Hydrogel dressing and dressing plaster
Technical Field
The invention relates to the field of medical dressings, in particular to a hydrogel dressing and a dressing patch prepared from the dressing.
Background
Wounds are skin defects caused by mechanical, electrical, thermal, chemical, etc. factors or formed by medical or physiological allergies. Wounds can be classified into three major categories, chronic wounds, traumatic wounds and surgical wounds, according to the medical background of the wounds. Among them, the most typical examples of chronic wounds are bedsores and leg ulcers; wounds include cuts, abrasions, burns and the like; the formation of surgical wounds is conscious and controlled, and healing of such wounds is generally problematic. In order to promote faster healing of a wound, the wound is typically dressed to provide a suitable healing environment for the wound.
In accordance with the "wet healing theory" of wounds, suitable dressings provide a moist healing environment for the wound. The wound keeps a certain degree of wetness, epidermal cells can be prevented from creeping around the crust, normal potential gradient from the wound edge to the center of the wound surface can be maintained, the growth of endothelial cells, capillaries and fibroblasts is stimulated, the division and proliferation of keratinocytes are facilitated, and the combination of growth factor receptors and growth factors is promoted, so that the healing of the wound surface is accelerated. However, the wound exudate is accumulated too much, which will impregnate the surrounding normal tissues to enlarge the wound area and increase the chance of wound infection.
At present, the dressings which are most used clinically are traditional medical dressings represented by cotton balls, bandages and gauzes, although the inert dressings have the advantages of certain absorbability, simplicity in manufacturing, low price, reusability and the like, the dressings cannot keep the wound surfaces moist, the wounds are easily infected due to the pollution of exudates after secretion is absorbed, and meanwhile granulation tissues of the wound surfaces can grow into meshes of the dressings to be adhered to the dressings, so that secondary damage to new tissues is easily caused when the dressings are changed or removed, and patients feel pain; furthermore, those new dressings marketed, such as hydrogel and hydrocolloid dressings, have a good moisturizing effect but a poor ability to absorb exudates, whereas foam dressings can absorb a large amount of exudates but have no very poor moisturizing ability.
Therefore, there is a need to develop a dressing that can keep the wound surface wet and absorb the exudate well.
Disclosure of Invention
In view of the above, an object of the present invention is to provide a hydrogel dressing, which is prepared by adding polymalic acid during synthesis, wherein the low pH of the hydrogel dressing can achieve good bacteriostatic effect, and has good biocompatibility and biodegradability; the second purpose of the invention is to provide a dressing patch which can maintain the moisture degree of a wound and absorb exudates so as to accelerate the healing of the wound. The invention also aims to provide a hydrogel dressing or an application of the dressing as a bacteriostatic material.
In order to achieve the purpose, the invention provides the following technical scheme:
1. the hydrogel dressing is prepared by cross-linking polymalic acid and a high polymer material. The crosslinking can be prepared by physical or chemical methods.
In the invention, the mass fraction of the polymalic acid in the hydrogel dressing is 0.25-2%; the mass fraction of the high polymer material is 5-7%.
Wherein the polymer material can be natural polymer material, artificially synthesized polymer material, inorganic material, such as: polyvinyl alcohol.
Preferably, the hydrogel dressing is prepared by the following method: and (3) blending the polyvinyl alcohol aqueous solution with the concentration of 10wt% and the polymalic acid aqueous solution with the concentration of 10wt% according to a proportion, fully and uniformly mixing, and repeatedly freezing and thawing to obtain the hydrogel dressing.
More preferably, the method for fully and uniformly mixing is to stir the mixed solution at room temperature at a rotation speed of 500r/min for 30min, and then ultrasonically treat the mixed solution for 10min.
More preferably, the repeated freezing-thawing is freezing at-20 ℃ for 20h, thawing at room temperature for 4h, and repeating the cycle 3 times.
2. A dressing patch containing the hydrogel dressing.
The dressing patch comprises an adhesion layer, a dressing layer and release paper, wherein the dressing layer is positioned between the adhesion layer and the release paper, and the length and the width of the dressing layer are both smaller than those of the adhesion layer and the release paper;
the dressing layer consists of a waterproof breathable layer, a water absorption layer and a hydrogel layer, wherein one side of the waterproof breathable layer is connected with the adhesion layer, the other side of the waterproof breathable layer is connected with the water absorption layer, and the hydrogel layer is embedded in the water absorption layer.
The dressing patch adopting the structure has good moisture retention, air permeability and water resistance, and can ensure the maximum play of bacteriostasis and drug effect.
In the invention, the surface area of the hydrogel layer accounts for 20-70% of the surface area of the water absorbing layer; more preferably, the surface area of the hydrogel layer is about 50% of the surface area of the entire absorbent layer.
In the invention, a groove structure is arranged in the middle of the water absorption layer, and the hydrogel layer is attached to the groove structure in the middle of the water absorption layer. The groove structure can be various, including square, rectangular, circular, oval, polygonal, etc.
More preferably, the waterproof breathable layer is a microporous film, the size of micropores is 0.1-50 microns, and a polyvinylidene fluoride film (PVDF) or a polyurethane film (Pu) is preferred.
In the invention, drugs can be added into the hydrogel, or the hydrogel is freeze-dried and put into a drug solution for inhalation; the medicine types are also various, can be western medicines, also can be traditional Chinese medicines, and simultaneously can be the combination of the western medicines and the Chinese medicines; may be a single one or a mixture of a plurality of them.
3. The hydrogel dressing or the dressing paste is applied to being used as a bacteriostatic material.
The invention has the beneficial effects that: the invention discloses a hydrogel dressing, which is prepared by adding polymalic acid during synthesis, has a good bacteriostatic action at a low pH value and good biocompatibility and biodegradability, is used for wound repair, and is embedded into a water absorbing layer in order to obtain an optimal using effect, namely, the hydrogel dressing has the moisturizing and bacteriostatic action on a wound, and also has the capability of absorbing exudate, small volume and good comfort in practical use.
Drawings
In order to make the object, technical scheme and beneficial effect of the invention more clear, the invention provides the following drawings for explanation:
FIG. 1 is a schematic representation of a hydrogel.
FIG. 2 shows the bacteriostatic effect of the proportional composite hydrogel (a is the bacteriostatic effect of Escherichia coli, b is the bacteriostatic effect of Staphylococcus aureus).
FIG. 3 shows the water absorption effect of composite hydrogels with different ratios.
Figure 4 moisturizing effect of composite hydrogels of different proportions.
Fig. 5 is a three-dimensional structure of the dressing patch.
Fig. 6 is a three-dimensional cross-sectional structure of the dressing patch.
Detailed Description
The present invention is further described below in conjunction with the drawings and the embodiments so that those skilled in the art can better understand the present invention and can implement the present invention, but the embodiments are not to be construed as limiting the present invention.
Example 1 preparation of hydrogel Material
Accurately weighing appropriate amount of PVA (polyvinyl alcohol) into ultrapure water, swelling for 2h under 70 deg.C water bath heating, and stirring at 500r/min for 1h at 90 deg.C to obtain uniform PVA solution of 10wt%; accurately weighing 50% PMLA aqueous solution, adding ultrapure water, and stirring to obtain 10wt% PMLA solution. Respectively controlling the final concentration of PVA to be 5-7 wt% and the final concentration of PMLA to be 0-1 wt% according to a certain proportion for the PMLA solution and the PVA solution; after mixing, stirring the mixed solution at the room temperature at the rotating speed of 500r/min for 30min, then carrying out ultrasonic treatment on the mixed solution for 10min, pouring the uniformly mixed solution into a culture dish, freezing for 20h at the temperature of minus 20 ℃, taking out and unfreezing for 4h at the room temperature, and carrying out freezing-unfreezing cycle for 3 times to prepare the PMLA/PVA composite hydrogel, as shown in figure 1.
The prepared hydrogel is subjected to an antibacterial experiment, composite hydrogel with 5% of PVA and 0%, 0.25%, 0.5% and 1% of PMLA is taken as a research object, and the antibacterial performance of the gel is evaluated by an antibacterial ring method. Appropriate amounts of escherichia coli and staphylococcus aureus were respectively and uniformly spread on the surface of nutrient agar plate medium, composite hydrogel (D =6 mm) gel sheets were placed on the medium, incubated at 37 ℃ for 12 hours, and the bacterial growth around the sheets was observed, with the results shown in fig. 2. The result shows that the prepared hydrogel has antibacterial effect on both escherichia coli and staphylococcus aureus.
And (3) swelling ratio determination: weighing a proper amount of hydrogel after freeze drying and recording as m0, soaking the xerogel in pure water, taking out the gel after 24h, wiping off the moisture on the surface of the gel by using filter paper, weighing the mass as mt, and taking an average value of three parallel samples in each group. The swelling degree SR (%) of the hydrogel for 24h was calculated as follows: SR = (mt-m 0)/m 0 × 100%. The results are shown in FIG. 3, which shows that the swelling degree is highest at 0.25% PMLA.
And (3) measuring the moisture supply rate: a35% (w/v) gelatin solution is prepared by using deionized water, the gelatin solution is naturally solidified after cooling to serve as simulated dry skin, the weight of the simulated skin at the moment is measured to be w2, material samples (D =13mm, T = 0.2cm) are attached to the surface of the simulated skin, and the mass of the simulated skin attached to each sample is fixed to be w2. After standing at room temperature for 24h, the material was removed, the weight of the simulated skin at this time was determined as w3, and the moisture uptake (MG) of the material was calculated by taking the average of three parallel samples in each group as follows: MG = (w 3-w 2)/w 2 × 100%, and the results are shown in fig. 4. The results show that the moisture permeability is highest at a PMLA of 0.25% and the effect is best at a PVA of 5%.
Example 2 dressing Patch
The dressing patch structure is shown in fig. 5 and 6. The moisture-keeping and water-absorbing dressing structure comprises an adhesion layer 1, a dressing layer and release paper 5, wherein the dressing layer is located between the adhesion layer 1 and the release paper 5, the length and the width of the dressing layer are both smaller than the adhesion layer 1 and the release paper 5, the length and the width of the release paper 5 are not smaller than the adhesion layer 1, small air holes are formed in the adhesion layer 1, good air permeability is achieved, and the dressing can be applied to a wound part through adhesion.
Wherein the dressing layer is composed of a waterproof breathable layer 2, a water absorption layer 3 and a hydrogel layer 4, wherein one side of the waterproof breathable layer 2 is connected with the adhesion layer 1, the other side is connected with the water absorption layer 3, and the hydrogel layer 4 is embedded in the water absorption layer 3.
In this embodiment, the waterproof breathable layer 2 is a microporous film, such as a polyvinylidene fluoride (PVDF) film or a polyurethane (Pu) film, the size of the micropores is 0.1 to 50 μm, and water vapor can penetrate through the film but liquid cannot penetrate through the film; the water absorption layer 3 is used for absorbing secretion and can be made of foam material; the middle of the water absorption layer 3 is provided with a groove structure, and the shape of the groove can be square, rectangular, circular, oval, polygonal and the like. The hydrogel layer 4 is attached to the groove structure in the middle of the water absorption layer 3. Preferably, the surface area of the hydrogel layer 4 occupies at least 20% to 70% of the surface area of the water-absorbing layer 3, and the surface area of the hydrogel layer 4 occupies about 50% of the surface area of the whole water-absorbing layer 3, so that a large amount of exudate can be absorbed while keeping moisture.
When in use, the release paper 5 is taken away and then attached to an affected part, the adhesive is adhered to the skin without binding, and the foam layer and the hydrogel layer of the dressing can be in contact with the skin, so that moisture can be preserved, and water can be absorbed.
The hydrogel layer is prepared by using polymalic acid and other high polymer materials through a freezing and thawing method, functional medicines can be added in the preparation process, the types of the medicines are also various, and the medicines can be western medicines, chinese medicines and Chinese and western medicines; may be a single one or a mixture of a plurality of the above. The use of the drug can be selected according to the specific situation of the wound, and the curcumin is taken as an example in the invention.
The prepared dressing paste is subjected to cytotoxicity experiments, and specifically comprises the following steps:
the MTT method was used to determine the cytotoxicity of the composite hydrogel (PVA 5wt%, PMLA0.25wt%) with the best water absorption. Completely soaking the dressing subjected to ultraviolet sterilization for 1h in a complete culture medium according to the proportion of m dressing/v complete culture medium =50mg/mL, leaching in a water bath at 37 ℃ for 24h to obtain a leaching liquor stock solution, filtering and sterilizing the leaching liquor, and storing at 4 ℃ for later use.
Taking L-929 in logarithmic phase, digesting, and regulating L-929 concentration to 2 × 10 4 One/ml, 100. Mu.l per well were inoculated into 96-well plates and 200. Mu.l of complete medium was added to the marginal wells. Standing at 37 deg.C, 5% CO 2 After the cells adhere to the wall, 100 mul of leaching liquor is added into each hole. Complete culture medium is used as a blank control, complete culture medium plus cells are used as a negative control, complete culture medium plus a commercial dressing 50mg/mL leaching liquor is used as a positive control, and each group is provided with 5 multiple wells. Adding sample solution, culturing for 5 days, taking plate every day, adding 20 μ LMTT (PBS prepared 5 mg/ml) in each well, culturing for 4h to form formazan, removing all liquid in the well, adding 150 μ LDMSO solution in each well, shaking for 15min in a microplate reader at low speed, and measuring its absorbance value at λ =490 nm. Toxicity of cells was determined by calculating Relative Growth Rate (RGR)%) of cells: RGR = (OD experimental-OD blank)/(OD negative control-OD blank), toxicity rating of material is shown in table 1, wherein above grade 2 is considered as the presence of cytotoxic reaction, and scoring results are shown in table 2.
TABLE 1 comparison of material toxicity scores
TABLE 2 cytotoxicity of composite hydrogels
Note: the blank gel is PVA/PMLA composite hydrogel without curcumin, and the positive control is a commercially available hydrogel dressing.
From the above results, it can be seen that the hydrogel dressing prepared by the present invention has low cytotoxicity and no cytotoxic reaction.
The above-mentioned embodiments are merely preferred embodiments for fully illustrating the present invention, and the scope of the present invention is not limited thereto. The equivalent substitution or change made by the technical personnel in the technical field on the basis of the invention is all within the protection scope of the invention. The protection scope of the invention is subject to the claims.