Hemostatic and anti-infection bifunctional algal glue and preparation method thereof
By preparing a hemostatic and anti-infection dual-functional alginic gel composed of phycocyanin, sodium alginate, polydopamine-piperidine nanoparticles and calcium chloride, the problems of poor hemostasis and susceptibility to infection of irregular wounds were solved, effective hemostasis and photothermal sterilization were achieved, and it is suitable for large-scale production.
Patent Information
- Application Number
- CN202510913539.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-03
- Publication Date
- 2025-09-19
AI Technical Summary
Existing hemostatic excipients are not very effective in stopping bleeding on irregular wounds that are difficult to press, or that bleed rapidly and in large quantities. Irregular wounds are prone to infection and are difficult to effectively fight bacteria.
Phycocyanin, sodium alginate, polydopamine-piperidine nanoparticles and calcium chloride were used to prepare hemostatic and anti-infection dual-functional alginate. Appropriate rheological properties and shape retention were obtained by adjusting the ratio, and photothermal sterilization was achieved by adjusting the content of nano-polydopamine-piperidine complex.
It can effectively stop bleeding of irregular wounds and sterilize wounds through infrared light without the need for additional anti-infection drugs. The raw materials are widely available and suitable for large-scale production.
Smart Images
Figure CN120661726A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of medical materials, and particularly relates to a hemostatic and anti-infection dual-functional alginic gel and a preparation method thereof. Background Art
[0002] Many factors, such as traffic accidents, war, and surgery, can cause wound bleeding and lead to death. First aid for hemostasis is the beginning of the "treatment chain" for bleeding on the battlefield (or on-site). Using hemostatic dressings to stop bleeding is a common method, far more effective than conventional methods such as electrocoagulation, compression, and sutures. Existing hemostatic dressings have several mechanisms for stopping bleeding: concentrating blood (such as chitosan hemostatic dressings), adhering to wound tissue to seal bleeding (such as cyanoacrylate hemostatic dressings), and utilizing active substances (such as microfiber collagen hemostatic dressings). However, existing commercially available hemostatic dressings are ineffective for irregular, incompressible wounds, and those with rapid and heavy bleeding. Gel-based hemostatic dressings have gained widespread recognition in the field of hemostatic treatment for irregular, incompressible wounds, and those with rapid and heavy bleeding.
[0003] The present invention uses phycocyanin, sodium alginate, polydopamine-piperidine nanoparticles, calcium chloride, and water / ethanol as raw materials to prepare a dual-function alginic gel that is both hemostatic and anti-infective. On the one hand, irregular wounds require the hemostatic dressing to have suitable rheological properties that can adapt to the wound shape so that it can reach the bleeding site. At the same time, the inability to press and the rapid and heavy bleeding require the dressing to have suitable shape retention properties so that once the material reaches the bleeding site, it will not be washed away by the blood flow. The dual-function alginic gel provided by the present invention can achieve different rheological and shape retention properties by adjusting the ratio of phycocyanin and sodium alginate, thereby solving this problem. On the other hand, the wound's exposure to air and irregular shape make it difficult for antibacterial measures to effectively reach the wound site. In addition, improper care can easily cause infection, leading to an inflammatory response in the body. This requires the hemostatic dressing itself to have the ability to repeatedly sterilize. The dual-function alginic gel provided by the present invention can achieve photothermal sterilization properties by adjusting the content of the nano-polydopamine-piperidine complex, thereby solving the problem of repeated wound infection simply by light exposure. Summary of the Invention
[0004] In order to overcome the problems existing in the prior art, the present invention provides a hemostatic and anti-infection dual-functional alginic gel and a preparation method.
[0005] Disclosed is a hemostatic and anti-infective dual-functional alginic gel, which consists of phycocyanin, sodium alginate, polydopamine-piperidine nanoparticles, calcium chloride and water / ethanol.
[0006] The present invention provides a method for preparing the above-mentioned hemostatic and anti-infection dual-functional alginic gel, which comprises the following steps:
[0007] (1) Preparation of polydopamine-piperidine nanoparticles by reaction of 2,2,6,6-tetramethylpiperidinyl oxide and dopamine hydrochloride;
[0008] (2) fully dissolving phycocyanin, sodium alginate and polydopamine-piperidine nanoparticles in a water / ethanol mixed solution;
[0009] (3) Add an equal volume of calcium chloride aqueous solution to the above solution and stir at room temperature to obtain the hemostatic and anti-infective dual-functional alginic gel.
[0010] Furthermore, the weight fraction of the phycocyanin is 1-10%, the weight fraction of the sodium alginate is 1-5%, the weight fraction of the polydopamine-piperidine nanoparticles is 0.1-0.5%, the weight fraction of the calcium chloride is 0.1%, and the ethanol concentration in the water / ethanol mixed solution is 40%.
[0011] Beneficial effects:
[0012] 1. The hemostatic and anti-infection dual-function alginic gel provided by the present invention can treat irregular, inpressible, rapid and heavy bleeding wounds.
[0013] 2. The hemostatic and anti-infection dual-function alginic acid provided by the present invention can sterilize wounds with the help of infrared light, without the need to apply anti-infection drugs, which facilitates subsequent anti-infection operations.
[0014] 3. The raw materials are widely available, the preparation method is easy to operate, suitable for large-scale industrial production, and has broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS
[0015] Figure 1 : Macroscopic photo of the hemostatic and anti-infective dual-functional alginate prepared in Example 10 (A), its extrudability operation photo (B) and viscosity change curve with shear rate (C).
[0016] Figure 2 : Infrared spectrum of the hemostatic and anti-infection dual-functional algin prepared in Example 8.
[0017] Figure 3 : Scanning electron micrographs of the hemostatic and anti-infective dual-functional alginic gel prepared in Example 3 (A) and Example 6 (B).
[0018] Figure 4 : The hemostatic and anti-infective dual-function algin prepared in Example 10 was heated to 1 W / cm 2 , 2W / cm 2 and 3W / cm 2 Temperature change diagram under 808nm infrared light.
[0019] Figure 5: Effects of the hemostatic and anti-infection dual-functional algin prepared in Example 10 on the survival of Escherichia coli and Staphylococcus aureus under conditions without infrared light (A and C) and irradiation with 808 nm infrared light for 30 min (B and D).
[0020] Figure 6 : Macroscopic photograph of in vitro coagulation test of the hemostatic and anti-infective dual-function algin prepared in Example 10 (A); In vitro coagulation time test results of the hemostatic and anti-infective dual-function algin prepared in Examples 7 and 10 (B).
[0021] Figure 7 Results of testing the hemostatic ability of the dual-function hemostatic and anti-infective alginic acid prepared in Example 10 in a New Zealand rabbit femoral artery puncture model. (A) Femoral artery isolation; (B) Femoral artery puncture and free bleeding for 5 seconds; (C) Application of the dual-function hemostatic and anti-infective alginic acid; (D) 4 hours after hemostasis. DETAILED DESCRIPTION
[0022] The present invention will be described in detail below through examples and drawings.
[0023] Example 1
[0024] A 10 mg / mL aqueous solution of dopamine hydrochloride was rapidly injected into a 5 mg / mL aqueous solution of 2,2,6,6-tetramethylpiperidinium oxide at a volume ratio of 4:1. The reaction was stirred at room temperature for 18 hours. The precipitate was then collected by centrifugation at 2000 rpm for 10 minutes. Polydopamine-piperidinium nanoparticles were obtained after freeze-drying.
[0025] Example 2
[0026] (1) 1% by weight of phycocyanin and 1% by weight of sodium alginate were dissolved in a 48.95% by weight water / ethanol mixed solution.
[0027] (2) Dissolve 0.1% by weight of calcium chloride in 48.95% by weight of aqueous solution.
[0028] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0029] Example 3
[0030] (1) 1% by weight of phycocyanin, 1% by weight of sodium alginate, and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 48.9% by weight water / ethanol mixed solution.
[0031] (2) Dissolve 0.1% by weight of calcium chloride in 48.9% by weight of aqueous solution.
[0032] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0033] from Figure 3 It can be seen that the hemostatic and anti-infection dual-functional alginic gel prepared in Example 3 (A) has a porous structure.
[0034] Example 4
[0035] (1) 5% by weight of phycocyanin, 1% by weight of sodium alginate and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 46.9% by weight water / ethanol mixed solution.
[0036] (2) Dissolve 0.1% by weight of calcium chloride in 46.9% by weight of aqueous solution.
[0037] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0038] Example 5
[0039] (1) 10% by weight of phycocyanin, 1% by weight of sodium alginate, and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 44.4% by weight water / ethanol mixed solution.
[0040] (2) Dissolve 0.1% by weight of calcium chloride in 44.4% by weight of aqueous solution.
[0041] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0042] Example 6
[0043] (1) 1% by weight of phycocyanin, 3% by weight of sodium alginate, and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 47.9% by weight water / ethanol mixed solution.
[0044] (2) Dissolve 0.1% by weight of calcium chloride in 47.9% by weight of aqueous solution.
[0045] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0046] from Figure 3 It can be seen that the hemostatic and anti-infective dual-functional alginic gel prepared in Example 6 (B) has a porous structure.
[0047] Example 7
[0048] (1) 5% by weight of phycocyanin, 3% by weight of sodium alginate and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 45.9% by weight water / ethanol mixed solution.
[0049] (2) Dissolve 0.1% by weight of calcium chloride in 45.9% by weight of aqueous solution.
[0050] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0051] Example 8
[0052] (1) 10% by weight of phycocyanin, 3% by weight of sodium alginate and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 43.4% by weight water / ethanol mixed solution.
[0053] (2) Dissolve 0.1% by weight of calcium chloride in 43.4% by weight of aqueous solution.
[0054] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0055] from Figure 2 In the infrared spectrum of the hemostatic and anti-infective dual-function algin prepared in Example 8, it can be seen that the antisymmetric stretching and symmetric stretching peaks of the carboxylic acid group in the sodium alginate molecule appear at 1596 cm -1 and 1412cm -1 The C=O stretching peaks of amide I and NH bending / CN stretching peaks of amide II in the phycocyanin molecule appeared at 1650 cm-1 and 1536 cm-1, respectively, proving the existence of two main components of hemostatic and anti-infective dual-functional algin.
[0056] Example 9
[0057] (1) 1% by weight of phycocyanin, 5% by weight of sodium alginate and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 46.9% by weight water / ethanol mixed solution.
[0058] (2) Dissolve 0.1% by weight of calcium chloride in 46.9% by weight of aqueous solution.
[0059] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0060] Example 10
[0061] (1) 5% by weight of phycocyanin, 5% by weight of sodium alginate and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 44.9% by weight water / ethanol mixed solution.
[0062] (2) Dissolve 0.1% by weight of calcium chloride in 44.9% by weight of aqueous solution.
[0063] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0064] from Figure 1 It can be seen that the hemostatic and anti-infective dual-function algin prepared in Example 10 is gel-like (A) and can be pushed out of the syringe under external force (B). The viscosity versus shear rate curve (C) shows that its viscosity range is 4.5×10 4 ±0.7×10 4 ~1.7×10 7 ±4.6×10 6 .
[0065] from Figure 4 As can be seen from the image, the hemostatic and anti-infective dual-function algin prepared in Example 10 responds to 808nm infrared light, causing the alginic gel to increase in temperature. This photothermal conversion process is positively correlated with the light intensity and duration. The maximum temperature reaches over 250°C, enabling temperature control. This is because the hemostatic and anti-infective dual-function algin prepared in Example 10 contains polydopamine piperidine, which exhibits photothermal conversion properties.
[0066] from Figure 5 As can be seen in the figures, the hemostatic and anti-infective dual-function algin prepared in Example 10 had no effect on the survival of E. coli and Staphylococcus aureus in the absence of light (A and C). However, after irradiation with 808 nm infrared light for 30 minutes, it inhibited the survival of both E. coli and Staphylococcus aureus (B and D). This is because the hemostatic and anti-infective dual-function algin prepared in Example 10 contains polydopamine piperidine, which has photothermal conversion bactericidal activity.
[0067] from Figure 6 As can be seen from the figure, the hemostatic and anti-infective dual-functional algae can induce blood coagulation (A). Compared with the blank control, the hemostatic and anti-infective dual-functional algins prepared in Examples 7 and 10 significantly promoted blood coagulation, shortening the coagulation time by 5 times and 7 times, respectively.
[0068] from Figure 7As can be seen in the figure, bleeding after femoral artery puncture was substantial and rapid. The hemostatic and anti-infective dual-function alginic gel prepared in Example 10 was injected into the bleeding site and effectively stopped bleeding. Four hours after hemostasis, bleeding ceased, and the animal remained alive. (A) Femoral artery isolation; (B) Femoral artery puncture and free bleeding for 5 seconds; (C) Application of the hemostatic and anti-infective dual-function alginic gel; (D) 4 hours after hemostasis.
[0069] Example 11
[0070] (1) 10% by weight of phycocyanin, 5% by weight of sodium alginate and 0.1% by weight of polydopamine-piperidine nanoparticles were dissolved in a 42.4% by weight water / ethanol mixed solution.
[0071] (2) Dissolve 0.1% by weight of calcium chloride in 42.4% by weight of aqueous solution.
[0072] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0073] Example 12
[0074] (1) 5% by weight of phycocyanin, 3% by weight of sodium alginate and 0.3% by weight of polydopamine-piperidine nanoparticles were dissolved in a 45.8% by weight water / ethanol mixed solution.
[0075] (2) Dissolve 0.1% by weight of calcium chloride in 45.8% by weight of aqueous solution.
[0076] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0077] Example 13
[0078] (1) 5% by weight of phycocyanin, 3% by weight of sodium alginate and 0.5% by weight of polydopamine-piperidine nanoparticles were dissolved in a 45.7% by weight water / ethanol mixed solution.
[0079] (2) Dissolve 0.1% by weight of calcium chloride in 45.7% by weight of aqueous solution.
[0080] Finally, the solutions of step 1 and step 2 were mixed in equal volumes, and stirred at room temperature until gelation occurred to obtain hemostatic and anti-infection dual-functional alginate.
[0081] Table 1. Viscosity of the hemostatic and anti-infective dual-function algin obtained in the examples at a shear rate of 0.01 (1 / s) and 25°C
[0082]
Claims
1. A hemostatic and anti-infective dual-function alginic gel, characterized in that: The algin consists of phycocyanin, sodium alginate, polydopamine-piperidine nanoparticles, calcium chloride and water / ethanol.
2. The method for preparing a hemostatic and anti-infective dual-function alginic gel according to claim 1, characterized in that: The preparation includes the following steps: (1) Preparation of polydopamine-piperidine nanoparticles by reaction of 2,2,6,6-tetramethylpiperidinyl oxide and dopamine hydrochloride; Phycocyanin, sodium alginate and polydopamine-piperidine nanoparticles are fully dissolved in a water / ethanol mixed solution; (3) Add an equal volume of calcium chloride aqueous solution to the above solution and stir at room temperature to obtain the hemostatic and anti-infective dual-functional alginic gel.
3. The method for preparing a hemostatic and anti-infective dual-function alginic gel according to claim 2, characterized in that: The weight fraction of the phycocyanin is 1-10%, the weight fraction of the sodium alginate is 1-5%, the weight fraction of the polydopamine-piperidine nanoparticles is 0.1-0.5%, and the weight fraction of the calcium chloride is 0.1%. The ethanol concentration in the water / ethanol mixed solution is 40%.