Application of bivalent iron salt in preparation of products for treating pressure sores and medicine
By preparing ferrous saline gel and combining it with various excipients, the contraction and closure of pressure ulcer wounds are promoted, overcoming the limitations of existing pressure ulcer treatment methods and achieving safe, effective, and low-cost pressure ulcer treatment.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-03-06
- Publication Date
- 2026-04-10
AI Technical Summary
Current treatments for pressure ulcers have limitations, especially drug therapy, which may suppress the immune system's self-healing function, and has a long healing period and a high recurrence rate. There is a lack of safe, effective and affordable treatment strategies.
By combining ferrous salts with various pharmaceutically acceptable excipients, drugs can be prepared in solution, colloidal, suspension, emulsion, or hydrogel form. These drugs promote wound contraction and closure through anti-inflammatory effects. Specifically, the hydrogel-type drugs use ferrous salts as the active ingredient, combined with excipients such as nicotinamide, vitamin B2, sodium alginate, hyaluronic acid, and carbomer, at concentrations ranging from 0.5 mM to 2 mM.
Ferrous saline gel significantly accelerates pressure ulcer recovery, reduces inflammation, has almost no acute irritation or allergic reactions, promotes wound healing, shortens healing time, and improves patient compliance.
Smart Images
Figure CN121818705A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of biomedical technology, specifically to the application of ferrous salts in the preparation of products for treating pressure ulcers and related pharmaceuticals. Background Technology
[0002] Pressure ulcers, also known as bedsores or pressure injuries, are focal injuries to the skin and underlying soft tissue caused by continuous or repeated pressure, often accompanied by shear and friction forces, leading to long-term restricted tissue perfusion. They commonly occur at bony prominences or areas in contact with medical devices. Compared to traumatic wounds, burns, diabetic foot ulcers, and venous ulcers, pressure ulcers have significantly different pathological mechanisms and injury characteristics. Trauma or burns involve direct damage to tissues from external force or heat; diabetic foot ulcers and vascular ulcers are mostly caused by systemic metabolic and blood flow disorders, and their depth of injury is relatively consistent with their surface appearance. Pressure ulcers, however, often exhibit a hidden progression characteristic of "light on the outside but severe on the inside," with deep muscles and fascia potentially dying even when the skin is still intact, forming the typical "cone-shaped injury" of pressure wounds. Pressure ulcers also feature deep tissue damage, high recurrence rates, and long healing periods, making them one of the most difficult types of chronic wounds to treat.
[0003] Pressure ulcers can be classified into several stages: Stage I is characterized by unbearable redness upon pressure application; Stage II involves superficial skin defects; Stages III and IV involve exposure of deep tissues, tendons, or bones; and stages that are unstageable are those where the depth cannot be determined due to eschar or necrotic tissue covering the ulcer. The core pathogenic factors are ischemia-hypoxia injury caused by continuous pressure and ischemia-reperfusion injury after pressure relief. This process generates a large amount of reactive oxygen species, inflammatory mediators, and cellular metabolic products, further exacerbating necrosis of deep tissues.
[0004] Pressure ulcers develop not only from prolonged pressure on the skin and underlying tissues but also from shear and friction forces. Shear force refers to the parallel or relative movement between the skin and underlying tissues, while friction occurs between the skin and surfaces such as sheets and clothing. When the skin slides against deeper tissues, the epidermis may remain fixed while the underlying tissues are stretched and twisted. This shear force compresses and stretches blood vessels, hindering blood flow. Obstructed local blood flow prevents oxygen and nutrients from being effectively supplied to the pressure area, leading to tissue hypoxia, malnutrition, and cell death. Friction can also cause skin surface damage, resulting in redness, swelling, or blisters, which can develop into more severe ulcers. Meanwhile, the impact of a moist environment cannot be ignored, especially in cases of urinary incontinence or retention of other secretions. Increased humidity makes the skin more vulnerable, further increasing the risk of pressure ulcers. In patients with malnutrition, weakened immune function, or circulatory disorders such as diabetes or cardiovascular disease, local tissue hypoxia will be even more severe.
[0005] Currently, clinical treatments for pressure ulcers mainly include medication, physical therapy, and surgery, but all have certain limitations. Medication treatment requires initial debridement based on the severity of the pressure ulcer, followed by the application of ointments that promote tissue regeneration and repair. While these ointments protect the skin and promote wound healing, their antibiotic components may inhibit the immune system's self-healing mechanisms, such as by killing active cells involved in repair within the exudate, thus reducing healing efficiency. Therefore, it is necessary to develop safe, effective, affordable pressure ulcer treatment strategies that improve patient compliance. Summary of the Invention
[0006] To develop a safe, effective, and low-cost treatment strategy for pressure ulcers, this invention provides the application of ferrous salts in the preparation of products for treating pressure ulcers and related pharmaceuticals. The ferrous salts provided by this invention treat pressure ulcers by reducing inflammation and promoting wound contraction and closure.
[0007] This invention provides the application of ferrous salts in the preparation of products for treating pressure ulcers.
[0008] The ferrous salt provided by this invention treats pressure ulcers by reducing inflammation and promoting wound contraction and closure.
[0009] Furthermore, the ferrous salt is any one or a combination of several of ferrous sulfate, ferrous lactate, ferrous chloride, and ferrous gluconate.
[0010] Furthermore, the ferrous salt is used for anti-inflammatory purposes, promoting wound contraction and closure.
[0011] Furthermore, the product is a medicine, disinfectant, or antibacterial agent.
[0012] Furthermore, the drug dosage form is a solution, colloidal, suspension, emulsion, or hydrogel.
[0013] Furthermore, the hydrogel-type drug uses ferrous salt as the active ingredient and is formulated with pharmaceutically acceptable excipients.
[0014] Furthermore, the concentration of ferrous salt in the hydrogel-type drug is 0.5 mM to 2 mM.
[0015] Further, the preparation steps of the hydrogel-type drug are as follows: prepare a ferrous salt solution with a final concentration of 0.5 mM to 2 mM, then add nicotinamide, vitamin B2, sodium alginate, hyaluronic acid and carbomer, and stir until a stable colloid is formed to obtain the hydrogel-type drug.
[0016] Furthermore, the mass fractions of each component in the hydrogel-type drug are: 0.2%–0.3% nicotinamide, 0.01%–0.02% vitamin B2, 0.05%–0.1% sodium alginate, 0.05%–0.1% hyaluronic acid, 0.6%–0.7% carbomer, with the balance being the ferrous salt solution.
[0017] This invention also provides a hydrogel-type drug for treating pressure ulcers, the preparation steps of which are as follows: ferrous lactate and ascorbic acid are dissolved in sterile ultrapure water until the final concentrations of both ferrous salt and ascorbic acid are 0.5 mM to 2 mM, to obtain a mixed solution. The following excipients are added to the mixed solution by mass percentage: 0.2% to 0.3% nicotinamide, 0.01% to 0.02% vitamin B2, 0.05% to 0.1% sodium alginate, 0.05% to 0.1% hyaluronic acid, and 0.6% to 0.7% carbomer. The mixture is stirred at 200 rpm to 300 rpm and 20°C to 24°C until a stable colloid is formed. The final pH of the colloid is adjusted to 5.3 to 5.5 to obtain a ferrous lactate hydrogel.
[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: This invention reveals for the first time the specific application of ferrous salts in treating pressure ulcers, a type of wound distinct from ordinary wounds. Using ferrous salts as the main component, this invention can be combined with various materials such as physiological saline, carrageenan, xanthan gum, low-acyl colloids, hyaluronic acid, carbomer, sodium alginate, and collagen to formulate various dosage forms including solutions, colloids, suspensions, and emulsions. Ferrous ions are naturally abundant and inexpensive, beneficial for the repair of pressure ulcer wounds, and are key substances in promoting wound healing and reducing inflammation. Animal experiments have shown that ferrous saline gel can accelerate the recovery of pressure ulcers, indicating that ferrous ion compound hydrogels can effectively treat pressure ulcers. Furthermore, the prepared ferrous saline gel has no acute skin irritation or acute allergic reaction, exhibiting almost no adverse reactions. Therefore, it can be used as a medicine or daily product for the treatment and care of pressure ulcers, solving the problems of large trauma, complications, and long recovery times associated with existing pressure ulcer treatments. Attached Figure Description
[0019] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0020] Figure 1 Characterization of the rabbit pressure ulcer model.
[0021] Figure 2Comparison of the effects of ferrous saline gel on pressure ulcers on the back of rabbits; Figure 3 Statistical chart of wound closure rate for pressure sores on the back of rabbits treated with ferrous saline gel; Figure 4 Statistical graph of TNF-α expression, a pro-inflammatory factor, on days 3, 7, and 14 after treatment of pressure sores on the back of rabbits with ferrous saline gel. Detailed Implementation
[0022] The specific embodiments of the present invention are described in detail below, but it should be understood that the scope of protection of the present invention is not limited to the specific embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise specified, the experimental methods described in the embodiments of the present invention are conventional methods, and the materials and reagents used in the following embodiments are commercially available unless otherwise specified.
[0023] Example 1: Application of ferrous salts in the preparation of drugs for treating pressure ulcers.
[0024] I. Experimental Methods 1. Preparation of ferrous lactate hydrogel (1) The preparation steps of 0.5mM ferrous lactate hydrogel are as follows: S1. Weigh appropriate amounts of ferrous lactate and ascorbic acid, dissolve them in sterile ultrapure water and stir thoroughly to obtain a mixed solution; wherein the final concentrations of ferrous lactate and ascorbic acid are both 0.5 mM.
[0025] S2, based on the mass percentage of the mixed solution obtained in S1, add the following raw materials in sequence: 0.3% nicotinamide, 0.01% vitamin B2, 0.1% sodium alginate, 0.1% hyaluronic acid, and 0.7% carbomer. Stir at 200 rpm and 20°C for 3 h until a stable colloid is formed.
[0026] S3. Triethanolamine was added dropwise to the colloid obtained in S2 to adjust the final pH of the colloid to 5.5, resulting in a 0.5 mM ferrous lactate hydrogel.
[0027] (2) Preparation of 1 mM ferrous lactate hydrogel S1. Weigh appropriate amounts of ferrous lactate and ascorbic acid, dissolve them in sterile ultrapure water and stir thoroughly to obtain a mixed solution; wherein the final concentration of both ferrous lactate and ascorbic acid is 1 mM.
[0028] S2, based on the mass percentage of the mixed solution obtained in S1, add the following raw materials in sequence: 0.3% nicotinamide, 0.01% vitamin B2, 0.1% sodium alginate, 0.1% hyaluronic acid, and 0.7% carbomer. Stir at 200 rpm and 20°C for 3 h until a stable colloid is formed.
[0029] S3. Triethanolamine was added dropwise to the colloid obtained in S2 to adjust the final pH of the colloid to 5.4, resulting in a 1 mM ferrous lactate hydrogel.
[0030] (3) Preparation of 2 mM ferrous lactate hydrogel S1. Weigh appropriate amounts of ferrous lactate and ascorbic acid, dissolve them in sterile ultrapure water and stir thoroughly to obtain a mixed solution; wherein the final concentrations of both ferrous lactate and ascorbic acid are 2 mM.
[0031] S2, based on the mass percentage of the mixed solution obtained in S1, add the following raw materials in sequence: 0.3% nicotinamide, 0.01% vitamin B2, 0.1% sodium alginate, 0.1% hyaluronic acid, and 0.7% carbomer. Stir at 200 rpm and 20°C for 3 h until a stable colloid is formed.
[0032] S3. Triethanolamine was added dropwise to the colloid obtained in S2 to make the final pH of the colloid 5.3, resulting in a 2 mM ferrous lactate hydrogel.
[0033] (4) Preparation of blank hydrogel The following excipients were added to sterile ultrapure water in the following order, based on the mass percentage of sterile ultrapure water: 0.3% nicotinamide, 0.01% vitamin B2, 0.1% sodium alginate, 0.1% hyaluronic acid, and 0.7% carbomer. The mixture was stirred at 200 rpm and 20°C for 3 h until a stable colloid was formed. Triethanolamine was then added dropwise to the colloid to bring the final pH to 5.5, yielding a blank hydrogel.
[0034] 2. Evaluation of the therapeutic effect of ferrous salt gel on pressure ulcers (1) Establishing a rabbit experimental pressure ulcer model Healthy male rabbits weighing 2.5 kg were selected and acclimatized for one week until their mental state and appetite were stable. All experimental procedures were approved by the Experimental Animal Ethics Committee of Henan University of Science and Technology (Approval No.: LLSC2025078). A dorsal pressure ulcer model was replicated using the magnetic suction method. First, the hair in the modeling area on the back was removed with a trimmer, and depilatory cream was applied to a cotton swab and left to stand for 2 minutes. The residue was then wiped clean with sterile gauze. Anesthesia was then administered, and sodium pentobarbital was injected into the marginal ear vein (dosage adjusted according to body weight). During the procedure, the depth of anesthesia was monitored by corneal reflex, marginal ear reflex, and pain response. The anesthesia was maintained in a suitable state with weakened corneal reflex and no obvious struggling in response to mild pain, avoiding respiratory depression or agitation that could affect model formation.
[0035] After anesthesia takes effect, the midline of the back and the neodymium magnet placement area are marked with a skin marker to ensure consistent compression. Four circular neodymium magnets, each 12 mm in diameter and 5 mm thick, are selected and clamped onto the marked skin area, with approximately 1 cm between the edges of adjacent magnets. After 24 hours of compression, all magnets are removed and relaxed for 24 hours, constituting one cycle of modeling (I / R). Analgesia is administered throughout the process, with daily subcutaneous injections of meloxicam. Pain is assessed based on mental state, activity level, and eating response, and the dosage is adjusted as needed.
[0036] During the modeling period, all animals were housed individually. The modeling area was cleaned with sterile saline solution, and gauze and bandages were used to secure the pressure sores to prevent infection. The animals' mental state, appetite, and weight were monitored daily throughout the process, and any abnormalities were recorded. This cycle was repeated five times, and modeling was considered complete when stage III / IV pressure ulcers were formed.
[0037] Modeling results: The rabbits tolerated the modeling process well. Figure 1 As shown, after the first cycle of magnet pressure, the skin under pressure remained intact, with persistent ischemic pallor at the center of the pressure. After the second cycle of magnet pressure, the skin under pressure showed slight indentation, peripheral redness, and edema in the surrounding tissues. After the fourth cycle of magnet pressure, the integrity of the skin under pressure was compromised, the skin at the center of pressure turned yellow and hardened, and yellow exudate could be expelled upon squeezing, with ulceration around the skin. After the fifth cycle of magnet pressure, eschar formed on the skin under pressure, peripheral redness, and edema in the surrounding muscles.
[0038] (3) Group administration After the pressure ulcer animal model was successfully established, the rabbits were weighed and numbered again, and divided into 5 groups of 3 rabbits each according to the random number table method. The specific grouping is as follows: model control group (CK), blank hydrogel group (KB), 0.5 mM ferrous lactate hydrogel group, 1 mM ferrous lactate hydrogel group, and 2 mM ferrous lactate hydrogel group (the latter 3 groups are collectively referred to as the experimental group).
[0039] After the modeling was completed, all pressure sores on the rabbits were cleaned and treated uniformly, and then different drug administration regimens were implemented according to the groups.
[0040] Model control group (CK): No treatment was applied after debridement; Blank hydrogel group (KB): After debridement, 50 μL of blank hydrogel was applied to the wound. Experimental group: After debridement, 50 μL of ferrous lactate hydrogel of the corresponding concentration was applied to the wounds of rabbits in the corresponding groups (0.5 mM, 1 mM and 2 mM groups used the corresponding concentration of the preparation).
[0041] All treatment groups received twice-daily dosing.
[0042] Wound healing was observed on days 3, 7, 10, and 14, and the healing process was continuously monitored using macroscopic photography. Results were obtained from... Figure 1 It can be seen that, from day 3 to day 7 of healing, the wound shrinkage in the experimental group was more obvious compared with the model group (CK) and the blank hydrogel group (KB); from day 10 to day 14 of healing, the wound area in the experimental group continued to decrease significantly. Among them, the wound shrinkage rate of 2mM ferrous lactate hydrogel (ferrous hydrogel) was the highest, the new epithelial coverage was the most complete, and the wound was basically closed by day 14, with the most significant healing effect.
[0043] Wound closure rate statistics: such as Figure 2 As shown, this invention quantifies the wound area. The wound closure rate in the experimental groups with different concentrations of ferrous lactate hydrogel was significantly higher than that in the model control group at all time points (p<0.05). Particularly on days 7 and 14, the closure rate in the treatment group was significantly higher than that in the model control group. This data demonstrates that ferrous lactate hydrogel can significantly accelerate the healing process of pressure ulcers.
[0044] Wound inflammatory factor expression: The therapeutic effect of ferrous salts was assessed by detecting the levels of key inflammatory factors on days 3, 7, and 14. Figure 3 As shown, compared with the model control group (CK) and the blank hydrogel group (KB), the hydrogel containing ferrous salts (experimental group) significantly modulated the inflammatory microenvironment of the wound. Specifically, the expression of the pro-inflammatory factor TNF-α was significantly inhibited, with the 2 mM ferrous lactate hydrogel showing the most significant inhibitory effect. This demonstrates that ferrous lactate hydrogel can effectively correct the excessive inflammatory response of pressure ulcers by downregulating the pro-inflammatory factor TNF-α, thereby promoting tissue repair.
[0045] Therefore, it can be seen that the preparation containing ferrous salts is effective on the rabbit back model and has the function of treating and caring for pressure sores.
[0046] Although preferred embodiments of the invention have been described, those skilled in the art, once they have learned the basic inventive concept, can make other changes and modifications to these embodiments.
[0047] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.
Claims
1. Application of ferrous salts in the preparation of products for treating pressure ulcers.
2. The application of the divalent ferric salt according to claim 1 in the preparation of products for treating pressure ulcers, characterized in that, The ferrous salt is any one or a combination of several of ferrous sulfate, ferrous lactate, ferrous chloride, and ferrous gluconate.
3. The application of the divalent ferric salt according to claim 2 in the preparation of products for treating pressure ulcers, characterized in that, The ferrous salts are used for anti-inflammatory purposes, promoting wound contraction and closure.
4. The application of the divalent ferric salt according to claim 3 in the preparation of products for treating pressure ulcers, characterized in that, The product is a medicine, disinfectant, or antibacterial agent.
5. The application of the divalent ferric salt according to claim 4 in the preparation of products for treating pressure ulcers, characterized in that, The drug dosage form is a solution, colloidal, suspension, emulsion, or hydrogel.
6. The application of the divalent ferric salt according to claim 5 in the preparation of products for treating pressure ulcers, characterized in that, The hydrogel-type drug uses ferrous salt as the active ingredient and is formulated with pharmaceutically acceptable excipients.
7. The application of the divalent ferric salt according to claim 7 in the preparation of products for treating pressure ulcers, characterized in that, The concentration of ferrous salt in the hydrogel-type drug is 0.5 mM to 2 mM.
8. The application of the divalent ferric salt according to claim 7 in the preparation of products for treating pressure ulcers, characterized in that, The preparation steps of the hydrogel-type drug are as follows: prepare a ferrous salt solution with a final concentration of 0.5 mM to 2 mM, then add nicotinamide, vitamin B2, sodium alginate, hyaluronic acid and carbomer, and stir until a stable colloid is formed to obtain the hydrogel-type drug.
9. The application of the divalent ferric salt according to claim 8 in the preparation of products for treating pressure ulcers, characterized in that, The mass fractions of each component in the hydrogel-type drug are: 0.2%–0.3% nicotinamide, 0.01%–0.02% vitamin B2, 0.05%–0.1% sodium alginate, 0.05%–0.1% hyaluronic acid, 0.6%–0.7% carbomer, and the balance is the ferrous salt solution.
10. A hydrogel-type medicine for treating pressure ulcers, characterized in that, The hydrogel-type drug is the hydrogel-type drug of claim 9, and its preparation steps are as follows: ferrous salt and ascorbic acid are dissolved in sterile ultrapure water until the final concentrations of ferrous lactate and ascorbic acid are both 0.5 mM to 2 mM to obtain a mixed solution. The following excipients are added to the mixed solution by mass percentage: 0.2% to 0.3% nicotinamide, 0.01% to 0.02% vitamin B2, 0.05% to 0.1% sodium alginate, 0.05% to 0.1% hyaluronic acid, and 0.6% to 0.7% carbomer. The mixture is stirred at 200 rpm to 300 rpm and 20°C to 24°C until a stable colloid is formed. The final pH of the colloid is adjusted to 5.3 to 5.5 to obtain ferrous lactate hydrogel.