Sprayable hydrogel and application thereof

Abstract

The invention relates to the technical field of wound treatment and sprayable hydrogel preparations, in particular to sprayable hydrogel and application thereof. The sprayable hydrogel comprises a first spraying agent and a second spraying agent, and the first spraying agent and the second spraying agent are alternately sprayed to form the hydrogel; the first spray is an aqueous solution of an amino-containing substance; the second spraying agent is an aqueous solution of an aldehyde group-containing substance; the pH of the first spraying agent and the pH of the second spraying agent are both 7.5-8.5; the amino-containing substance is gelatin or carboxylated chitosan. The invention further discloses application of the sprayable hydrogel to preparation of a hydrogel preparation for irregular wound healing. By adjusting the concentration of the gelatin solution and the dialdehyde cellulose solution, the mechanical strength of the hydrogel is improved on the basis of improving the gel forming speed of the hydrogel, and the problems of low gel forming speed and insufficient mechanical strength of the existing sprayable hydrogel are solved.

Description

Technical Field

[0001] The present invention relates to the technical field of wound treatment and sprayable hydrogel preparations, and particularly relates to a sprayable hydrogel and its uses. Background Art

[0002] In the field of wound treatment, the selection of wound dressings and drugs plays a crucial role in accelerating wound healing and reducing the risk of infection. With the development of biomedical materials, hydrogels have gradually become an important wound treatment material due to their good biocompatibility, moisturizing ability, and drug-carrying function. Especially in the care of wounds such as surgical operations, burns, and ulcers, hydrogels can form a physical barrier on the wound surface by constructing a three-dimensional network structure, effectively protecting the wound surface from external contamination and promoting healing.

[0003] However, there are still many problems in the actual application of current hydrogel products on the market. For example, traditional hydrogels often need to be formed into stable hydrogels by means of ultraviolet light curing or the action of chemical cross-linking agents such as glutaraldehyde. However, this process results in a slow gelation rate of the product and requires specific operating environments or equipment support, making it impossible to be quickly applied to the wound surface in emergency situations. In addition, many existing hydrogel products exist in the form of blocks or sheets, which are not only inconvenient to carry, but also difficult to flexibly adapt to complex and variable wound shapes. Especially when dealing with large-area and irregular wounds, it is particularly difficult. Moreover, in actual use, it often needs to directly contact the wound for smearing, which not only increases the pain of the patient, but also may increase the risk of wound infection.

[0004] Based on this, some researchers have proposed an innovative sprayable hydrogel technology. However, the current sprayable hydrogels have problems such as slow gelation rate and insufficient mechanical strength. Summary of the Invention

[0005] In order to solve the problems of slow gelation rate and insufficient mechanical strength of the current sprayable hydrogels, the purpose of the present invention is to provide a sprayable hydrogel and its uses, so as to improve the mechanical strength on the basis of increasing the gelation rate of the hydrogel.

[0006] To achieve the above purpose, the technical solution of the present invention is as follows.

[0007] The first aspect of the present invention provides a sprayable hydrogel, which includes a first spray and a second spray. By alternately spraying the first spray and the second spray, a hydrogel is formed. The first spray is an aqueous solution of a substance containing amino groups; the second spray is an aqueous solution of a substance containing aldehyde groups. The pH values of both the first spray and the second spray are 7.5 - 8.5. The substance containing amino groups is gelatin or carboxylated chitosan; the substance containing aldehyde groups is dialdehyde cellulose. The mass percentage of the substance containing amino groups in the first spray is 1.9 wt% - 12 wt%; the mass percentage of the substance containing aldehyde groups in the second spray is 3.8 wt% - 6 wt%.

[0008] The present invention mainly uses an aqueous solution of a substance containing amino groups and an aqueous solution of a substance containing aldehyde groups as two sprays. By alternately spraying, a Schiff base reaction occurs to form a hydrogel. The present invention adjusts the concentrations and pH values of the aqueous solution of the substance containing amino groups and the aqueous solution of the substance containing aldehyde groups to shorten the gelation time of the hydrogel to be between 2 min and 3 min. On the basis of improving the gelation speed of the hydrogel, the mechanical strength of the hydrogel is enhanced. Moreover, the sprayable hydrogel of the present invention has good fluidity and ductility, can automatically adapt to and cover irregular wounds, ensure that the wounds are fully protected, promote healing, and solve the problems of slow gelation speed and insufficient mechanical strength existing in the current sprayable hydrogels.

[0009] Preferably, when the first spray is a gelatin solution, the mass percentage of gelatin in the gelatin solution is 8 wt% - 12 wt%. Further preferably, the mass percentage of gelatin in the gelatin solution is 10 wt%; the mass percentage of dialdehyde cellulose in the second spray is 3 wt% - 5 wt%. The present invention improves the fluidity and ductility of the gelatin solution and the dialdehyde cellulose solution by adjusting their concentrations to automatically adapt to and cover irregular wounds and promote the healing of irregular wounds.

[0010] Preferably, when the first spray is a carboxylated chitosan solution, the mass percentage of carboxylated chitosan in the carboxylated chitosan solution is 1.9 wt% - 4 wt%.

[0011] Preferably, the pH of the gelatin solution is 8 - 8.5; the pH of the dialdehyde cellulose solution is 8 - 8.5. In the range of 8 - 8.5 for pH, the influence on the gelation time of the hydrogel is not significant.

[0012] Preferably, the gelatin solution is obtained by mixing gelatin and water and then adjusting the pH to 8 - 8.5; the dialdehyde cellulose solution is obtained by mixing dialdehyde cellulose and water and then adjusting the pH to 8 - 8.5. By adjusting the gelatin solution and the dialdehyde cellulose solution with different concentrations, the gelation time of the hydrogel is controlled.

[0013] Preferably, the specific preparation method of the dialdehyde cellulose solution is as follows:

[0014] React microcrystalline cellulose, sodium periodate and water in the dark, then add ethylene glycol, mix and centrifuge. After the obtained precipitate is washed with water, it is freeze-dried to obtain dialdehyde cellulose; the dialdehyde cellulose is mixed evenly with water, and then the pH is adjusted to 8-8.5 to obtain a dialdehyde cellulose solution.

[0015] Preferably, the dosage ratio of microcrystalline cellulose, sodium periodate and water is 7g-13g: 12g-20g: 500 mL.

[0016] Preferably, the dosage ratio of microcrystalline cellulose to ethylene glycol is 7g-13g: 6mL-10mL.

[0017] Preferably, the time for forming the hydrogel is 120s-160s. In existing research, the gelation time of dialdehyde cellulose and gelatin is generally about 10 min, and the gelation time is too long. Based on this, the present invention adjusts the concentration and pH value of the two to shorten the gelation time to between 120s and 160s, and can improve the mechanical strength of the hydrogel on the basis of increasing the gelation speed of the hydrogel.

[0018] Preferably, the number of times of alternately spraying the first spray and the second spray is 1-5 times. The present invention does not limit the number of times of alternate spraying, which can be selected according to the size of the wound surface.

[0019] The second aspect of the present invention provides the use of the sprayable hydrogel of gelatin and dialdehyde cellulose described in the first aspect in the preparation of a hydrogel preparation for irregular wound healing. The present invention prepares and forms a gelatin spray and a dialdehyde cellulose spray. By mixing gelatin and dialdehyde cellulose in a specific ratio, it is ensured that the hydrogel can quickly form a gel after spraying, and a stable gel layer can be formed in a short time. The product of the present invention can be applied to the healing of irregular wounds, and the product is light and easy to carry, and is suitable for carrying around outdoors or in emergency rescue. Using a non-contact spray application method can reduce the pain of patients, and is particularly suitable for the treatment of sensitive parts or severe wounds.

[0020] The beneficial effects of the present invention:

[0021] 1. The present invention mainly uses an aqueous solution of an amino - containing substance and an aqueous solution of an aldehyde - containing substance as two sprays. Through alternating spraying, a Schiff base reaction occurs to form a hydrogel. By adjusting the concentrations and pH values of the aqueous solution of the amino - containing substance and the aqueous solution of the aldehyde - containing substance, the gelation time of the hydrogel is shortened to be between 2 min and 3 min. On the basis of improving the gelation speed of the hydrogel, the mechanical strength of the hydrogel is enhanced. Moreover, the sprayable hydrogel of the present invention has good fluidity and ductility, can automatically adapt to and cover irregular wounds, ensuring that the wounds are comprehensively protected and promoting healing, and solving the problems of slow gelation speed and insufficient mechanical strength existing in the current sprayable hydrogels.

[0022] 2. Through the Schiff base reaction, the present invention realizes rapid gelation, can form a stable hydrogel network in a short time, and improves the efficiency of wound treatment. The present invention is designed in a spray form, which can simplify the usage process, without the need for additional mixing or activation steps, and is convenient to use without professional equipment or personnel. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is the stress - strain curves of four groups of hydrogels of Example 2, Example 3, Example 11 and Example 12.

[0024] Figure 2 It is the test result diagram of the Young's modulus of four groups of hydrogels of Example 2, Example 3, Example 11 and Example 12.

[0025] Figure 3 It is a photo of the hydrogel formed by alternately spraying the first spray and the second spray of Example 2 on the surface of a petri dish. Among them, (a) is a top - view schematic diagram; (b) is a side - view schematic diagram. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0026] In order to make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the following further describes the present invention in detail with reference to embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0027] Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the scope of protection of the present invention.

[0028] Existing hydrogel products still have some problems in practical applications, such as slow gelation speed, complex operation, inconvenient use for patients, and difficulty in treating irregular wounds. Therefore, it is of great clinical significance to study a hydrogel that can rapidly gel, is easy to use, convenient to carry, and suitable for treating large - area irregular wounds.

[0029] Existing hydrogel products are mainly based on natural or synthetic polymer materials and form a three-dimensional network structure through physical or chemical cross-linking for wound care. Traditional hydrogels, such as those based on sodium carboxymethyl cellulose and polyvinyl alcohol, usually require complex physical mixing or chemical cross-linking steps to achieve gelation. For example, stable gel structures are formed through ultraviolet light irradiation, freeze-thaw cycles, or the action of chemical cross-linking agents such as glutaraldehyde. These operation steps are cumbersome, may require specific equipment or environments, and the gelation process may take a long time. In addition, traditional hydrogels mostly exist in block or sheet forms, are not suitable for carrying around, and are difficult to be quickly applied to large-area irregular wounds, especially in emergency rescue.

[0030] It can be seen from this that although the existing hydrogel technology meets the needs of wound care to a certain extent, there are still the above-mentioned deficiencies, and there is an urgent need to develop a more efficient and convenient hydrogel product. First of all, in terms of structural design, existing hydrogels are usually prepared by physical mixing or chemical cross-linking. These steps are complex and time-consuming, resulting in a slow gelation speed of the product and unable to be quickly applied to the wound in an emergency. In addition, many existing hydrogel products exist in block or sheet forms, are difficult to adapt to irregular wounds, and often need to be directly applied to the wound during actual use, which not only increases the pain of the patient but also may increase the risk of wound infection.

[0031] In contrast, the sprayable hydrogel of the present invention can achieve rapid gelation through optimized formulation and structural design, and adopts a non-contact spray application method, solving problems such as slow gelation, complex use, and patient pain. At the same time, its good fluidity and ductility enable it to adapt to and cover various irregular wounds. At the same time, the materials used in the present invention are mainly cellulose, which is simple to obtain and low in cost.

[0032] In this context, the present invention proposes an innovative sprayable hydrogel technology. Through elaborate formulation design and structural optimization, this technology realizes the rapid gelation of the hydrogel and innovatively adopts a spray application method, completely abandoning the cumbersome and inconvenient traditional smearing. This non-contact application method not only reduces the pain of the patient but also greatly reduces the infection risk. At the same time, the sprayable hydrogel of the present invention has good fluidity and ductility, can easily cover and fit various complex wounds, providing a more efficient, convenient, and user-friendly solution for wound care. In addition, the present invention uses cellulose as the main material, which not only has a wide source and low cost but also further improves the biocompatibility and environmental friendliness of the product.

[0033] The technical solution of the present invention is further described below by means of specific examples. In the following examples, the methods described are conventional methods unless otherwise specified; the reagents and materials described are commercially available unless otherwise specified.

[0034] In the following embodiments, the full English name of dialdehyde cellulose is Dialdehyde Cellulose, abbreviated as DAC. The full English name of gelatin is Gelatin, abbreviated as Gel.

[0035] In the following examples, the reagent used to adjust the pH is 1 mol / L NaOH solution or 1 mol / L HCl solution. Gelatin, Sigma-Aldrich, CAS: 9000-70-8. Microcrystalline cellulose, Sigma-Aldrich, CAS: 9004-34-6. Sodium periodate, AR, Sinopharm Chemical Reagent Co., Ltd. Ethylene glycol, AR, Aladdin, CAS: 107-21-1.

[0036] Example 1

[0037] A sprayable hydrogel of gelatin and dialdehyde cellulose comprises a first spray and a second spray, wherein the first spray is a gelatin solution, which is prepared by adding gelatin to deionized water, stirring until the solution is uniform, and adjusting the pH to 8 to obtain a gelatin solution; wherein the mass percentage of gelatin in the gelatin solution is 10.7wt%; and the obtained gelatin solution is put into a first spray bottle for standby use.

[0038] The second spray is a dialdehyde cellulose solution, and the specific preparation method of the dialdehyde cellulose solution is as follows: add 10g of microcrystalline cellulose and 18g of sodium periodate to 500mL of deionized water, stir with a magnetic stirrer and react in the dark for 72h, then add 8mL of ethylene glycol and continue stirring for 2h; centrifuge the obtained solution with a centrifuge, the centrifugation time is 3min, the speed is 4300rpm, the obtained precipitate is washed with deionized water 3 times, freeze the washed precipitate in a refrigerator for 12h, then use a freeze dryer to dry for 24h, grind into powder, and obtain dialdehyde cellulose powder; record as DAC powder. Add DAC powder to deionized water, stir until the solution is uniform, adjust the pH to 8, and obtain a dialdehyde cellulose solution; the mass percentage of dialdehyde cellulose in the second spray is 5.7wt%; put the obtained dialdehyde cellulose solution into the second spray bottle for standby use.

[0039] Spray once alternately with the first spray and the second spray to form a hydrogel.

[0040] Example 2

[0041] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed into a hydrogel by alternately spraying the first spray and the second spray once.

[0042] The first spray and the second spray of Example 2 are substantially the same as those of Example 1. Specifically, the differences are that the first spray is a gelatin solution with a pH of 8 and a concentration of 10 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 5 wt%.

[0043] Example 3

[0044] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed into a hydrogel by alternately spraying the first spray and the second spray once.

[0045] The first spray and the second spray of Example 3 are substantially the same as those of Example 1. Specifically, the differences are that the first spray is a gelatin solution with a pH of 8 and a concentration of 10 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 3 wt%.

[0046] Example 4

[0047] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed into a hydrogel by alternately spraying the first spray and the second spray once.

[0048] The first spray and the second spray of Example 4 are substantially the same as those of Example 1. Specifically, the differences are that the first spray is a gelatin solution with a pH of 8 and a concentration of 10 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 1 wt%.

[0049] Example 5

[0050] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed into a hydrogel by alternately spraying the first spray and the second spray once.

[0051] The first spray and the second spray of Example 5 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8 and a concentration of 5 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 5 wt%.

[0052] Example 6

[0053] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0054] The first spray and the second spray of Example 6 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8 and a concentration of 5 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 3 wt%.

[0055] Example 7

[0056] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0057] The first spray and the second spray of Example 7 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8 and a concentration of 5 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 1 wt%.

[0058] Example 8

[0059] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0060] The first spray and the second spray of Example 8 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8 and a concentration of 20 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 5 wt%.

[0061] Example 9

[0062] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed by alternately spraying the first spray and the second spray once.

[0063] The first spray and the second spray of Example 9 are substantially the same as those of Example 1. Specifically, the differences are as follows: the first spray is a gelatin solution with a pH of 8 and a concentration of 20 wt%. The second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 3 wt%.

[0064] Example 10

[0065] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed by alternately spraying the first spray and the second spray once.

[0066] The first spray and the second spray of Example 10 are substantially the same as those of Example 1. Specifically, the differences are as follows: the first spray is a gelatin solution with a pH of 8 and a concentration of 20 wt%. The second spray is a dialdehyde cellulose solution with a pH of 8 and a concentration of 1 wt%.

[0067] Example 11

[0068] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed by alternately spraying the first spray and the second spray once.

[0069] The first spray and the second spray of Example 11 are substantially the same as those of Example 1. Specifically, the differences are as follows: the first spray is a gelatin solution with a pH of 8.5 and a concentration of 10 wt%. The second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 5 wt%.

[0070] Example 12

[0071] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, is formed by alternately spraying the first spray and the second spray once.

[0072] The first spray and the second spray of Example 12 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 10 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 3 wt%.

[0073] Example 13

[0074] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0075] The first spray and the second spray of Example 13 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 10 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 1 wt%.

[0076] Example 14

[0077] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0078] The first spray and the second spray of Example 14 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 5 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 5 wt%.

[0079] Example 15

[0080] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0081] The first spray and the second spray of Example 15 are basically the same as the first spray and the second spray of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 5 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 3 wt%.

[0082] Example 16

[0083] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0084] The first spray and the second spray of Example 16 are substantially the same as the first spray and the second spray of Example 1. The specific difference is that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 5 wt%. The second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 1 wt%.

[0085] Example 17

[0086] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0087] The first spray and the second spray of Example 17 are substantially the same as the first spray and the second spray of Example 1. The specific difference is that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 20 wt%. The second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 5 wt%.

[0088] Example 18

[0089] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0090] The first spray and the second spray of Example 18 are substantially the same as the first spray and the second spray of Example 1. The specific difference is that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 20 wt%. The second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 3 wt%.

[0091] Example 19

[0092] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray. By alternately spraying the first spray and the second spray once, a hydrogel is formed.

[0093] The first and second sprays of Example 19 are basically the same as the first and second sprays of Example 1. The specific differences are that the first spray is a gelatin solution with a pH of 8.5 and a concentration of 20 wt%, and the second spray is a dialdehyde cellulose solution with a pH of 8.5 and a concentration of 1 wt%.

[0094] The time for forming hydrogels in the above examples was compared to explore the influence of the concentrations of the two sprays under different pH conditions on the time for forming hydrogels. The results are shown in Tables 1 and 2.

[0095] Table 1 Influence of the concentrations of the two sprays on the time for forming hydrogels at pH = 8

[0096] Concentration of Gel solution Concentration of DAC solution pH Time to form hydrogel Example 1 10.7wt% 5.7wt% 8 160s Example 2 10wt% 5wt% 8 2 min Example 3 10wt% 3wt% 8 137s Example 4 10wt% 1wt% 8 5 min Example 5 5wt% 5wt% 8 14 min Example 6 5wt% 3wt% 8 17 min Example 7 5wt% 1wt% 8 30 min Example 8 20wt% 5wt% 8 30s Example 9 20wt% 3wt% 8 1 min Example 10 20wt% 1wt% 8 2 min

[0097] Table 2 Influence of the concentrations of the two sprays on the time for forming hydrogels at pH = 8.5

[0098]

[0099]

[0100] Note: pH represents the pH values of the Gel solution and the DAC solution.

[0101] It can be seen from the results in Tables 1 and 2 that under the conditions of the same pH and the same concentration of the Gel solution, as the concentration of the DAC solution decreases, the time for forming hydrogels gradually increases. Under the conditions of the same pH and the same concentration of the DAC solution, as the concentration of the Gel solution decreases, the time for forming hydrogels gradually increases. Under the conditions of the same concentration of the Gel solution and the same concentration of the DAC solution, the influence of the pH of the solution on the time for forming hydrogels can be ignored. This shows that by appropriately increasing the concentrations of the Gel solution and the DAC solution, the gelation time of the hydrogel can be significantly shortened.

[0102] However, it was found during the experiment that when the concentration of the Gel solution is 20 wt%, the Gel solution sprays out as a linear solution rather than a misty solution in the first spray bottle, and the formed hydrogel is uneven rather than a uniform network structure.

[0103] When the concentration of the Gel solution is 5 wt%, the gelation time is too slow; therefore, the concentration of the Gel solution is preferably 10 wt% - 10.7 wt%.

[0104] When the concentration of the DAC solution is 1 wt%, the gelation time is relatively slow; when the concentration of the DAC solution is between 3 wt% and 5 wt%, the gelation time meets the usage requirements; as the concentration of the DAC solution further increases, that is, when the concentration of the DAC solution is greater than 5 wt%, it may lead to poor biosafety. Therefore, in the embodiments of the present invention, the concentration of the DAC solution is preferably 3 wt% - 5 wt%.

[0105] It should be noted that in the embodiments of the present invention, a sprayable hydrogel with a gelation time of 2 min - 3 min is preferably selected. This is mainly because when the concentration of gelatin is too high, the hydrogel precursor obtained is linearly sprayed rather than atomized, and the prepared hydrogel is uneven and has a non-uniform network structure, resulting in a decline in the properties of the hydrogel. Therefore, a concentration ratio with a relatively slower gelation speed, between 2 min and 3 min, but better sprayability and gelation performance is selected as the hydrogel of the present invention.

[0106] Example 20

[0107] A sprayable hydrogel of gelatin and dialdehyde cellulose, comprising a first spray and a second spray, and the hydrogel is formed by alternately spraying the first spray and the second spray once.

[0108] The first spray and the second spray of Example 20 are basically the same as those of Example 2. The specific differences are that the first spray is a gelatin solution, the pH of the gelatin solution is 7 - 9, and the concentration of the gelatin solution is 10 wt%. The second spray is a dialdehyde cellulose solution, the pH of the dialdehyde cellulose solution is 7 - 9, and the concentration of the dialdehyde cellulose solution is 5 wt%.

[0109] The gelation time of the hydrogel formed in the above examples was compared to explore the influence of different pH conditions on the gelation time. The results are shown in Table 3.

[0110] Table 3 Influence of different pH on the gelation time

[0111] Number Concentration of Gel solution Concentration of DAC solution pH Time to form hydrogel A1 10wt% 5wt% 7.0 / A2 10wt% 5wt% 7.5 8 min A3 10wt% 5wt% 8.0 2 min A4 10wt% 5wt% 8.5 150s A5 10wt% 5wt% 9.0 /

[0112] Note: pH represents the pH values of the Gel solution and the DAC solution.

[0113] According to experimental analysis, the smaller the pH value, the slower the time to form the hydrogel. Therefore, in the embodiments of the present invention, the gelation time analysis was carried out at pH = 7.5 - 8.5. When pH = 7.5, the gelation time was too slow; when pH = 8 - 8.5, the gelation time was between 120 s and 150 s, which had met the usage requirements. With the further increase of the pH value, that is, when pH > 8.5, the too high pH value made the hydrogel in an alkaline condition, which was likely to cause discomfort to the wound or human skin. Therefore, in the embodiments of the present invention, the pH value of the hydrogel was preferably in the range of pH = 8.0 - 8.5.

[0114] Based on the above analysis, it can be known that the pH of the Gel solution and the DAC solution is preferably 8 - 8.5; the concentration of the Gel solution is preferably 10 wt% - 10.7 wt%, and the concentration of the DAC solution is preferably 3 wt% - 5 wt%.

[0115] Mechanical property tests were carried out on the four groups of hydrogels prepared in Example 2, Example 3, Example 11, and Example 12. A universal material testing machine was used for the mechanical property test. The hydrogel sample was prepared into a cube of 13 mm × 13 mm × 13 mm as the specimen. The range of the universal material testing machine used for the test was 100 N, and the compression speed was set to 1 mm·min -1 , select a suitable fixture and install it on the universal material testing machine, then fix the specimen in the fixture to ensure the accurate position and alignment of the specimen. After that, set the test parameters and termination conditions on the control panel or software interface. Start the test, and the equipment will start applying the load according to the set parameters. During the test, observe the corresponding stress-strain curve and compressive strength. After the test, record and save the test data.

[0116] The stress-strain curves of the four groups of hydrogels are as Figure 1 . The Young's moduli of the four groups of hydrogels are as Figure 2 . According to Figure 1 and Figure 2 the mechanical property test results were obtained, as shown in Table 4.

[0117] Table 4 Mechanical property test results of four groups of hydrogels

[0118] Hydrogel Yield strength / kPa Tensile strength / kPa Young's modulus / kPa Example 2 1.5688±0.1857 167.52±46.85 32.90±0.76 Example 3 0.96±0.11 142.12±14.35 22.56±1.91 Example 11 1.21±0.03 112.01±16.01 30.66±0.79 Example 12 0.92±0.05 151.39±36.19 20.08±0.83

[0119] According to the results in Table 4, it can be known that there is no obvious difference in the yield strength and tensile strength of the 4 composite hydrogels, and the yield strength of the material is independent of pH and only related to the concentration of the material. When the concentration of DAC is increased from 3% to 5%, the demonstration modulus is significantly improved.

[0120] The first spray and the second spray of Example 2 were alternately sprayed on the surface of the culture dish to form a hydrogel, as Figure 3 shown. Figure 3It is a photograph of the hydrogel formed by alternately spraying the first spray and the second spray of Example 2 on the surface of a petri dish. Among them, (a) is a top view schematic diagram; (b) is a side view schematic diagram.

[0121] It can be seen from Figure 3 that by adjusting the concentrations and pH values of the gelatin solution and the dialdehyde cellulose solution, the hydrogel can quickly gel after spraying, achieving the formation of a stable gel layer within a short time. It is speculated from this that the method of using the gelatin solution and the dialdehyde cellulose solution as two sprays and forming a hydrogel by alternating spraying in the embodiments of the present invention can be applied to the healing of irregular wounds, improving the efficiency of wound treatment.

[0122] Example 21

[0123] A sprayable hydrogel of carboxymethyl chitosan and dialdehyde cellulose, comprising a first spray and a second spray. The first spray is a carboxymethyl chitosan solution, which is prepared by adding carboxymethyl chitosan to deionized water, stirring until the solution is uniform, and then adjusting the pH to 8 to obtain the carboxymethyl chitosan solution; wherein, the mass percentage of carboxymethyl chitosan in the carboxymethyl chitosan solution is 1.96 wt%; the obtained carboxymethyl chitosan solution is placed in a first spray bottle for later use.

[0124] The second spray is a dialdehyde cellulose solution, which is prepared by adding DAC powder to deionized water, stirring until the solution is uniform, and then adjusting the pH to 8 to obtain the dialdehyde cellulose solution; the mass percentage of dialdehyde cellulose in the second spray is 3.85 wt%; the obtained dialdehyde cellulose solution is placed in a second spray bottle for later use.

[0125] The first spray and the second spray are alternately sprayed 3 times to form a hydrogel. The gelation time is 5 min.

[0126] Example 22

[0127] A sprayable hydrogel of carboxymethyl chitosan and dialdehyde cellulose, comprising a first spray and a second spray. The first spray is a carboxymethyl chitosan solution, which is prepared by adding carboxymethyl chitosan to deionized water, stirring until the solution is uniform, and then adjusting the pH to 8 to obtain the carboxymethyl chitosan solution; wherein, the mass percentage of carboxymethyl chitosan in the carboxymethyl chitosan solution is 3.85 wt%; the obtained carboxymethyl chitosan solution is placed in a first spray bottle for later use.

[0128] The second spray is a dialdehyde cellulose solution, which is prepared by adding DAC powder to deionized water, stirring until the solution is uniform, and then adjusting the pH to 8 to obtain the dialdehyde cellulose solution; the mass percentage of dialdehyde cellulose in the second spray is 5.66 wt%; the obtained dialdehyde cellulose solution is placed in a second spray bottle for later use.

[0129] The hydrogel is formed by alternately spraying the first spray and the second spray three times. The gelation time is 5 minutes.

[0130] From the results of Example 21 and Example 22, it can be seen that an aqueous solution of a substance containing an amino group and an aqueous solution of a substance containing an aldehyde group are used as the two sprays, and a Schiff base reaction occurs through alternate spraying to form a hydrogel.

[0131] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, and improvements made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. A sprayable hydrogel, characterized in that: The method comprises a first spray and a second spray, wherein the first spray and the second spray are sprayed alternately to form a hydrogel; The first spray is an aqueous solution of a substance containing an amino group; the second spray is an aqueous solution of a substance containing an aldehyde group; the pH of the first spray and the second spray are both 7.5 to 8.5; The amino-containing substance is gelatin or carboxylated chitosan; the aldehyde-containing substance is dialdehyde cellulose; the mass percentage of the amino-containing substance in the first spray is 1.9wt% to 12wt%; The mass percentage of the aldehyde-containing substance in the second spray is 3.8wt% to 6wt%.

2. The sprayable hydrogel of gelatin and dialdehyde cellulose according to claim 1, characterized in that When the first spray is a gelatin solution, the mass percentage of gelatin in the gelatin solution is 8wt% to 12wt%.

3. The sprayable hydrogel according to claim 1, characterized in that When the first spray is a carboxylated chitosan solution, the mass percentage of the carboxylated chitosan in the carboxylated chitosan solution is 1.9 wt % to 4 wt %.

4. The sprayable hydrogel according to claim 1, characterized in that The pH of the gelatin solution is 8 to 8.5; the pH of the dialdehyde cellulose solution is 8 to 8.

5.

5. The sprayable hydrogel according to claim 4, characterized in that The specific preparation method of the dialdehyde cellulose solution is: Microcrystalline cellulose, sodium periodate and water are reacted in the dark, and then ethylene glycol is added, mixed and centrifuged, and the obtained precipitate is washed with water and freeze-dried to obtain dialdehyde cellulose; The dialdehyde cellulose and water are mixed evenly, and then the pH is adjusted to 8-8.5 to obtain a dialdehyde cellulose solution.

6. The sprayable hydrogel according to claim 5, characterized in that The dosage ratio of microcrystalline cellulose, sodium periodate and water is 7g-13g:12g-20g:500mL.

7. The sprayable hydrogel according to claim 5, characterized in that The usage ratio of microcrystalline cellulose to ethylene glycol is 7g-13g:6mL-10mL.

8. The sprayable hydrogel according to claim 1, characterized in that The time for forming the hydrogel is 120s to 160s.

9. The sprayable hydrogel according to claim 1, characterized in that The first spray and the second spray are sprayed alternately 1 to 5 times.

10. Use of the sprayable hydrogel according to claim 1 in preparing a hydrogel preparation for healing irregular wounds.

Images