Use of ferrous ions in preparation of burn infection treatment drugs and burn care products

By using ferrous sulfate hydrogel, antibiotic resistance problems in treating Pseudomonas aeruginosa scald infection were solved, and the effect of efficient bactericidal and wound healing was achieved, providing a new antibacterial treatment plan that can replace antibiotics.

WO2025030704A1PCT designated stage expired Publication Date: 2025-02-13SHAANXI UNIV OF SCI & TECH
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Patent Information

Application Number
PCT/CN2023/132424
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-08-07
Filing Date
2023-11-17
Publication Date
2025-02-13

AI Technical Summary

Technical Problem

Existing antibiotics for the treatment of scald infection caused by Pseudomonas aeruginosa are at risk of drug resistance, cannot effectively promote wound healing, and cannot prevent bacteria from migrating and colonizing in the body.

Method used

Using ferrous sulfate hydrogel as a therapeutic drug, its effective bactericidal and wound healing effect was verified through in vitro antibacterial activity experiments and animal experiments.

Benefits of technology

Ferrous sulfate hydrogel has a bactericidal rate of up to 99.9% for Pseudomonas aeruginosa, which can effectively promote wound healing, avoid antibiotic resistance, and reduce treatment costs.

✦ Generated by Eureka AI based on patent content.

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Abstract

The present invention relates to the technical field of biomedicine. Disclosed is a use of ferrous ions in the preparation of burn infection treatment drugs and burn care products. The ferrous compound formulation comprises a ferrous compound, a protective agent, a dressing matrix, and a solvent; the ferrous compound includes but is not limited to ferrous sulfate; and the dressing matrix includes but is not limited to sodium alginate and hyaluronic acid. During preparation, the ferrous compound, the protective agent, the dressing matrix and the solvent are mixed and heated to obtain a ferrous compound hydrogel. The ferrous compound hydrogel can solve the problem of burn infection caused by pseudomonas aeruginosa while avoiding antibiotic resistance, and can promote wound healing.
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Description

Application of ferrous ions in the preparation of scald infection treatment drugs and scald care products Technical Field

[0001] The invention belongs to the technical field of biomedicine, and particularly relates to the application of ferrous ions in the preparation of scald infection treatment drugs and scald care products. Background Art

[0002] Burns and surgical procedures are the most common causes of wound infection in patients. Improper prevention and control of many wound infections can further lead to adverse consequences such as difficulty in wound healing, deep tissue infection, and even systemic infection. In the case of burns, the presence of a large amount of necrotic and degenerated tissue in the burn wound destroys the skin, the body's natural barrier against microbial invasion, and easily causes bacterial colonization. When bacteria invade the exudate or necrotic tissue on the skin surface and reach a certain number, systemic symptoms such as suppurative infection and sepsis will appear. In terms of surgical procedures, patients with trauma are prone to secondary infections after undergoing open surgery due to their reduced immunity. These secondary infections have now become a top priority in hospital postoperative health management.

[0003] Common wound infection pathogens include Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, and Citrobacter freundii, with Pseudomonas aeruginosa (PA) infection being the most common. Antibiotic therapy remains a common treatment strategy for P. aeruginosa infections. Commonly used treatments for P. aeruginosa burns on the market primarily include medical antibiotic hydrogels and some essential topical steroid ointments, such as ciprofloxacin hydrochloride hydrogel, gentamicin sulfate hydrogel, and silver sulfadiazine ointment. Although antibiotic treatment has high efficiency and low-dose bactericidal effect in killing infectious pathogens, antibiotic treatment still has the following problems: 1) It does not play a beneficial role in the healing of skin wounds; 2) The large-scale use of antibiotics will increase the risk of bacterial resistance. Drug dependence forces increased drug dosage, creating a vicious cycle. When the human body is repeatedly infected with bacteria, the body's resistance to the antibiotic ointment will make the antibiotic ineffective in the human body. In other words, the irregular use and abuse of antibiotics increase the body's resistance to antibiotics; 3) Antibiotic treatment cannot effectively prevent the migration and colonization of bacteria in the body, which can easily cause lesions in other tissues and organs.

[0004] In recent years, clinical research on interventions for colonization with multidrug-resistant Pseudomonas aeruginosa (MRPA) has received increasing attention. Open wounds have a high rate of MRPA colonization, a long course of infection, and are relatively difficult to manage, with significant physiological and psychological impacts on patients. Therefore, new antimicrobial therapies are urgently needed to address this crisis.

[0005] Summary of the Invention

[0006] In order to overcome the shortcomings of the above-mentioned prior art, the purpose of the present invention is to provide the use of ferrous ions in the preparation of burn infection treatment drugs and burn care products, so as to solve the problem of wound infection such as burns caused by Pseudomonas aeruginosa while avoiding antibiotic resistance.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] According to a first aspect of the present invention, there is provided use of ferrous ions in preparing a product for treating burn infection.

[0009] According to a second aspect of the present invention, there is provided use of ferrous sulfate in preparing a product for treating burn infection.

[0010] According to a third aspect of the present invention, there is provided use of ferrous sulfate hydrogel in preparing a product for treating burn infection.

[0011] According to the application as described above, it is characterized in that the ferrous ion is ferrous sulfate.

[0012] According to the application as described above, it is characterized in that the dosage form of the product is a hydrogel.

[0013] According to the application as described above, it is characterized in that the product is a therapeutic drug for burn infection and / or a burn care product.

[0014] According to the application as described above, it is characterized in that the burn infection is a burn infection caused by Pseudomonas aeruginosa.

[0015] According to the application as described above, it is characterized in that the burn infection is a burn infection caused by multidrug-resistant Pseudomonas aeruginosa (MRPA).

[0016] According to the application as described above, it is characterized in that the hydrogel comprises a preparation prepared by containing a ferrous compound, a protective agent and a solvent.

[0017] According to the application as described above, it is characterized in that the ferrous compound is ferrous sulfate, and the content of the ferrous sulfate is 1 mM to 2 mM.

[0018] According to the application as described above, it is characterized in that the protective agent is ascorbic acid, and its content is 1mM to 2mM.

[0019] According to the application as described above, it is characterized in that the solvent is a combination of or any one of carrageenan, xanthan gum, low acyl colloid, sodium alginate, hyaluronic acid, carbomer or physiological saline.

[0020] According to the application as described above, it is characterized in that the solvent is sodium alginate with a content of 2% to 3.5%.

[0021] According to the application as described above, it is characterized in that it also includes other drugs for treating burn infections.

[0022] According to a fourth aspect of the present invention, there is provided a ferrous sulfate hydrogel for treating burn infections caused by Pseudomonas aeruginosa, the preparation method of which is as follows:

[0023] S1. Dissolving ferrous sulfate and ascorbic acid in a concentration ratio of 1:1 in sterile ultrapure water to obtain a mixed solution, and heating the mixed solution to 50° C., wherein the concentration of ferrous sulfate in the mixed solution is 2 mM;

[0024] S2. Under heating conditions, continue to add sodium alginate powder in an amount of 3.5% by mass of the mixed solution, and stir until the sodium alginate powder is dissolved to form a stable colloid, thereby obtaining a 2 mM ferrous sulfate hydrogel.

[0025] According to a fifth aspect of the present invention, a method for preparing ferrous sulfate hydrogel is provided, characterized in that:

[0026] S1. Dissolving ferrous sulfate and ascorbic acid in a concentration ratio of 1:1 in sterile ultrapure water to obtain a mixed solution, and heating the mixed solution to 50° C., wherein the concentration of ferrous sulfate in the mixed solution is 2 mM;

[0027] S2. Continue to add sodium alginate powder in an amount of 3.5% by mass of the mixed solution under heating conditions, and stir until the sodium alginate powder is dissolved to form a stable colloid, thereby obtaining a 2 mM ferrous sulfate hydrogel.

[0028] According to a sixth aspect of the present invention, there is provided a pharmaceutical composition for treating burn infections caused by Pseudomonas aeruginosa, comprising the ferrous sulfate hydrogel as described above.

[0029] The pharmaceutical composition as described above also includes other drugs for treating burn infections.

[0030] According to a seventh aspect of the present invention, there is provided a method for treating burn infection caused by Pseudomonas aeruginosa, using the aforementioned ferrous sulfate hydrogel for treatment.

[0031] Compared with the prior art, the present invention has the following beneficial effects:

[0032] The present invention provides a scald infection treatment drug and scald care product prepared using ferrous ions, as well as the use of ferrous ions in the preparation of scald infection treatment drugs and scald care products. Hydrogels are used as carriers of ferrous ions for scald treatment. In vitro antibacterial activity experiments revealed that 2 mM ferrous sulfate hydrogels had a bactericidal rate of up to 99.9% against Pseudomonas aeruginosa, with significantly higher bactericidal activity than an antibiotic group. Animal experiments revealed that, compared with the infection group, antibiotic group, and scald ointment group, 15 days after treatment with the ferrous ion-containing hydrogel, the wounds of scalded rats completely healed, accompanied by abundant hair growth and complete epidermal formation, demonstrating that the ferrous ion-containing hydrogels have a highly effective bactericidal effect against Pseudomonas aeruginosa. Furthermore, compared with current antibiotic treatments, ferrous ion hydrogels are inexpensive and highly effective in killing bacteria. While achieving this high bactericidal efficiency, they not only do not induce drug resistance but also promote the healing of PA-infected wounds, such as those following surgery. Therefore, they can be used as a drug to combat the current antibiotic crisis. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 shows images of hydrogels in different treatment groups; 1 is a blank hydrogel, 2 is a ferrous sulfate hydrogel, 3 is a hydrogel containing 1 mM ascorbic acid and ferrous sulfate, 4 is a hydrogel containing 2 mM ascorbic acid and ferrous sulfate, and 5 is a hydrogel containing 1 mg / mL ciprofloxacin hydrochloride;

[0034] Figure 2 shows the in vitro bactericidal effects of hydrogels in different treatment groups; A shows the bactericidal effects of hydrogels in different treatment groups on PA; B shows the bactericidal effects of hydrogels in different treatment groups on MRPA;

[0035] Figure 3 is a fluorescence staining micrograph of the bactericidal effect of hydrogels in different treatment groups on Pseudomonas aeruginosa; wherein, the first row from left to right are white field images of the bactericidal effect of hydrogels in different treatment groups on PA; the second row from left to right are fluorescence images of the bactericidal effect of hydrogels in different treatment groups on PA; the third row from left to right are white field images of the bactericidal effect of hydrogels in different treatment groups on MRPA; the fourth row from left to right are fluorescence images of the bactericidal effect of hydrogels in different treatment groups on MRPA;

[0036] FIG4 is a scanning electron microscopy (SEM) image of hydrogels in different treatment groups; from left to right, they are a blank group hydrogel, a group containing 1 mM ascorbic acid and ferrous sulfate hydrogel, and a group containing 2 mM ascorbic acid and ferrous sulfate hydrogel;

[0037] Figure 5 shows the Fourier transform infrared (FT-IR) structural conformation images of hydrogels in different treatment groups; from bottom to top, they are the blank group hydrogel (SA-control), the hydrogel containing 1mM ascorbic acid and ferrous sulfate (SA-1mM Fe+V C) and hydrogels containing 2 mM ascorbic acid and ferrous sulfate (SA-2 mM Fe+Vc);

[0038] Figure 6 shows the healing rates of PA-infected rat scald models treated with different treatments; the colors from left to right represent the scald group, infection group, scald ointment group, antibiotic group, ferrous sulfate hydrogel group, and blank group, respectively;

[0039] Figure 7 shows the therapeutic effects of different treatment methods on the PA-infected rat scald model after 5, 10, and 15 days of treatment; from left to right are the scald group, infection group, scald ointment group, antibiotic group, 2 mM ascorbic acid and ferrous sulfate hydrogel group, 1 mM ascorbic acid and ferrous sulfate hydrogel group, and blank group, and from top to bottom are before treatment, 5, 10, and 15 days later. DETAILED DESCRIPTION

[0040] To facilitate understanding of the features and effects of the present invention by those skilled in the art, the following provides a general description and definition of the terms and expressions used in the specification and claims. Unless otherwise indicated, all technical and scientific terms used herein have the ordinary meanings as understood by those skilled in the art regarding the present invention. In the event of conflict, the definitions in this specification shall prevail.

[0041] The theories or mechanisms described and disclosed herein, whether correct or incorrect, should not limit the scope of the present invention in any way, that is, the present invention can be implemented without being limited by any specific theory or mechanism.

[0042] Herein, all features such as values, amounts, amounts, and concentrations defined in numerical ranges or percentage ranges are for brevity and convenience only. Accordingly, the description of numerical ranges or percentage ranges should be considered to include and specifically disclose all possible subranges and individual values ​​within the range (including integers and fractions).

[0043] In this document, unless otherwise specified, “include,” “including,” “contains,” “has” or similar terms cover the meanings of “consisting of” and “mainly consisting of,” for example, “A includes a” covers the meanings of “A includes a and other” and “A only includes a.”

[0044] In this document, for the sake of brevity, not all possible combinations of the various technical features in each embodiment or example are described. Therefore, as long as there are no contradictions in the combination of these technical features, the various technical features in each embodiment or example can be combined in any way, and all possible combinations should be considered to be within the scope of this specification.

[0045] The present invention provides the use of ferrous ions in the preparation of scald infection treatment drugs and scald care products. In vivo and in vitro experiments have shown that ferrous ions have a good bactericidal effect on Pseudomonas aeruginosa, can also effectively promote the healing of wounds after scalds, and promote epidermal formation, and can be used in the preparation of scald infection products.

[0046] Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiments are only used to illustrate the present invention and are not used in limiting the scope of the present invention.In addition, should be understood that after reading the content taught by the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms fall equally within the scope limited by the appended claims of the application.

[0047] The following examples were prepared using conventional instruments and equipment in the art. Experimental methods in the following examples, where specific conditions are not specified, were generally performed under conventional conditions or according to the conditions recommended by the manufacturer. The various raw materials used in the following examples, unless otherwise specified, were conventional commercially available products, with specifications conventional in the art. In the present specification and the following examples, unless otherwise specified, "%" indicates percentage by weight, "part" indicates parts by weight, and "ratio" indicates weight ratio.

[0048] Example 1: In vitro antibacterial activity of ferrous ions

[0049] 1. Preparation of Hydrogels of Different Groups

[0050] 1) Blank group

[0051] Sterile ultrapure water was heated to 50° C., and then sodium alginate powder whose mass was 2% of the mass of sterile ultrapure water was slowly added, and the mixture was stirred until the sodium alginate powder was dissolved to form a stable colloid, thereby obtaining a blank hydrogel.

[0052] 2) Ferrous sulfate group

[0053] S1. Dissolve 1 mM ferrous sulfate (FeSO4) in sterile ultrapure water to obtain a ferrous sulfate solution, and heat the solution to 50° C. to obtain a mixed solution;

[0054] S2. Continue to add sodium alginate powder in an amount of 2% by mass of the mixed solution under heating conditions, and stir until the sodium alginate powder is dissolved to form a stable colloid, thereby obtaining ferrous sulfate hydrogel.

[0055] 3) Antibiotic group

[0056] S1. Dissolve 1 mg / mL ciprofloxacin hydrochloride in sterile ultrapure water to obtain a mixed solution, and heat the mixed solution to 50° C.

[0057] S2. Continue to add sodium alginate powder in an amount of 2% by mass of the mixed solution under heating conditions, and stir until the sodium alginate powder dissolves to form a stable colloid, thereby obtaining a hydrogel containing 1 mg / mL ciprofloxacin hydrochloride.

[0058] 4) Group containing 1 mM ascorbic acid and ferrous sulfate

[0059] S1, the concentration ratio of 1:1 ferrous sulfate (FeSO4) and ascorbic acid (V C ) is dissolved in sterile ultrapure water to obtain a mixed solution, and the mixed solution is heated to 50° C. The concentration of ferrous sulfate (FeSO4) in the mixed solution is 1 mM;

[0060] S2. Continue to add sodium alginate powder in an amount of 2% by mass of the mixed solution under heating conditions, and stir until the sodium alginate powder dissolves to form a stable colloid, thereby obtaining a hydrogel containing 1 mM ascorbic acid and ferrous sulfate.

[0061] 5) Group containing 2mM ascorbic acid and ferrous sulfate

[0062] S1, the concentration ratio of 1:1 ferrous sulfate (FeSO4) and ascorbic acid (V C ) is dissolved in sterile ultrapure water to obtain a mixed solution, and the mixed solution is heated to 50° C. The concentration of ferrous sulfate (FeSO4) in the mixed solution is 2 mM;

[0063] S2. Continue to add sodium alginate powder in an amount of 3.5% by mass of the mixed solution under heating conditions, and stir until the sodium alginate powder dissolves to form a stable colloid, thereby obtaining a hydrogel containing 2 mM ascorbic acid and ferrous sulfate.

[0064] 2. Pour the blank group hydrogel, ferrous sulfate hydrogel, antibiotic group hydrogel, 1 mM ascorbic acid and ferrous sulfate group hydrogel, and 2 mM ascorbic acid and ferrous sulfate group hydrogel into sterile disposable culture dishes for later use.

[0065] See Figure 1 for prepared hydrogels, which show images of hydrogels from different treatment groups. Because ferrous sulfate is unstable, the hydrogel containing only ferrous sulfate (Figure 1, No. 2) undergoes oxidation of the active ingredient, ferrous iron, into ferric iron during preparation due to factors such as heating and stirring. This generation of ferric iron weakens the bactericidal activity of the hydrogels in this protocol. Therefore, ascorbic acid (Vc) was added as a protective agent to improve the preparation of hydrogels containing ascorbic acid and ferrous sulfate, such as Figures 1, No. 3 and 4. This significantly slows the oxidation of ferrous iron and ensures its bactericidal activity.

[0066] 3. Put 10 8Pseudomonas aeruginosa (PA) with a CFU / mL was washed twice with physiological saline and collected into 1 cm diameter circular sterile filter papers respectively; then, the circular sterile filter papers with PA cells collected were placed face up in each group of hydrogel culture dishes in step 2, sealed, and cultured in a 37°C incubator for 12 hours. After that, the filter papers were carefully removed with sterile tweezers, and the excess hydrogel on the back of the filter papers was wiped off with a sterile cotton swab. They were then placed in sterile EP tubes respectively, and 1 mL of sterile physiological saline was added to the sterile EP tubes. The cells were sonicated for 30 seconds to collect the cells on the filter papers, and the total bacterial colony count was finally determined by the drop plate method.

[0067] In addition, consistent with the above method, the bactericidal effect of each group of hydrogels against drug-resistant Pseudomonas aeruginosa (MRPA) was also tested.

[0068] The results in Figure 2 show that, through an in vitro surface contact experiment simulating PA with ferrous ion-containing hydrogels, hydrogels containing ascorbic acid and ferrous sulfate demonstrated excellent bactericidal efficacy against both PA and MRPA. In particular, the hydrogel containing 2 mM ascorbic acid and ferrous sulfate achieved a 99.9% bactericidal rate against both bacteria. Regarding the antibiotic hydrogels, while ciprofloxacin hydrochloride treatment effectively eliminated common PA with a 99% bactericidal rate, it only achieved a 50% bactericidal rate against clinically isolated drug-resistant bacteria, demonstrating its ineffectiveness in addressing the current antibiotic crisis and highly consistent with existing research findings.

[0069] Example 2: Antibacterial model determination of ferrous sulfate hydrogel

[0070] To determine the antibacterial effect of ferrous sulfate-loaded hydrogels, blank group hydrogels (100 μL), antibiotic group hydrogels (100 μL), hydrogels containing 1 mM ascorbic acid and ferrous sulfate group hydrogels (100 μL), and hydrogels containing 2 mM ascorbic acid and ferrous sulfate group hydrogels (100 μL) were added to the center of the glass slide, and 5 μL of saline-washed PA and MRPA (10 μL) were added to the center of the glass slide. 8 CFU / mL) were vertically dropped on the surface of each group of hydrogels. After incubation at 37°C for 3 h, polyimide (PI; final concentration of 1 μg / mL) was dropped on the hydrogels containing PA cells or MRPA cells and incubated at 37°C for 20 min. The antibacterial model of each group of hydrogels was determined using fluorescence microscopy.

[0071] The results in Figure 3 show that, overall, both Pseudomonas aeruginosa (PA) and drug-resistant Pseudomonas aeruginosa (MRPA) exhibited significant red fluorescence after treatment with hydrogels containing ascorbic acid and ferrous sulfate, compared to blank hydrogels, with the color development becoming more intense with increasing concentration. Furthermore, after antibiotic treatment, standard PA exhibited a strong fluorescence response, confirming the antibiotic's bactericidal activity against standard PA. However, for MRPA, antibiotic treatment resulted in bacterial red fluorescence, but the fluorescence intensity was significantly weaker than that observed after treatment with hydrogels containing ascorbic acid and ferrous sulfate, indicating that the antibiotic group exhibited weaker bactericidal activity and was unable to effectively kill drug-resistant bacteria, further confirming the ineffectiveness of antibiotics against drug-resistant bacteria. These results support those in Figure 2, demonstrating that hydrogels containing ascorbic acid and ferrous sulfate are effective in killing Pseudomonas aeruginosa and its drug-resistant counterpart (MRPA). In summary, hydrogels containing ferrous compounds have the potential to replace antibiotics as novel antimicrobial agents.

[0072] Example 3: Gel Properties and Conformation Detection of Ferrous Sulfate Hydrogel

[0073] The gel properties of the blank group hydrogel, the group hydrogel containing 1 mM ascorbic acid and ferrous sulfate, and the group hydrogel containing 2 mM ascorbic acid and ferrous sulfate were characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR).

[0074] 1 mL of the blank hydrogel, the hydrogel containing 1 mM ascorbic acid and ferrous sulfate, and the hydrogel containing 2 mM ascorbic acid and ferrous sulfate were freeze-dried for at least 24 hours until the water in the hydrogel was completely volatilized, and then ground into powder using liquid nitrogen for later use. The particle size and morphology of the hydrogels were observed using a field emission scanning electron microscope (SEM) with a voltage set to 20 kV and a magnification of 500 times. The structure of the hydrogels was directly tested using the ATR mode of a Fourier transform infrared spectrometer (FT-IR). The white powder obtained by freeze-drying each group was ground together with potassium bromide and pressed into tablets. The resolution of the infrared spectrometer was set to 2 cm -1 , the number of scans is 32.

[0075] The results in Figure 4 show that the addition of ferrous sulfate makes the hydrogel produce more uneven porous structures. This porous structure is conducive to the hydrogel storing a large amount of water. This shows that the sodium alginate-based ferrous sulfate hydrogel will have good water retention and water locking properties, and is suitable for the epidermis that is dehydrated after burns. This will enable the epidermis to be fully in a humid environment, which is conducive to the formation of skin.

[0076] Furthermore, the structural conformation of the hydrogels with two concentrations was detected by FT-IR. The results in Figure 5 showed that compared with the hydrogel in the blank group, the hydrogel in the group containing ascorbic acid and ferrous sulfate had a -1There is an obvious absorption peak right-shifted to 1607 cm -1 (containing 1 mM ascorbic acid and ferrous sulfate group hydrogel) and 1609 cm -1 (Hydrogels containing 2 mM ascorbic acid and ferrous sulfate) show that C=C stretching bonds are replaced by more H bonds, which are converted to C-H bending vibrations. This further demonstrates that the addition of ferrous sulfate increases the water content of the hydrogel. In summary, the addition of ferrous sulfate can change the properties of the hydrogel, making the sodium alginate in the hydrogel more water-locking and water-retaining, which is beneficial for its application in burn treatment.

[0077] Example 4: In vivo therapeutic effect of ferrous sulfate hydrogel on burn infection

[0078] 1. Establishment of a rat scald model of Pseudomonas aeruginosa (PA) infection

[0079] 1) Thirty male Sprague-Dawley rats, weighing 200-220 g and aged 6-8 weeks, were adaptively fed for 3-7 days.

[0080] 2) Anesthesia: Sprague-Dawley rats were intraperitoneally injected with a mixture of ketamine and hydroxyzine (0.3 mL / 100 g). The rats were observed until their breathing stabilized.

[0081] 3) Burn Injury Establishment: SD rats were initially depilated using a hair removal device and depilatory cream until the skin was exposed and smooth. A 1-cm-diameter brass block was placed in boiling water for 10 minutes to reach thermal equilibrium. The block was then removed and placed on the rat's epidermis and allowed to rest for 2 minutes to establish a rat model of deep second-degree / third-degree burns.

[0082] 4) One hour after the rat deep second-degree / third-degree burn model was established, necrotic tissue was removed using a biopsy punch of the same diameter to simulate the clinical practice of removing severely burned skin;

[0083] 5) Infection: 50 μL of Pseudomonas aeruginosa (PA) (10 7 ~10 8 CFU / mL) and covered with a sterile medical film to prevent foreign objects from entering the wound and affecting observation. After 1-2 days of culture (25-30°C), the wound surface was observed for PA infection, successfully establishing a PA infection burn wound model.

[0084] 2. Processing group settings

[0085] Burn group (5 rats): Rats were only constructed with a burn model. After being washed with normal saline every day, the surface was wiped with iodine and covered with a sterile medical film.

[0086] Infection group (PA infection) (5 rats): After the PA infection burn wound model was successfully established in rats, the wounds were washed with normal saline every day, wiped with iodine tincture, and covered with sterile medical film.

[0087] Burn gel group (5 rats): After the PA infection burn wound model was successfully established in rats, the wound was washed with normal saline every day, the surface was wiped with iodine, and 1 mL of burn gel was thickly applied, and then covered with a sterile medical film.

[0088] Antibiotic group (5 rats): After the PA infection burn wound model was successfully established in rats, the wounds were cleaned with normal saline every day, wiped with iodine tincture, and treated with 1 mL of hydrogel containing 1 mg / mL ciprofloxacin hydrochloride, and then covered with a sterile medical film.

[0089] Ferrous sulfate hydrogel group (SA-Fe+Vc) (5 rats): After the PA infection scald wound model was successfully established in rats, the wounds were cleaned with normal saline every day, wiped with iodine tincture, and treated with hydrogel containing ascorbic acid and ferrous sulfate (containing 1mM ascorbic acid and ferrous sulfate hydrogel or containing 2mM ascorbic acid and ferrous sulfate hydrogel), and then covered with a sterile medical film.

[0090] Blank group (SA) (5 rats): After the PA infection burn wound model was successfully established in rats, the wound was washed with normal saline every day, the surface was wiped with iodine, and treated with 1 mL of blank hydrogel, and then covered with a sterile medical film.

[0091] 3. Early stage (0-10 days after infection): treat twice a day with an interval of 12 hours; late stage (11-15 days): treat once a day and take photos to record the wound healing status.

[0092] The results of the hydrogel burn repair experiment on rats are shown in Figures 6 and 7. The wound healing ability of the ferrous iron treatment group was better than that of the other groups on the 5th day. The burn group still had more callus tissue accompanied by the formation of new granulation tissue on the wound surface. In the other PA infection groups, the wound healing was not effectively alleviated, and the wound surface was seriously pus and blood. Compared with the antibiotic treatment group, the ferrous iron hydrogel was conducive to wound healing. No pus and blood were seen on the wound surface, and the wound area was significantly smaller than the wound area on day 0. On the 10th day after treatment with the hydrogel containing ascorbic acid and ferrous sulfate, the rat wound was basically completely healed with a large amount of hair growth, and the healing rate was as high as over 80%. The rats in the other treatment groups still had a large area of ​​wound tissue, accompanied by trace amounts of pus and blood, which again showed that the rats were severely infected, the wound was repeatedly inflamed, and the recovery effect was slow. Compared with other groups, the wounds of rats treated with ascorbic acid and ferrous sulfate hydrogel for 15 days were completely healed, especially after treatment with 2mM ascorbic acid and ferrous sulfate hydrogel, the burn wounds of rats were completely healed. After treatment with 1mM ascorbic acid and ferrous sulfate hydrogel, the wound healing rate also reached more than 95%, and at the same time, a large amount of hair was still generated and the epidermis was fully generated. However, the wounds of rats in other groups recovered poorly, and the wounds of the infected group still had more serious infections.

[0093] In summary, the hydrogel containing ferrous compounds has antibacterial activity. While having a good bactericidal effect, it can also effectively promote wound healing.

[0094] The above content is only for explaining the technical idea of ​​the present invention and cannot be used to limit the protection scope of the present invention. Any changes made on the basis of the technical solution in accordance with the technical idea proposed by the present invention shall fall within the protection scope of the claims of the present invention.

Claims

1. Application of ferrous ions in the preparation of products for treating burn infections.

2. Application of ferrous sulfate in the preparation of products for treating burn infections.

3. Application of ferrous sulfate hydrogel in the preparation of products for treating burn infections.

4. The use according to claim 1, characterized in that: The ferrous ion is ferrous sulfate.

5. The use according to any one of claims 1-2 and 4, characterized in that: The dosage form of the product is a hydrogel.

6. The use according to any one of claims 1 to 3, characterized in that: The product is a therapeutic medicine for burn infection and / or a burn care product.

7. The use according to any one of claims 1 to 3, characterized in that: The scald infection is a scald infection caused by Pseudomonas aeruginosa.

8. The use according to any one of claims 1 to 3, characterized in that: The scald infection is a scald infection caused by multidrug-resistant Pseudomonas aeruginosa (MRPA).

9. The use according to any one of claims 3 and 5, characterized in that: The hydrogel comprises a preparation prepared by containing a ferrous compound, a protective agent and a solvent.

10. The use according to claim 9, characterized in that: The ferrous compound is ferrous sulfate, and the content of the ferrous sulfate is 1 mM to 2 mM.

11. The use according to claim 9, characterized in that: The protective agent is ascorbic acid, and its content is 1mM to 2mM.

12. The use according to claim 9, characterized in that: The solvent is a combination or any one of carrageenan, xanthan gum, low acyl colloid, sodium alginate, hyaluronic acid, carbomer or physiological saline.

13. The use according to claim 12, characterized in that: The solvent is sodium alginate, and the content thereof is 2% to 3.5%.

14. The use according to claim 9, characterized in that: Other medicines for treating burn infections are also included.

15. A ferrous sulfate hydrogel for treating burns and infections caused by Pseudomonas aeruginosa, wherein the preparation method thereof is as follows: S1. Dissolve ferrous sulfate and ascorbic acid in a concentration ratio of 1:1 in sterile ultrapure water to obtain a mixed solution, and heat the mixed solution to 50° C., wherein: The concentration of ferrous sulfate in the mixed solution was 2 mM; S2. Continue to add sodium alginate powder in an amount of 3.5% of the mixed solution under heating conditions, and stir until the sodium alginate powder is dissolved to form a stable colloid, thereby obtaining a 2 mM ferrous sulfate hydrogel.

16. A method for preparing the ferrous sulfate hydrogel according to claim 15, characterized in that: S1, dissolving ferrous sulfate and ascorbic acid in a concentration ratio of 1:1 in sterile ultrapure water to obtain a mixed solution, and heating the mixed solution to 50° C., wherein the concentration of ferrous sulfate in the mixed solution is 2 mM; S2. Continue to add sodium alginate powder in an amount of 3.5% of the mixed solution under heating conditions, and stir until the sodium alginate powder is dissolved to form a stable colloid, thereby obtaining a 2 mM ferrous sulfate hydrogel.

17. A pharmaceutical composition for treating burn infection caused by Pseudomonas aeruginosa, comprising the ferrous sulfate hydrogel according to claim 15.

18. The pharmaceutical composition according to claim 17, further comprising other drugs for treating burn infection.

19. A method for treating burn infection caused by Pseudomonas aeruginosa, characterized in that: The ferrous sulfate hydrogel according to claim 15 is used for treatment.

Citation Information

Patent Citations

  • Wound medicine powder for treating various wounds and inflammations and preparing method thereof

    CN109394936A

  • Application of ferrous ions in preparation of product for treating bacterial infection

    CN116421551A

  • Application of ferrous ions in preparation of scald infection treatment medicines and scald nursing materials

    CN116942696A

  • External-use Chinese medicine

    CN1207901A

  • Synthetic antimicrobial mineral compositions, methods of making and using same

    US20220000912A1