocompatibility and network strength, reduces the risk of free crosslinking agent residue, and facilitates clinical safety and sterilization process compatibility. Attached Figure Description

[0026] Figure 1 This is a flowchart illustrating the preparation method of a hemostatic gel nanobiomedical dressing according to the present invention. Detailed Implementation

[0027] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0028] Example 1:

[0029] Please see Figure 1 As shown, the materials and testing conditions are as follows:

[0030] Raw material specifications and requirements (all medical / reagent grade):

[0031] nHAP (nano-hydroxyapatite), target particle size 50–80 nm;

[0032] Ginseng and Panax notoginseng total saponins (PNS), pharmaceutical grade;

[0033] Vitamin E succinate (VES), pharmaceutical grade;

[0034] Chitosan (CS, degree of deacetylation ≥90%, Mw≈50 kDa);

[0035] Chitosan-dopamine (CS-DA) is used as a grafting precursor or grafted using the EDC / NHS method;

[0036] Poly(N-isopropylacrylamide) (PNIPAM, LCST≈32℃);

[0037] Tannins (pharmaceutical grade);

[0038] Genipin (cross-linking agent) or transglutaminase (TGase); PBS buffer (pH 7.4, 0.01 M).

[0039] Instruments and conditions: ultrasonic treatment (adjustable power, 150–300 W intermittent mode), high-speed centrifuge (8000 rpm), freeze dryer, 37℃ incubator, materials mechanics testing machine (tensile / compression module), wet adhesion test apparatus (tensile gauge), HPLC (PNS content / release), cell culture and MTT detection equipment, colony counter, and precision balance for weighing (reading 0.1 mg).

[0040] Statistics: In vitro experiments n = 6 (mean ± SD), animal experiments (rat liver parenchymal hemorrhage model) n = 8 (per group).

[0041] Differences between groups were analyzed using a two-tailed Student's t-test, with p < 0.05 considered significant.

[0042] A hemostatic gel nanobiomedical dressing.

[0043] Formula (based on 100 g yield):

[0044] CS: 2.5 g; CS-DA: 0.3 g (grafting rate ~1–2 mol%); PNIPAM: 6.0 g; Tannin: 1.2 g; Composite nanoparticles nHAP-PNS-VES (powder basis): 1.6 g (where nHAP ≈1.0 g, PNS loading ≈0.4 g, VES modification ≈0.2 g); PBS (pH 7.4): 87.0 g; Genipin: 0.03 g (0.03%). Note: No additional antibacterial metal ions added.

[0045] Preparation method steps:

[0046] S1. Nanoparticle preparation: 1.0 g nHAP was added to 50 mL PBS and ultrasonically dispersed (power 250 W, intermittent 5 s on / 5 s off, total duration 12 min, cooled in an ice bath to prevent temperature rise).

[0047] Dissolve 0.4 g PNS and 0.2 g VES in 5 mL of ethanol-water (ethanol volume <5%), and slowly add the solution dropwise to the nHAP suspension at 40 °C. Stir for 2 h to allow PNS to adsorb onto the nHAP surface. Centrifuge (8000 rpm, 10 min) to remove unbound material, wash once, and freeze-dry to obtain composite nanopowder (record yield and adsorption rate: PNS adsorption rate was determined by HPLC; the example showed a loading efficiency of approximately 72%).

[0048] S2. Preparation of chitosan solution: At 25°C, 2.5 g of CS was dissolved in 50 mL of dilute acidified PBS at pH 5.5 and magnetically stirred for 30 min until dissolved (forming a 2.5% w / w solution); 0.3 g of CS-DA was added and stirred for 20 min to obtain a cationic polymer solution with wet adhesion.

[0049] S3, PNIPAM + Tannin Pregel: Dissolve 6.0 g PNIPAM in 30 mL PBS at 45–50 °C (heat briefly to aid dissolution), then cool to 30 °C; slowly mix the chitosan solution from step S2 into the PNIPAM solution and stir for 15 min; add 1.2 g tannin and stir for 30 min to obtain the pregel (operate below PNIPAM LCST to maintain flow).

[0050] S4. In-situ dispersion of nanoparticles: The composite nanoparticles (1.6 g) obtained in step S1 were added to the pregel and dispersed by low-power ultrasonication (150 W, intermittent for 8 min) or by high-shear stirring at 1500 rpm for 5 min to obtain a uniform dispersion (final nanoparticle mass fraction 1.6% w / w). The pH was adjusted to 6.9–7.1 (using a small amount of NaOH or HCl).

[0051] S5. Temperature-sensitive induction + chemical crosslinking: Add Genipin (0.03 g) to the dispersion, mix well, and place in a 37°C constant temperature oven; PNIPAM undergoes a phase transition at 37°C to promote initial setting (initial setting time in the experiment was 120–300 s; depending on the amount, in this example, initial setting was about 3 min, and complete curing was 20–40 min). Mild chemical crosslinking (reaction of Genipin with amine groups) is maintained at 37°C for 30–60 min to obtain a semi-cured gel.

[0052] S6. Washing, moisture adjustment, and sterilization: Rinse three times (15 min each time) with PBS to remove free Genipin and dissolved small molecules (collect the washing solution and determine the content of free Genipin and free PNS to confirm thorough washing). Controlling drying / moisture content: Vacuum drying to stabilize the moisture content at 60–70% (by weighing). After aseptic packaging, sterilize with γ-rays at 25 kGy (EtO was used as an alternative in small laboratory batches to verify residues), yielding the final hemostatic gel nanobiomedical dressing.

[0053] Small batch yield and test results:

[0054] PNS loading efficiency on nHAP surface (HPLC): 72% ± 3% (n = 3).

[0055] Initial setting time (37℃): 3.0 ± 0.5 min (n = 6).

[0056] Moisture content: 66.0% ± 2.5% (n = 6).

[0057] Example 2:

[0058] The difference between this hemostatic gel nanobiomedical dressing and Example 1 is that the cross-linking agent is enzymatically cross-linked, using transglutaminase (TGase).

[0059] Formula (per 100g)

[0060] CS: 2.5 g; CS-DA: 0.2 g (slightly lower grafting rate); PNIPAM: 5.0 g (lower content); Tannin: 1.0 g; Composite nanoparticles nHAP-PNS-VES: 1.2 g (nHAP ≈ 0.75 g, PNS approximately 0.3 g, VES 0.15 g); PBS: 89.0 g; Transglutaminase (TGase): Activity introduced at 5 U / g dry basis (for enzymatic cross-linking).

[0061] The preparation method steps are as follows:

[0062] The other steps are the same as in Example 1 (including: S1, nanoparticle preparation; S2, chitosan solution dissolution; S3, PNIPAM + tannin pregelation; S4, in-situ dispersion of nanoparticles), the difference being in step S5:

[0063] Temperature-sensitive induction and enzymatic cross-linking: After dispersing the composite nanoparticles and adjusting the pH to 6.8–7.0, TGase (5 U / g dry basis) was added, and the system was placed at 37°C. PNIPAM induced initial coagulation (4–6 min), and TGase underwent enzymatic cross-linking with polyamine groups at 37°C (complete curing time 30–90 min, depending on enzyme activity), resulting in a semi-cured gel F2. Washing / water conditioning / sterilization were performed as in Example 1 (washed 3 times with PBS, moisture content 60–70%, EtO or γ-ray sterilization verification). The final product of Example 2, a hemostatic gel nanobiomedical dressing, was obtained.

[0064] Small batch yield and test results:

[0065] PNS loading efficiency on nHAP surface (HPLC): 68% ± 4% (n = 3).

[0066] Initial setting time (37℃): 4.5 ± 0.8 min (n = 6).

[0067] Moisture content: 64.0% ± 3.0% (n = 6).

[0068] Example 3:

[0069] Preparation of comparative examples (control samples):

[0070] For objective comparison, a typical control sample (CS-only gel) was prepared:

[0071] CS: 3.0 g (3.0% w / w) dissolved in PBS; no PNIPAM, tannins, or nanoparticles added. Chemical crosslinking: 0.1% glutaraldehyde (GA) was used as the crosslinking agent (typical conventional method). Washing / drying / sterilization were performed as above. This control sample was used to measure hemostasis, adhesion, mechanical and biological properties.

[0072] The performance testing method is as follows:

[0073] Note: All in vitro experiments were performed at 37°C and physiological pH. The number of replicates is shown below. Statistical methods: mean ± standard deviation (SD). Two-tailed Student's t-test was used for comparisons between groups.

[0074] Blood clotting related (in vitro):

[0075] Methods: Peripheral venous blood was collected from healthy volunteers, anticoagulated, and recalcified with 0.2 M CaCl2 (finally 10 mM). Whole blood clotting time (WBCT) was measured using the tilt method or a clotting time meter.

[0076] Place 0.2 mL of whole blood on the sample surface and record the time (s) required for clot formation at 37°C. Repeat: n = 6 per group.

[0077] Animal model—Rat liver parenchymal hemorrhage model (in vivo hemostasis efficiency):

[0078] Methods: Male Sprague-Dawley rats (250–300 g) were anesthetized and their livers were exposed via laparotomy. A standardized incision (1.0 cm long × 0.5 cm deep) was made in the left hepatic lobe (using a uniform scalpel). The test dressing was immediately applied to the wound and the following data were recorded: Bleeding volume (mg): Blood was absorbed by covering the wound with pre-weighed filter paper / gauze, and then weighed after removal (the change in total weight is the blood volume); Hemostasis time (s): The time from when the dressing came into contact with the wound until no active bleeding occurred was recorded (in seconds).

[0079] Repetition: n = 8 per group; the experiment followed animal ethics guidelines.

[0080] Wet adhesion strength (wet pigskin tensile shear test):

[0081] Method: The sample was attached to a moistened pigskin specimen (moistened with PBS at 37°C), and shear peel / tensile tests were performed according to a method similar to ASTM F2255-05. The maximum adhesion strength (kPa) was recorded. n = 5.

[0082] Liquid absorption rate (water absorption / permeation):

[0083] Method: Weigh the dry weight of the sample m0, immerse it in PBS at 37℃ for 30 min, remove it, remove excess liquid from the surface, and weigh it m1. Liquid absorption volume = (m1−m0) / m0 (mL / g). n = 6.

[0084] Compression modulus (mechanical property):

[0085] Method: Cylindrical samples (10 mm in diameter and 5 mm in height) were compressed to 30% strain at a rate of 1 mm / min under PBS humidification at 37 °C. The initial linear slope (kPa) was measured. n = 5.

[0086] Cytotoxicity (MTT, ISO 10993-5):

[0087] Methods: Sample extract was prepared using the extraction buffer method (1:10 volume ratio). L929 cells were cultured for 24 h and co-incubated with the extract. MTT absorbance was measured and the survival rate (%) was calculated (control was 100%). n=6.

[0088] Antibacterial activity (colony counting method)

[0089] Method: Using S. aureus and E. coli, initial inoculation was performed at 10... 6 CFU / mL, incubated on the sample surface for 24 h, the incubation system was collected and plate counted according to the dilution gradient, and the log10 reduction value was calculated. n=3.

[0090] PNS release (HPLC)

[0091] Method: The sample was placed in PBS (pH 7.4) at 37℃. The cumulative release percentage of PNS was quantified by HPLC at 0, 1, 6, 24, 48, and 72 h. n=3.

[0092] Experimental results:

[0093] Note: The following are mean ± SD values ​​obtained from laboratory small-scale tests (units: s, mg, kPa, mL / g, % etc.).

[0094] For "reduction-related indicators" (such as clotting time, bleeding volume, and hemostasis time):

[0095] Reduction rate = (Comparative example mean - Example mean) / Comparative example mean × 100%;

[0096] For "increased indicators" (such as adhesion strength, liquid absorption rate, compressive modulus, cell viability, antibacterial logreduction, and PNS release):

[0097] Increase rate = (mean of examples - mean of comparative examples) / mean of comparative examples × 100%;

[0098] The summary table is shown in Table 1 below:

[0099] Table 1

[0100] Indicators (units) Example 1: mean ± SD(n) Example 2: mean±SD(n) Comparative proportion mean ± SD(n) The improvement rate relative to the comparative example (Ex1 / Ex2) In vitro whole blood clotting time (WBCT) (s) 130 ± 8 (n=6) 145 ± 10 (n=6) 200 ± 12 (n=6) Reduced by 35.0% / 27.5% Hepatic parenchymal hemorrhage volume in rats (mg) 260 ± 30 (n=8) 310 ± 35 (n=8) 540 ± 45 (n=8) Reduced by 51.9% / 42.6% Hemostasis time in rats (s) 70 ± 10 (n=8) 95 ± 12 (n=8) 180 ± 15 (n=8) Reduced by 61.1% / 47.2% Wet adhesion strength (pigskin) (kPa) 22 ± 2.5 (n=5) 18 ± 2.2 (n=5) 8 ± 1.2 (n=5) Increased by 175.0% / 125.0% Liquid absorption rate (mL / g) 6.8 ± 0.5 (n=6) 6.2 ± 0.6 (n=6) 3.5 ± 0.4 (n=6) Increased by 94.3% / 77.1% Compression modulus (kPa) 28 ± 3.0 (n=5) 24 ± 2.8 (n=5) 12 ± 1.5 (n=5) Increased by 133.3% / 100.0% Cell viability (MTT) (%) 92 ± 4 (n=6) 93 ± 3 (n=6) 88 ± 5 (n=6) Increase by 4.5% / 5.7% Antibacterial activity (S. aureus) log10 reduction (24h) 2.2 ± 0.2 (n=3) 1.9 ± 0.3 (n=3) 0.9 ± 0.2 (n=3) Increased by 144.4% / 111.1% PNS cumulative release (72 h) (%) 78 ± 4 (n=3) 72 ± 5 (n=3) 0 (No PNS) — / —

[0101] As can be seen from the above, accelerating coagulation (WBCT and animal hemostasis time):

[0102] Example 1 reduced WBCT from 200 s to 130 s (approximately 35% reduction) and hemostasis time in animals from 180 s to 70 s (approximately 61% reduction). This demonstrates that the thermosensitive rapid gelation of PNIPAM, the enhanced wet adhesion of CS-DA, and the local procoagulant / pro-healing effects of nHAP-PNS in this invention synergistically and significantly accelerate wound closure and blood coagulation.

[0103] Reduced blood loss (animal model): Example 1 showed a reduction of approximately 52% in blood loss, demonstrating that the dressing was significantly superior to the traditional CS-only control in actual bleeding control scenarios, reflecting the combined advantages of nano-load (nHAP provides hemostatic activity at the bone / mineral interface) and high permeability.

[0104] Improved adhesion (wet adhesion strength): Example 1 showed an adhesion strength of 22 kPa, which was 175% higher than the control of 8 kPa, verifying the enhanced adhesion of CS-DA (dopamine) modification on wet tissue.

[0105] Absorption and mechanical properties: Absorption rate and compressive modulus are significantly improved (nearly doubled and 1.3–2.3 times higher, respectively), ensuring that the dressing can maintain its structure and pressure transmission while absorbing exudate, which is beneficial for hemostasis and healing.

[0106] Biocompatibility and antibacterial properties: MTT cell survival rate ≥ 92% (Example 1), and 24h log reduction ≈ 2.2 against Staphylococcus aureus, showing good antibacterial effect without sacrificing cell compatibility. This is related to the natural antibacterial / anti-inflammatory activity of tannins and PNS, as well as the interfacial effect of nanoparticles.

[0107] Sustained drug release (PNS release): Example 1 shows a cumulative release of ~78% over 72 hours, providing local sustained-release support for tissue repair and anti-inflammation, thereby contributing to long-term healing.

[0108] Example 1 (Genipin chemical crosslinking) showed faster initial hemostasis and greater reduction in bleeding volume with a shorter initial coagulation time (3.0 min) and slightly higher PNS loading / release (this example represents the optimal balance).

[0109] Example 2 (TGase enzymatic crosslinking) showed a milder crosslinking method and slightly better biocompatibility (MTT 93% vs 92%), but slightly slower initial coagulation and slightly lower PNS release rate (due to slightly different crosslinking density / nanoload). This indicates that the crosslinking method and nano content can serve as alternative implementation schemes for different clinical scenarios.

[0110] As shown above, by constructing a ternary composite gel network, thermosensitive polymers, cationic chitosan, and polyphenols (tannins) are synergistically crosslinked, balancing rapid on-site molding, wet adhesion, and mechanical stability, significantly improving wound adhesion and initial hemostasis durability. Loading the active ingredient of traditional Chinese medicine, ginseng and Panax notoginseng total saponins, onto nano-hydroxyapatite and dispersing it in situ within the gel achieves local sustained release at the wound site and synergistic drug-carrier effects in promoting coagulation, anti-inflammation, and healing, while reducing the risk of drug loss and aggregation. Using natural / enzymatic or trace amounts of low-toxicity crosslinking agents combined with physical phase change crosslinking balances biocompatibility and network strength, reduces the risk of free crosslinking agent residue, and facilitates clinical safety and sterilization process compatibility.

[0111] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A hemostatic gel nanobiomedical dressing, characterized in that, Including by mass percentage: The composition includes 0.5–4.0 parts of composite nanoparticles, 1.5–4.0 parts of chitosan, 0–0.8 parts of chitosan-dopamine graft, 4.0–10.0 parts of poly-N-isopropylacrylamide, 0.5–2.5 parts of tannins, 0–0.10 parts of crosslinking agent, 0–0.20 parts of glutaraldehyde, 800–1.0 parts of polysorbate, 0–0.2 parts of silver ions, and 80–95 parts of PBS buffer.

2. The hemostatic gel nanobiomedical dressing according to claim 1, characterized in that, The composite nanoparticles are composed of: 60%–75% nano hydroxyapatite, 25%–35% total saponins of ginseng and Panax notoginseng, and 8%–12% vitamin E succinate.

3. A hemostatic gel nanobiomedical dressing according to any one of claims 1-2, characterized in that, The preparation method of the dressing includes the following steps: S1. Nano-hydroxyapatite is mixed with the effective components of traditional Chinese medicine, ginseng and Panax notoginseng saponins and vitamin E succinate, and then subjected to ultrasonic dispersion and adsorption treatment to obtain composite nanoparticles. S2. Chitosan is dissolved in an acidic buffer solution and chitosan-dopamine graft is added to prepare a cationic polymer solution with wet adhesion. S3. Dissolve poly-N-isopropylacrylamide in a buffer solution and mix it with the cationic polymer solution. At the same time, add polyphenolic tannins to construct a pregel system containing thermosensitive components and polyphenol interactions to obtain a pregel body. S4. The composite nanoparticles are dispersed in situ into the pregel and homogenized by ultrasonication or high shear to ensure uniform dispersion of the nanoparticles in the pregel, thereby obtaining a uniform dispersion. S5. Add a crosslinking agent to the dispersion and induce a thermosensitive phase transition and chemical crosslinking under conditions close to human body temperature to enable the pregel to form rapidly and complete the secondary crosslinking, thereby obtaining a semi-cured gel. S6. The semi-cured gel is washed, its moisture content is adjusted, and it is sterilized to remove free small molecules and obtain a final hemostatic gel nano-biomedical dressing with target moisture content and biocompatibility.

4. The hemostatic gel nanobiomedical dressing according to claim 3, characterized in that, The chitosan has a mass fraction of 1.0%–4.0% (w / w), the dopamine grafting rate is 0.5–3.0 mol%, and the cationic polymer solution is prepared by EDC / NHS.

5. The hemostatic gel nanobiomedical dressing according to claim 3, characterized in that, The mass fraction of the poly(N-isopropylacrylamide) is 4.0%–8.0% (w / w), the amount of tannin added is 0.5%–2.0% (w / w), and the pregel is mixed below the critical solution temperature of poly(N-isopropylacrylamide) PNIPAM to maintain good flowability.

6. The hemostatic gel nanobiomedical dressing according to claim 3, characterized in that, The in-situ dispersion is achieved by ultrasonic-assisted or high-shear homogenization to obtain a dispersion with a nanoparticle mass fraction of 0.5%–3.0% (w / w) and uniform particle size distribution, and the pH of the dispersion is adjusted to 6.8–7.

2.

7. The hemostatic gel nanobiomedical dressing according to claim 3, characterized in that, The crosslinking agent is Genipin or transglutaminase (TGase), and the induction conditions are to keep the dispersion at 34–39°C to trigger PNIPAM phase separation and complete initial coagulation and subsequent chemical crosslinking within 15–60 min, thereby obtaining a semi-cured gel.

8. The hemostatic gel nanobiomedical dressing according to claim 7, characterized in that, The transglutaminase has an enzyme activity of 2–6 U / 100 portions.

9. The hemostatic gel nanobiomedical dressing according to claim 3, characterized in that, The washing process includes rinsing 2–4 times with physiological saline or PBS to remove free crosslinking agents, the moisture content is adjusted to 55%–75% (w / w), and the aseptic treatment is preferably performed by gamma irradiation or ethylene oxide sterilization.

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