A medical dressing containing seaweed extract and a method of making the same

Abstract

The application discloses a medical dressing containing seaweed extract and a preparation method thereof. The preparation method of the medical dressing containing seaweed extract comprises the following steps: under the action of sodium periodate, sodium alginate is subjected to an oxidation reaction to generate an oxidation derivative of sodium alginate; the oxidation derivative of sodium alginate is reacted with sodium alginate, chitosan and p-tolylsulfonylmethyl isocyanide to generate a seaweed acid derivative; the seaweed acid derivative is mixed with sodium alginate and deionized water to obtain a seaweed acid spinning solution; the seaweed acid spinning solution is spun into an electrostatic spinning fiber dressing through an electrostatic spinning process; the electrostatic spinning fiber dressing is placed in a calcium chloride solution for immersion; after the immersion is completed, the electrostatic spinning fiber dressing is washed, dried and the medical dressing containing seaweed extract is obtained. In the application, the seaweed acid spinning solution prepared has low conductivity, small surface tension and good electrostatic spinning performance, and the prepared medical dressing containing seaweed extract has good mechanical strength and excellent antibacterial property.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical supplies, in particular to a medical dressing containing seaweed extract and a preparation method thereof. BACKGROUND

[0002] Medical dressings have the functions of protecting wounds, controlling infection, and providing a wet environment for wound healing during the wound healing process. Alginate is a natural polysaccharide extracted from natural brown algae. It is widely used in the medical field due to its excellent biocompatibility, biodegradability, and no toxic side effects. In particular, alginate biological dressings prepared by electrospinning combine the material characteristics of alginate and the structural characteristics of electrospun fiber membranes, and have good air permeability, hemostasis, liquid absorption, and biocompatibility, which are suitable for the treatment of surgical infected wounds.

[0003] However, due to the presence of hydroxyl and carboxyl hydrophilic groups on the aldehyde acid monomer of alginate, intramolecular hydrogen bonds are easily formed in aqueous solution, causing the rigidity of the molecular chain to increase. The presence of a large number of negatively charged carboxyl groups on the molecular backbone makes it have a high electrical conductivity, and its surface activity is low, which makes it difficult to form effective chain entanglements, making it difficult to be electrospun. In order to improve this functional defect of alginate, functional modification of alginate is required. In the paper "Preparation of Drug-loaded Electrospun Nanocomposite Fibers Based on Oxidation-reduction Amination Reaction Modified Alginate" by Huiqiong Yan, a method of hydrophobic modification of alginate by oxidation-reduction amination reaction is disclosed. Polyvinyl alcohol is used as a spinning aid, and an electrospun nanocomposite fiber membrane wound dressing that can load hydrophobic anti-inflammatory drug ibuprofen is developed by combining electrospinning technology. However, during the oxidation process, the molecular weight of alginate will decrease significantly, and a too low molecular weight is not conducive to the electrospinning of alginate. SUMMARY

[0004] The present application provides a medical dressing containing seaweed extract and a preparation method thereof to solve the problem of poor spinnability of alginate electrospinning in the prior art.

[0005] To achieve the above purpose, the technical scheme adopted by the present application is as follows:

[0006] A preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0007] Step one, mix sodium alginate, deionized water and ethanol uniformly, add sodium periodate, stir and react, then add ethylene glycol, continue to stir to terminate the reaction, separate and purify after stirring, dry to obtain the oxidized derivative of sodium alginate;

[0008] Step two, add sodium alginate, oxidized derivative of sodium alginate into deionized water, adjust pH value to 3-4, add chitosan and p-toluenesulfonylmethyl isocyanide solution, stir and react, after reaction, separate, purify, dry, obtain alginate derivative;

[0009] Step three, mix sodium alginate, alginate derivative with deionized water, stir, after stirring is completed, stand and defoam, obtain alginate spinning solution;

[0010] Spin alginate spinning solution into electrospun fiber dressing through electrospinning process;

[0011] Step four, place electrospun fiber dressing in calcium chloride solution, immerse, after immersion is completed, wash, dry, obtain medical dressing containing seaweed extract.

[0012] Preferably, in the step one: the mass ratio of sodium alginate, deionized water, ethanol, sodium periodate is 5:(200-300):(40-60):(1.6-1.8); the stirring reaction conditions are: reaction at room temperature, in dark environment, at a stirring speed of 300-500 r / min for 20-30 h; the addition amount of ethylene glycol is 2-2.5 times of the mass of sodium alginate.

[0013] Preferably, in the step one: the separation and purification includes adding sodium chloride and ethanol for precipitation, centrifugation, redissolving the centrifugal precipitate in deionized water, repeating the process of precipitation, centrifugation, and dissolution, after the process of separation and purification, obtain solution, fill the solution into dialysis bag, dialysis in deionized water.

[0014] Preferably, in the step two: the mass ratio of sodium alginate, oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is (30-40):(20-30):(2500-3500):(25-35):(160-215); the stirring reaction conditions are: reaction at room temperature, at a stirring speed of 300-500 r / min for 20-30 h.

[0015] Preferably, in the step two: the pH value is adjusted by adding hydrochloric acid aqueous solution, the concentration of hydrochloric acid aqueous solution is 0.1 mol / L; the p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to the mass ratio (1.3-1.4):4.

[0016] Preferably, in the step two: the separation and purification includes first diluting with deionized water, then adding ethanol to precipitate reaction product, centrifuging the precipitated reaction product, washing with ethanol, then centrifuging, filling into dialysis bag with a relative molecular mass of 8000, dialysis in deionized water for 5 d to remove residual small molecular impurities.

[0017] Preferably, in the step three, the mass ratio of sodium alginate, alginate derivative and deionized water is (1-2):(1-3):(150-250).

[0018] Preferably, in the step three, the electrospinning process comprises spraying the sodium alginate spinning solution through the spinneret of the electrospinning device onto the receiving device for fixation.

[0019] Preferably, the electrospinning condition is that the electrospinning is carried out under the condition of room temperature, relative humidity of 40%, electrostatic voltage of 30kV, distance between the spinneret and the receiving plate of 10cm and flow rate of 0.5mL / h.

[0020] Preferably, in the step four, the calcium chloride solution comprises calcium chloride and ethanol, and the impregnation condition is that the impregnation is carried out at room temperature for 20-30h.

[0021] Further, in the calcium chloride solution, the mass-volume ratio of calcium chloride and ethanol is 1.5g / 50mL.

[0022] Preferably, the application discloses a medical dressing containing seaweed extract prepared by the preparation method of the medical dressing containing seaweed extract.

[0023] Preferably, the prepared alginate derivative, as the product of Ugi reaction, has good amphiphilicity and certain colloid interface performance, can load anti-inflammatory and antibacterial drugs such as ibuprofen, and the drug has sustained release property, thereby improving the antibacterial property of the dressing.

[0024] Compared with the prior art, the application has the following beneficial effects:

[0025] In the application, sodium alginate as the seaweed extract is used as the basic raw material for preparing the medical dressing. Firstly, the sodium alginate is subjected to ring-opening oxidation reaction under the action of sodium periodate to generate an oxidation derivative of sodium alginate containing an aldehyde group. The aldehyde group in the molecule of the oxidation derivative of sodium alginate reacts with the carboxyl group in the molecule of sodium alginate, the amino group in the molecule of chitosan and the isonitrile in the molecule of p-toluenesulfonylmethyl isonitrile through Ugi reaction to prepare the alginate derivative. Since the intramolecular hydrogen bond on the glycuronate skeleton of the grafted sodium alginate is destroyed, the rigidity of the molecular chain is weakened, and the grafted side chain can help the sodium alginate molecules to form effective chain entanglement, thereby enhancing the spinnability of the electrospinning of the sodium alginate.

[0026] In the preparation process of the alginate derivative, the chitosan molecule is introduced through an amine group, and the chitosan has good inhibitory effect on a plurality of common bacteria. The medical dressing prepared from the alginate derivative has good antibacterial property, and the chitosan molecule and the sodium alginate molecule are connected through a stable chemical bond, so that the antibacterial effect is long-lasting. Meanwhile, the chitosan has good moisturizing property, can protect the wound in a suitable humidity environment, and promotes the healing of the wound.

[0027] Since the molecular weight of sodium alginate is reduced in the oxidation process, the alginate derivative is used in combination with sodium alginate to prepare alginate spinning liquid, so that the problem of poor spinnability of pure sodium alginate in electrospinning is solved, and the problem that the alginate derivative is not conducive to electrospinning due to the reduction of molecular weight in the preparation process is prevented.

[0028] In the present application, the electrospun fiber dressing prepared by the electrospinning process is immersed in a calcium chloride solution. Sodium alginate exchanges with divalent calcium ions to form calcium alginate, so that the alginate is crosslinked into a stable three-dimensional structure, which can improve the mechanical strength of the dressing. When the dressing contacts with pus and blood liquid on the wound, sodium ions in the human body exchange with calcium ions in the dressing. With the entry of sodium ions into the dressing, water-insoluble calcium alginate is converted into water-soluble sodium alginate, absorbs the liquid on the wound to form a colloid, provides a moist healing environment, and the wound and the dressing do not adhere to each other. BRIEF DESCRIPTION OF DRAWINGS

[0029] Figure 1 The preparation process flow chart of the medical dressing containing seaweed extract in the present application is shown in the figure.

[0030] Figure 2 The surface tension test result line graph of the alginate spinning liquid in examples 1-7 and comparative examples 1-2 in the present application is shown in the figure.

[0031] Figure 3 The conductivity test result line graph of the alginate spinning liquid in examples 1-7 and comparative examples 1-2 in the present application is shown in the figure.

[0032] Figure 4 The tensile property test result line graph of the medical dressing containing seaweed extract prepared in examples 1-7 and comparative examples 1-2 in the present application is shown in the figure.

[0033] Figure 5 The antibacterial property test result column chart of the medical dressing containing seaweed extract prepared in examples 1-7 and comparative examples 1-2 in the present application is shown in the figure. DETAILED DESCRIPTION

[0034] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the embodiments of the present application. Obviously, the described embodiments are only a part of the embodiments of the present application, rather than all the embodiments of the present application. Based on the embodiments of the present application, all other embodiments obtained by those skilled in the art without creative work fall within the scope of the present application.

[0035] Embodiment 1

[0036] The present embodiment discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0037] Step one, sodium alginate, deionized water and ethanol are stirred and mixed uniformly, and sodium periodate is added, the mass ratio of sodium alginate, deionized water, ethanol and sodium periodate is 5:200:40:1.6, the reaction is carried out at room temperature, in a dark environment, at a stirring speed of 300 r / min for 30 h, after the reaction, 2 times the mass of sodium alginate of ethylene glycol is added, the stirring is continued at a stirring speed of 300 r / min for 2 h to terminate the reaction, after the stirring is completed, sodium chloride with the same mass as sodium alginate and 4 times the volume of deionized water of the ethanol used for precipitation are added, centrifugation is carried out at a speed of 3000 r / min for 20 min, the centrifugal precipitate is redissolved in deionized water, the amount of deionized water accounts for 1 / 8 of the volume of the ethanol used for precipitation, the process of precipitation, centrifugation and dissolution is repeated three times, a solution is obtained, the solution is loaded into a dialysis bag with a molecular weight cut-off of 3500, dialysis is carried out in deionized water for 5 d, and freeze-drying is carried out, to obtain an oxidized derivative of sodium alginate;

[0038] Step two, sodium alginate and the oxidized derivative of sodium alginate are added into deionized water, 0.1 mol / L hydrochloric acid aqueous solution is added to adjust the pH value to 3, a chitosan solution and a p-toluenesulfonylmethyl isocyanide solution are added, the mass ratio of sodium alginate, the oxidized derivative of sodium alginate, deionized water, chitosan and the p-toluenesulfonylmethyl isocyanide solution is 30:20:2500:25:160, the reaction is carried out at room temperature, at a stirring speed of 300 r / min for 30 h, after the reaction, a reaction mixture is obtained, deionized water with the same volume as the reaction mixture is added for dilution, and ethanol with 5 times the volume of the reaction mixture is added for precipitation, centrifugation is carried out at a speed of 3000 r / min for 20 min, the supernatant of the centrifugation is removed, ethanol with 2 times the volume of the reaction mixture is added for washing, centrifugation is carried out at a speed of 3000 r / min for 20 min again, the centrifugal precipitate is loaded into a dialysis bag with a relative molecular weight cut-off of 8000, dialysis is carried out in deionized water for 5 d, and freeze-drying is carried out, to obtain a seaweed acid derivative;

[0039] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to a mass ratio of 1.3:4;

[0040] Step three, mix sodium alginate, alginate derivative and deionized water, stir at 300 r / min for 1 h, after stirring, stand for 24 h to defoam, obtain sodium alginate spinning solution;

[0041] The mass ratio of sodium alginate, alginate derivative and deionized water is 1:1:150;

[0042] The sodium alginate spinning solution is spun into electrospun fiber dressing through electrospinning process;

[0043] The electrospinning process is that the sodium alginate spinning solution is sprayed out of the spinning port of the electrospinning machine to the receiving plate for fixation;

[0044] The electrospinning conditions are that the electrospinning is carried out under the conditions of room temperature, relative humidity of 40%, electrostatic voltage of 30 kV, distance between the spinning port and the receiving plate of 10 cm and flow rate of 0.5 mL / h;

[0045] Step four, place the electrospun fiber dressing in calcium chloride solution, immerse at room temperature for 20 h, after immersion, wash with ethanol, dry at 50℃ under vacuum degree of 0.08 MPa for 12 h, obtain medical dressing containing seaweed extract;

[0046] The thickness of the prepared medical dressing containing seaweed extract is 0.2 mm;

[0047] The calcium chloride solution is prepared from calcium chloride and ethanol aqueous solution, and the mass-volume ratio of calcium chloride and ethanol is 1.5 g / 50 mL.

[0048] Example 2

[0049] The embodiment discloses a preparation method of medical dressing containing seaweed extract, comprising the following steps:

[0050] Step one, mix sodium alginate, deionized water and ethanol uniformly, add sodium periodate, react at room temperature in dark environment under stirring speed of 500 r / min for 20 h, after reaction, add 2 times of ethylene glycol of the mass of sodium alginate, continue to stir in dark environment under stirring speed of 500 r / min for 2 h to terminate the reaction, after stirring, add sodium chloride with equal mass of sodium alginate and ethanol with 4 times of volume of deionized water for precipitation, centrifuge at speed of 4000 r / min for 10 min, redissolve the centrifugal precipitate in deionized water, the amount of deionized water is 1 / 8 of the volume of precipitated ethanol, repeat the process of precipitation, centrifugation and dissolution for three times, obtain solution, pack the solution in dialysis bag with molecular weight cut-off of 3500, dialyze in deionized water for 5 d, freeze-dry to obtain oxidized derivative of sodium alginate;

[0051] Step two, sodium alginate, oxidized derivative of sodium alginate is added to deionized water, 0.1 mol / L hydrochloric acid aqueous solution is added to adjust the pH value to 4, chitosan and p-toluenesulfonylmethyl isocyanide solution is added, the mass ratio of sodium alginate, oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is 40:30:3500:35:215, the reaction is carried out at room temperature under the stirring speed of 500 r / min for 20 h, after the reaction, the reaction mixture is obtained, the reaction mixture is diluted with an equal volume of deionized water, then precipitated with 5 times the volume of ethanol of the reaction mixture, centrifuged at the speed of 4000 r / min for 10 min, the supernatant is removed, washed with 2 times the volume of ethanol of the reaction mixture, then centrifuged at the speed of 4000 r / min for 10 min, the centrifugal precipitate is loaded into a dialysis bag with a relative molecular mass of 8000, dialyzed in deionized water for 5 d, and then freeze-dried to obtain the alginate derivative;

[0052] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to a mass ratio of 1.4:4;

[0053] Step three, sodium alginate, alginate derivative and deionized water are mixed, and stirred at 200 r / min for 2 h, after the stirring is completed, the foam is removed by standing for 24 h, and the sodium alginate spinning solution is obtained;

[0054] The mass ratio of sodium alginate, alginate derivative and deionized water is 1:3:200;

[0055] The sodium alginate spinning solution is spun into an electrospun fiber dressing by an electrospinning process;

[0056] The electrospinning process is that the sodium alginate spinning solution is sprayed out of the spinning nozzle of the electrospinning machine to the receiving plate for receiving and fixing;

[0057] The electrospinning conditions are that the electrospinning is carried out under the conditions of room temperature, a relative humidity of 40%, an electrostatic voltage of 30 kV, a distance between the spinning nozzle and the receiving plate of 10 cm, and a flow rate of 0.5 mL / h;

[0058] Step four, the electrospun fiber dressing is placed in a calcium chloride solution, immersed at room temperature for 30 h, after the immersion is completed, washed with ethanol, dried at 50℃ under a vacuum degree of 0.08 MPa for 12 h, and a medical dressing containing seaweed extract is obtained;

[0059] The thickness of the prepared medical dressing containing seaweed extract is 0.2 mm;

[0060] The calcium chloride solution is prepared by mixing calcium chloride and an ethanol aqueous solution, and the mass-volume ratio of calcium chloride to ethanol is 1.5 g / 50 mL.

[0061] Example 3

[0062] The present embodiment discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0063] Step one, mix sodium alginate, deionized water and ethanol uniformly, add sodium periodate, react for 24 hours at room temperature in dark environment under the stirring speed of 400 r / min, after the reaction, add 2 times of ethylene glycol of the mass of sodium alginate, continue to stir for 2 hours under the stirring speed of 400 r / min to terminate the reaction, after the stirring is completed, add sodium chloride with the same mass of sodium alginate and 4 times of deionized water of the volume of ethanol used for precipitation, centrifuge for 15 minutes at the speed of 3500 r / min, redissolve the centrifugal precipitate in deionized water, the amount of deionized water is 1 / 8 of the volume of ethanol used for precipitation, repeat the process of precipitation, centrifugation and dissolution for three times, obtain the solution, fill the solution into a dialysis bag with a molecular weight cut-off of 3500, dialyze in deionized water for 5 days, freeze-dry to obtain the oxidized derivative of sodium alginate;

[0064] Step two, add sodium alginate and the oxidized derivative of sodium alginate into deionized water, add 0.1 mol / L hydrochloric acid solution to adjust the pH value to 3, add chitosan and p-toluenesulfonylmethyl isocyanide solution, the mass ratio of sodium alginate, the oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is 32:22:2700:27:172, react for 24 hours at room temperature under the stirring speed of 400 r / min, after the reaction, obtain the reaction mixture, dilute by adding deionized water with the same volume as the reaction mixture, add ethanol with 5 times of the volume of the reaction mixture to precipitate, centrifuge for 15 minutes at the speed of 3500 r / min, remove the supernatant, add ethanol with 2 times of the volume of the reaction mixture to wash, then centrifuge for 20 minutes at the speed of 3000 r / min, fill the centrifugal precipitate into a dialysis bag with a relative molecular mass cut-off of 8000, dialyze in deionized water for 5 days, freeze-dry to obtain the alginate derivative;

[0065] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to the mass ratio of 1.38:4;

[0066] Step three, mix sodium alginate, alginate derivative and deionized water, stir at 150 r / min for 1.5 hours, after the stirring is completed, stand for 24 hours to defoam, obtain the sodium alginate spinning solution;

[0067] The mass ratio of sodium alginate, alginate derivative and deionized water is 2:1:150;

[0068] The sodium alginate spinning solution is spun into an electrospun fiber dressing by an electrospinning process;

[0069] The electrospinning process is that the alginate spinning solution is sprayed through the spinning nozzle of the electrospinning machine to the receiving plate for fixation;

[0070] The electrospinning conditions are that the electrospinning is carried out at room temperature, a relative humidity of 40%, an electrostatic voltage of 30 kV, a distance between the spinning nozzle and the receiving plate of 10 cm, and a flow rate of 0.5 mL / h;

[0071] Step four, the electrospun fiber dressing is placed in a calcium chloride solution, immersed at room temperature for 24 h, after the immersion is completed, washed with ethanol, dried at 50℃, 0.08 MPa vacuum degree for 12 h, to obtain a medical dressing containing seaweed extract;

[0072] The prepared medical dressing containing seaweed extract has a thickness of 0.2 mm;

[0073] The calcium chloride solution is prepared by mixing calcium chloride and ethanol aqueous solution, and the mass-volume ratio of calcium chloride and ethanol is 1.5 g / 50 mL.

[0074] Example 4

[0075] The present embodiment discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0076] Step one, sodium alginate, deionized water and ethanol are stirred and mixed uniformly, sodium periodate is added, and the reaction is carried out at room temperature, in a dark environment, at a stirring speed of 400 r / min for 24 h. After the reaction, 2 times of ethylene glycol by the mass of sodium alginate is added, and the reaction is terminated by continuing to stir at a stirring speed of 400 r / min for 2 h in the dark. After the stirring is completed, sodium chloride with the same mass as sodium alginate and 4 times the volume of deionized water and ethanol are added for precipitation. Centrifugation is carried out at a speed of 3500 r / min for 15 min, the centrifugation precipitate is redissolved in deionized water, the amount of deionized water is 1 / 8 of the volume of the precipitated ethanol, and the process of precipitation, centrifugation and dissolution is repeated three times. The solution is obtained, the solution is loaded into a dialysis bag with a molecular weight cut-off of 3500, dialysis is carried out in deionized water for 5 d, and freeze-drying is carried out to obtain an oxidized derivative of sodium alginate;

[0077] Step two, sodium alginate, oxidized derivative of sodium alginate is added to deionized water, 0.1 mol / L hydrochloric acid aqueous solution is added to adjust the pH value to 3, chitosan and p-toluenesulfonylmethyl isocyanide solution is added, the mass ratio of sodium alginate, oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is 34:24:2900:29:185, the reaction is carried out at room temperature under the stirring speed of 400 r / min for 24 h, after the reaction, the reaction mixture is obtained, the reaction mixture is diluted with an equal volume of deionized water, then precipitated with 5 times the volume of ethanol of the reaction mixture, centrifuged at the speed of 3500 r / min for 15 min, the supernatant is removed, washed with 2 times the volume of ethanol of the reaction mixture, then centrifuged at the speed of 3000 r / min for 20 min, the centrifugal precipitate is loaded into a dialysis bag with a relative molecular mass of 8000, dialyzed in deionized water for 5 d, then freeze-dried to obtain the alginate derivative;

[0078] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to the mass ratio of 1.38:4;

[0079] Step three, sodium alginate, alginate derivative and deionized water are mixed, and stirred at 150 r / min for 1.5 h, after the stirring is completed, the defoaming is carried out for 24 h, and the sodium alginate spinning solution is obtained;

[0080] The mass ratio of sodium alginate, alginate derivative and deionized water is 2:3:250;

[0081] The sodium alginate spinning solution is spun into an electrospun fiber dressing by an electrospinning process;

[0082] The electrospinning process is that the sodium alginate spinning solution is sprayed out of the spinning nozzle of the electrospinning machine to the receiving plate for receiving and fixing;

[0083] The electrospinning conditions are that the electrospinning is carried out under the conditions of room temperature, the relative humidity of 40%, the electrostatic voltage of 30 kV, the distance between the spinning nozzle and the receiving plate of 10 cm and the flow rate of 0.5 mL / h;

[0084] Step four, the electrospun fiber dressing is placed in a calcium chloride solution, and is immersed at room temperature for 24 h, after the immersion is completed, washed with ethanol, and dried at 50°C under the vacuum degree of 0.08 MPa for 12 h to obtain a medical dressing containing seaweed extract;

[0085] The thickness of the prepared medical dressing containing seaweed extract is 0.2 mm;

[0086] The calcium chloride solution is prepared by mixing calcium chloride and ethanol aqueous solution, and the mass-volume ratio of calcium chloride and ethanol is 1.5 g / 50 mL.

[0087] Example 5

[0088] The present embodiment discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0089] Step one, mix sodium alginate with deionized water and ethanol uniformly, add sodium periodate, react for 24 hours at room temperature in dark environment under the stirring speed of 400 r / min, after the reaction, add 2 times of ethylene glycol of the mass of sodium alginate, continue to stir for 2 hours under the stirring speed of 400 r / min to terminate the reaction, after the stirring is completed, add sodium chloride with the same mass of sodium alginate and 4 times of deionized water of the volume of ethanol used for precipitation, centrifuge for 15 minutes at the speed of 3500 r / min, redissolve the centrifugal precipitate in deionized water, the amount of deionized water is 1 / 8 of the volume of ethanol used for precipitation, repeat the process of precipitation, centrifugation and dissolution for three times, obtain the solution, fill the solution into a dialysis bag with a molecular weight cut-off of 3500, dialyze in deionized water for 5 days, freeze-dry to obtain the oxidized derivative of sodium alginate;

[0090] Step two, add sodium alginate and the oxidized derivative of sodium alginate into deionized water, add 0.1 mol / L hydrochloric acid solution to adjust the pH value to 3, add chitosan and p-toluenesulfonylmethyl isocyanide solution, the mass ratio of sodium alginate, the oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is 36:26:3100:31:195, react for 24 hours at room temperature under the stirring speed of 400 r / min, after the reaction, obtain the reaction mixture, dilute by adding deionized water with the same volume as the reaction mixture, then add ethanol with 5 times of the volume of the reaction mixture to precipitate, centrifuge for 15 minutes at the speed of 3500 r / min, remove the supernatant, wash by adding ethanol with 2 times of the volume of the reaction mixture, then centrifuge for 20 minutes at the speed of 3000 r / min, fill the centrifugal precipitate into a dialysis bag with a relative molecular mass cut-off of 8000, dialyze in deionized water for 5 days, freeze-dry to obtain the alginate derivative;

[0091] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to the mass ratio of 1.38:4;

[0092] Step three, mix sodium alginate and the alginate derivative with deionized water, stir at 150 r / min for 1.5 hours, after the stirring is completed, stand for 24 hours to defoam, obtain the sodium alginate spinning solution;

[0093] The mass ratio of sodium alginate, the alginate derivative and deionized water is 1.5:2:200;

[0094] The sodium alginate spinning solution is spun into an electrospun fiber dressing by electrospinning process.

[0095] The electrospinning process is that the alginate spinning solution is sprayed through the spinning nozzle of the electrospinning machine to the receiving plate for fixation;

[0096] The electrospinning conditions are that the electrospinning is carried out at room temperature, a relative humidity of 40%, an electrostatic voltage of 30 kV, a distance between the spinning nozzle and the receiving plate of 10 cm, and a flow rate of 0.5 mL / h;

[0097] Step four, the electrospun fiber dressing is placed in a calcium chloride solution, immersed at room temperature for 24 h, after the immersion is completed, washed with ethanol, dried at 50℃, 0.08 MPa vacuum degree for 12 h, to obtain a medical dressing containing seaweed extract;

[0098] The prepared medical dressing containing seaweed extract has a thickness of 0.2 mm;

[0099] The calcium chloride solution is prepared by mixing calcium chloride and ethanol aqueous solution, and the mass-volume ratio of calcium chloride to ethanol is 1.5 g / 50 mL.

[0100] Example 6

[0101] The present embodiment discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0102] Step one, sodium alginate, deionized water and ethanol are stirred and mixed uniformly, sodium periodate is added, and the reaction is carried out at room temperature, in a dark environment, at a stirring speed of 400 r / min for 24 h. After the reaction, 2 times of ethylene glycol by the mass of sodium alginate is added, and the reaction is continued to be stirred at a stirring speed of 400 r / min for 2 h in a dark environment to terminate the reaction. After the stirring is completed, sodium chloride with the same mass as sodium alginate and 4 times of deionized water by volume of ethanol are added for precipitation. Centrifugation is carried out at a speed of 3500 r / min for 15 min, the centrifugation precipitate is redissolved in deionized water, the amount of deionized water is 1 / 8 of the volume of the precipitated ethanol, and the process of precipitation, centrifugation and dissolution is repeated three times. The solution is obtained, the solution is loaded into a dialysis bag with a molecular weight cut-off of 3500, dialysis is carried out in deionized water for 5 d, and freeze-drying is carried out to obtain an oxidized derivative of sodium alginate;

[0103] Step two, sodium alginate, oxidized derivative of sodium alginate is added to deionized water, 0.1 mol / L hydrochloric acid aqueous solution is added to adjust the pH value to 3, chitosan and p-toluenesulfonylmethyl isocyanide solution is added, the mass ratio of sodium alginate, oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is 38:28:3300:33:205, the reaction is carried out at room temperature under the stirring speed of 400 r / min for 24 h, after the reaction, the reaction mixture is obtained, the reaction mixture is diluted with an equal volume of deionized water, then precipitated with 5 times the volume of ethanol of the reaction mixture, centrifuged at the speed of 3500 r / min for 15 min, the supernatant is removed, washed with 2 times the volume of ethanol of the reaction mixture, then centrifuged at the speed of 3000 r / min for 20 min, the centrifugal precipitate is loaded into a dialysis bag with a relative molecular mass of 8000, dialyzed in deionized water for 5 d, then freeze-dried to obtain the alginate derivative;

[0104] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to the mass ratio of 1.38:4;

[0105] Step three, sodium alginate, alginate derivative and deionized water are mixed, and stirred at 150 r / min for 1.5 h, after the stirring is completed, the foam is removed by standing for 24 h, to obtain the alginate spinning solution;

[0106] The mass ratio of sodium alginate, alginate derivative and deionized water is 1.5:2:200;

[0107] The alginate spinning solution is spun into an electrospun fiber dressing by an electrospinning process;

[0108] The electrospinning process is that the alginate spinning solution is sprayed through the spinneret of the electrospinning machine to the receiving plate for fixation;

[0109] The electrospinning conditions are that the electrospinning is carried out under the conditions of room temperature, relative humidity of 40%, electrostatic voltage of 30 kV, distance between the spinneret and the receiving plate of 10 cm and flow rate of 0.5 mL / h;

[0110] Step four, the electrospun fiber dressing is immersed in a calcium chloride solution at room temperature for 24 h, after the immersion is completed, the dressing is washed with ethanol, and then dried at 50°C under a vacuum degree of 0.08 MPa for 12 h to obtain a medical dressing containing seaweed extract;

[0111] The thickness of the prepared medical dressing containing seaweed extract is 0.2 mm;

[0112] The calcium chloride solution is prepared by mixing calcium chloride and ethanol aqueous solution, and the mass-volume ratio of calcium chloride and ethanol is 1.5 g / 50 mL.

[0113] Example 7

[0114] The present embodiment discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0115] Step one, mix sodium alginate, deionized water and ethanol uniformly, add sodium periodate, the mass ratio of sodium alginate, deionized water, ethanol and sodium periodate is 5:200:40:1.6, react for 30h at room temperature in dark environment under the stirring speed of 300r / min, after the reaction, add 2 times of the mass of sodium alginate of ethylene glycol, continue to stir for 2h under the stirring speed of 300r / min to terminate the reaction, after the stirring is completed, add sodium chloride with the same mass of sodium alginate and 4 times of the volume of deionized water to precipitate, centrifuge at the speed of 3000r / min for 20min, redissolve the centrifugal precipitate in deionized water, the amount of deionized water is 1 / 8 of the volume of precipitated ethanol, repeat the process of precipitation, centrifugation and dissolution for three times, obtain the solution, load the solution into a dialysis bag with a molecular weight cut-off of 3500, dialyze in deionized water for 5d, freeze-dry to obtain the oxidized derivative of sodium alginate;

[0116] Step two, add sodium alginate and the oxidized derivative of sodium alginate into deionized water, add 0.1mol / L hydrochloric acid solution to adjust the pH value to 3, add chitosan and p-toluenesulfonylmethyl isocyanide solution, the mass ratio of sodium alginate, the oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is 30:20:2500:25:160, react for 30h at room temperature under the stirring speed of 300r / min, after the reaction, obtain the reaction mixture, dilute by adding deionized water with the same volume as the reaction mixture, then add ethanol with 5 times the volume of the reaction mixture to precipitate, centrifuge at the speed of 3000r / min for 20min, remove the supernatant, wash with ethanol with 2 times the volume of the reaction mixture, then centrifuge at the speed of 3000r / min for 20min, load the centrifugal precipitate into a dialysis bag with a relative molecular mass cut-off of 8000, dialyze in deionized water for 5d, freeze-dry to obtain the alginate derivative;

[0117] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to the mass ratio of 1.3:4;

[0118] Step three, mix sodium alginate, alginate derivative and deionized water, stir at 300r / min for 2h, after the stirring is completed, add ibuprofen solution, mix, shear at the speed of 3000r / min for 10min, stand for 24h to defoam, obtain the alginate spinning solution;

[0119] Sodium alginate, alginate derivatives, deionized water, ibuprofen solution, mass ratio is 1:1:125:25;

[0120] The ibuprofen solution is an ibuprofen ethanol solution, and the mass-volume ratio of ibuprofen to ethanol is 12 mg / mL;

[0121] The sodium alginate spinning solution is spun into an electrospun fiber dressing through an electrospinning process;

[0122] The electrospinning process is that the sodium alginate spinning solution is sprayed through the spinning nozzle of the electrospinning machine to the receiving plate for receiving and fixing;

[0123] The electrospinning conditions are that the electrospinning is carried out under the conditions of room temperature, a relative humidity of 40%, an electrostatic voltage of 30 kV, a distance between the spinning nozzle and the receiving plate of 10 cm, and a flow rate of 0.5 mL / h;

[0124] Step four, the electrospun fiber dressing is placed in a calcium chloride solution, immersed at room temperature for 30 h, after immersion, washed with ethanol, dried at 50 DEG C, 0.08 MPa vacuum degree for 12 h, to obtain a medical dressing containing seaweed extract;

[0125] The thickness of the prepared medical dressing containing seaweed extract is 0.2 mm;

[0126] The calcium chloride solution is prepared by calcium chloride and ethanol aqueous solution, and the mass-volume ratio of calcium chloride to ethanol is 1.5 g / 50 mL.

[0127] Comparative Example 1

[0128] The present comparative example discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0129] Step one, mix sodium alginate, chitosan and deionized water, stir at 300 r / min for 1 h, after stirring, stand for 24 h to defoam, to obtain a sodium alginate spinning solution;

[0130] The mass ratio of sodium alginate, chitosan and deionized water is 1.67:0.33:150;

[0131] The sodium alginate spinning solution is spun into an electrospun fiber dressing through an electrospinning process;

[0132] The electrospinning process is that the sodium alginate spinning solution is sprayed through the spinning nozzle of the electrospinning machine to the receiving plate for receiving and fixing;

[0133] The electrospinning conditions are that the electrospinning is carried out under the conditions of room temperature, a relative humidity of 40%, an electrostatic voltage of 30 kV, a distance between the spinning nozzle and the receiving plate of 10 cm, and a flow rate of 0.5 mL / h;

[0134] Step two, the electrostatic spinning fiber dressing is placed in calcium chloride solution, immersed at room temperature for 20h, after the completion of immersion, washed with ethanol, dried at 50℃, 0.08MPa vacuum degree for 12h, to obtain a medical dressing containing seaweed extract;

[0135] The thickness of the prepared medical dressing containing seaweed extract is 0.2mm;

[0136] The calcium chloride solution is prepared by calcium chloride and ethanol aqueous solution, the mass-volume ratio of calcium chloride and ethanol is 1.5g / 50mL.

[0137] Comparative example 2

[0138] The present comparative example discloses a preparation method of a medical dressing containing seaweed extract, comprising the following steps:

[0139] Step one, sodium alginate, deionized water and ethanol are stirred and mixed uniformly, sodium periodate is added, the mass ratio of sodium alginate, deionized water, ethanol and sodium periodate is 5:200:40:1.6, the reaction is carried out at room temperature, in dark environment, at a stirring speed of 300r / min for 30h, after the reaction, 2 times of the mass of sodium alginate of ethylene glycol is added, the stirring is continued at a stirring speed of 300r / min for 2h to terminate the reaction, after the completion of stirring, equal mass of sodium alginate of sodium chloride and 4 times of the volume of deionized water of ethanol are added for precipitation, centrifugation is carried out at a speed of 3000r / min for 20min, the centrifugal precipitate is redissolved in deionized water, the amount of deionized water is 1 / 8 of the volume of the precipitated ethanol, the process of precipitation, centrifugation and dissolution is repeated three times, to obtain a solution, the solution is loaded into a dialysis bag with a molecular weight cut-off of 3500, dialysis is carried out in deionized water for 5d, and freeze-drying is carried out, to obtain an oxidized derivative of sodium alginate;

[0140] Step two, sodium alginate and the oxidized derivative of sodium alginate are added into deionized water, 0.1mol / L hydrochloric acid aqueous solution is added to adjust the pH value to 3, chitosan and p-toluenesulfonylmethyl isocyanide solution are added, the mass ratio of sodium alginate, the oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is 30:20:2500:25:160, the reaction is carried out at room temperature, at a stirring speed of 300r / min for 30h, after the reaction, a reaction mixture is obtained, the reaction mixture is diluted by adding an equal volume of deionized water, and precipitated by adding 5 times of the volume of the reaction mixture of ethanol, centrifugation is carried out at a speed of 3000r / min for 20min, the supernatant is removed, the reaction mixture is washed by adding 2 times of the volume of ethanol, and centrifugation is carried out at a speed of 3000r / min for 20min, the centrifugal precipitate is loaded into a dialysis bag with a relative molecular weight cut-off of 8000, dialysis is carried out in deionized water for 5d, and freeze-drying is carried out, to obtain a seaweed acid derivative;

[0141] The p-toluenesulfonylmethyl isocyanide solution is prepared by mixing p-toluenesulfonylmethyl isocyanide and methanol at a mass ratio of 1.3:4.

[0142] Step three, mixing sodium alginate, alginate derivative and deionized water, stirring at 300 r / min for 1 h, and then standing for 24 h to defoam, to obtain the sodium alginate spinning solution;

[0143] The mass ratio of sodium alginate, alginate derivative and deionized water is 1:1:150.

[0144] The sodium alginate spinning solution is spun into an electrospun fiber dressing by an electrospinning process, to obtain the medical dressing containing seaweed extract.

[0145] The prepared medical dressing containing seaweed extract has a thickness of 0.2 mm.

[0146] The electrospinning process is that the sodium alginate spinning solution is sprayed out of the spinning nozzle of the electrospinning machine to be received and fixed on the receiving plate.

[0147] The electrospinning conditions are that the electrospinning is carried out at room temperature, a relative humidity of 40%, an electrostatic voltage of 30 kV, a distance between the spinning nozzle and the receiving plate of 10 cm, and a flow rate of 0.5 mL / h.

[0148] The freeze-drying process in steps one and two of Examples 1-7 and Comparative Example 2 is the same, including three stages:

[0149] (1) Pre-freezing stage: pre-freezing at -50℃ for 3 h;

[0150] (2) Sublimation drying stage: drying at a vacuum degree of 30 Pa and a temperature of 0℃ for 8 h;

[0151] (3) Desorption drying stage: drying at a vacuum degree of 10 Pa and a temperature of 30℃ for 6 h.

[0152] In Examples 1-6 and Comparative Examples 1-2, the sodium alginate is purchased from Qingdao Mingyue Seaweed Group Co., Ltd., with a CAS number of 9005-38-3, a model of food grade, and a particle size of 80 mesh; and the chitosan is a water-soluble chitosan provided by Jiangsu Jiayuan Biological Technology Co., Ltd., with a grade of food grade and a product number of 1054.

[0153] Test Example

[0154] (1) The surface tension (γ) and conductivity (κ) of the sodium alginate spinning solution in Examples 1-6 and Comparative Examples 1-2 are determined, and the determination results are shown in Table 1:

[0155] Table 1

[0156]

[0157] From Table 1, it can be seen that the surface tension of the alginic acid spinning solution in the application is small, the conductivity is low, and the electrospinning performance is good. Through the Ugi reaction of the negatively charged carboxyl group on the molecular main chain of sodium alginate and the oxidation derivative of sodium alginate, chitosan, and p-toluenesulfonylmethyl isothiocyanate, the negatively charged carboxyl group on the molecular main chain of sodium alginate is reduced and a hydrophobic side chain is grafted, which greatly reduces the conductivity of the spinning solution, enhances the molecular flexibility, significantly improves the surface activity, effectively reduces the surface tension of the spinning solution, and is beneficial to electrospinning. Compared with Example 1, in Comparative Example 1, because no hydrophobic side chain is grafted on the molecular main chain of sodium alginate through the Ugi reaction, the negatively charged carboxyl group is not reduced, and the surface tension and conductivity of the spinning solution are both relatively large, which is not conducive to electrospinning.

[0158] (2) The tensile property test of the medical dressings containing seaweed extract prepared in Examples 1-6 and Comparative Examples 1-2 was performed: the medical dressings containing seaweed extract prepared in Examples 1-6 and Comparative Examples 1-2 were all cut into samples with a length of 5 cm and a width of 2 mm, and the tensile strength of the samples was determined using an LLY-06E type electronic single fiber strength tester under the conditions of a temperature of 20°C and a humidity of 65%, and each sample was measured three times to take an average value;

[0159] The determination results are shown in Table 2:

[0160] Table 2

[0161]

[0162] From Table 2, it can be seen that the medical dressings containing seaweed extract prepared in the application have good mechanical strength. The electrospun fiber dressing prepared by the electrospinning process of sodium alginate and seaweed acid derivative is immersed in a calcium chloride solution, sodium alginate exchanges with divalent calcium ions to form calcium alginate, so that the alginic acid is crosslinked into a stable three-dimensional structure, which can effectively improve the mechanical strength of the dressing. Compared with Example 1, in Comparative Example 2, the electrospun fiber dressing spun by the electrospinning process is not subjected to the immersion treatment of the calcium chloride solution, and the alginic acid molecules cannot be crosslinked, so the tensile strength of the dressing is significantly reduced.

[0163] (3) The antibacterial property test of the medical dressings containing seaweed extract prepared in Examples 1-6 and Comparative Examples 1-2 was performed, and the test results are shown in Table 3:

[0164] Table 3

[0165]

[0166] It can be seen from Table 3 that the medical dressing containing seaweed extract prepared by the application has good antibacterial performance. Seaweed salt fiber itself has good antibacterial effect, and the antibacterial effect of fresh fruit is more significant after grafting chitosan. In Example 7, compared with Example 1, the antibacterial performance is obviously enhanced because ibuprofen with antibacterial effect is loaded in the preparation process of the dressing; in Comparative Example 1, chitosan is not grafted to the molecular chain of sodium alginate, and the chitosan molecules will partially separate from the electrospun fiber dressing when impregnated and crosslinked with calcium chloride solution, resulting in a decrease in antibacterial performance.

[0167] Although embodiments of the application have been shown and described, it is to be understood that various modifications, substitutions, replacements and changes can be made to these embodiments without departing from the principles and spirit of the application, and the scope of the application is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a medical dressing containing seaweed extract, characterized by, It comprises the following steps: Step one, stirring and mixing sodium alginate, deionized water and ethanol uniformly, adding sodium periodate, stirring and reacting, after the reaction, adding ethylene glycol, continuing to stir to terminate the reaction, after the stirring is completed, separating and purifying, drying to obtain the oxidized derivative of sodium alginate; Step two, adding sodium alginate and the oxidized derivative of sodium alginate into deionized water, adjusting the pH value to 3-4, adding chitosan and p-toluenesulfonylmethyl isocyanide solution, stirring and reacting, after the reaction, separating and purifying, drying to obtain the alginate derivative; Step three, mixing sodium alginate and the alginate derivative with deionized water, stirring, after the stirring is completed, standing and defoaming to obtain the alginate spinning solution; Spinning the alginate spinning solution into electrospun fiber dressing through the electrospinning process; Step four, placing the electrospun fiber dressing in calcium chloride solution, immersing, after the immersing is completed, washing, drying to obtain the medical dressing containing seaweed extract.

2. The method of claim 1, wherein the medical dressing containing the seaweed extract is prepared by the steps of: In the step one, the mass ratio of sodium alginate, deionized water, ethanol and sodium periodate is 5:(200-300):(40-60):(1.6-1.8); the stirring and reaction conditions are: reacting at room temperature, in a dark environment, at a stirring speed of 300-500 r / min for 20-30 h; the adding amount of ethylene glycol is 2-2.5 times of the mass of sodium alginate.

3. The method of claim 1, wherein the medical dressing containing the seaweed extract is prepared by the steps of: In the step two, the mass ratio of sodium alginate, the oxidized derivative of sodium alginate, deionized water, chitosan and p-toluenesulfonylmethyl isocyanide solution is (30-40):(20-30):(2500-3500):(25-35):(160-215); the stirring and reaction conditions are: reacting at room temperature, at a stirring speed of 300-500 r / min for 20-30 h.

4. The method of claim 1, wherein the medical dressing containing the seaweed extract is prepared by the steps of: In the step two, the pH value is adjusted by adding hydrochloric acid aqueous solution, and the concentration of the hydrochloric acid aqueous solution is 0.1 mol / L; the p-toluenesulfonylmethyl isocyanide solution is prepared by mixing toluenesulfonylmethyl isocyanide and methanol according to the mass ratio (1.3-1.4):

4.

5. The method of claim 1, wherein the medical dressing containing the seaweed extract is prepared by the steps of: In the step three, the mass ratio of sodium alginate, the alginate derivative and deionized water is (1-2):(1-3):(150-250).

6. The method of claim 1, wherein the medical dressing containing the seaweed extract is prepared by the steps of: In the step three, the electrospinning process comprises spraying the alginate spinning solution through the spinning nozzle of the electrospinning device onto the receiving device for receiving and fixing.

7. The method of claim 6, wherein the medical dressing is prepared by the steps of: The electrospinning conditions are: electrospinning at room temperature, at a relative humidity of 40%, at an electrostatic voltage of 30 kV, at a distance of 10 cm from the spinning nozzle to the receiving plate and at a flow rate of 0.5 mL / h.

8. The method of claim 1, wherein the medical dressing containing the seaweed extract is prepared by the steps of: In the step four, the calcium chloride solution is prepared by mixing calcium chloride and ethanol, and the immersing conditions are: immersing at room temperature for 20-30 h.

9. The method of claim 8, wherein the medical dressing is prepared by the steps of: a) mixing the seaweed extract with a pharmaceutically acceptable carrier; b) sterilizing the mixture; and c) filling the mixture into a container. In the calcium chloride solution, the mass-volume ratio of calcium chloride to ethanol is 1.5 g / 50 mL.

10. A medical dressing containing seaweed extract prepared by the method according to any one of claims 1-9.

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