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CN-121987660-A - Sodium alginate-beta-glucan composite wound repair spray and preparation method thereof

CN121987660ACN 121987660 ACN121987660 ACN 121987660ACN-121987660-A

Abstract

The invention discloses sodium alginate-beta-glucan composite wound repair spray with rapid film forming and long-acting repair functions and a preparation method thereof. The sodium alginate is subjected to low-oxidation-degree modification to form a high-ion-response composite system with hydroxypropyl methylcellulose with viscosity regulated by gradient, so that the obtained spray can be rapidly formed into a film after spraying, and the yeast beta-glucan is subjected to phosphorylation modification to improve the water solubility and targeting property, enhance the binding force with macrophage receptors and improve the anti-inflammatory efficiency. The obtained spray has multiple effects of rapid film formation, mild bacteriostasis and long-acting repair, can break the vicious circle of chronic wound repair, and provides an innovative thought for the development of wound care products.

Inventors

  • ZHANG JIN
  • Wang Yanlang
  • YANG HUANGHAO
  • PAN JUN
  • YANG YUHANG
  • LIN HAIRONG

Assignees

  • 福州大学
  • 福建博艾思医疗科技有限公司

Dates

Publication Date
20260508
Application Date
20260306

Claims (10)

  1. 1. The preparation method of the sodium alginate-beta-glucan composite wound repair spray with the rapid film forming and long-acting repair functions is characterized by comprising the following steps of: (1) Adding calcium chloride into purified water, and stirring until the calcium chloride is completely dissolved to obtain a solution S1; (2) Sequentially adding sodium dihydrogen phosphate, disodium hydrogen phosphate and EDTA-2Na into purified water, and stirring until the sodium dihydrogen phosphate, the disodium hydrogen phosphate and the EDTA-2Na are completely dissolved to obtain a solution S2; (3) Adding sodium alginate into purified water, adding EDTA-2Na, uniformly stirring, then dropwise adding hydrogen peroxide for reaction, heating to decompose residual hydrogen peroxide after the reaction, and cooling to obtain a solution S3 containing modified sodium alginate with low oxidation degree; (4) Adding hypromellose into the solution S2 prepared in the step (2), stirring for 1-5 min at 10-35 ℃, heating to 35-45 ℃, stirring for 1-10 min, cooling to 30 ℃, adding the solution S3 prepared in the step (3), swelling by adopting ultrasonic-microwave synergistic treatment, and standing to obtain a solution S4; (5) Uniformly mixing yeast beta-glucan and sodium dihydrogen phosphate, reacting, cooling, dispersing with purified water, dialyzing to remove free phosphate, and freeze-drying to obtain phosphorylated beta-glucan; (6) Sequentially adding mannitol, the phosphorylated beta-glucan prepared in the step (5) and phenoxyethanol into the solution S4 obtained in the step (4), and stirring until the materials are completely dissolved to obtain a solution S5; (7) Slowly dripping the solution S1 obtained in the step (1) into the solution S5 obtained in the step (6) at a gradient increasing dripping rate by using a dropper, synchronously and dynamically shearing in the dripping process, and standing after dripping to obtain the solution S6; (8) And (3) regulating the pH value of the solution S6 obtained in the step (7), performing in-situ degassing treatment, sub-packaging, sealing and sectionally sterilizing by adopting electron beam irradiation to prepare the sodium alginate-beta-glucan composite wound repair spray, and refrigerating and preserving.
  2. 2. The preparation method of the sodium alginate-beta-glucan composite wound repair spray according to claim 1, wherein the mass concentration of the solution S1 obtained in the step (1) is 0.01% -0.50%.
  3. 3. The method for preparing the sodium alginate-beta-glucan composite wound repair spray according to claim 1, wherein the proportion of the purified water, the sodium dihydrogen phosphate, the disodium hydrogen phosphate and the EDTA-2Na used in the step (2) is (700-900) mL (0.1-4.0) g (0.5-8.5) g (0.05-0.5) g.
  4. 4. The preparation method of the sodium alginate-beta-glucan composite wound repair spray according to claim 1, wherein the proportion of sodium alginate, purified water, EDTA-2Na and hydrogen peroxide used in the step (3) is (1.0-10.0) g, (500-1000) mL, (0.1-0.5) g, (0.01-1.0) g, the reaction temperature is 20-35 ℃ for 1-2 h, the reaction time is 60-80 ℃ and the heat preservation is carried out for 10-50 min to enable residual hydrogen peroxide to be completely decomposed, and the oxidation degree of the obtained low-oxidation-degree modified sodium alginate is 5% -10%.
  5. 5. The preparation method of the sodium alginate-beta-glucan composite wound repair spray according to claim 1 is characterized in that the mass ratio of the added hydroxypropyl methylcellulose to the sodium alginate used in the step (4) is (1.0-6.0): (1.0-6.0), and the ultrasonic-microwave cooperative treatment parameters are that ultrasonic power is 100-120W, microwave power is 200-300W, the temperature is 20-45 ℃ and the treatment time is 5-20 min, and ultrasonic and microwave are switched every 1-4 min.
  6. 6. The preparation method of the sodium alginate-beta-glucan composite wound repair spray according to claim 1 is characterized in that the mass ratio of yeast beta-glucan to sodium dihydrogen phosphate used in the step (5) is (1.0-3.0) (1.0-5.0), the reaction temperature is 90-120 ℃ and the reaction time is 2-4 hours, a dialysis membrane with the molecular weight cutoff of 8000Da is adopted in the dialysis, the dialysis time is 12-36 hours, and the phosphorylation substitution degree of the obtained phosphorylated beta-glucan is 0.15-0.3.
  7. 7. The preparation method of the sodium alginate-beta-glucan composite wound repair spray according to claim 1 is characterized in that the temperature in the step (7) is kept at 20-30 ℃, the dripping is performed in two stages, the dripping is performed at a rate of 1 drop/sec in the first 1-5 min and at a rate of 3 drops/sec in the second 1-5 min, the change time of dynamic shearing is synchronous with the change time of the dripping rate, and the stirring rotation speed is gradually increased from 100-300 r/min to 300-500 r/min.
  8. 8. The preparation method of the sodium alginate-beta-glucan composite wound repair spray according to claim 1, wherein the mass ratio of hydroxypropyl methylcellulose, mannitol, phosphorylated beta-glucan, phenoxyethanol and calcium chloride in the solution S6 obtained in the step (7) is (1.0-6.0): 5.0-12.5): 1.0-6.0): 0.1-8.0): 0.01-2.0.
  9. 9. The preparation method of the sodium alginate-beta-glucan composite wound repair spray according to claim 1 is characterized in that in the step (8), the pH is adjusted to 6.0-6.5, the vacuum degree of the in-situ degassing treatment is-0.05-0.08 MPa, the temperature is 1-25 ℃, the treatment time is 5-15 min, the segmented electron beam irradiation sterilization is carried out by irradiating for 0.5-1.0 h at a dose of 10-15 kGy, then stopping irradiation and standing and cooling for 10-30 min, and then re-irradiating for 1-2 h at a dose of 15-20 kGy.
  10. 10. A sodium alginate-beta-glucan composite wound repair spray with rapid film formation and long-acting repair functions prepared by the method of any one of claims 1-9.

Description

Sodium alginate-beta-glucan composite wound repair spray and preparation method thereof Technical Field The invention belongs to the field of biological material preparation, and in particular relates to sodium alginate-beta-glucan composite wound repair spray with rapid film formation and long-acting repair functions and a preparation method thereof. Background Skin wounds refer to the destruction of the integrity of the epidermis and dermis layers caused by physical, chemical or biological factors, accompanied by problems such as inflammatory reactions, degradation of extracellular matrix, and delayed repair. It is counted that more than 1 hundred million cases of acute and chronic wounds are caused by burns and scalds, operation incisions, diabetic ulcers and the like in the world each year, wherein about 30% of chronic wounds are not healed due to the maintenance of micro-environment imbalance (such as continuous infection, excessive inflammation or uncontrolled humidity), so that not only is the medical burden increased, but also the life quality of the patients is remarkably reduced. Current clinical treatments mainly include topical antibiotic ointments after debridement, covering traditional dressings (e.g. gauze, hydrocolloid dressing) or using growth factor formulations (e.g. EGF gel). Although the methods can partially meet the wound protection requirements, the methods have obvious limitations that the passive dressing (such as gauze) cannot maintain a moist environment and is easy to cause secondary damage during replacement, and the single active ingredient preparation (such as antibiotics or growth factors) has poor effect of the active ingredient due to short residence time of wound surfaces, poor permeability or insufficient stability. Therefore, development of a multifunctional integrated spray system is needed to construct a self-adaptive physical barrier of wound surface, realize anti-infection, repair promotion and anti-inflammatory regulation synchronously, and break the vicious circle of chronic wound repair. The existing wound spray products are often focused on a single link, and the bottleneck with single function is not broken through yet. For example, patent CN 118873730a discloses a repair spray containing recombinant collagen, which uses recombinant collagen microemulsion as an active component, and is matched with porous hydroxyapatite to enhance permeability, although the repair spray can mildly promote wound healing and shorten healing time, the repair spray does not contain antibacterial components, cannot control wound infection risk, lacks a high polymer film forming system, is difficult to form a stable physical barrier, and has insufficient wound protection persistence. Patent CN 119405871a discloses a composite spray for improving hemostasis, which uses nano platelets to match sodium alginate to realize rapid hemostasis, and aims at solving the problem of wound blood loss, but lacks anti-inflammatory components and active components for promoting epidermis re-epithelialization, and cannot break the vicious circle of chronic wounds. Patent CN 114984132a discloses a procoagulant repair promoting spray, which uses hyperbranched polylysine and crinis carbonisatus extract as cores, although procoagulant and antibacterial can be achieved, an adaptive film forming system is not designed, self-regulation cannot be carried out according to wound exudates, and the regulation and control capability on inflammatory factors is lacking. Disclosure of Invention The prior related technology is mainly focused on optimizing the component proportion, and has the bottlenecks of improving the performance, such as poor water solubility and insufficient targeting of yeast beta-glucan, requirement of ultrasonic dispersion, limited anti-inflammatory efficiency, difficulty in considering the film forming speed and moisture permeability of sodium alginate, easiness in abrasion and falling of a film body, outstanding contradiction between the viscosity adaptation of hydroxypropyl methylcellulose, easiness in atomization with low viscosity, poor film forming, good film forming with high viscosity, uneven atomization, low swelling efficiency, uneven crosslinking, easiness in irradiation damage of active ingredients, residual bubbles of the film body and the like. Based on the above, the invention provides the sodium alginate-beta-glucan composite wound repair spray with rapid film formation and long-acting repair functions and the preparation method thereof, which enable the obtained wound repair spray to rapidly form a film to form a physical barrier through the double-dimensional breakthrough of 'component green modification and process precise optimization', simultaneously realize broad-spectrum bacteriostasis without skin sensitization risk, and also can bidirectionally regulate and control wound inflammation, promote tissue repair, solve the performance bottleneck problem of the prior art, bre