Polylipoic acid-based composite sponge wound dressing as well as preparation method and application thereof

Abstract

The invention discloses a polylipoic acid-based composite sponge wound dressing and a preparation method and application thereof.The preparation method comprises the following steps that polylipoic acid amide with amino is obtained through disulfide bond ring opening polymerization, and the polylipoic acid amide and an aldehyde cross-linking agent are jointly dissolved in ethyl alcohol to form a solution A; carrying out high-speed shearing, dispersing and foaming on the water-soluble polymer, and freeze-drying to form porous sponge B; the porous sponge B is soaked in the solution A to be subjected to a cross-linking reaction, vacuum drying is conducted, and the polylipoic acid-based composite sponge wound dressing is obtained. The preparation method has the characteristics of simple preparation process, safety and no toxicity, the polylipoic acid with excellent oxidation resistance is introduced into the medical sponge material, the preparation method of the polylipoic acid medical porous structure material is obtained, the oxidation resistance and the wet viscosity of the medical sponge material are improved, and the medical sponge material has good application prospects. The application of the polylipoic acid-based porous material in the fields of hemostatic materials and wound dressings is realized.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of biomedical materials, more particularly to a poly-lipoic acid-based composite sponge wound dressing and a preparation method and application thereof. BACKGROUND

[0002] Medical wound dressings are an important class of biomedical materials used to cover sores, wounds or other injuries. Traditional gauze dressings generally have the problems of single product type and function, lack of series products, and functional defects during use. With the development of medical treatment technology and the needs of patients, people have higher requirements for the performance of dressings. New dressings can keep the wound moist, accelerate wound repair, reduce wound infection, improve the cure rate, shorten the course of the disease, and reduce the pain of patients. However, in the actual use process, the traditional dressings and new dressings need to be fixed on the skin surface when they contact the skin wound, and the common means is to fix them on the skin surface by bandaging or using adhesive-coated adhesives, which has the problems of complex bandaging operation process (while consuming a large amount of bandage material), and the adhesive easily causes skin allergy, resulting in unsatisfactory wound repair effect. The self-adhesive wound dressing can be independently adhered to the skin surface, does not cause skin allergic reaction, can solve the skin surface fixation problem of the current dressing in the use process, and can improve the wound healing effect. In addition, from the aspect of wound healing mechanism, the level of reactive oxygen species (ROS) at the wound site increases after the skin is injured, causing chronic inflammation and bacterial infection. Therefore, effectively inhibiting oxidative stress and bacterial infection during wound healing has a positive significance for promoting wound healing.

[0003] Alpha-lipoic acid (LA) is a natural antioxidant small molecule and an important coenzyme of aerobic metabolism. LA has strong five-membered ring tension and can undergo ring-opening polymerization under heating conditions to form a polymer chain. The hydrogen bonds formed by the carboxyl groups endow it with excellent ductility, rapid self-healing and reversible adhesion. The introduction of LA into wound dressings can effectively scavenge excess intracellular ROS, reduce the level of reactive oxygen species (ROS) at the wound site, and significantly improve the wound healing effect. The introduction of LA into wound dressings is an effective method for preparing medical dressings. For example, patent CN202210943867.5 controls the temperature and the molar ratio of lipoic acid and sodium lipoate in water to realize the self-assembly of lipoic acid, and a lipoic acid hydrogel is prepared. Patent CN202411348069.3 uses silk fibroin grafted coffee acid to complex with lipoic acid to obtain a mussel-like poly-lipoic acid-based hydrogel adhesive, which is used as a wound dressing and is beneficial to providing a good repair environment for the wound. Patent CN202110142821.9 introduces lipoic acid into nanofibers to prepare a lipoic acid-containing dressing. Patent CN202211634034.7 uses lipoic acid to modify polyethylene glycol and silk fibroin to obtain a self-adhesive hydrogel film type wound dressing.

[0004] Sponge material with porous structure can absorb wound exudate, maintain moist environment of wound surface, and is a new type of wound dressing, mainly suitable for wound care with more exudate, such as leg ulcer, pressure sore, degree I burn, shallow degree II burn, skin donor site wound, postoperative wound and skin abrasion care, and the sponge material can also be used as a hemostatic material. The sponge dressing has the following advantages: it can quickly absorb wound exudate, reduce skin immersion around the wound; it provides a moist environment for the wound, so that the wound will not form a scab, and accelerates wound healing; it is soft, comfortable, breathable and has good plasticity, and is suitable for various parts of the body; and it does not cause secondary damage when the dressing is replaced. Common sponge dressing materials are polyvinyl alcohol, gelatin, polyurethane and the like. At present, the sponge dressing is mainly focused on simple material preparation, and the function of the dressing is single, which cannot meet the functional requirements of the wound dressing, especially the skin surface fixation problem during use of the dressing and how to inhibit the increase of the active oxygen (ROS) level at the wound site. There is no related literature and patent report on the preparation of functional sponge dressing by combining lipoic acid with sponge dressing material.

[0005] In view of the skin surface fixation problem and the problem of how to inhibit the increase of the active oxygen (ROS) level at the wound site of the existing sponge dressing material, the application provides a poly-lipoic acid-based composite sponge wound dressing. SUMMARY

[0006] The application aims to obtain a poly-lipoic acid-based composite sponge wound dressing and a preparation method thereof, which has the characteristics of simple preparation process and safety and non-toxicity, introduces poly-lipoic acid with excellent antioxidant property into the medical sponge material, and obtains a preparation method of poly-lipoic acid medical porous structure material. The poly-lipoic acid-based composite sponge material is obtained by introducing poly-lipoic acid into the porous sponge through foaming and cross-linking, the antioxidant property and wet adhesion of the sponge material are improved, and the application of the poly-lipoic acid-based porous material in the field of hemostatic materials and wound dressings is realized.

[0007] In order to achieve the above-mentioned purpose, the application adopts the following technical scheme:

[0008] A preparation method of a poly-lipoic acid-based composite sponge wound dressing, comprising the following steps:

[0009] (1) obtain poly-lipoic acid amide with amino groups by ring-opening polymerization of disulfide bond, and dissolve the poly-lipoic acid amide and an aldehyde cross-linking agent in ethanol to form a solution A;

[0010] (2) disperse and foam the water-soluble polymer by high-speed shearing, and freeze-dry to form a porous sponge B;

[0011] (3) The porous sponge B is immersed in solution A to undergo a cross-linking reaction, and the solvent is removed by vacuum drying to obtain polythiooctanoic acid composite sponge wound dressing.

[0012] The polythioctic acid-based composite sponge prepared by this invention has good antioxidant properties and wet adhesion. The polythioctic acid-based composite sponge with a porous structure has good liquid absorption and can be used as a hemostatic material and wound dressing.

[0013] Preferably, the disulfide ring-opening polymerization is carried out by directly heating a mixture of thioctic acid with a five-membered ring disulfide structure and N-ethylamine thiocamide in a certain proportion to induce disulfide ring-opening polymerization.

[0014] The synthesis route is as follows:

[0015]

[0016] Preferably, the mass ratio of thioctic acid to N-ethylamine thiocamide is (10-4):1.

[0017] Preferably, the direct heating is a reaction at 70°C for 6 hours.

[0018] Preferably, the mass concentration of polythiooctanoamide in solution A is 5%-40%, and the concentration of the aldehyde crosslinking agent is 0.1%-0.5%.

[0019] Preferably, the aldehyde crosslinking agent includes one or more of formaldehyde, glutaraldehyde, etc.

[0020] Preferably, the water-soluble polymer includes one or more of polyvinyl alcohol, gelatin, sodium alginate, and sodium carboxymethyl cellulose; the high-speed shear dispersion foaming is carried out by stirring at 2000 r / min for 1 h; and the freeze drying is carried out at -40℃ and 10 kPa.

[0021] Preferably, the crosslinking reaction is carried out at 25°C for 12 hours; the vacuum drying is carried out at 25°C and 10 kPa; and the polythiooctanoic acid content in the polythiooctanoic acid-based composite sponge wound dressing is 10%-20%.

[0022] As can be seen from the above technical solution, compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. This invention obtains an amino-containing polythioctic acid amide by directly heating a mixture of thioctic acid with a five-membered ring disulfide structure and N-ethylamine thioctic amide in a certain proportion to induce disulfide ring-opening polymerization. This amide is then introduced into medical sponge materials and crosslinked to obtain polythioctic acid-based composite sponges. This process prepares a polythioctic acid-functionalized porous material, achieving thioctic acid modification of porous sponge materials and significantly improving the wet tack of porous sponge materials.

[0024] 2. The polythioctic acid-based composite sponge of the present invention is safe and non-toxic, does not harm the skin, and has good antioxidant properties, wet adhesion, and good liquid absorption. It can be used as a hemostatic material and wound dressing.

[0025] 3. The polythioctic acid-based composite sponge of the present invention is prepared by foaming and molding followed by soaking and crosslinking, which realizes the preparation of polythioctic acid porous materials. The process is simple, the preparation process is reliable, and the material properties are adjustable. Attached Figure Description

[0026] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0027] Figure 1 Photograph of the polythiooctanoic acid-based composite gelatin sponge material prepared according to the present invention. Detailed Implementation

[0028] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0029] Example 1: Synthesis of amino-containing polythioctic amide and preparation of solution A

[0030] Weigh 5g of lipoic acid and 1g of N-ethylamine lipoamide, mix them evenly, and place them in a 70℃ oven to react for 6 hours to form a yellow transparent gel. After cooling to room temperature, add 30g of anhydrous ethanol and let it stand for 24 hours to form a yellow solution. Add 0.1g of formaldehyde solution and mix evenly to form a solution, which is denoted as A1.

[0031] Weigh 5g of lipoic acid and 2g of N-ethylamine lipoamide, mix them evenly, and place them in a 70℃ oven to react for 6 hours to form a yellow transparent gel. After cooling to room temperature, add 30g of anhydrous ethanol and let it stand for 24 hours to form a yellow solution. Add 0.2g of formaldehyde solution and mix evenly to form a solution, which is denoted as A2.

[0032] Weigh 7g of lipoic acid and 1g of N-ethylamine lipoamide, mix them evenly, and place them in a 70℃ oven to react for 6h to form a yellow transparent gel. After cooling to room temperature, add 30g of anhydrous ethanol and let stand for 24h to form a yellow solution. Add 0.1g of formaldehyde solution and mix evenly to form a solution, which is denoted as A3.

[0033] Weigh 5g of lipoic acid and 1g of N-ethylamine lipoamide, mix them evenly, and place them in a 70℃ oven to react for 6 hours to form a yellow transparent gel. After cooling to room temperature, add 40g of anhydrous ethanol and let it stand for 24 hours to form a yellow solution. Add 0.2g of formaldehyde solution and mix evenly to form a solution, which is denoted as A4.

[0034] Weigh 7g of lipoic acid and 1g of N-ethylamine lipoamide, mix them evenly, and place them in a 70℃ oven to react for 6h to form a yellow transparent gel. After cooling to room temperature, add 40g of anhydrous ethanol and let stand for 24h to form a yellow solution. Add 0.1g of glutaraldehyde solution and mix evenly to form a solution, which is denoted as A5.

[0035] Dissolve 0.1g of formaldehyde in 30g of ethanol to form a solution, denoted as A6.

[0036] Example 2: Preparation of polythiooctanoic acid-based composite sponge

[0037] Weigh 5g of gelatin (Gel 200) and add 50g of deionized water. Dissolve the gelatin in a 50℃ water bath and freeze it in a -70℃ refrigerator for 12 hours. Then, freeze it in a freeze dryer to obtain a sponge B with a porous structure. Immerse sponge B in solution A1 for a crosslinking reaction for 12 hours. Remove the ethanol by vacuum drying to obtain a polythiooctanoic acid composite sponge, denoted as S1.

[0038] Example 3: Preparation of polythiooctanoic acid-based composite sponge

[0039] Weigh 2.5g of gelatin (Gel 200) and add 50g of deionized water. Dissolve the gelatin in a 50℃ water bath and freeze it in a -70℃ freezer for 12 hours. Then, freeze it in a freeze dryer to obtain a sponge B with a porous structure. Immerse sponge B in solution A2 for a crosslinking reaction for 12 hours. Remove the ethanol by vacuum drying to obtain a polythioctic acid composite sponge, denoted as S2.

[0040] Example 4: Preparation of polythiooctanoic acid-based composite sponge

[0041] Weigh 5g of polyvinyl alcohol (brand name PVA 1788) and add 50g of deionized water. Dissolve the polyvinyl alcohol by heating in a water bath at 50℃ and freeze it in a -70℃ refrigerator for 12 hours. Then, freeze it in a freeze dryer to obtain a sponge B with a porous structure. Immerse the sponge B in solution A3 for a crosslinking reaction for 12 hours and remove the ethanol by vacuum drying to obtain a polythioctic acid composite sponge, denoted as S3.

[0042] Example 5: Preparation of polythiooctanoic acid-based composite sponge

[0043] Weigh 5g of polyvinyl alcohol (brand name PVA 1799) and add 50g of deionized water. Dissolve the polyvinyl alcohol by heating in a water bath at 50℃ and freeze it in a -70℃ refrigerator for 12 hours. Then, freeze it in a freeze dryer to obtain a sponge B with a porous structure. Immerse the sponge B in solution A4 for a crosslinking reaction for 12 hours and remove the ethanol by vacuum drying to obtain a polythioctic acid composite sponge, denoted as S4.

[0044] Example 6: Preparation of polythiooctanoic acid-based composite sponge

[0045] Weigh 5g of gelatin (Gel 180) and add 50g of deionized water. Dissolve the gelatin in a 50℃ water bath and freeze it in a -70℃ freezer for 12 hours. Then, freeze it in a freeze dryer to obtain a sponge B with a porous structure. Immerse sponge B in solution A5 for a crosslinking reaction for 12 hours and remove ethanol by vacuum drying to obtain a polythiooctanoic acid composite sponge, denoted as S5.

[0046] Example 7: Preparation of polythiooctanoic acid-based composite sponge

[0047] Weigh 5g of gelatin (Gel 140) and add 50g of deionized water. Dissolve the gelatin in a 50℃ water bath and freeze it in a -70℃ freezer for 12 hours. Then, freeze it in a freeze dryer to obtain a sponge B with a porous structure. Immerse sponge B in solution A1 for a crosslinking reaction for 12 hours and remove ethanol by vacuum drying to obtain a polythiooctanoic acid composite sponge, denoted as S6.

[0048] Comparative Example 1: Preparation of Gelatin Sponge

[0049] Compared with Examples 1 and 2, 5g of gelatin (Gel-Force 180) was weighed and added to 50g of deionized water. It was dissolved by heating in a water bath at 50°C and placed in a freezer at -70°C for 12 hours. Then, it was placed in a freeze dryer and processed by freeze-drying to obtain a sponge B with a porous structure. It was then immersed in solution A6 for a cross-linking reaction for 12 hours and vacuum dried to remove ethanol to obtain a gelatin sponge, which was denoted as D1.

[0050] Comparative Example 2: Preparation of Polyvinyl Alcohol Sponge

[0051] Compared with Examples 1 and 4, 5g of polyvinyl alcohol (brand name PVA 1788) was weighed and added to 50g of deionized water. The mixture was dissolved by heating in a water bath at 50°C and then frozen in a freezer at -70°C for 12 hours. The mixture was then placed in a freeze dryer and processed by freeze drying to obtain a sponge B with a porous structure. The sponge B was then immersed in solution A6 for a crosslinking reaction for 12 hours and vacuum dried to remove ethanol to obtain a polyvinyl alcohol sponge, denoted as D2.

[0052] Method for testing the liquid absorption ratio of sponge materials

[0053] Accurately weigh the sponge (m0), completely immerse the sample in PBS solution with a pH of 7.4, and shake in a shaking water bath (37℃, 100 rpm) for 30 min. After removing excess water from the sample surface, weigh the sample (mt). Each material was tested in triplicate, and the liquid absorption ratio of the sponge was calculated as mt / m0 (g / g).

[0054] Wet tack test method for sponge materials

[0055] The adhesion of materials to tissues was determined using a pigskin adhesion test. Pigskin was purchased from a supermarket; before use, as much surface fat as possible was removed, and the pigskin was then cut into 2cm x 2cm pieces. The pigskin was then glued together...

[0056] The hemostatic material was adhered to two T-shaped aluminum plates respectively. Before testing, the two aluminum plates were brought into contact and fixed to a fixture. The test was conducted at a tensile speed of 5 mm / min. The adhesion performance of the hemostatic material was determined by calculating the modulus at maximum load. The test results are shown in Table 1.

[0057] Table 1

[0058] Sample No. Amino polythioctic acid amide Sponge B Liquid absorption capacity (g / g) Wet tack (kPa) Example 2 S1 6 5 (gelatin) 23.5 23.6 Example 3 S2 7 2.5 (gelatin) 27.5 30.1 Example 4 S3 8 5 (PVA) 21.8 25.5 Example 5 S4 6 5 (PVA) 23.2 21.3 Example 6 S5 8 5 (gelatin) 25.1 24.3 Example 7 S6 6 5 (gelatin) 24.6 22.1 Comparative Example 1 D1 0 Gelatin sponge 25.7 0 Comparative Example 2 D2 0 PVA sponge 24.1 0

[0059] As shown in the table above, the wet tack of the comparative sponge material is 0 kPa, while the wet tack of the polythiooctanoic acid-based composite sponge material is significantly improved and increases with the increase of polythiooctanoic acid content. The liquid absorption ratio of the polythiooctanoic acid-based composite sponge material is still above 20 g / g, indicating good liquid absorption.

[0060] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. For the apparatus disclosed in the embodiments, since it corresponds to the method disclosed in the embodiments, the description is relatively simple; relevant parts can be referred to the method section.

[0061] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a polythiooctanoic acid-based composite sponge wound dressing, characterized in that, Includes the following steps: (1) A polythiooctanoic acid amide with an amino group was obtained by ring-opening polymerization of disulfide bonds, and then dissolved in ethanol with an aldehyde crosslinking agent to form solution A; (2) Water-soluble polymers are dispersed and foamed by high-speed shearing and then freeze-dried to form porous sponge B; (3) The porous sponge B is immersed in solution A to undergo a cross-linking reaction, and then vacuum dried to obtain a polythiooctanoic acid-based composite sponge wound dressing.

2. The method for preparing a polythiooctanoic acid-based composite sponge wound dressing according to claim 1, characterized in that, The disulfide ring-opening polymerization is carried out by directly heating a mixture of thioctic acid with a five-membered ring disulfide structure and N-ethylamine thiocamide in a certain proportion to induce disulfide ring-opening polymerization. The synthesis route is as follows:

3. The method for preparing a polythiooctanoic acid-based composite sponge wound dressing according to claim 2, characterized in that, The mass ratio of thioctic acid to N-ethylamine thiocamide is (10-4):

1.

4. The method for preparing a polythiooctanoic acid-based composite sponge wound dressing according to claim 2, characterized in that, The direct heating refers to reacting at 70°C for 6 hours.

5. The method for preparing a polythiooctanoic acid-based composite sponge wound dressing according to claim 1, characterized in that, The mass concentration of polythiooctanoamide in solution A is 5%-40%, and the concentration of the aldehyde crosslinking agent is 0.1%-0.5%.

6. The method for preparing a polythiooctanoic acid-based composite sponge wound dressing according to claim 1, characterized in that, The aldehyde crosslinking agent includes one or more of formaldehyde and glutaraldehyde.

7. The method for preparing a polythiooctanoic acid-based composite sponge wound dressing according to claim 1, characterized in that, The water-soluble polymer includes one or more of polyvinyl alcohol, gelatin, sodium alginate, and sodium carboxymethyl cellulose; the high-speed shear dispersion foaming is carried out by stirring at 2000 r / min for 1 h; the freeze drying is carried out at -40℃ and 10 kPa.

8. The method for preparing a polythiooctanoic acid-based composite sponge wound dressing according to claim 1, characterized in that, The crosslinking reaction is carried out at 25°C for 12 hours; the vacuum drying is carried out at 25°C and 10 kPa; the polythioctic acid content in the polythioctic acid-based composite sponge wound dressing is 10%-20%.

9. A polythiooctanoic acid-based composite sponge wound dressing, characterized in that, It is prepared by the preparation method according to any one of claims 1-8.

10. The application of the polythiooctanoic acid-based composite sponge wound dressing as described in claim 9 in hemostatic materials and wound dressings.

Images