A medical dressing containing a high concentration of lactic acid and a method for its preparation

Abstract

The present application relates to a kind of medical dressings containing high concentration lactic acid and its preparation method, belong to medical dressing technical field.The present application is combined by chemical crosslinking and ion coordination to carboxymethyl cellulose, solve the problem that medical dressing contact wound exudate contact gel leads to gel collapse, further through octadecyl methacrylate grafting carboxymethyl cellulose form hydrophobic core and double crosslinking carboxymethyl cellulose form hydrophilic shell;Octadecyl methacrylate long chain alkyl forms dense hydrophobic region, and hydrophilic shell is swollen by contacting wound exudate, not only further solve the problem of gel collapse, but also effectively control the release of lactic acid, promote wound healing.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of medical dressings, and relates to a medical dressing containing high-concentration lactic acid and a preparation method thereof. BACKGROUND

[0002] Medical dressings are widely used in various wound care, and their main functions are to protect wounds, promote healing and prevent infection. In recent years, with the development of biomaterial science, medical dressings containing active ingredients have attracted more and more attention. Among these active ingredients, lactic acid is favored due to its good biocompatibility and antibacterial properties. Medical dressings containing high-concentration lactic acid can release lactic acid at the wound site, regulate the local pH, and inhibit the growth of pathogenic microorganisms, thereby promoting wound healing. In addition, lactic acid can stimulate the proliferation of fibroblasts and accelerate tissue regeneration. Therefore, the development of medical dressings containing high-concentration lactic acid is of great significance to improve the level of wound care. However, due to the nature of lactic acid itself, its stability and release control in preparation and application are still technical challenges.

[0003] Although lactic acid has significant advantages in medical dressings, traditional medical dressings still have some shortcomings in practical application. In particular, when in contact with wound exudate, carbomer will undergo gel collapse in exudate containing Ca 2+ , resulting in poor physical properties of the dressing, such as reduced strength, weakened adhesion, and decreased absorption capacity. These performance reductions not only affect the protective effect of the wound, but also may prolong the healing time. In addition, enzymes and proteins in the exudate may react with the dressing material, further affecting its structure and function. Therefore, how to improve the stability and functionality of medical dressings in a wet environment has become a key issue to improve the effect of wound care.

[0004] When developing medical dressings, existing technologies often face some technical difficulties. In order to improve its stability and physical properties in a wet environment, carbomer usually needs to be modified. For example, through grafting reaction or crosslinking reaction to enhance its hydrophobicity and structural stability. However, these modification methods, although to some extent, improve the performance of carbomer, but also cause new problems. First, excessive hydrophobicity may lead to a decrease in the solubility of carbomer in wound exudate, thereby reducing the water absorption capacity of the dressing and affecting its adsorption and cleaning function of wound secretions. Second, the crosslinking modification of carbomer may make its molecular chain more rigid, resulting in a decrease in the softness of the dressing, and thus affecting its comfort and conformability during use. Therefore, although the modification of carbomer can enhance the performance of the dressing, how to balance its water absorption, stability and biocompatibility in the modification process, and avoid new adverse effects, is still a technical problem to be solved. SUMMARY

[0005] The present application aims to provide a medical dressing containing high concentration of lactic acid and a preparation method thereof, wherein the carbomer is modified to enhance the gel stability when contacting with wound exudate.

[0006] The object of the present application can be achieved by the following technical solutions:

[0007] A medical dressing containing high concentration of lactic acid and a preparation method thereof, comprising the following raw materials by weight ratio: 10-50% of L-lactic acid, 0.2-1% of carbomer, and the balance of deionized water;

[0008] The carbomer is obtained by a modification method comprising the following steps:

[0009] S1, slowly add carbomer 940 powder to pre-cooled phosphate buffer solution, stir at 500 rpm for 2h, and obtain a carbomer homogeneous solution with a concentration of 1-1.5%;

[0010] Phosphate buffer: select Na2HPO4 / NaH2PO4 buffer system (molar ratio 3:1), prepare a buffer solution with a concentration of 0.05-0.15M and a pH of 7.5-8.0 to avoid hydrolysis of carbomer under alkaline conditions;

[0011] Add carbomer: octadecyl methacrylate: azobisisobutyronitrile = 1:0.2-0.5:0.05-0.1 by mass ratio to a reaction vessel, heat to 60-70℃ under nitrogen atmosphere, and react at constant temperature for 2-4h. The double bond in octadecyl methacrylate breaks, and the hydroxyl group on the carbomer backbone forms a covalent bond through free radical graft polymerization;

[0012] After cooling the reaction solution, precipitate with acetone, centrifuge (8000 rpm x 10 min) to collect the precipitate, wash with ethanol / water (1:1) for 3 times, and vacuum dry (40℃ x 24h) to obtain the polyacrylic acid grafted carbomer product;

[0013] S2, disperse the carbomer in MES buffer solution (2-(N-morpholino) ethanesulfonic acid, pH 5.5-6.0) with a concentration of 1-2%, stir at 20-60 rpm at 4℃ for 10-15h; add 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, pre-activate for 20-40min at 25℃ to form an active ester intermediate, and react at a temperature of 35-45℃ for 4-6h to form an amide bond crosslinking;

[0014] The reaction endpoint is reached when the free amino group concentration is reduced to less than 10% of the initial value by using ninhydrin colorimetric method;

[0015] Quench the unreacted EDC with 0.1M glycine, dialyze the reaction solution for more than 72h, and freeze-dry to obtain the product;

[0016] S3, ZrOCl2.8H2O is dissolved in deionized water to prepare a 0.05-0.15M solution, and the pH is adjusted to 2.5-3.0 with a 0.1M HC1 solution;

[0017] According to the mass ratio of ZrOCl2.8H2O solution: cross-linked carbomer powder prepared in step S2 = 1:5-10, the ZrOCl2.8H2O solution is added dropwise into the carbomer dispersion at a rate of 1 mL / min, the temperature is maintained at 40-50°C, and the stirring speed is 300 rpm for 2-4h;

[0018] The pH of the system is adjusted to 4.2-4.8, and the uncomplexed Zr is removed by centrifugation 4+ After dialysis, the hydrophilic carbomer is obtained by freeze-drying;

[0019] S4, the polyacrylic acid grafted carbomer product (S1 product) is dissolved in ethyl acetate to prepare an oil phase carbomer with a concentration of 3% w / v, and Span-80 (0.5% w / v) is added;

[0020] The hydrophilic carbomer (S3 product) is dispersed in deionized water to prepare a water phase carbomer with a concentration of 2% w / v, and Tween-80 (0.2% w / v) is added;

[0021] The oil phase carbomer is slowly added to the water phase carbomer (volume ratio 1:3-5), and high-speed homogenization (10000 rpm x 5min) is performed to form a W / O emulsion;

[0022] The W / O emulsion is added to a 1% PVA solution, and low-speed stirring (500 rpm x 10min) is performed to form a W / O / W re-emulsion; stirring at 40°C for 6h, volatilizing ethyl acetate, and solidifying the microgel, and then freeze-drying to obtain a core-shell microgel modified carbomer.

[0023] As a preferred technical solution of the present application, the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to the carboxyl group in the carbomer in step S2 is 0.8-1.5:1; and the molar ratio of N-hydroxysuccinimide to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide is 1-1.5:1.

[0024] Further, the medical dressing containing high-concentration lactic acid and the preparation method thereof comprise the following steps:

[0025] (1) The modified carbomer microgel is dispersed in deionized water, and low-speed stirring is performed at 20-30 rpm to avoid structure damage, and the temperature is raised to 80-90°C for 20min to promote the swelling and cross-linking of the microgel;

[0026] (2) cooling to 35-45℃, adding L-lactic acid, stirring for 20-40 min until homogenization;

[0027] (3) dispensing into sterile aluminum foil bags, using gamma ray sterilization to avoid high temperature damage to the gel structure.

[0028] The beneficial effects of the present application are:

[0029] (1) The present application forms a covalent amide bond chemical cross-linking carbomer product through 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, providing a rigid backbone to resist Ca 2+ binding to the carboxyl groups in the carbomer; and then through the coordination of Zr 4+ ions with the carboxyl groups of the carbomer, competitively inhibiting the gel collapse caused by Ca 2+ .

[0030] (2) The present application forms a hydrophobic core and a hydrophilic shell through the grafting of octadecyl methacrylate onto the carbomer; the long alkyl chain of octadecyl methacrylate forms a dense hydrophobic region, and the hydrophilic shell swells when it comes into contact with wound exudate, not only further solving the problem of gel collapse, but also effectively controlling the release of lactic acid and promoting wound healing. DETAILED DESCRIPTION

[0031] To further illustrate the technical means and effects adopted by the present application to achieve the predetermined invention purpose, the specific embodiments, structures, features and effects according to the present application are described in detail as follows in combination with examples.

[0032] Example 1

[0033] A medical dressing containing high-concentration lactic acid and a preparation method thereof, comprising the following raw materials by weight ratio: 30% L-lactic acid, 0.6% carbomer, and the balance being deionized water.

[0034] The carbomer is obtained by a modification method comprising the following steps:

[0035] S1, slowly add carbomer 940 powder to a phosphate buffer solution pre-cooled to 4℃, stir at 500 rpm for 2h to obtain a carbomer homogenate solution with a concentration of 1.2%;

[0036] Add the reaction container with carbomer: octadecyl methacrylate: azobisisobutyronitrile = 1:0.2-0.5:0.05-0.1 by mass ratio, and heat to 65℃ under nitrogen atmosphere, and react for 3h to obtain octadecyl methacrylate grafted carbomer;

[0037] After the reaction solution was cooled, it was precipitated with acetone, centrifuged (8000 rpm x 10 min) to collect the precipitate, washed with ethanol / water (1:1) for 3 times, and vacuum dried (40°C x 24h) to obtain the polyacrylic acid grafted carbomer product;

[0038] S2, the carbomer was dispersed in MES buffer (2-(N-morpholino)ethanesulfonic acid, pH 5.8) at a concentration of 1.5%, and stirred at 4°C at 40 rpm for 12h; 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide were added, pre-activated at 25°C for 30 min, and then reacted at a temperature of 35-45°C for 4-6h to form amide bond crosslinking;

[0039] The reaction endpoint was determined when the free amino group concentration was reduced to 8% of the initial value by using the ninhydrin colorimetric method;

[0040] The reaction solution was quenched with 0.1M glycine to terminate the unreacted EDC, and then dialyzed for 72h to obtain the product by freeze-drying;

[0041] S3, ZrOCl2·8H2O was dissolved in deionized water to prepare a 0.1M solution, and the pH was adjusted to 2.7 with 0.1M HCl solution;

[0042] ZrOCl2·8H2O solution: crosslinked carbomer powder prepared in step S2 = 1:5-10 (mass ratio), ZrOCl2·8H2O solution was added to the carbomer dispersion at a rate of 1mL / min, and the temperature was maintained at 45°C with stirring at 300rpm for 3h;

[0043] The pH of the system was adjusted to 4.2-4.8, and uncomplexed Zr was removed by centrifugation 4+ , and the hydrophilic carbomer was obtained by freeze-drying after dialysis;

[0044] S4, the polyacrylic acid grafted carbomer product (S1 product) was dissolved in ethyl acetate to prepare a carbomer oil phase with a concentration of 3% w / v, and Span-80 (0.5% w / v) was added; the hydrophilic carbomer (S3 product) was dispersed in deionized water to prepare a carbomer aqueous phase with a concentration of 2% w / v, and Tween-80 (0.2% w / v) was added;

[0045] The oil phase carbomer was slowly added to the water phase carbomer (volume ratio 1:3-5), and high-speed homogenization (10000 rpm x 5 min) was performed to form a W / O emulsion; then the W / O emulsion was added to a 1% PVA solution, and low-speed stirring (500 rpm x 10 min) was performed to form a W / O / W re-emulsion;

[0046] Stirring at 40°C for 6h, volatilizing ethyl acetate, and solidifying the microgel, and then freeze-drying to obtain the core-shell microgel modified carbomer.

[0047] The phosphate buffer solution in step S1: a Na2HPO4 / NaH2PO4 buffer system (molar ratio 3:1) is selected, and a buffer solution with a concentration of 0.1 M and a pH of 7.7 is prepared;

[0048] The molar ratio of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to the carboxyl group in the carbomer is 1:1; and the molar ratio of N-hydroxysuccinimide to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide is 1.2:1.

[0049] The medical dressing containing high-concentration lactic acid and the preparation method thereof include the following steps:

[0050] (1) The modified carbomer microgel is dispersed in deionized water, and low-speed stirring is performed at 25 rpm to avoid structural damage. The temperature is raised to 85°C, and the microgel is kept at this temperature for 20 min to promote swelling and crosslinking;

[0051] (2) The temperature is lowered to 40°C, and L-lactic acid is added. Stirring is performed for 30 min until homogenization is achieved;

[0052] (3) The product is divided into sterile aluminum foil bags, and γ-ray sterilization is performed to avoid high-temperature damage to the gel structure.

[0053] Example 2

[0054] Different from Example 1, a low-concentration L-lactic acid and a high-modified carbomer are set for sensitive groups or children.

[0055] A medical dressing containing high-concentration lactic acid and a preparation method thereof include the following raw materials by weight: 10% L-lactic acid, 0.5% carbomer, and the balance being deionized water.

[0056] The carbomer is obtained by a modification method including the following steps:

[0057] S1, slowly add carbomer 940 powder to pre-cooled phosphate buffer solution, stir at 500 rpm for 2 h, and obtain a 1% carbomer homogenate solution;

[0058] Add carbomer: methacrylic acid octadecyl ester: azobisdimethylamide = 1:0.5:0.7 by mass ratio to a reaction container, and heat to 60°C under a nitrogen atmosphere. The reaction is kept at a constant temperature for 4 h to obtain methacrylic acid octadecyl ester grafted carbomer;

[0059] After the reaction solution is cooled, it is precipitated with acetone, centrifuged (8000 rpm x 10 min) to collect the precipitate, washed with ethanol / water (1:1) for 3 times, and vacuum dried (40°C x 24 h) to obtain the polyacrylic acid grafted carbomer product;

[0060] S2, Carbopol was dispersed in MES buffer (2-(N-morpholino)ethanesulfonic acid, pH 6.0) at a concentration of 1%, stirred at 4°C for 15h at 20rpm; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were added, pre-activated at 25°C for 40min to form active ester intermediates, and then the temperature was raised to 35°C for 6h to form amide bond crosslinking;

[0061] The reaction was terminated when the free amino group concentration decreased to 5% of the initial value by ninhydrin colorimetric method;

[0062] The reaction solution was quenched with 0.1M glycine to terminate the unreacted EDC, and then dialyzed for 80h and freeze-dried to obtain the product.

[0063] S3, Zirconium ion coordination:

[0064] ZrOCl2·8H2O was dissolved in deionized water to prepare a 0.15M solution, and the pH was adjusted to 3.0 with 0.1M HCl solution.

[0065] ZrOCl2·8H2O solution: crosslinked Carbopol powder prepared in step S2 = 1:5 (mass ratio), ZrOCl2·8H2O solution was added to the Carbopol dispersion at a rate of 1mL / min, the temperature was maintained at 40°C, and the stirring speed was 300rpm for 4h.

[0066] The pH of the system was adjusted to 4.8, and the uncoordinated Zr was removed by centrifugation 4+ , and the hydrophilic Carbopol was obtained by freeze-drying after dialysis.

[0067] S4, The polyacrylic acid grafted Carbopol product (S1 product) was dissolved in ethyl acetate to prepare a Carbopol oil phase with a concentration of 3% w / v, and Span-80 (0.5% w / v) was added; the hydrophilic Carbopol (S3 product) was dispersed in deionized water to prepare a Carbopol water phase with a concentration of 2% w / v, and Tween-80 (0.2% w / v) was added;

[0068] The oil phase was slowly poured into the water phase (volume ratio 1:5), and high-speed homogenization (10000 rpm x 5min) was performed to form a W / O emulsion; the W / O emulsion was added to a 1% PVA solution, and low-speed stirring (500 rpm x 10min) was performed to form a W / O / W re-emulsion;

[0069] Stirring at 40°C for 6h, volatilizing ethyl acetate, and freeze-drying after solidification of the microgel obtained the core-shell microgel modified Carbopol.

[0070] The phosphate buffer solution in step S1: Na2HPO4 / NaH2PO4 buffer system (molar ratio 3:1) was selected, and a buffer solution with a concentration of 0.05M and a pH of 7.5 was prepared;

[0071] The molar ratio of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to the carboxyl group in the carbomer is 1.5:1; the molar ratio of N-hydroxysuccinimide to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide is 1.5:1.

[0072] The medical dressing containing high-concentration lactic acid and the preparation method thereof, comprising the following steps:

[0073] (1) The modified carbomer microgel is dispersed in deionized water, and low-speed stirring is performed at 20 rpm to avoid structure damage, and the temperature is raised to 80℃, and the temperature is kept for 20 min to promote the swelling and crosslinking of the microgel;

[0074] (2) The temperature is lowered to 35℃, and the left lactic acid is added, and stirred for 20 min until homogeneous;

[0075] (3) The product is packaged into sterile aluminum foil bags, and γ-ray sterilization is performed to avoid high-temperature damage to the gel structure.

[0076] Example 3

[0077] In order to promote wound healing faster, high left lactic acid and low modified carbomer are set;

[0078] A medical dressing containing high-concentration lactic acid and a preparation method thereof, comprising the following raw materials by weight ratio: 50% left lactic acid, 0.2% carbomer, and the balance is deionized water;

[0079] The carbomer is obtained by a modification method comprising the following steps:

[0080] S1, slowly add carbomer 940 powder to pre-cooled phosphate buffer, stir at 500 rpm for 2h, and obtain a 1% carbomer homogeneous solution;

[0081] Grafting reaction:

[0082] Carbomer: octadecyl methacrylate: azobisisobutyronitrile = 1:0.2:0.05 by mass ratio is added to the reaction container, and the temperature is raised to 60℃ under nitrogen atmosphere, and the temperature is kept for 2h to obtain octadecyl methacrylate grafted carbomer;

[0083] After cooling the reaction solution, precipitate with acetone, centrifuge (8000 rpm x 10 min) to collect the precipitate, wash with ethanol / water (1:1) for 3 times, and vacuum dry (40℃ x 24h) to obtain the polyacrylic acid grafted carbomer product;

[0084] S2, Carbopol was dispersed in MES buffer (2-(N-morpholino)ethanesulfonic acid, pH 5.5) at a concentration of 1%, stirred at 60 rpm for 10 h at 4°C; 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide were added, pre-activated at 25°C for 20 min to form an active ester intermediate, and then reacted at 45°C for 4 h to form an amide bond crosslinking;

[0085] The reaction was terminated when the free amino group concentration decreased to 10% of the initial value by ninhydrin colorimetric method;

[0086] The reaction solution was quenched with 0.1 M glycine to terminate the unreacted EDC, and then dialyzed for 72 h and freeze-dried to obtain the product.

[0087] S3, ZrOCl2·8H2O was dissolved in deionized water to prepare a 0.05 solution, and the pH was adjusted to 3.0 with 0.1 M HCl solution;

[0088] ZrOCl2·8H2O solution: crosslinked Carbopol powder prepared in step S2 = 1:10 (mass ratio), ZrOCl2·8H2O solution was added to the Carbopol dispersion at a rate of 1 mL / min, and the temperature was maintained at 50°C with stirring at 300 rpm for 2 h;

[0089] The pH of the system was adjusted to 4.8, and the uncomplexed Zr was removed by centrifugation 4+ , and the hydrophilic Carbopol was obtained by freeze-drying after dialysis;

[0090] S4, the polyacrylic acid grafted Carbopol product (S1 product) was dissolved in ethyl acetate to prepare a Carbopol oil phase with a concentration of 3% w / v, and Span-80 (0.5% w / v) was added; the hydrophilic Carbopol (S3 product) was dispersed in deionized water to prepare a Carbopol water phase with a concentration of 2% w / v, and Tween-80 (0.2% w / v) was added;

[0091] The oil phase was slowly poured into the water phase (volume ratio 1:3), and homogenized at high speed (10000 rpm x 5 min) to form a W / O emulsion;

[0092] The W / O emulsion was added to a 1% PVA solution and stirred at low speed (500 rpm x 10 min) to form a W / O / W re-emulsion; the mixture was stirred at 40°C for 6 h to volatilize the ethyl acetate, and the microgel was solidified. After freeze-drying, the core-shell microgel modified Carbopol was obtained.

[0093] The phosphate buffer solution in step S1: a Na2HPO4 / NaH2PO4 buffer system (molar ratio 3:1) was selected to prepare a buffer solution with a concentration of 0.15 M and a pH of 8.0 to avoid hydrolysis of Carbopol under alkaline conditions;

[0094] The molar ratio of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to the carboxyl group in the carbomer is 0.8:1; the molar ratio of N-hydroxysuccinimide to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide is 1:1.

[0095] The medical dressing containing high-concentration lactic acid and the preparation method thereof include the following steps:

[0096] (1) The modified carbomer microgel is dispersed in deionized water, and low-speed stirring is performed at 20 rpm to avoid structural damage. The temperature is raised to 90°C, and the microgel is kept at this temperature for 20 min to promote swelling and crosslinking;

[0097] (2) The temperature is lowered to 45°C, and L-lactic acid is added. Stirring is performed for 20 min until homogenization is achieved;

[0098] (3) The product is divided into sterile aluminum foil bags and sterilized using γ-rays to avoid high-temperature damage to the gel structure.

[0099] Example 4

[0100] For the demand for longer-acting sustained release, high L-lactic acid and high modified carbomer are set:

[0101] A medical dressing containing high-concentration lactic acid and a preparation method thereof, including the following raw materials by weight ratio: 50% L-lactic acid, 1% carbomer, and the balance being deionized water;

[0102] The carbomer is obtained by a modification method including the following steps:

[0103] S1, slowly add carbomer 940 powder to pre-cooled phosphate buffer solution, stir at 500 rpm for 2 h, and obtain a carbomer homogeneous solution with a concentration of 1.5%;

[0104] Phosphate buffer: select Na2HPO4 / NaH2PO4 buffer system (molar ratio 3:1), prepare a buffer solution with a concentration of 0.15 M and a pH of 7.5 to avoid hydrolysis of carbomer under alkaline conditions;

[0105] Add carbomer: stearyl methacrylate: azobisisobutyronitrile = 1:0.5:0.1 by mass ratio to a reaction container, heat to 70°C under a nitrogen atmosphere, and keep the temperature constant for 4 h to obtain stearyl methacrylate grafted carbomer;

[0106] After cooling the reaction solution, precipitate with acetone, centrifuge (8000 rpm x 10 min) to collect the precipitate, wash with ethanol / water (1:1) for 3 times, and vacuum dry (40°C x 24 h) to obtain the polyacrylic acid grafted carbomer product;

[0107] S2, dispersing carbomer in MES buffer (2-(N-morpholino)ethanesulfonic acid, pH 5.5) with a concentration of 2%, stirring at 60 rpm for 15 h at 4℃; adding 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide, pre-activating for 40 min at 25℃ to generate active ester intermediates, and then reacting for 6 h at a temperature of 45℃ to form amide bond cross-linking;

[0108] The reaction endpoint is reached when the free amino group concentration is reduced to 5% of the initial value by using the ninhydrin colorimetric method;

[0109] The reaction solution is quenched with 0.1M glycine to terminate the unreacted EDC, and then the reaction solution is dialyzed for 72 h and freeze-dried to obtain the product.

[0110] S3, dissolving ZrOCl2·8H2O in deionized water to prepare a 0.15M solution, and adjusting the pH to 2.5 with 0.1M HCl solution;

[0111] The mass ratio of ZrOCl2·8H2O solution to cross-linked carbomer powder prepared in step S2 is 1:5, and the ZrOCl2·8H2O solution is added to the carbomer dispersion at a rate of 1 mL / min while maintaining the temperature at 40-50℃ and stirring at 300 rpm for 4 h;

[0112] Adjusting the pH of the system to 4.8 and removing the un-coordinated Zr by centrifugation 4+ Freeze-drying after dialysis to obtain hydrophilic carbomer;

[0113] S4, dissolving the polyacrylic acid grafted carbomer product (S1 product) in ethyl acetate to prepare a carbomer oil phase with a concentration of 3% w / v, and adding Span-80 (0.5% w / v); dispersing the hydrophilic carbomer (S3 product) in deionized water to prepare a carbomer aqueous phase with a concentration of 2% w / v, and adding Tween-80 (0.2% w / v);

[0114] Slowly pouring the oil phase into the water phase (volume ratio 1:4), and homogenizing at high speed (10000 rpm x 5 min) to form a W / O emulsion;

[0115] Adding the W / O emulsion to a 1% PVA solution and stirring at low speed (500 rpm x 10 min) to form a W / O / W re-emulsion; stirring at 40℃ for 6 h to volatilize the ethyl acetate and solidify the microgel, and then freeze-drying to obtain the core-shell microgel modified carbomer.

[0116] The molar ratio of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide to the carboxyl groups in the carbomer in step S2 is 1.5:1; and the molar ratio of N-hydroxysuccinimide to 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide is 1.5:1.

[0117] The medical dressing containing high-concentration lactic acid and a preparation method thereof, comprising the following steps:

[0118] (1) disperse the modified carbomer microgel in deionized water, stir at a low speed of 30 rpm to avoid structure damage, heat to 90°C, and keep for 20 min to promote microgel swelling and crosslinking;

[0119] (2) cool to 45°C, add L-lactic acid, and stir for 40 min until homogeneous;

[0120] (3) sub-pack into sterile aluminum foil bags, and sterilize by γ-rays to avoid high-temperature damage to the gel structure.

[0121] Comparative Example 1

[0122] Based on Example 1, step S1 octadecyl methacrylate grafting is not performed, and the rest is consistent with Example 1.

[0123] Comparative Example 2

[0124] Based on Example 1, step S2 chemical crosslinking treatment is not performed, and the rest is consistent with Example 1.

[0125] Comparative Example 3

[0126] Based on Example 1, ZrOCl2 in step S3 is replaced by titanium isopropylate, and the rest is consistent with Example 1.

[0127] Comparative Example 4

[0128] Based on Example 1, step S3 is performed before step S2, and the rest is consistent with Example 1.

[0129] Comparative Example 5

[0130] Based on Example 1, step S4 only proceeds to W / O emulsion, and the rest is consistent with Example 1.

[0131] Performance test:

[0132] Stability test: measure the energy storage (elasticity) and dissipation (viscosity) characteristics G' of the material in deformation by applying oscillatory stress by a rheometer; measure the change in G' before and after the sample prepared by the example and the comparative example is immersed in 5mM CaCl solution for 72h.

[0133]

[0134] As can be seen from the test results, Examples 1-4 all show a high G' retention rate, indicating that the modified carbomer has good mechanical stability in a humid environment;

[0135] The retention rate of Comparative Example 1 and Comparative Example 2 is significantly lower than that of the examples, indicating that the modification effect of grafting and chemical crosslinking on the carbomer is significant;

[0136] Comparative Example 3 uses titanium isopropylate to replace ZrOCl2, and the retention rate decreases, indicating that ZrOCl2

[0137] The effect is better in coordination crosslinking;

[0138] The retention rate decreases after changing the order of steps in Comparative Example 4.

[0139] The retention rate significantly decreases in Comparative Example 5 without W / O / W re-emulsification, only to W / O emulsion, indicating the importance of the re-emulsification step to the structural stability of the microgel.

[0140] The above is only a preferred embodiment of the present application, and does not limit the present application in any form. Although the present application has been disclosed as above with a preferred embodiment, it is not intended to limit the present application. Any person skilled in the art can make some changes or modifications to the above disclosed technical content to obtain equivalent embodiments with equivalent changes, without departing from the technical solution of the present application. Any indirect modification, equivalent change and modification of the above embodiments according to the technical essence of the present application, which does not depart from the technical solution of the present application, still belongs to the scope of the technical solution of the present application.

Claims

1. A medical dressing containing a high concentration of lactic acid, characterized in that: By weight, it includes the following raw materials: 10-50% L-lactic acid, 0.2-1% carbomer, and the balance being deionized water; The carbomer is obtained through a modification method including the following steps: S1. Carbomer was dissolved in phosphate buffer, and octadecyl methacrylate and an initiator were added to carry out free radical polymerization to obtain polyacrylic acid-grafted carbomer product. S2. Carbomer is dispersed in MES buffer at pH 5.0-6.0, and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide are added to react and form an amide crosslinked carbomer product. S3. Add ZrOCl2·8H2O solution dropwise to the product obtained in step S2 to react and form zirconium ion coordination, thus obtaining hydrophilic carbomer. S4. Mix the ethyl acetate solution of the polyacrylic acid grafted carbomer product obtained in step S1 and the deionized aqueous solution of the hydrophilic carbomer product obtained in step S3, add an emulsifier, homogenize to form a W / O emulsion, then add a PVA solution to form a W / O / W emulsion, and freeze-dry to obtain modified carbomer.

2. The medical dressing containing high concentration of lactic acid according to claim 1, characterized in that: In step S1, the carbomer solution has a carbomer concentration of 1-1.5% and a pH of 7.5-8.0; the initiator is azobisisobutyronitrile.

3. The medical dressing containing high concentration of lactic acid according to claim 1, characterized in that: The mass ratio of carbomer, octadecyl methacrylate, and initiator in step S1 is 1:0.2-0.5:0.05-0.

1.

4. The medical dressing containing high concentration of lactic acid according to claim 1, characterized in that: The grafting reaction in step S1 is carried out at a temperature of 60-70℃ for 2-4 hours.

5. A medical dressing containing high concentration of lactic acid according to claim 1, characterized in that: In step S2, the carbomer concentration is 1-2%; the molar ratio of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide to the carboxyl group in the carbomer is 0.8-1.5:1; and the molar ratio of N-hydroxysuccinimide to 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide is 1-1.5:

1.

6. A medical dressing containing high concentration of lactic acid according to claim 1, characterized in that: The crosslinking reaction in step S2 is carried out at a temperature of 35-45°C for 4-6 hours.

7. A medical dressing containing high concentration of lactic acid according to claim 1, characterized in that: The concentration of the ZrOCl2·8H2O solution in step S3 is 0.05-0.15M; the mass ratio of the ZrOCl2·8H2O solution to the product in step S2 is 1:5-10.

8. A medical dressing containing high concentration of lactic acid according to claim 1, characterized in that: The emulsifiers in step S4 are Span-80 and Tween-80 in a mass ratio of 1:1.5-3; the mass ratio of the product in step S1, the product in step S3, and the emulsifier is 1:3-5:0.1-0.

3.

9. A method for preparing a medical dressing containing high concentration of lactic acid as described in any one of claims 1-8, characterized in that: The preparation method includes the following steps: adding deionized water and modified carbomer into an emulsifier, stirring evenly and heating to 80-90℃, keeping it at that temperature for 15-25 minutes; then stirring and cooling to 35-45℃, adding L-lactic acid, and mixing evenly.

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