A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic and a preparation method thereof

Abstract

The present invention relates to the field of medical material technology, and specifically to an antibacterial and anti-allergic wound dressing and a preparation method thereof. The wound dressing comprises the following raw materials in parts by weight: 20 to 30 parts of a composite carrier and 3 to 6 parts of a calcium alginate complex; the composite carrier is a mixture of an antibacterial carrier and cellulose fiber. The wound dressing disclosed in the present invention has good hemostatic effect, excellent antibacterial performance and wide universality, and almost no allergies occur, which can meet the needs of wound care.

Description

Technical Field

[0001] The invention relates to the technical field of medical materials, and in particular to a wound dressing capable of preventing drug extravasation and being antibacterial and anti-allergic, and a preparation method thereof. Background Art

[0002] Excessive blood loss is one of the main causes of death from trauma. At the same time, uncontrollable wound infection can also endanger life safety, especially in wars, major natural disasters and field operations. Therefore, post-traumatic hemostasis and infection control are key parts of pre-hospital rescue. In addition to heavy bleeding, chronic inflammation is an important factor hindering wound healing during wound healing, and wound infection is a chronic inflammation caused by a large number of bacteria colonizing the wound. Wound healing is a complex and orderly biological process, including hemostasis and inflammation, proliferation, and maturation. After trauma, inflammatory reactions occur within hours. At present, large-scale hemostasis first aid in pre-hospital settings is mainly gauze, which has a weak hemostatic effect and no antibacterial properties.

[0003] The invention patent with the publication number CN117919485A discloses a hemostatic and antibacterial medical material and its preparation method, wherein the hemostatic and antibacterial medical material is composed of synergistic gel microspheres and a hydrogel base; the synergistic gel microspheres are composed of sodium alginate, carboxymethyl cellulose, tamarind polysaccharide and tannic acid; the hydrogel base is composed of hyaluronic acid, water-soluble silk protein and calcium chloride; the invention embeds the synergistic gel microspheres into the hydrogel matrix, and the multi-level gel structure formed has high porosity and huge surface area, making the physical barrier more rigorous and complex, better isolating bacteria, adhering bacteria and killing bacteria, achieving efficient antibacterial effect, and also making the gel system have stronger adhesion and adsorption, which can better play the role of hemostasis. However, in actual application, the medical material may have a reduced antibacterial effect due to the bacterial production of lytic enzymes to promote the degradation of hyaluronic acid. Summary of the invention

[0004] In view of the defects of the prior art, the present invention discloses a wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, and a preparation method thereof. The wound dressing disclosed in the present invention has good hemostatic effect, excellent antibacterial performance and wide universality, almost no allergy, and is not prone to drug extravasation, which can meet the needs of wound care.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0006] The first aspect of the present invention provides a wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, the wound dressing comprising the following raw materials in parts by weight: 20 to 30 parts of a composite carrier and 3 to 6 parts of a calcium alginate complex; the composite carrier is a mixture of an antibacterial carrier and a calcium alginate complex.

[0007] Preferably, the mass ratio of the antibacterial carrier to the cellulose fiber is (0.1-0.5):1.

[0008] Further preferably, the mass ratio of the antibacterial carrier to the cellulose fiber is 0.3:1.

[0009] In some embodiments of the present invention, the antibacterial carrier is grafted modified chitosan.

[0010] In some embodiments of the present invention, the preparation steps of the grafted modified chitosan are as follows:

[0011] (1) dissolving chitosan in acetic acid solution, adding phenolic acid monomer and mixing evenly, then adding initiator, introducing nitrogen, reacting at 40-50° C. for 8-12 h, cooling and drying, and obtaining phenolic acid modified chitosan;

[0012] (2) adding bronopol to deionized water and stirring evenly, adding the phenolic acid modified chitosan of step (1), adding a catalyst under stirring and reacting at 30-40° C. for 10-13 hours to obtain the grafted modified chitosan.

[0013] In some embodiments of the present invention, in step (1), the phenolic acid monomer is p-hydroxybenzoic acid.

[0014] In some embodiments of the present invention, the mass ratio of chitosan, phenolic acid monomer and bronopol is 10:(1.4-2):(0.3-0.7).

[0015] Preferably, the mass ratio of the chitosan, the phenolic acid monomer and bronopol is 10:1.7:0.5.

[0016] In some embodiments of the present invention, the number average molecular weight of the chitosan is 8,000-20,000.

[0017] Chitosan is a natural antibacterial agent that has a good inhibitory effect on microorganisms such as bacteria, yeast, and fungi, especially on bacteria that exist on the human epidermis, such as Staphylococcus epidermidis and Escherichia coli. However, its antibacterial effect when used as a wound dressing still needs to be further improved. The invention grafts phenolic acid monomers and bronopol onto chitosan. Compared with the prior art, the mechanical properties of chitosan are greatly improved due to the introduction of the benzene ring on the p-hydroxybenzoic acid, and the use performance of the wound dressing is further guaranteed. The chitosan is not easy to break and the drug extravasation is not easy to occur under the use environment. At the same time, the introduction of the p-hydroxybenzoic acid further improves the free radical scavenging ability of the chitosan, inhibits bacterial growth, and promotes wound healing. On the other hand, by introducing bronopol, the active sites on the chitosan are stimulated by O-substitution reaction, and the loss of active properties caused by the change of the basic skeleton of the chitosan after the amino group is replaced is eliminated. The possible reason is that the chemical modification of the hydroxyl position of the phenolic acid modified chitosan by grafting bronopol further stimulates the biological activity of the chitosan, and the antibacterial effect thereof is greatly improved. The substitution of the hydroxyl group in the chitosan also improves the water solubility of the modified chitosan, and increases the moisture retention ability of the wound dressing.

[0018] In some embodiments of the present invention, the preparation steps of the calcium alginate complex are as follows:

[0019] The short cotton fiber and sodium alginate are mixed, pearl powder and polyol are added under stirring, the mixture is stirred evenly, a spinning aid is added and electrostatic spinning is performed to obtain a calcium alginate complex.

[0020] In some embodiments of the present invention, the mass ratio of the short cotton fiber, sodium alginate and pearl powder is (0.1-0.2):1:(0.1-0.3).

[0021] Preferably, the mass ratio of the short cotton fiber, sodium alginate and pearl powder is 0.15:1:0.2.

[0022] In some embodiments of the present invention, the spinning aid is polycaprolactone and / or polylactic acid.

[0023] Preferably, the electrospinning is performed by injecting the electrospinning material into an electrospinning needle under the conditions of a voltage of 15 to 20 kV, a receiving distance of 10 to 20 cm, and a liquid inlet flow rate of 0.5 to 1.5 mL / h.

[0024] The present invention prepares the sodium alginate complex by electrospinning. When the sodium alginate is used in the wound dressing system, the short cotton fiber provides a pore structure in which the sodium alginate can exist. The pearl powder loaded with a large specific surface area can also promote the orderly arrangement of the structures of the components of the wound dressing through sufficient physical adsorption, further balance the air permeability and moisture retention of the wound dressing, and avoid the allergic inflammation caused by the wound dressing irritating the skin of patients with sensitive skin. At the same time, the applicant also found that the trace elements carried by the pearl powder also play a certain synergistic function of promoting wound healing.

[0025] Another aspect of the present invention provides a method for preparing a wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, comprising the following steps:

[0026] The composite carrier and the sodium alginate composite are blended by a needle-punched non-woven fabric process to obtain a fabric, which is then cut, packaged and sterilized to obtain the wound dressing.

[0027] Preferably, the preparation method comprises mixing the antibacterial carrier and the cellulose fibers, loosening them with a loosening machine, feeding them into a carding machine for further mixing to obtain a fiber web, and obtaining a non-woven fabric by web laying and needle punching, and then cutting, packaging and sterilizing with ethylene oxide.

[0028] Compared with the prior art, the present invention has the following beneficial effects:

[0029] (1) The wound dressing disclosed in the present invention has good hemostatic effect, excellent antibacterial performance and wide universality, almost no allergies, and is not prone to drug extravasation, which can meet the needs of wound care.

[0030] (2) The present invention further ensures the performance and antibacterial effect of the wound dressing by grafting phenolic acid monomers and bronopol onto chitosan, and the substitution of hydroxyl groups in chitosan also improves the water solubility of the modified chitosan and increases the moisture retention capacity of the wound dressing.

[0031] (3) The present invention prepares the sodium alginate complex by electrospinning. When the sodium alginate complex is used in the wound dressing system, it further balances the air permeability and moisture retention of the wound dressing, thereby avoiding allergic inflammation caused by the wound dressing on the skin of patients with sensitive skin; at the same time, the trace elements carried by the pearl powder also play a certain synergistic function in promoting wound healing. DETAILED DESCRIPTION

[0032] The present invention will be described below in conjunction with specific embodiments. It should be noted that the following examples are examples of the present invention and are only used to illustrate the present invention, but not to limit the present invention. At the same time, all the professional terms mentioned below have the same meaning as those generally understood by those skilled in the art. The professional terms used herein are only for the purpose of describing specific embodiments, and are not intended to limit the scope of protection of the present invention. Other combinations and various improvements within the concept of the present invention may be performed without departing from the gist or scope of the present invention.

[0033] Unless otherwise specified, the reagents used below are all easily available from commercial companies and are of medical grade.

[0034] Unless otherwise specified, the number average molecular weight of the chitosan used below is 15,000, the cellulose fibers used are all carboxymethyl cellulose, and the polylactic acid used is purchased from Hubei Xinghengye Technology Co., Ltd.

[0035] Unless otherwise specified, the post-processing steps of "cooling and drying", "stirring", "opening", "netting", "needling", "cutting", "packaging" and "sterilization" used below are routine operations of those skilled in the art and can be selected according to actual operations.

[0036] Preparation Example 1

[0037] The preparation steps of grafted modified chitosan are as follows:

[0038] (1) 10 g of chitosan was dissolved in 40 mL of 3% (v / v) acetic acid solution, 1.7 g of p-hydroxybenzoic acid was added and mixed evenly, and then an initiator (0.1 g of vitamin C was added first, and then 1 mL of 30% (v / v) H2O2) was added, nitrogen was introduced, and the mixture was reacted at 45°C for 10 h, and cooled and dried to obtain phenolic acid-modified chitosan;

[0039] (2) 0.5 g of bronopol was added to 20 mL of deionized water and stirred evenly, and all of the phenolic acid-modified chitosan in step (1) was added. Under stirring, 1 mL of a 15 wt % aqueous sodium hydroxide solution was added and reacted at 35° C. for 12 h to obtain a grafted modified chitosan.

[0040] Preparation Example 2

[0041] The preparation steps of grafted modified chitosan are the same as those in Preparation Example 1, except that the amount of p-hydroxybenzoic acid added in step (1) is 2.5 g.

[0042] Preparation Example 3

[0043] The preparation steps of grafted modified chitosan are the same as those in Preparation Example 1, except that the amount of bronopol added in step (2) is 0.8 g.

[0044] Preparation Example 4

[0045] The preparation steps of calcium alginate complex are as follows:

[0046] Mix 1.5g of short cotton fiber and 10g of sodium alginate, add 2g of pearl powder and 100mL of hexafluoroisopropanol while stirring, stir evenly, add 8g of polylactic acid and inject into an electrospinning needle with an inner diameter of 0.50mm, and perform electrospinning under the conditions of voltage 17kV, receiving distance 15cm, and liquid inlet flow rate 1mL / h to obtain a calcium alginate complex.

[0047] Preparation Example 5

[0048] The preparation steps of the calcium alginate composite are the same as those of Preparation Example 3, except that the amount of short cotton fiber added is 3 g.

[0049] Preparation Example 6

[0050] The preparation steps of the calcium alginate composite are the same as those of Preparation Example 3, except that the amount of pearl powder added is 4 g.

[0051] Example 1

[0052] A wound dressing capable of preventing drug extravasation and being antibacterial and anti-allergic comprises the following raw materials in parts by weight: 25 parts of a composite carrier (obtained by mixing an antibacterial carrier and cellulose fibers in a mass ratio of 0.3:1) and 4.5 parts of a calcium alginate complex.

[0053] The preparation method of the wound dressing that prevents drug extravasation and is antibacterial and anti-allergic in this embodiment comprises the following steps: mixing the composite carrier and the calcium alginate complex and loosening them with a loosening machine, feeding them into a carding machine for further mixing to obtain a fiber web, and preparing a non-woven fabric by laying the web and needle punching, and then cutting, packaging and sterilizing with ethylene oxide to obtain a wound dressing.

[0054] The antibacterial carrier used in this example is obtained from Preparation Example 1, and the calcium alginate complex is obtained from Preparation Example 4.

[0055] Example 2

[0056] A wound dressing capable of preventing drug extravasation and being antibacterial and anti-allergic comprises the following raw materials in parts by weight: 20 parts of a composite carrier (obtained by mixing an antibacterial carrier and cellulose fibers in a mass ratio of 0.3:1) and 3 parts of a calcium alginate complex.

[0057] The method for preparing the wound dressing that prevents drug extravasation and is antibacterial and anti-allergic in this embodiment has the same specific steps as in Example 1.

[0058] The antibacterial carrier used in this example is obtained from Preparation Example 1, and the calcium alginate complex is obtained from Preparation Example 4.

[0059] Example 3

[0060] A wound dressing capable of preventing drug extravasation and being antibacterial and anti-allergic comprises the following raw materials in parts by weight: 30 parts of a composite carrier (obtained by mixing an antibacterial carrier and cellulose fibers in a mass ratio of 0.3:1) and 6 parts of a calcium alginate complex.

[0061] The method for preparing the wound dressing that prevents drug extravasation and is antibacterial and anti-allergic in this embodiment has the same specific steps as in Example 1.

[0062] The antibacterial carrier used in this example is obtained from Preparation Example 1, and the calcium alginate complex is obtained from Preparation Example 4.

[0063] Example 4

[0064] A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that the antibacterial carrier used is obtained from Preparation Example 2.

[0065] Example 5

[0066] A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that the antibacterial carrier used is obtained from Preparation Example 3.

[0067] Example 6

[0068] A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that the calcium alginate complex used is obtained from Preparation Example 5.

[0069] Example 7

[0070] A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that the calcium alginate complex used is obtained from Preparation Example 6.

[0071] Example 8

[0072] A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, and a preparation method thereof. The specific implementation manner is the same as that of Example 1, except that the antibacterial carrier used is chitosan.

[0073] Comparative Example 1

[0074] A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, and a preparation method thereof. The specific implementation method is the same as that of Example 1, except that an equal amount of sodium alginate is used to replace the sodium alginate complex.

[0075] Performance Testing

[0076] 1. Cytotoxicity test: According to the requirements of ISO1-5 (Biological evaluation of medical devices - Part 5: In vitro cytotoxicity test): The test was performed using the culture wells of a six-well tissue culture plate containing a subconfluent monolayer of L-929 mouse fibroblasts. Each wound dressing prepared in Examples 1-8 and Comparative Example 1 was added to the triplicate wells, respectively, with high-density polyethylene as a negative control or latex as a positive control. Each wound dressing was directly contacted with L-929 cells, and after incubation for 24 to 26 hours, the culture was examined under a microscope (100X) to observe whether there were any abnormal cell morphology and cell lysis. The observation results showed that each wound dressing showed slight cytotoxicity to L-929 cells and was determined to meet regulatory requirements.

[0077] 2. Skin allergy test: According to the requirements of ISO10993-10 (Biological evaluation of medical devices, Part 10: Irritation and skin sensitization tests): The wound dressings obtained in Examples 1-8 and Comparative Example 1 were cut into samples of 25 mm × 25 mm × 2 mm in size, topically applied to the skin of a corresponding number of rabbits, and left for at least 23 hours. The erythema and edema of the test site were observed and recorded at 1 hour, 24 hours, 48 ​​hours and 72 hours after each sample was removed, and graded. The observation results showed that no erythema and edema were observed on the skin of the animals (rabbits) treated with each wound dressing.

[0078] 3. Hemostatic performance test: Male BALB / C mice, weighing 20±2g, were randomly divided into 9 groups according to their weight, with 20 mice in each group, and the hemostatic performance of the wound dressings obtained in Examples 1-8 and Comparative Example 1 was tested. The mice were fixed, the tails were exposed, and a 1 cm wound was cut at the tail end of the mice with a surgical blade to make them bleed. After the incision, the wound dressings obtained in each example and comparative example were quickly administered. The time when the tail end of each group of mice stopped bleeding was recorded with a timer, and the average value was taken as the hemostatic time.

[0079] 4. Wound healing performance test: Male BALB / C mice, weighing 20±2g, were randomly divided into 9 groups according to their weight, with 20 mice in each group. Each group of mice was anesthetized by intraperitoneal injection of chloral hydrate (10%), and a circular wound with a diameter of 2cm was cut on the back skin of the mice with scissors. Then 100μL of Escherichia coli (1×10 6 CFU / mL), and each wound dressing was added 30 minutes later. The drugs were administered every other day for 14 consecutive days, and the wound healing areas of each group of mice were measured on the 3rd, 7th and 14th days of administration, and the average value was taken to characterize the wound healing performance.

[0080] 5. Antibacterial performance test: The common Staphylococcus aureus was selected as the experimental bacteria for antibacterial experiments. Each wound dressing was prepared into a 12mm×12mm×2mm flat cylinder. After ultraviolet sterilization, it was placed on a plate coated with 1×10 6 CFU / mL of bacterial solution on agar medium, turn the culture dish upside down, place it in a constant temperature incubator at 37°C for 24 hours, take it out and observe the growth of the inhibition zone. The larger the diameter of the inhibition zone, the better the surface antibacterial performance.

[0081] Table 1

[0082]

[0083]

[0084] It can be seen from Table 1 that the wound dressings provided by Examples 1 to 3 of the present invention have excellent antibacterial properties, good hemostatic and healing effects, and no allergic reactions.

[0085] By comparing Example 4 and Example 5 with Example 1, it can be seen that when the amount of p-hydroxybenzoic acid added in step (1) and the amount of bronopol in step (2) are changed respectively during the preparation of grafted modified chitosan, the antibacterial properties of the wound dressing will decrease.

[0086] By comparing Example 6 and Example 7 with Example 1, it can be seen that when the addition amounts of short cotton fiber and pearl powder are changed respectively when preparing the calcium alginate composite, the balance between the air permeability and moisture retention of the wound dressing is affected, thereby affecting the comprehensive performance of the wound dressing.

[0087] By comparing Example 8 with Example 1, it can be seen that when the antibacterial carrier used is unmodified chitosan, the performance and antibacterial properties of the wound dressing are reduced, and due to the reduced moisturizing ability, the wound dressing has a poor healing effect.

[0088] From the comparison between Comparative Example 1 and Example 1, it can be seen that when the sodium alginate complex is replaced by an equal amount of sodium alginate, the comprehensive performance of the wound dressing decreases to varying degrees.

[0089] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Although the present invention has been disclosed as a preferred embodiment as above, it is not used to limit the present invention. Any technician familiar with this profession can make some changes or modifications to equivalent embodiments of equivalent changes using the technical contents disclosed above without departing from the scope of the technical solution of the present invention. However, any simple modification, equivalent change and modification made to the above embodiments based on the technical essence of the present invention without departing from the content of the technical solution of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A wound dressing that prevents drug extravasation and is antibacterial and anti-allergic, characterized in that: The wound dressing comprises the following raw materials in parts by weight: 20 to 30 parts of a composite carrier and 3 to 6 parts of a calcium alginate complex; the composite carrier is a mixture of an antibacterial carrier and cellulose fibers.

2. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 1, characterized in that: The antibacterial carrier is grafted modified chitosan.

3. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 2, characterized in that: The preparation steps of the grafted modified chitosan are as follows: (1) dissolving chitosan in acetic acid solution, adding phenolic acid monomer and mixing evenly, then adding initiator, introducing nitrogen, reacting at 40-50° C. for 8-12 h, cooling and drying, and obtaining phenolic acid modified chitosan; (2) Add bronopol to deionized water and stir evenly, add the phenolic acid modified chitosan of step (1), add a catalyst under stirring, and react at 30-40° C. for 10-13 hours to obtain the grafted modified chitosan.

4. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 3, characterized in that: In step (1), the phenolic acid monomer is p-hydroxybenzoic acid.

5. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 3, characterized in that: In step (2), the number average molecular weight of the chitosan is 8000 to 20000.

6. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 3, characterized in that: The mass ratio of the chitosan, the phenolic acid monomer and bronopol is 10:(1.4-2):(0.3-0.7).

7. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 1, characterized in that: The preparation steps of the calcium alginate complex are as follows: The short cotton fiber and sodium alginate are mixed, pearl powder and polyol are added under stirring, the mixture is stirred evenly, a spinning aid is added and electrostatic spinning is performed to obtain a calcium alginate complex.

8. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 7, characterized in that: The mass ratio of the short cotton fiber, sodium alginate and pearl powder is (0.1-0.2):1:(0.1-0.3).

9. The anti-drug extravasation and antibacterial and anti-allergic wound dressing according to claim 7, characterized in that: The spinning aid is polycaprolactone and / or polylactic acid.

10. A method for preparing the anti-drug extravasation and antibacterial and anti-allergic wound dressing according to any one of claims 1 to 9, characterized in that: The following steps are involved: The composite carrier and the sodium alginate composite are blended by a needle-punched non-woven fabric process to obtain a fabric, which is then cut, packaged and sterilized to obtain the wound dressing.

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