Aerogel for promoting wound healing and preparation method thereof

Abstract

The invention discloses an aerogel for promoting wound healing and a preparation method thereof. The preparation method of the gas comprises the following steps: (1) dissolving different matrix materials in water, normal saline or a buffer solution to obtain hydrogel with different proportions and different viscosities; and (2) fully mixing the pre-filled hydrogel obtained in the step (1) with single gas or combined gas to obtain the gel containing gas bubbles. The invention provides a preparation method of gas gel with different activities, the method is simple, the gas gel can be obtained by mixing pre-filled gel and gas, bubbles are loaded by using the viscosity of the gel, and efficient carrier gas is maintained, so that the problems of addition of a gas production material, low gas production rate, poor biocompatibility, limited production and the like in the existing gas gel technology are solved.

Description

Technical Field

[0001] The present invention belongs to the technical field of medical supplies, and relates to a gas gel and its preparation method and application. Background Art

[0002] Injuries caused by acute trauma, burns or chronic diseases such as diabetes, etc., lead to difficult wound healing, which is a difficult problem in wound repair in current clinical practice. Gas therapy plays an important role in anti-inflammation, anti-bacterial, promoting cell proliferation and migration, promoting angiogenesis and extracellular matrix remodeling at all stages of wound repair. Research reports that gas molecules with therapeutic functions include oxygen, hydrogen, nitric oxide, hydrogen sulfide, carbon monoxide, etc., which can promote wound healing. Therefore, it is of great significance to develop long-acting, high gas-loading / gas-producing and biocompatible gel dressings.

[0003] Currently, some gas-producing or gas-carrying materials are commonly used in the preparation of gas gels to achieve the delivery of active gases at the wound site. For example, for oxygen, oxygen-releasing materials are usually used, including inorganic peroxide materials, in-situ catalytic nanozymes such as catalase, and biological oxygen production (using algae to produce oxygen) systems; in addition, there are oxygen-carrying materials based on perfluorocarbon and hemoglobin. In the prior art, oxygen therapy methods are used to promote wound healing, and the conventional methods are hyperbaric oxygen or topical oxygen therapy. For example, Patent 200520069038.0 discloses an oxygen boot for treating ulcerative lower limbs, which maintains a high-oxygen environment in the lower limb part through exogenous oxygen. In addition, topical oxygen therapy mainly uses some oxygen-releasing materials. For example, in Patent CV111905142A and CN113797380A, the supply of oxygen is achieved by the hydrolysis or catalytic reaction of peroxides to produce oxygen, or the high oxygen-carrying capacity of the gel is achieved by using oxygen-carrying materials such as perfluorocarbon. This method requires adding other substances to the gel, and has problems such as limited clinical use, complex preparation, and poor stability. Summary of the Invention

[0004] In order to achieve the object of the present invention, the technology of the present invention is as follows:

[0005] A method for preparing a gas gel for promoting wound healing, the preparation method comprising the following steps:

[0006] Dissolve different matrix materials in water, physiological saline or buffer solution to obtain hydrogels with different proportions and viscosities; (2) fully mix the pre-filled hydrogel in step (1) with a single gas or a gas combination to obtain a gel containing gas bubbles.

[0007] According to an embodiment of the present invention, in step (1). The gel matrix is selected from materials known in the art. Preferably, the gel matrix is selected from one or more combinations of poloxamer, carbomer, sodium hyaluronate, gelatin, sodium alginate, etc.

[0008] According to an embodiment of the present invention, the active gas component in step (2) is selected from one or more mixtures of oxygen, hydrogen, hydrogen sulfide, nitric oxide, and carbon monoxide.

[0009] According to an embodiment of the present invention, the solvent in step (1) is water, physiological saline, buffer solution, etc.

[0010] According to an embodiment of the present invention, a preservative is further added to the gel in step (1), and the preservative is selected from one or more of ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, sodium benzoate, disodium ethylenediaminetetraacetate, etc.

[0011] According to an embodiment of the present invention, a humectant is added to the gel in step (1), and the humectant is selected from one or more of propylene glycol, glycerol, sorbitol, etc.

[0012] According to an embodiment of the present invention, the gel viscosity in step (1) is in the range of 0.1 - 100 Pa, preferably 1 - 60 Pa, and most preferably 10 - 50 Pa.

[0013] According to an embodiment of the present invention, in step (2), the method for preparing the gas gel, characterized in that the method for mixing the gel and the gas in step (2) may include a gas blowing method and a pre-filled two-phase mixing method.

[0014] According to an embodiment of the present invention, in step (2), the gas mixing method is used to prepare the gas gel. Under uniform stirring, an active gas is blown into the gel to obtain a gel containing the active gas; wherein, the stirring speed is 0.1 - 1000 rpm, preferably 100 - 500 rpm, and the flow rate of the blown gas is 0.1 - 10 L / min, preferably 1 - 5 L / min.

[0015] According to an embodiment of the present invention, in step (2), the pre-filled two-phase mixing method is used to prepare the gas gel. The gel obtained in step (1) is pre-filled into a syringe, and another syringe is pre-filled with the active gas. When in use, the two syringes are connected through a medical two-way joint, and then repeatedly pushed and mixed to obtain a gel containing the active gas; wherein, the optional specifications of the syringe are 1 mL, 2 mL, 5 mL, 10 mL, and the number of times of repeated pushing is 1 - 50 times, preferably 10 - 50 times.

[0016] According to an embodiment of the present invention, for the gas gel, the retention and release time of the active gas is 0.1 - 48 hours.

[0017] According to an exemplary embodiment of the present invention, the preparation method includes the following steps:

[0018] (a1) Weigh a certain amount of poloxamer and prepare a hydrogel with pure water.

[0019] (a2) While stirring the prepared poloxamer gel, continuously introduce oxygen into it to obtain a hydrogel containing oxygen.

[0020] Preferably, in step (a1), the poloxamer gel is 20% - 30%.

[0021] Preferably, in step (a1), the viscosity of the poloxamer gel is 0.1 - 50 Pa.

[0022] Preferably, in step (a2), the stirring speed is 10 - 1000 rpm / min.

[0023] Preferably, in step (a2), the oxygen bubbling rate is 0.1 - 5 L / min.

[0024] Preferably, in step (a2), the oxygen continuous release time in the oxygen hydrogel is 0.1 - 48 h.

[0025] According to the solution of the embodiment of the present invention, the preparation method includes the following steps:

[0026] (b1) Weigh a certain amount of carbomer and prepare a hydrogel with pure water; wherein, a wetting agent and a preservative are added.

[0027] (b2) Fill the prepared carbomer gel into a 5 mL syringe, and at the same time fill another syringe with oxygen. Connect the two syringes with a medical two-way connector and repeatedly push and mix to obtain an oxygen hydrogel.

[0028] Preferably, in step (b1), the concentration of the carbomer gel is 0.1% - 1%.

[0029] Preferably, in step (b1), the viscosity of the poloxamer gel is 0.1 - 40 Pa.

[0030] Preferably, in step (b1), the lubricant added to the carbomer gel is glycerol.

[0031] Preferably, in step (b2), the number of repeated pushing and injecting is 1 - 50 times.

[0032] Preferably, in step (b2), the oxygen continuous release time in the oxygen hydrogel is 0.1 - 24 h.

[0033] The present invention has the following beneficial effects:

[0034] The gas gel preparation method described in the present invention can prepare various active gas gels for promoting wound healing.

[0035] Compared with the prior art, the gas gel described in the present invention adopts a gel material with good biocompatibility, has no use risk, and does not add other active ingredients.

[0036] The gas gel of the present invention isolates the wound surface from the external environment through an airtight lining layer, so that the active gas will not leak out, and the wound surface is prevented from contacting pathogens in the external environment.

[0037] The gas gel of the present invention has a large gas storage capacity and a long duration, can deliver active gas for promoting wound healing in a long term, has no other reaction gas production principle, and has low cost.

[0038] Description of the drawings.

[0039] Figure 1 It is a device for preparing the pre-filled mixed gas gel in the present invention.

[0040] Figure 2 The viscosity parameters of the gels of poloxamer 407 and 188 in different ratios in Example 1 vary with temperature.

[0041] Figure 3 This is the morphology of the oxygen gel in Example 1.

[0042] Figure 4 The concentration and maintenance time of oxygen in poloxamer gel of different proportions in Example 1.

[0043] Figure 5 This is a photo of the poloxamer oxygen gel in Example 1 promoting wound healing in mice.

[0044] Figure 6 This is a graph showing the wound healing rate of mice in Example 1. DETAILED DESCRIPTION

[0045] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0046] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0047] Example 1

[0048] The preparation of oxygen hydrogel is characterized by comprising the following steps:

[0049] Weigh poloxamer 407 and poloxamer 188 to prepare gels with different ratios (407:188, A = 30:0; B = 25:5; C = 20:10; D = 15:15; E = 10:20), and then measure the viscosities of the gels with different ratios as Figure 2 shown.

[0050] Fill the prepared poloxamer gel into a 5 mL syringe, and at the same time fill another syringe with oxygen. Connect the two syringes with a medical two-way connector and push and mix repeatedly 20 times (the device is as Figure 1 ), to obtain an oxygen hydrogel, as Figure 3 shown. Test the oxygen concentration and oxygen maintenance time in the gels with different ratios through an oxygen electrode as Figure 4 .

[0051] To verify the therapeutic effect of the oxygen hydrogel on mouse wounds, we randomly divided the mice into four groups: a control group, an oxygen-rich normal saline group, a gel group, and an oxygen hydrogel group. Remove a circular full-thickness skin with a diameter of about 1 cm on the back of the mice. Then locally cover the wound with the freshly prepared gel dressing, and then apply an airtight backing layer, change it once a day, and take pictures to record the wound area every two days, and then statistically analyze the wound area, as Figure 5 , shown in Figure 6, the oxygen hydrogel can promote the healing of mouse wounds.

[0052] Example 2

[0053] Weigh 30 g of poloxamer 407 and dissolve it in 100 g of pure water, stir to form a transparent solution, then add 5 g of glycerol and 1 g of sodium benzoate in sequence, stir to form a uniform solution, and measure the viscosity of the gel to be 36 Pa.

[0054] Fill the prepared poloxamer gel into a 5 mL syringe, and at the same time fill another syringe with oxygen. Connect the two syringes with a medical two-way connector and push and mix repeatedly 30 times to obtain an oxygen hydrogel. Test the oxygen concentration in the gel through an oxygen electrode to be 1250 μM, which can be maintained continuously for 30 h.

[0055] Example 3

[0056] (1) Weigh 0.1 g of carbomer and dissolve it in 100 g of pure water, stir to form a transparent solution, then add 10 g of glycerol and 1 g of sodium benzoate in sequence, stir to form a uniform solution, and measure the viscosity of the gel to be 20 Pa.

[0057] (2) Under the stirring state with a rotation speed of 500 rpm, fill hydrogen with a flow rate of 300 mL / min into the prepared carbomer gel and maintain it for 10 min to obtain a hydrogen gel.

[0058] Example 4

[0059] Weigh 0.3 g of carbomer and dissolve it in 100 g of pure water, stir to form a transparent solution, then add 10 g of glycerol and 1 g of sodium benzoate in sequence, stir to form a homogeneous solution, and measure the viscosity of the gel to be 30 Pa.

[0060] Fill the prepared poloxamer gel into a 5 mL syringe, and at the same time fill another syringe with hydrogen. Connect the two syringes with a medical two-way connector, and repeatedly push and mix 20 times to obtain a hydrogen hydrogel.

[0061] Example 5

[0062] (1) Weigh 1 g of sodium hyaluronate and dissolve it in 100 g of pure water, stir to form a transparent solution, and measure the viscosity of the gel to be 23 Pa.

[0063] (2) Fill the prepared sodium hyaluronate gel into a 5 mL syringe, and at the same time fill another syringe with oxygen. Connect the two syringes with a medical two-way connector, and repeatedly push and mix 20 times to obtain an oxygen hydrogel.

[0064] Example 6

[0065] (1) Weigh 0.2 g of carbomer and dissolve it in 100 g of pure water, stir to form a transparent solution, then add 10 g of glycerol and 1 g of sodium benzoate in sequence, stir to form a homogeneous solution, and measure the viscosity of the gel to be 28 Pa.

[0066] (2) Under the stirring state with a rotation speed of 500 rpm, fill the prepared carbomer gel with hydrogen sulfide gas at a flow rate of 300 mL / min and maintain it for 10 min to obtain a hydrogen sulfide gas gel.

Claims

1. A gel with slow-release active gas, which is used to promote the healing of wounds and chronic ulcers, is characterized in that, (1) The active gas component in the gel is a mixture of one or more of oxygen, hydrogen, hydrogen sulfide, nitric oxide, and carbon monoxide; (2) The gel matrix is ​​a combination of one or more of poloxamer, carbomer, sodium hyaluronate, gelatin, sodium alginate, etc.; (3) The viscosity of the gel ranges from 0.1 to 100 Pa, and the gas can be slowly released for 0.1 to 48 hours.

2. Method for preparing aerogel, characterized in that, The method comprises the following steps: (1) dissolving different matrix materials in water, physiological saline or buffer solution to obtain hydrogels with different proportions and viscosities; and (2) fully mixing the pre-filled hydrogel in step (1) with a single gas or a combination of gases to obtain a gel containing gas bubbles.

3. The aerogel according to claim 1, wherein The active gas that promotes wound healing is oxygen, hydrogen, hydrogen sulfide, nitric oxide, carbon monoxide, etc.

4. The aerogel according to claim 1, characterized in that, The concentration of the active gas contained in the gel is between 0.1 and 2000 μM.

5. The aerogel according to claim 1, wherein, The gel matrix is ​​poloxamer, carbomer, sodium hyaluronate, gelatin, sodium alginate and the like.

6. The aerogel according to claim 1, wherein, The viscosity of the gel is in the range of 0.1-100 Pa.

7. The aerogel according to claim 1, wherein The retention and release time of the active gas in the aerogel is between 0.1 and 48 hours.

8. The method for preparing the aerogel according to claim 2, wherein In step (1), the solvent is water, physiological saline, buffer solution, etc.

9. The method for preparing a gas gel according to claim 2, wherein A preservative is added to the gel obtained in step (1), wherein the preservative is selected from one or more of ethyl p-hydroxybenzoate, propyl p-hydroxybenzoate, sodium benzoate, disodium ethylenediaminetetraacetate, and the like.

10. The method for preparing a gas gel according to claim 2, characterized in that, A moisturizer is added to the gel obtained in step (1), wherein the moisturizer is selected from one or more of propylene glycol, glycerol, sorbitol, etc.

11. The method for preparing a gas gel according to claim 2, wherein The method for mixing the gel and the gas in step (2) may include a gas blowing method and a pre-filled two-phase mixing method.

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