Inductive gelation antibacterial dressing

Abstract

The invention discloses an induction type gelation antibacterial dressing, and belongs to the technical field of medical instruments. According to the induction type gelation antibacterial dressing, the hypochlorous acid and the white pine essential oil are used as antibacterial agents, and the hypochlorous acid and the white pine essential oil are easy to penetrate through cell walls and cell membranes of microorganisms and invade into the cells to carry out oxidation reaction by utilizing the neutral small molecule characteristics of the hypochlorous acid and the white pine essential oil, so that the microorganisms are killed; the gel further comprises a gel induction agent, namely boloxamer, sophorolipid, ethylenediamine tetraacetic acid and undecylenamide propyl betaine. By utilizing the characteristic that the boloxamer is sensitive to temperature and taking the boloxamer as a gelling agent of the dressing, the conversion between a gel state and a liquid state of the dressing is realized through temperature change, and necrotic tissues can be softened in 2-5 minutes, so that the residual dressing, the necrotic tissues and pollutants on a wound surface can be conveniently removed, and painless debridement is realized.

Description

Technical Field

[0001] The invention relates to the technical field of medical devices, and in particular to an induction-type gelled antibacterial dressing. Background Art

[0002] Medical dressings are commonly used medical devices for wound treatment. Their types mainly include traditional dressings, hydrogel dressings, alginate dressings, foam dressings, antibacterial dressings, etc.

[0003] Antibacterial dressings include silver ion dressings, polyhexamethylene biguanide hydrochloride (PHMB) dressings, chlorhexidine gluconate (CHG) transparent dressings, etc. Silver ion dressings are broad-spectrum antibacterial dressings. The main ingredients are polyurethane foam, sodium carboxymethyl cellulose, silver, etc. They can quickly kill bacteria and continuously release low-concentration silver ions. Positively charged silver ions hinder the synthesis of bacterial cell wall proteins, prevent the division of nuclear DNA, and destroy the synthesis of the bacterial respiratory energy chain, causing the bacterial cell wall to rupture and die. They are highly toxic to microorganisms, fungi, and some viruses, and can inhibit the growth of microorganisms to achieve antibacterial and inactivation effects. The bactericidal effect of silver ion dressings is maintained for 3 to 7 days. The guanidine group in polyhexamethylene biguanide hydrochloride (PHMB) dressings is highly active, which can make the polymer positively charged and easily adsorbed by various negatively charged bacteria and viruses, thereby inhibiting the division function of bacteria and viruses and making them lose their reproductive ability. In addition, the film formed by the polymer blocks the respiratory tract of microorganisms, causing the microorganisms to suffocate and die quickly. Chlorhexidine gluconate (CHG) transparent dressing has antimicrobial activity. At pH 5.0-8.0, it is most effective against Gram-positive and Gram-negative bacteria.

[0004] The main ingredients of hydrogel dressings are pure water, carboxymethyl cellulose and some other auxiliary ingredients. Carboxymethyl cellulose swells after absorbing exudate and can be attached to the wound and the edge of the skin. Keep the wound moist. In a moist environment, the collagen degrading enzyme in the wound exudate decomposes necrotic substances, which can achieve the effect of autolysis and debridement.

[0005] However, the above antibacterial dressings have the following disadvantages:

[0006] (1) Silver ion and PHMB dressings can easily cause allergic reactions in patients; high concentrations of silver ions and PHMB are toxic to fibroblasts and may inhibit the activity of keratinocytes, leading to impaired wound healing and affecting the process of wound epithelialization.

[0007] (2) After the care is completed, the dressing adheres to the wound, causing severe pain when changing the dressing, and may even cause secondary damage to the wound.

[0008] (3) After using the above dressings for care, the main debridement methods include surgical debridement, autolytic debridement, mechanical debridement, biological debridement, enzyme debridement, etc. Surgical debridement cannot remove biofilm, may remove healthy tissue, and there is a risk of bleeding and pain; autolytic debridement takes a long time to take effect and may take several days; biological debridement has a high level of pain and the patient's psychological acceptance is low; enzyme debridement is expensive and attention must be paid to maintaining enzyme activity.

[0009] (4) After carboxymethyl cellulose forms a gel, it is adsorbed on the wound surface, making it difficult to clean. Summary of the invention

[0010] Purpose of the invention: The purpose of the present invention is to provide an induction-type gelled antibacterial dressing which is fast-acting, safe, non-cytotoxic and non-wound-adhesive and a preparation method thereof; after using the induction-type gelled antibacterial dressing to care for the wound, the dressing can be separated from the wound simply and painlessly.

[0011] The induction-type gelled antibacterial dressing includes a first liquid and a second liquid. The first liquid includes an antibacterial agent, and the rest is water; the antibacterial agent is one or two of hypochlorous acid and white rosin essential oil; the second liquid includes a gel induction agent poloxamer, and the rest is water; the second liquid also includes one or more of sophorolipids, ethylenediaminetetraacetic acid, and undecylenamide propyl betaine; the first liquid and the second liquid are separately arranged.

[0012] Hypochlorous acid and white rosin essential oil are antibacterial ingredients that can achieve rapid sterilization. Biofilm is a complex environment in which microorganisms are wrapped in a matrix. The surface of the biofilm is usually negatively charged. Since hypochlorous acid and white rosin essential oil are neutral small molecules, there will be no attraction between charges. They can easily penetrate the cell walls and cell membranes of microorganisms, invade the interior of the cells, perform oxidation reactions, and kill microorganisms.

[0013] Betaine and sophorolipids can lyse biofilms and destroy the interactions between biofilm molecules. When the biofilm is destroyed, the antibacterial ingredients are accelerated to enter the biofilm to kill microorganisms, thereby completely disintegrating the biofilm and achieving rapid removal of the biofilm.

[0014] Poloxamer is a sensible gelling agent, which is liquid at room temperature. After being applied to the wound surface, it contacts the wound and quickly changes to a gel state under the action of body temperature, so that the dressing forms a gel, adheres to the wound, and is in close and full contact with the wound, providing a moist environment for the wound, softening and decomposing necrotic tissue. After the nursing is completed, flushing with a flushing fluid such as sterile water or saline. Since the flushing fluid is at room temperature, the temperature is lower than the dressing temperature and lower than the gelation temperature of poloxamer, poloxamer changes from a gel state to a liquid state, thereby facilitating the removal of the dressing on the wound surface and achieving painless debridement.

[0015] As a preferred embodiment, the concentration of the hypochlorous acid is 280 mg / L to 320 mg / L.

[0016] As a preferred solution, the mass concentration of the white pine essential oil is 1.5% to 2.5%.

[0017] As a preferred embodiment, the concentration of the poloxamer is 2.5 g / L to 3.5 g / L.

[0018] As a preferred embodiment, the mass concentration of the sophorolipid is 2.5% to 3.5%.

[0019] As a preferred embodiment, the mass concentration of the undecylenamide propyl betaine is 1.5% to 2.5%.

[0020] As a preferred solution, the mass concentration of the ethylenediaminetetraacetic acid is 4.5% to 5.5%.

[0021] As a preferred embodiment, the second liquid further includes a moisturizer, and the moisturizer is chitosan.

[0022] As a preferred embodiment, the second liquid also includes a buffer, and the buffer is tromethamine, which keeps the pH of the dressing stable.

[0023] As a preferred embodiment, the second liquid also includes cell growth factors to promote cell growth and tissue healing.

[0024] As a preferred embodiment, the second liquid further includes a coagulation factor, and the coagulation factor is one or both of thrombin and fibrinogen.

[0025] As a preferred embodiment, the second liquid further comprises an antioxidant, and the antioxidant is one or both of catechins and flavonoids.

[0026] As a preferred embodiment, the induction-type gel antibacterial dressing further includes a booster. The first liquid and the second liquid are respectively sealed in the A cavity and the B cavity of the booster. When in use, the plug is pushed to puncture the seals of the A cavity and the B cavity, so that the first liquid and the second liquid flow out. The first liquid and the second liquid are mixed at the front end of the booster and applied to the wound. The booster structure is as follows Figure 1 shown.

[0027] The second aspect of the present invention provides a method for preparing an induction-type gelled antibacterial dressing, wherein the first liquid and the second liquid are aseptically filled into the A cavity and the B cavity of the booster respectively, and after being sealed, they are placed in a paper-plastic bag and sterilized with ethylene oxide (EO).

[0028] Through the above technical solution, the present invention produces the following beneficial effects:

[0029] (1) Taking advantage of the temperature-sensitive property of poloxamer, poloxamer is used as a gelling agent for dressings. The dressing can be transformed from a gel state to a liquid state through temperature changes. Necrotic tissue can be softened in 2 to 5 minutes, thereby facilitating the removal of residual dressings, necrotic tissue, and contaminants on the wound surface, achieving painless debridement.

[0030] (2) Utilizing the neutral small molecule characteristics of hypochlorous acid and white rosin essential oil, they can easily penetrate the cell walls and cell membranes of microorganisms, invade the interior of the cells to carry out oxidation reactions, and kill the microorganisms.

[0031] (3) Betaine and sophorolipids can lyse biofilms, quickly remove biofilms, and accelerate the entry of antibacterial ingredients into the biofilms, quickly and effectively killing bacteria within 15 seconds. The sterilization rate of common bacteria in wounds is 99.99% to 99.999%.

[0032] (4) The product concentration is designed to be safe, non-cytotoxic, and safe for the human body. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 : is a structural diagram of the booster of the present invention; wherein A represents the A cavity, and B represents the B cavity;

[0034] Figure 2 These are the cell cytotoxicity test results of Examples 1 to 4; the red line is the limit required by the national standard. DETAILED DESCRIPTION

[0035] In order to make the technical solution of the present invention clearer, the present invention is further described in detail below with reference to the accompanying drawings and specific embodiments.

[0036] Example 1

[0037] The first liquid is a 280mg / L to 320mg / L hypochlorous acid aqueous solution; the second liquid includes EDTA (ethylenediaminetetraacetic acid) with a mass concentration of 4.5% to 5.5%, sophorolipids (SL) with a mass concentration of 2.5% to 3.5%, and poloxamer with a mass concentration of 2.5g / L to 3.5g / L, and the rest is water. The two liquids are aseptically canned into the booster and sealed, and the whole product is placed in a paper-plastic bag for EO ethylene oxide sterilization to prepare an induction-type gelled antibacterial dressing.

[0038] Example 2

[0039] The first liquid is a 1.5% to 2.5% aqueous solution of white rosin essential oil (GEO); the second liquid includes 4.5% to 5.5% EDTA (ethylenediaminetetraacetic acid), 2.5% to 3.5% sophorolipids (SL), 2.5g / L to 3.5g / L poloxamer, and the rest is water. The two liquids are aseptically canned into a booster and sealed, and the whole product is placed in a paper-plastic bag for EO ethylene oxide sterilization to prepare an induction-type gelled antibacterial dressing.

[0040] Example 3

[0041] The first liquid is a 280mg / L to 320mg / L hypochlorous acid aqueous solution; the second liquid includes betaine (undecylenamidopropyl betaine) with a mass concentration of 1.5% to 2.5%, sophorolipids (SL) with a mass concentration of 2.5% to 3.5%, poloxamer with a mass concentration of 2.5g / L to 3.5g / L, and the rest is water. The two liquids are aseptically canned into a booster and sealed, and the entire product is placed in a paper-plastic bag for EO ethylene oxide sterilization to prepare an induction-type gelled antibacterial dressing.

[0042] Example 4

[0043] The first liquid is a 1.5% to 2.5% mass concentration of white rosin essential oil (GEO) aqueous solution; the second liquid includes 1.5% to 2.5% mass concentration of betaine (undecylenamidopropyl betaine), 2.5% to 3.5% mass concentration of sophorolipids (SL), 2.5g / L to 3.5g / L of poloxamer, and the rest is water. The two liquids are aseptically canned into a booster and sealed, and the whole product is placed in a paper-plastic bag for EO ethylene oxide sterilization to prepare an induction-type gelled antibacterial dressing.

[0044] The samples prepared in Examples 1 to 4 were tested and evaluated for cytotoxicity, in vitro bactericidal effect, in vitro biofilm removal effect, and debridement effect.

[0045] (1) Cytotoxicity

[0046] 1. Test method: The test was conducted in accordance with the MTT method in GB / T 16886.5-2017 Biological evaluation of medical devices Part 5: In vitro cytotoxicity test method.

[0047] 2. Test results and analysis: The test results are as follows: Figure 2 The cell survival rates of the samples prepared in Examples 1 to 4 were all greater than ≥ 70%, meeting the national standard requirement (≥ 70%), indicating that the antibacterial gelling dressing prepared by the technical solution of the present invention has good biocompatibility.

[0048] (2) In vitro bactericidal effect

[0049] 1. Test method: Refer to Section 2.1.1.7.4 Suspension quantitative method of Disinfection Technical Specifications-2002 for testing.

[0050] 2. Test results and analysis: The test results are shown in the following table: The samples prepared in Examples 1 to 4 can effectively kill common bacteria and drug-resistant bacteria in wounds after an in vitro action time of 1 minute.

[0051] Table 1: In vitro bactericidal effect

[0052]

[0053] (3) Effect of removing biofilm in vitro

[0054] 1. Test method: Refer to the literature "Comparative Antimicrobial Activity of Commercial Wound-Care Solutions on Bacterial and Fungal Biofilms".

[0055] 2. Test results and analysis: The test results are shown in the following table. The in vitro biofilm removal effects of the samples prepared in Examples 1 to 4 were tested. The results showed that except for Pseudomonas aeruginosa and Candida albicans, which required 24 hours to be removed, the biofilms formed by other strains could be removed within 1 to 10 minutes.

[0056] Table 2: In vitro biofilm removal effect

[0057]

[0058]

[0059] (4) Debridement effect

[0060] Test method: Use an 8mm skin biopsy device to create a full-thickness skin defect wound with a diameter of 8mm on fresh pork. The specific steps are as follows:

[0061] 1. Wound preparation: Use an 8 mm skin biopsy device to create a full-thickness skin defect wound with a diameter of 8 mm on pig skin.

[0062] 2. Wound size: The wound diameter is 8mm, the height is 3mm, and the lower end of one side is cut 45 degrees.

[0063] 3. Place the wound with full-thickness skin defect in a 37℃ constant temperature box for 30 minutes to balance it to 37℃. After taking it out, squeeze out the induction gel antibacterial dressing and apply it on the wound. Under the action of temperature, it changes from liquid state to hydrogel state. After 2 to 5 minutes, rinse with saline or sterile water.

[0064] 4. Test results and analysis: The debridement effect of the samples prepared in Examples 1 to 4 was tested. After the induction-type gelled antibacterial dressing was applied to the wound for 2 to 5 minutes, it was rinsed with normal saline. The induction-type gelled antibacterial dressing changed from a gel state to a liquid state and was rinsed away together with the necrotic tissue and contaminants. No surgical instrument was required, achieving painless debridement.

[0065] The above test results show that

[0066] Examples 1 to 4 prepare induction-type gelled antibacterial dressings, which have high safety, fast sterilization speed, good antibacterial effect, can quickly remove biofilm, achieve the effect of painless debridement, and thus alleviate the pain of patients.

[0067] The above-mentioned embodiments only express several implementation methods of the present invention, and the description thereof is relatively specific and detailed, but it cannot be understood as limiting the scope of the patent of the present invention. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, which all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. An induction-type gelling antibacterial dressing, characterized in that: It comprises a first liquid and a second liquid, and the first liquid and the second liquid are separately arranged; the first liquid comprises an antibacterial agent, and the rest is water; the antibacterial agent is one or two of hypochlorous acid and white rosin essential oil; the second liquid comprises a gel induction agent poloxamer, and the rest is water; the second liquid further comprises one or more of sophorolipids, ethylenediaminetetraacetic acid, and undecylenamide propyl betaine; the first liquid and the second liquid are separately arranged.

2. The induction-type gelling antibacterial dressing according to claim 1, characterized in that: The concentration of the hypochlorous acid is 280 mg / L to 320 mg / L.

3. The induction-type gelling antibacterial dressing according to claim 1, characterized in that: The mass concentration of the white rosin essential oil is 1.5% to 2.5%.

4. The induction-type gelling antibacterial dressing according to claim 1, characterized in that: The concentration of the poloxamer is 2.5 g / L to 3.5 g / L; the mass concentration of the sophorolipid is 2.5% to 3.5%; the mass concentration of ethylenediaminetetraacetic acid is 4.5% to 5.5%; and the mass concentration of undecylenamide propyl betaine is 1.5% to 2.5%.

5. The induction-type gelling antibacterial dressing according to claim 4, characterized in that: The second liquid further comprises a moisturizing agent, and the moisturizing agent is chitosan.

6. The induction-type gelling antibacterial dressing according to claim 5, characterized in that: The second liquid further comprises a buffer, and the buffer is tromethamine.

7. The induction-type gelling antibacterial dressing according to claim 6, characterized in that: The second liquid also includes cell growth factors.

8. The induction-type gelling antibacterial dressing according to claim 7, characterized in that: The second liquid also includes a coagulation factor, and the coagulation factor is one or both of thrombin and fibrinogen.

9. The induction-type gelling antibacterial dressing according to claim 7, characterized in that: The second liquid also includes an antioxidant, and the antioxidant is one or both of catechins and flavonoids.

10. The method for preparing the induction-type gelling antibacterial dressing according to claims 1 to 9, characterized in that: The first liquid and the second liquid are aseptically filled into the A cavity and the B cavity of the booster respectively, and after being sealed, they are placed in a paper plastic bag and sterilized with ethylene oxide (EO).

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